Case Reports

Trichoblastomas are rare cutaneous tumors that recapitulate the germinative hair bulb and the surrounding mesenchyme. Although benign, they can present diagnostic difficulties for both the clinician and pathologist because of their rarity and overlap both clinically and microscopically with other follicular neoplasms as well as basal cell carcinoma (BCC). Several classification schemes for hair follicle neoplasms have been established based on the relative proportions of epithelial and mesenchymal components as well as stromal inductive change, but nomenclature continues to be problematic, as individual neoplasms show varying degrees of differentiation that do not always uniformly fit within these categories.^1,2 One of these established categories is a pigmented trichoblastoma.³ An exceedingly rare variant of a pigmented trichoblastoma referred to as melanotrichoblastoma was first described in 2002⁴ and has only been documented in 3 cases, according to a PubMed search of articles indexed for MEDLINE using the term melanotrichoblastoma.^4-6 We report another case of this rare tumor and review the literature on this unique group of tumors.

Case Report

A 25-year-old white woman with a medical history of chronic migraines, myofascial syndrome, and Arnold-Chiari malformation type I presented to dermatology with a 1.5-cm, pedunculated, well-circumscribed tumor on the left side of the scalp (Figure 1). The tumor was grossly flesh colored with heterogeneous areas of dark pigmentation. Microscopic examination demonstrated that within the superficial and deep dermis were variable-sized nests of basaloid cells. Some of the nests had large central cystic spaces with brown pigment within some of these spaces and focal pigmentation of the basaloid cells (Figure 2A). Focal areas of keratinization were present. Mitotic figures were easily identified; however, no atypical mitotic figures were present. Areas of peripheral palisading were present but there was no retraction artifact. Connection to the overlying epidermis was not identified. Surrounding the basaloid nodules was a mildly cellular proliferation of cytologically bland spindle cells. Occasional pigment-laden macrophages were present in the dermis. Focal areas suggestive of papillary mesenchymal body formation were present (Figure 2B). Immunohistochemical staining for Melan-A was performed and demonstrated the presence of a prominent number of melanocytes in some of the nests (Figure 3) and minimal to no melanocytes in other nests. There was no evidence of a melanocytic lesion involving the overlying epidermis. Features of nevus sebaceus were not present. Immunohistochemical staining for cytokeratin (CK) 20 was performed and demonstrated no notable number of Merkel cells within the lesion.

Comment

Overview of Trichoblastomas
Trichoblastomas most often present as solitary, flesh-colored, well-circumscribed, slow-growing tumors that usually progress in size over months to years. Although they may be present at any age, they most commonly occur in adults in the fifth to seventh decades of life and are equally distributed between males and females.^7,8 They most often occur on the head and neck with a predilection for the scalp. Although they behave in a benign fashion, cases of malignant trichoblastomas have been reported.⁹

Histopathology
Histologically, these tumors are well circumscribed but unencapsulated and usually located within the deep dermis, often with extension into the subcutaneous tissue. An epidermal connection is not identified. The tumor typically is composed of variable-sized nests of basaloid cells surrounded by a variable cellular stromal component. Although peripheral palisading is present in the basaloid component, retraction artifact is not present. Several histologic variants of trichoblastomas have been reported including cribriform, racemiform, retiform, pigmented, giant, subcutaneous, rippled pattern, and clear cell.⁵ Pigmented trichoblastomas are histologically similar to typical trichoblastomas, except for the presence of large amounts of melanin deposited within and around the tumor nests.⁶ A melanotrichoblastoma is a rare variant of a pigmented trichoblastoma; pigment is present in the lesion and melanocytes are identified within the basaloid nests.

The stromal component of trichoblastomas may show areas of condensation associated with some of the basaloid cells, resembling an attempt at hair bulb formation. Staining for CD10 will be positive in these areas of papillary mesenchymal bodies.¹⁰

In an immunohistochemical study of 13 cases of trichoblastomas, there was diffuse positive staining for CK14 and CK17 in all cases (similar to BCC) and positive staining for CK19 in 70% (9/13) of cases compared to 21% (4/19) of BCC cases. Staining for CK8 and CK20 demonstrated the presence of numerous Merkel cells in all trichoblastomas but in none of the 19 cases of BCC tested.¹¹ However, other studies have reported the presence of Merkel cells in only 42% to 70% of trichoblastomas.^12,13 Despite the lack of Merkel cells in our case, the lesion was interpreted as a melanotrichoblastoma based on the histologic features in conjunction with the presence of the melanocytes.

Differential Diagnosis
The clinical and histologic differential diagnosis of trichoblastomas includes both trichoepithelioma and BCC. Clinically, all 3 lesions often are slow growing, dome shaped, and small in size (several millimeters), and are observed in the same anatomic distribution of the head and neck region. Furthermore, they often affect middle-aged to older individuals and those of Caucasian descent, though other ethnicities can be affected. Histologic evaluation often is necessary to differentiate between these 3 entities.

Histologically, trichoepitheliomas are composed of nodules of basaloid cells encircled by stromal spindle cells. Although there can be histologic overlap between trichoepitheliomas and trichoblastoma, trichoepitheliomas typically will display obvious features of hair follicle differentiation with the presence of small keratinous cysts and hair bulb structures, while trichoblastomas tend to display minimal changes suggestive of its hair follicle origin. Similar to trichoblastomas, BCC is composed of nests of basaloid cells; however, BCCs often demonstrate retraction artifact and connection to the overlying epidermis. In addition, BCCs typically demonstrate a fibromucinous stromal component that is distinct from the cellular stroma of trichoblastic tumors. Immunoperoxidase staining for androgen receptors has been reported to be positive in 78% (25/32) of BCCs and negative in trichoblastic tumors.¹⁴

Melanotrichoblastoma Differentiating Characteristics
An exceedingly rare variant of pigmented trichoblastoma is the melanotrichoblastoma. There are clinical and histologic similarities and differences between the reported cases. The first case, described by Kanitakis et al,⁴ reported a 32-year-old black woman with a 2-cm scalp mass that slowly enlarged over the course of 2 years. The second case, presented by Kim et al,⁵ described a 51-year-old Korean man with a subcutaneous 6-cm mass on the back that had been present and slowly enlarging over the course of 5 years. The third case, reported by Hung et al,⁶ described a 34-year-old Taiwanese man with a 1-cm, left-sided, temporal scalp mass present for 3 years, arising from a nevus sebaceous. Comparing these clinical findings with our case of a 25-year-old white woman with a 1.5-cm mass on the left side of the scalp, melanotrichoblastomas demonstrate a relatively similar age of onset in the early to middle-aged adult years. All 4 tumors were slow growing. Additionally, 3 of 4 cases demonstrated a predilection for the head, particularly the scalp, and grossly showed well-circumscribed lesions with notable pigmentation. Although age, size, location, and gross appearance were similar, a comparable ethnic and gender demographic was not identified.

Microscopic similarities between the 4 cases were present. Each case was characterized by a large, well-circumscribed, unencapsulated, basaloid tumor present in the lower dermis, with only 1 case having tumor cells occasionally reaching the undersurface of the epidermis. The tumor cells were monomorphic round-ovoid in appearance with scant cytoplasm. There was melanin pigment in the basaloid nests. The basaloid nests were surrounded by a proliferation of stromal cells. The mitotic rate was sparse in 2 cases, brisk in 1 case, and not discussed in 1 case. Melanocytes were identified in the basaloid nests in all 4 cases; however, in the current case, the melanocytes were seen in only some of the nests. None of the cases exhibited an overlying junctional melanocytic lesion, which would argue against a possible collision tumor or colonization of an epithelial lesion by a melanocytic lesion.

Although the histologic features of our cases are consistent with prior reports of melanotrichoblastoma, there is some question as to whether it represents a true variant of a pigmented trichoblastoma. There are relatively few articles in the literature that describe pigmented trichoblastomas, and of those, immunohistochemistry staining for melanocytes is uncommon. In one of the earliest descriptions of a pigmented trichoblastoma, dendritic melanocytes were present within the tumor lobules; however, the lesion was reported as a pigmented trichoblastoma and not a melanotrichoblastoma.³ It is possible that all pigmented trichoblastomas may contain some number of dendritic melanocytes, thus negating the existence of a melanotrichoblastoma as a true subtype of pigmented trichoblastomas. Additional study looking at multiple examples of pigmented trichoblastomas would be required to more definitively classify melanotrichoblastomas. It is important to appreciate that at least some cases of pigmented trichoblastomas may contain melanocytes and not to confuse the lesion as representing an example of colonization or collision tumor. A rare case of melanoma possibly arising from these dendritic melanocytes has been reported.¹⁵

Conclusion

Trichoblastomas are uncommon tumors of germinative hair bulb origin that can have several histologic variants. A well-documented subtype of trichoblastoma characterized by melanin deposits within and around tumor nests has been identified and classified as a pigmented trichoblastoma. Four cases of melanotrichoblastoma have been reported and represent a variant of a pigmented trichoblastoma characterized by the presence of melanocytes within the lesion. Whether they represent a true variant is of some debate and additional study is required. Although these tumors are exceedingly rare, it is important for the clinician and pathologist to be aware of this entity to prevent confusion with other similarly appearing follicular lesions, most notably BCCs, because of the difference in treatment and follow-up.

Trichoblastomas are rare cutaneous tumors that recapitulate the germinative hair bulb and the surrounding mesenchyme. Although benign, they can present diagnostic difficulties for both the clinician and pathologist because of their rarity and overlap both clinically and microscopically with other follicular neoplasms as well as basal cell carcinoma (BCC). Several classification schemes for hair follicle neoplasms have been established based on the relative proportions of epithelial and mesenchymal components as well as stromal inductive change, but nomenclature continues to be problematic, as individual neoplasms show varying degrees of differentiation that do not always uniformly fit within these categories.^1,2 One of these established categories is a pigmented trichoblastoma.³ An exceedingly rare variant of a pigmented trichoblastoma referred to as melanotrichoblastoma was first described in 2002⁴ and has only been documented in 3 cases, according to a PubMed search of articles indexed for MEDLINE using the term melanotrichoblastoma.^4-6 We report another case of this rare tumor and review the literature on this unique group of tumors.

Case Report

A 25-year-old white woman with a medical history of chronic migraines, myofascial syndrome, and Arnold-Chiari malformation type I presented to dermatology with a 1.5-cm, pedunculated, well-circumscribed tumor on the left side of the scalp (Figure 1). The tumor was grossly flesh colored with heterogeneous areas of dark pigmentation. Microscopic examination demonstrated that within the superficial and deep dermis were variable-sized nests of basaloid cells. Some of the nests had large central cystic spaces with brown pigment within some of these spaces and focal pigmentation of the basaloid cells (Figure 2A). Focal areas of keratinization were present. Mitotic figures were easily identified; however, no atypical mitotic figures were present. Areas of peripheral palisading were present but there was no retraction artifact. Connection to the overlying epidermis was not identified. Surrounding the basaloid nodules was a mildly cellular proliferation of cytologically bland spindle cells. Occasional pigment-laden macrophages were present in the dermis. Focal areas suggestive of papillary mesenchymal body formation were present (Figure 2B). Immunohistochemical staining for Melan-A was performed and demonstrated the presence of a prominent number of melanocytes in some of the nests (Figure 3) and minimal to no melanocytes in other nests. There was no evidence of a melanocytic lesion involving the overlying epidermis. Features of nevus sebaceus were not present. Immunohistochemical staining for cytokeratin (CK) 20 was performed and demonstrated no notable number of Merkel cells within the lesion.

Comment

Overview of Trichoblastomas
Trichoblastomas most often present as solitary, flesh-colored, well-circumscribed, slow-growing tumors that usually progress in size over months to years. Although they may be present at any age, they most commonly occur in adults in the fifth to seventh decades of life and are equally distributed between males and females.^7,8 They most often occur on the head and neck with a predilection for the scalp. Although they behave in a benign fashion, cases of malignant trichoblastomas have been reported.⁹

Histopathology
Histologically, these tumors are well circumscribed but unencapsulated and usually located within the deep dermis, often with extension into the subcutaneous tissue. An epidermal connection is not identified. The tumor typically is composed of variable-sized nests of basaloid cells surrounded by a variable cellular stromal component. Although peripheral palisading is present in the basaloid component, retraction artifact is not present. Several histologic variants of trichoblastomas have been reported including cribriform, racemiform, retiform, pigmented, giant, subcutaneous, rippled pattern, and clear cell.⁵ Pigmented trichoblastomas are histologically similar to typical trichoblastomas, except for the presence of large amounts of melanin deposited within and around the tumor nests.⁶ A melanotrichoblastoma is a rare variant of a pigmented trichoblastoma; pigment is present in the lesion and melanocytes are identified within the basaloid nests.

The stromal component of trichoblastomas may show areas of condensation associated with some of the basaloid cells, resembling an attempt at hair bulb formation. Staining for CD10 will be positive in these areas of papillary mesenchymal bodies.¹⁰

In an immunohistochemical study of 13 cases of trichoblastomas, there was diffuse positive staining for CK14 and CK17 in all cases (similar to BCC) and positive staining for CK19 in 70% (9/13) of cases compared to 21% (4/19) of BCC cases. Staining for CK8 and CK20 demonstrated the presence of numerous Merkel cells in all trichoblastomas but in none of the 19 cases of BCC tested.¹¹ However, other studies have reported the presence of Merkel cells in only 42% to 70% of trichoblastomas.^12,13 Despite the lack of Merkel cells in our case, the lesion was interpreted as a melanotrichoblastoma based on the histologic features in conjunction with the presence of the melanocytes.

Differential Diagnosis
The clinical and histologic differential diagnosis of trichoblastomas includes both trichoepithelioma and BCC. Clinically, all 3 lesions often are slow growing, dome shaped, and small in size (several millimeters), and are observed in the same anatomic distribution of the head and neck region. Furthermore, they often affect middle-aged to older individuals and those of Caucasian descent, though other ethnicities can be affected. Histologic evaluation often is necessary to differentiate between these 3 entities.

Histologically, trichoepitheliomas are composed of nodules of basaloid cells encircled by stromal spindle cells. Although there can be histologic overlap between trichoepitheliomas and trichoblastoma, trichoepitheliomas typically will display obvious features of hair follicle differentiation with the presence of small keratinous cysts and hair bulb structures, while trichoblastomas tend to display minimal changes suggestive of its hair follicle origin. Similar to trichoblastomas, BCC is composed of nests of basaloid cells; however, BCCs often demonstrate retraction artifact and connection to the overlying epidermis. In addition, BCCs typically demonstrate a fibromucinous stromal component that is distinct from the cellular stroma of trichoblastic tumors. Immunoperoxidase staining for androgen receptors has been reported to be positive in 78% (25/32) of BCCs and negative in trichoblastic tumors.¹⁴

Melanotrichoblastoma Differentiating Characteristics
An exceedingly rare variant of pigmented trichoblastoma is the melanotrichoblastoma. There are clinical and histologic similarities and differences between the reported cases. The first case, described by Kanitakis et al,⁴ reported a 32-year-old black woman with a 2-cm scalp mass that slowly enlarged over the course of 2 years. The second case, presented by Kim et al,⁵ described a 51-year-old Korean man with a subcutaneous 6-cm mass on the back that had been present and slowly enlarging over the course of 5 years. The third case, reported by Hung et al,⁶ described a 34-year-old Taiwanese man with a 1-cm, left-sided, temporal scalp mass present for 3 years, arising from a nevus sebaceous. Comparing these clinical findings with our case of a 25-year-old white woman with a 1.5-cm mass on the left side of the scalp, melanotrichoblastomas demonstrate a relatively similar age of onset in the early to middle-aged adult years. All 4 tumors were slow growing. Additionally, 3 of 4 cases demonstrated a predilection for the head, particularly the scalp, and grossly showed well-circumscribed lesions with notable pigmentation. Although age, size, location, and gross appearance were similar, a comparable ethnic and gender demographic was not identified.

Microscopic similarities between the 4 cases were present. Each case was characterized by a large, well-circumscribed, unencapsulated, basaloid tumor present in the lower dermis, with only 1 case having tumor cells occasionally reaching the undersurface of the epidermis. The tumor cells were monomorphic round-ovoid in appearance with scant cytoplasm. There was melanin pigment in the basaloid nests. The basaloid nests were surrounded by a proliferation of stromal cells. The mitotic rate was sparse in 2 cases, brisk in 1 case, and not discussed in 1 case. Melanocytes were identified in the basaloid nests in all 4 cases; however, in the current case, the melanocytes were seen in only some of the nests. None of the cases exhibited an overlying junctional melanocytic lesion, which would argue against a possible collision tumor or colonization of an epithelial lesion by a melanocytic lesion.

Although the histologic features of our cases are consistent with prior reports of melanotrichoblastoma, there is some question as to whether it represents a true variant of a pigmented trichoblastoma. There are relatively few articles in the literature that describe pigmented trichoblastomas, and of those, immunohistochemistry staining for melanocytes is uncommon. In one of the earliest descriptions of a pigmented trichoblastoma, dendritic melanocytes were present within the tumor lobules; however, the lesion was reported as a pigmented trichoblastoma and not a melanotrichoblastoma.³ It is possible that all pigmented trichoblastomas may contain some number of dendritic melanocytes, thus negating the existence of a melanotrichoblastoma as a true subtype of pigmented trichoblastomas. Additional study looking at multiple examples of pigmented trichoblastomas would be required to more definitively classify melanotrichoblastomas. It is important to appreciate that at least some cases of pigmented trichoblastomas may contain melanocytes and not to confuse the lesion as representing an example of colonization or collision tumor. A rare case of melanoma possibly arising from these dendritic melanocytes has been reported.¹⁵

Conclusion

Trichoblastomas are uncommon tumors of germinative hair bulb origin that can have several histologic variants. A well-documented subtype of trichoblastoma characterized by melanin deposits within and around tumor nests has been identified and classified as a pigmented trichoblastoma. Four cases of melanotrichoblastoma have been reported and represent a variant of a pigmented trichoblastoma characterized by the presence of melanocytes within the lesion. Whether they represent a true variant is of some debate and additional study is required. Although these tumors are exceedingly rare, it is important for the clinician and pathologist to be aware of this entity to prevent confusion with other similarly appearing follicular lesions, most notably BCCs, because of the difference in treatment and follow-up.

Trichoblastomas are rare cutaneous tumors that recapitulate the germinative hair bulb and the surrounding mesenchyme. Although benign, they can present diagnostic difficulties for both the clinician and pathologist because of their rarity and overlap both clinically and microscopically with other follicular neoplasms as well as basal cell carcinoma (BCC). Several classification schemes for hair follicle neoplasms have been established based on the relative proportions of epithelial and mesenchymal components as well as stromal inductive change, but nomenclature continues to be problematic, as individual neoplasms show varying degrees of differentiation that do not always uniformly fit within these categories.^1,2 One of these established categories is a pigmented trichoblastoma.³ An exceedingly rare variant of a pigmented trichoblastoma referred to as melanotrichoblastoma was first described in 2002⁴ and has only been documented in 3 cases, according to a PubMed search of articles indexed for MEDLINE using the term melanotrichoblastoma.^4-6 We report another case of this rare tumor and review the literature on this unique group of tumors.

Case Report

A 25-year-old white woman with a medical history of chronic migraines, myofascial syndrome, and Arnold-Chiari malformation type I presented to dermatology with a 1.5-cm, pedunculated, well-circumscribed tumor on the left side of the scalp (Figure 1). The tumor was grossly flesh colored with heterogeneous areas of dark pigmentation. Microscopic examination demonstrated that within the superficial and deep dermis were variable-sized nests of basaloid cells. Some of the nests had large central cystic spaces with brown pigment within some of these spaces and focal pigmentation of the basaloid cells (Figure 2A). Focal areas of keratinization were present. Mitotic figures were easily identified; however, no atypical mitotic figures were present. Areas of peripheral palisading were present but there was no retraction artifact. Connection to the overlying epidermis was not identified. Surrounding the basaloid nodules was a mildly cellular proliferation of cytologically bland spindle cells. Occasional pigment-laden macrophages were present in the dermis. Focal areas suggestive of papillary mesenchymal body formation were present (Figure 2B). Immunohistochemical staining for Melan-A was performed and demonstrated the presence of a prominent number of melanocytes in some of the nests (Figure 3) and minimal to no melanocytes in other nests. There was no evidence of a melanocytic lesion involving the overlying epidermis. Features of nevus sebaceus were not present. Immunohistochemical staining for cytokeratin (CK) 20 was performed and demonstrated no notable number of Merkel cells within the lesion.

Comment

Overview of Trichoblastomas
Trichoblastomas most often present as solitary, flesh-colored, well-circumscribed, slow-growing tumors that usually progress in size over months to years. Although they may be present at any age, they most commonly occur in adults in the fifth to seventh decades of life and are equally distributed between males and females.^7,8 They most often occur on the head and neck with a predilection for the scalp. Although they behave in a benign fashion, cases of malignant trichoblastomas have been reported.⁹

Histopathology
Histologically, these tumors are well circumscribed but unencapsulated and usually located within the deep dermis, often with extension into the subcutaneous tissue. An epidermal connection is not identified. The tumor typically is composed of variable-sized nests of basaloid cells surrounded by a variable cellular stromal component. Although peripheral palisading is present in the basaloid component, retraction artifact is not present. Several histologic variants of trichoblastomas have been reported including cribriform, racemiform, retiform, pigmented, giant, subcutaneous, rippled pattern, and clear cell.⁵ Pigmented trichoblastomas are histologically similar to typical trichoblastomas, except for the presence of large amounts of melanin deposited within and around the tumor nests.⁶ A melanotrichoblastoma is a rare variant of a pigmented trichoblastoma; pigment is present in the lesion and melanocytes are identified within the basaloid nests.

The stromal component of trichoblastomas may show areas of condensation associated with some of the basaloid cells, resembling an attempt at hair bulb formation. Staining for CD10 will be positive in these areas of papillary mesenchymal bodies.¹⁰

In an immunohistochemical study of 13 cases of trichoblastomas, there was diffuse positive staining for CK14 and CK17 in all cases (similar to BCC) and positive staining for CK19 in 70% (9/13) of cases compared to 21% (4/19) of BCC cases. Staining for CK8 and CK20 demonstrated the presence of numerous Merkel cells in all trichoblastomas but in none of the 19 cases of BCC tested.¹¹ However, other studies have reported the presence of Merkel cells in only 42% to 70% of trichoblastomas.^12,13 Despite the lack of Merkel cells in our case, the lesion was interpreted as a melanotrichoblastoma based on the histologic features in conjunction with the presence of the melanocytes.

Differential Diagnosis
The clinical and histologic differential diagnosis of trichoblastomas includes both trichoepithelioma and BCC. Clinically, all 3 lesions often are slow growing, dome shaped, and small in size (several millimeters), and are observed in the same anatomic distribution of the head and neck region. Furthermore, they often affect middle-aged to older individuals and those of Caucasian descent, though other ethnicities can be affected. Histologic evaluation often is necessary to differentiate between these 3 entities.

Histologically, trichoepitheliomas are composed of nodules of basaloid cells encircled by stromal spindle cells. Although there can be histologic overlap between trichoepitheliomas and trichoblastoma, trichoepitheliomas typically will display obvious features of hair follicle differentiation with the presence of small keratinous cysts and hair bulb structures, while trichoblastomas tend to display minimal changes suggestive of its hair follicle origin. Similar to trichoblastomas, BCC is composed of nests of basaloid cells; however, BCCs often demonstrate retraction artifact and connection to the overlying epidermis. In addition, BCCs typically demonstrate a fibromucinous stromal component that is distinct from the cellular stroma of trichoblastic tumors. Immunoperoxidase staining for androgen receptors has been reported to be positive in 78% (25/32) of BCCs and negative in trichoblastic tumors.¹⁴

Melanotrichoblastoma Differentiating Characteristics
An exceedingly rare variant of pigmented trichoblastoma is the melanotrichoblastoma. There are clinical and histologic similarities and differences between the reported cases. The first case, described by Kanitakis et al,⁴ reported a 32-year-old black woman with a 2-cm scalp mass that slowly enlarged over the course of 2 years. The second case, presented by Kim et al,⁵ described a 51-year-old Korean man with a subcutaneous 6-cm mass on the back that had been present and slowly enlarging over the course of 5 years. The third case, reported by Hung et al,⁶ described a 34-year-old Taiwanese man with a 1-cm, left-sided, temporal scalp mass present for 3 years, arising from a nevus sebaceous. Comparing these clinical findings with our case of a 25-year-old white woman with a 1.5-cm mass on the left side of the scalp, melanotrichoblastomas demonstrate a relatively similar age of onset in the early to middle-aged adult years. All 4 tumors were slow growing. Additionally, 3 of 4 cases demonstrated a predilection for the head, particularly the scalp, and grossly showed well-circumscribed lesions with notable pigmentation. Although age, size, location, and gross appearance were similar, a comparable ethnic and gender demographic was not identified.

Microscopic similarities between the 4 cases were present. Each case was characterized by a large, well-circumscribed, unencapsulated, basaloid tumor present in the lower dermis, with only 1 case having tumor cells occasionally reaching the undersurface of the epidermis. The tumor cells were monomorphic round-ovoid in appearance with scant cytoplasm. There was melanin pigment in the basaloid nests. The basaloid nests were surrounded by a proliferation of stromal cells. The mitotic rate was sparse in 2 cases, brisk in 1 case, and not discussed in 1 case. Melanocytes were identified in the basaloid nests in all 4 cases; however, in the current case, the melanocytes were seen in only some of the nests. None of the cases exhibited an overlying junctional melanocytic lesion, which would argue against a possible collision tumor or colonization of an epithelial lesion by a melanocytic lesion.

Although the histologic features of our cases are consistent with prior reports of melanotrichoblastoma, there is some question as to whether it represents a true variant of a pigmented trichoblastoma. There are relatively few articles in the literature that describe pigmented trichoblastomas, and of those, immunohistochemistry staining for melanocytes is uncommon. In one of the earliest descriptions of a pigmented trichoblastoma, dendritic melanocytes were present within the tumor lobules; however, the lesion was reported as a pigmented trichoblastoma and not a melanotrichoblastoma.³ It is possible that all pigmented trichoblastomas may contain some number of dendritic melanocytes, thus negating the existence of a melanotrichoblastoma as a true subtype of pigmented trichoblastomas. Additional study looking at multiple examples of pigmented trichoblastomas would be required to more definitively classify melanotrichoblastomas. It is important to appreciate that at least some cases of pigmented trichoblastomas may contain melanocytes and not to confuse the lesion as representing an example of colonization or collision tumor. A rare case of melanoma possibly arising from these dendritic melanocytes has been reported.¹⁵

Conclusion

Trichoblastomas are uncommon tumors of germinative hair bulb origin that can have several histologic variants. A well-documented subtype of trichoblastoma characterized by melanin deposits within and around tumor nests has been identified and classified as a pigmented trichoblastoma. Four cases of melanotrichoblastoma have been reported and represent a variant of a pigmented trichoblastoma characterized by the presence of melanocytes within the lesion. Whether they represent a true variant is of some debate and additional study is required. Although these tumors are exceedingly rare, it is important for the clinician and pathologist to be aware of this entity to prevent confusion with other similarly appearing follicular lesions, most notably BCCs, because of the difference in treatment and follow-up.

Pigmented purpuric dermatoses (PPDs) are a spectrum of chronic disorders that present as speckled brown to purpuric lesions and orange-brown discoloration of the skin.¹ Eruptions generally occur in middle-aged to elderly patients and commonly follow a chronic waxing and waning course.² Lesions usually are found in a localized distribution on the legs. Histologically, PPD presents with perivascular infiltrates of lymphocytes and macrophages centered around the superficial small blood vessels with narrowing of the lumina. Extravasation of red blood cells and hemosiderin deposition are commonly seen in the absence of vasculitis.

The etiology of PPD is unknown; however, important cofactors include venous hypertension, exercise and gravitational dependency, capillary fragility, focal infections, and chemical ingestions.¹ Drugs are the most important provoking factors, including acetaminophen, aspirin, adalin, carbromal, chlordiazepoxide, glipizide, glybuzole, hydralazine, meprobamate, dipyridamole, reserpine, thiamine, and interferon-alfa, as well as medroxyprogesterone acetate injection. Other phenomena include contact allergy and alcohol ingestion.¹

Although the diagnosis often is made clinically, many forms of PPD exist. The 4 main forms include Schaumberg disease, purpura annularis telangiectaticum of Majocchi, pigmented purpuric lichenoid dermatitis of Gougerot and Blum, and eczematoidlike purpura of Doucas and Kapetanakis. Less common variants include itching purpura of Lowenthal, lichen purpuricus, lichen aureus, granulomatous pigmented purpura, transitory pigmented purpuric dermatosis, and linear pigmented purpura.¹Granulomatous PPD (GPPD) is a rare histologic variant of PPD. Clinically, it is indistinguishable from other forms of PPD but reveals itself histologically with granulomatous infiltrates superimposed on classic PPD. We report a case of GPPD and provide a thorough literature review focusing on epidemiology, clinical symptoms, and treatment.^2-17 The eTable summarizes all reported cases of GPPD.

Case Report

An 86-year-old white man with no remarkable medical history presented with an asymptomatic eruption over the bilateral shins extending up both thighs of 6 years’ duration (Figure 1). It began as a 15-cm patch on the right medial thigh that rapidly spread over 1 year to involve the majority of the legs. Physical examination revealed scattered 1- to 2-mm brown macules coalescing into patches on both legs. The patches increased in density distally and extended from the bilateral thighs to the ankles. Edema of the legs was absent, and lesions were nonblanchable and without scale or induration. The differential diagnoses included stasis dermatitis, vasculitis, and PPD. All laboratory values were within reference range, including complete blood cell count, comprehensive metabolic panel, urine analysis, and lipid profile.

A punch biopsy from the distal right thigh revealed a superficial to mid dermal perivascular lymphocyte-predominant infiltrate with associated siderophages and a focal granulomatous infiltrate comprised of histiocytes (Figure 2). Periodic acid–Schiff, acid-fast bacilli, and Fite stains were negative for microorganisms. No eosinophils or leukocytoclasia were seen. The patient applied betamethasone dipropionate cream 0.05% twice daily for several weeks without improvement. Because the lesions were asymptomatic, he discontinued the topical medication.

Comment

Pathogenesis/Etiology of GPPD
Granulomatous PPD is a rare histological variant of PPD, which was first reported in 1996 by Saito and Matsuoka.³ Originally, GPPD was mainly thought to affect individuals in the Far East and be associated with the hepatitis C virus, antinuclear antibodies, or rheumatoid factor.³ Since its initial description, GPPD continues to predominantly be seen on the distal legs. According to a PubMed search of articles indexed for MEDLINE and the Michigan State University library database using the terms granulomatous pigmented purpuric dermatosis and pigmented purpuric dermatosis, 26 known cases including the current case (Asian, n=13; white, n=13) have been reported. The mean age of onset was 54.5 years and the female to male ratio was 2.5 to 1.

Currently, the etiology of GPPD is unknown; however, 13 reported cases have been associated with hyperlipidemia,^{2,4,5,7,8,10,14-16} which has led to the speculation that they may be related. Previous investigators have postulated that the granulomatous infiltrate is a response to lipid deposition in the endothelial cells or that the elevated lipid levels launch an incompetent helper T cell (T_H1) response, leading to granuloma formation.^5,7,8 Currently, hyperlipidemia is present in 50% of patients and appears to be trending downward as more cases present in the literature.

Medications have been implicated in the pathogenesis of PPD and may have a possible role in the development of the granulomatous variant.⁹ One case report noted preceding medication changes, alluding to the possibility of aminosalicylates being the culprit.⁶

Another case described GPPD appearing after an upper respiratory tract infection.¹¹ Comorbidities are not uncommon in patients presenting with GPPD. Although the majority of cases are single reports, they include systemic derangements such as hepatitis C,^3,5 Sjögren syndrome,¹³ hypertension,^{2,4,5,8,10,14,15} seizure disorder,^9,14 ulcerative colitis,⁶ diabetes mellitus,^5,15 meningioma,³ renal calculi,¹⁵ thrombocytopenia,⁵ chronic obstructive pulmonary disease,⁴ thyroid goiter,⁸ obstructive sleep apnea,^2,15 osteoporosis,¹² asthma,¹⁵ gastroesophageal reflux disease/Barrett esophagus,^2,15 hypothyroidism,^2,14,15 and hyperuricemia.⁵

Clinical Presentation
Clinically, GPPD commonly presents as asymptomatic petechiae and bronze discoloration of the lower legs. The clinical presentation can vary from a solitary lesion to a localized eruption typically on the lower legs or rarely a widespread eruption. A review of the literature revealed 5 cases presenting on the upper arms^2,5,11,16 and 4 on the trunk.^2,11,16,17 Four patients presented with pruritus^3,8,13,16 and 1 described pain and photosensitive lesions.¹⁵ No other clinical signs of hyperlipidemia were described (eg, xanthomas). The duration of the disease has a wide spectrum, ranging from 3 weeks to 20 years.^4,16

Histopathology
With the increasing trend toward dermatoscopic evaluation, 2 reviews evaluated dermatoscopic features of GPPD. These reports described scattered, round to oval, red dots, globules, and patches with a diffuse red-brown or coppery background of pigmentation.^14,17

The granulomatous variant of PPD is characterized histopathologically by ill-defined, nonnecrotizing granulomas admixed with a lymphocytic infiltrate. Commonly, erythrocyte extravasation and hemosiderin are seen with granulomas superimposed on classic changes of PPD.¹⁵ Vasculitis features including endothelial swelling, fibrinoid necrosis, and leukocytoclasia are absent. Rarely, eosinophils are seen.⁶ Mild epidermal spongiosis and exocytosis of lymphocytes may be seen in all variants of PPD, except lichen aureus.¹ This exocytosis was observed focally in one case of GPPD.⁴ Although loosely formed granulomas in the papillary dermis are characteristic, 7 cases have had a concomitant lichenoid infiltrate.^2,9-11,15,16

Kaplan et al² reported granulomatous and nongranulomatous PPD occurring together in different areas of the body. A new granulomatous variant was proposed in a 2015 report that revealed 2 patients with granulomatous infiltrates in the mid to deep dermis rather than the classic superficial dermis.¹⁵ One case of GPPD was suspicious for progression into mycosis fungoides (MF) and described a lichenoid infiltrate with mild atypical and small lymphocytes migrating into the epidermis.¹¹ Follow-up biopsy lacked epidermotropism and quantitative representation of T-cell subsets. The diagnosis of early-phase MF was based on the progressive clinical course rather than immunohistologic and molecular findings.¹¹ One other case exhibited minimal epidermotropism.¹⁵

Management of GPPD should require a lipid profile with other tests to assess cardiovascular risk.¹⁰ A thorough medication review and a punch rather than a shave biopsy should be performed, especially because granulomatous infiltrates have been found in the mid to deep dermis.¹⁵ With the lack of rebiopsies documented, follow-up and rebiopsy has been suggested if there is suspicion of MF; however, we favor rebiopsy at a later time to help reveal the course of this disease and rule out progression into MF.

Therapy
Thus far, therapy has mostly been with oral and topical steroids. Five case reports noted improvement,^2,3,6,15,16 2 with oral and 3 with topical steroids. However, therapy has been discouraging, with clinical improvement being transient in most treatment-responsive patients. One case spontaneously resolved.³ Ten cases did not document therapy or follow-up.^{4,5,7,10,14,17} Only 1 case reported follow-up after treatment with simvastatin; unfortunately, the patient had no improvement.² Our case revealed no improvement with topical steroids.

Conclusion

The exact pathogenesis of GPPD is unknown. The initial impression that GPPD was a disease in Far East Asians and patients with hyperlipidemia is becoming less clear. Based on the current literature including the addition of our case, the prevalence appears to be equal among white individuals and Asians, possibly due to increased awareness of this condition and documentation in the literature. Correlation with systemic disorders such as hyperlipidemia and hypertensive medications needs further review. Eight cases reported a medical history of hypertension.^4,5,8,10,14 With antihypertensive medications being a potential culprit of PPD, this etiology should not be overlooked. A punch biopsy should be performed, especially because granulomatous infiltrates may be lurking in the mid to deep dermis.¹⁵ Granulomatous PPD has a chronic course with a disappointing response to therapy but appears to be benign in nature.¹² A rebiopsy is recommended if MF is suspected. Evaluation of GPPD following therapy for hyperlipidemia is not well documented and should be pursued. Clinicians and pathologists should be aware of the suspected associations and consider this variant when dermal granulomatous infiltrates are present with a background of PPD.

Pigmented purpuric dermatoses (PPDs) are a spectrum of chronic disorders that present as speckled brown to purpuric lesions and orange-brown discoloration of the skin.¹ Eruptions generally occur in middle-aged to elderly patients and commonly follow a chronic waxing and waning course.² Lesions usually are found in a localized distribution on the legs. Histologically, PPD presents with perivascular infiltrates of lymphocytes and macrophages centered around the superficial small blood vessels with narrowing of the lumina. Extravasation of red blood cells and hemosiderin deposition are commonly seen in the absence of vasculitis.

The etiology of PPD is unknown; however, important cofactors include venous hypertension, exercise and gravitational dependency, capillary fragility, focal infections, and chemical ingestions.¹ Drugs are the most important provoking factors, including acetaminophen, aspirin, adalin, carbromal, chlordiazepoxide, glipizide, glybuzole, hydralazine, meprobamate, dipyridamole, reserpine, thiamine, and interferon-alfa, as well as medroxyprogesterone acetate injection. Other phenomena include contact allergy and alcohol ingestion.¹

Although the diagnosis often is made clinically, many forms of PPD exist. The 4 main forms include Schaumberg disease, purpura annularis telangiectaticum of Majocchi, pigmented purpuric lichenoid dermatitis of Gougerot and Blum, and eczematoidlike purpura of Doucas and Kapetanakis. Less common variants include itching purpura of Lowenthal, lichen purpuricus, lichen aureus, granulomatous pigmented purpura, transitory pigmented purpuric dermatosis, and linear pigmented purpura.¹Granulomatous PPD (GPPD) is a rare histologic variant of PPD. Clinically, it is indistinguishable from other forms of PPD but reveals itself histologically with granulomatous infiltrates superimposed on classic PPD. We report a case of GPPD and provide a thorough literature review focusing on epidemiology, clinical symptoms, and treatment.^2-17 The eTable summarizes all reported cases of GPPD.

Case Report

An 86-year-old white man with no remarkable medical history presented with an asymptomatic eruption over the bilateral shins extending up both thighs of 6 years’ duration (Figure 1). It began as a 15-cm patch on the right medial thigh that rapidly spread over 1 year to involve the majority of the legs. Physical examination revealed scattered 1- to 2-mm brown macules coalescing into patches on both legs. The patches increased in density distally and extended from the bilateral thighs to the ankles. Edema of the legs was absent, and lesions were nonblanchable and without scale or induration. The differential diagnoses included stasis dermatitis, vasculitis, and PPD. All laboratory values were within reference range, including complete blood cell count, comprehensive metabolic panel, urine analysis, and lipid profile.

A punch biopsy from the distal right thigh revealed a superficial to mid dermal perivascular lymphocyte-predominant infiltrate with associated siderophages and a focal granulomatous infiltrate comprised of histiocytes (Figure 2). Periodic acid–Schiff, acid-fast bacilli, and Fite stains were negative for microorganisms. No eosinophils or leukocytoclasia were seen. The patient applied betamethasone dipropionate cream 0.05% twice daily for several weeks without improvement. Because the lesions were asymptomatic, he discontinued the topical medication.

Comment

Pathogenesis/Etiology of GPPD
Granulomatous PPD is a rare histological variant of PPD, which was first reported in 1996 by Saito and Matsuoka.³ Originally, GPPD was mainly thought to affect individuals in the Far East and be associated with the hepatitis C virus, antinuclear antibodies, or rheumatoid factor.³ Since its initial description, GPPD continues to predominantly be seen on the distal legs. According to a PubMed search of articles indexed for MEDLINE and the Michigan State University library database using the terms granulomatous pigmented purpuric dermatosis and pigmented purpuric dermatosis, 26 known cases including the current case (Asian, n=13; white, n=13) have been reported. The mean age of onset was 54.5 years and the female to male ratio was 2.5 to 1.

Currently, the etiology of GPPD is unknown; however, 13 reported cases have been associated with hyperlipidemia,^{2,4,5,7,8,10,14-16} which has led to the speculation that they may be related. Previous investigators have postulated that the granulomatous infiltrate is a response to lipid deposition in the endothelial cells or that the elevated lipid levels launch an incompetent helper T cell (T_H1) response, leading to granuloma formation.^5,7,8 Currently, hyperlipidemia is present in 50% of patients and appears to be trending downward as more cases present in the literature.

Medications have been implicated in the pathogenesis of PPD and may have a possible role in the development of the granulomatous variant.⁹ One case report noted preceding medication changes, alluding to the possibility of aminosalicylates being the culprit.⁶

Another case described GPPD appearing after an upper respiratory tract infection.¹¹ Comorbidities are not uncommon in patients presenting with GPPD. Although the majority of cases are single reports, they include systemic derangements such as hepatitis C,^3,5 Sjögren syndrome,¹³ hypertension,^{2,4,5,8,10,14,15} seizure disorder,^9,14 ulcerative colitis,⁶ diabetes mellitus,^5,15 meningioma,³ renal calculi,¹⁵ thrombocytopenia,⁵ chronic obstructive pulmonary disease,⁴ thyroid goiter,⁸ obstructive sleep apnea,^2,15 osteoporosis,¹² asthma,¹⁵ gastroesophageal reflux disease/Barrett esophagus,^2,15 hypothyroidism,^2,14,15 and hyperuricemia.⁵

Clinical Presentation
Clinically, GPPD commonly presents as asymptomatic petechiae and bronze discoloration of the lower legs. The clinical presentation can vary from a solitary lesion to a localized eruption typically on the lower legs or rarely a widespread eruption. A review of the literature revealed 5 cases presenting on the upper arms^2,5,11,16 and 4 on the trunk.^2,11,16,17 Four patients presented with pruritus^3,8,13,16 and 1 described pain and photosensitive lesions.¹⁵ No other clinical signs of hyperlipidemia were described (eg, xanthomas). The duration of the disease has a wide spectrum, ranging from 3 weeks to 20 years.^4,16

Histopathology
With the increasing trend toward dermatoscopic evaluation, 2 reviews evaluated dermatoscopic features of GPPD. These reports described scattered, round to oval, red dots, globules, and patches with a diffuse red-brown or coppery background of pigmentation.^14,17

The granulomatous variant of PPD is characterized histopathologically by ill-defined, nonnecrotizing granulomas admixed with a lymphocytic infiltrate. Commonly, erythrocyte extravasation and hemosiderin are seen with granulomas superimposed on classic changes of PPD.¹⁵ Vasculitis features including endothelial swelling, fibrinoid necrosis, and leukocytoclasia are absent. Rarely, eosinophils are seen.⁶ Mild epidermal spongiosis and exocytosis of lymphocytes may be seen in all variants of PPD, except lichen aureus.¹ This exocytosis was observed focally in one case of GPPD.⁴ Although loosely formed granulomas in the papillary dermis are characteristic, 7 cases have had a concomitant lichenoid infiltrate.^2,9-11,15,16

Kaplan et al² reported granulomatous and nongranulomatous PPD occurring together in different areas of the body. A new granulomatous variant was proposed in a 2015 report that revealed 2 patients with granulomatous infiltrates in the mid to deep dermis rather than the classic superficial dermis.¹⁵ One case of GPPD was suspicious for progression into mycosis fungoides (MF) and described a lichenoid infiltrate with mild atypical and small lymphocytes migrating into the epidermis.¹¹ Follow-up biopsy lacked epidermotropism and quantitative representation of T-cell subsets. The diagnosis of early-phase MF was based on the progressive clinical course rather than immunohistologic and molecular findings.¹¹ One other case exhibited minimal epidermotropism.¹⁵

Management of GPPD should require a lipid profile with other tests to assess cardiovascular risk.¹⁰ A thorough medication review and a punch rather than a shave biopsy should be performed, especially because granulomatous infiltrates have been found in the mid to deep dermis.¹⁵ With the lack of rebiopsies documented, follow-up and rebiopsy has been suggested if there is suspicion of MF; however, we favor rebiopsy at a later time to help reveal the course of this disease and rule out progression into MF.

Therapy
Thus far, therapy has mostly been with oral and topical steroids. Five case reports noted improvement,^2,3,6,15,16 2 with oral and 3 with topical steroids. However, therapy has been discouraging, with clinical improvement being transient in most treatment-responsive patients. One case spontaneously resolved.³ Ten cases did not document therapy or follow-up.^{4,5,7,10,14,17} Only 1 case reported follow-up after treatment with simvastatin; unfortunately, the patient had no improvement.² Our case revealed no improvement with topical steroids.

Conclusion

The exact pathogenesis of GPPD is unknown. The initial impression that GPPD was a disease in Far East Asians and patients with hyperlipidemia is becoming less clear. Based on the current literature including the addition of our case, the prevalence appears to be equal among white individuals and Asians, possibly due to increased awareness of this condition and documentation in the literature. Correlation with systemic disorders such as hyperlipidemia and hypertensive medications needs further review. Eight cases reported a medical history of hypertension.^4,5,8,10,14 With antihypertensive medications being a potential culprit of PPD, this etiology should not be overlooked. A punch biopsy should be performed, especially because granulomatous infiltrates may be lurking in the mid to deep dermis.¹⁵ Granulomatous PPD has a chronic course with a disappointing response to therapy but appears to be benign in nature.¹² A rebiopsy is recommended if MF is suspected. Evaluation of GPPD following therapy for hyperlipidemia is not well documented and should be pursued. Clinicians and pathologists should be aware of the suspected associations and consider this variant when dermal granulomatous infiltrates are present with a background of PPD.

Pigmented purpuric dermatoses (PPDs) are a spectrum of chronic disorders that present as speckled brown to purpuric lesions and orange-brown discoloration of the skin.¹ Eruptions generally occur in middle-aged to elderly patients and commonly follow a chronic waxing and waning course.² Lesions usually are found in a localized distribution on the legs. Histologically, PPD presents with perivascular infiltrates of lymphocytes and macrophages centered around the superficial small blood vessels with narrowing of the lumina. Extravasation of red blood cells and hemosiderin deposition are commonly seen in the absence of vasculitis.

The etiology of PPD is unknown; however, important cofactors include venous hypertension, exercise and gravitational dependency, capillary fragility, focal infections, and chemical ingestions.¹ Drugs are the most important provoking factors, including acetaminophen, aspirin, adalin, carbromal, chlordiazepoxide, glipizide, glybuzole, hydralazine, meprobamate, dipyridamole, reserpine, thiamine, and interferon-alfa, as well as medroxyprogesterone acetate injection. Other phenomena include contact allergy and alcohol ingestion.¹

Although the diagnosis often is made clinically, many forms of PPD exist. The 4 main forms include Schaumberg disease, purpura annularis telangiectaticum of Majocchi, pigmented purpuric lichenoid dermatitis of Gougerot and Blum, and eczematoidlike purpura of Doucas and Kapetanakis. Less common variants include itching purpura of Lowenthal, lichen purpuricus, lichen aureus, granulomatous pigmented purpura, transitory pigmented purpuric dermatosis, and linear pigmented purpura.¹Granulomatous PPD (GPPD) is a rare histologic variant of PPD. Clinically, it is indistinguishable from other forms of PPD but reveals itself histologically with granulomatous infiltrates superimposed on classic PPD. We report a case of GPPD and provide a thorough literature review focusing on epidemiology, clinical symptoms, and treatment.^2-17 The eTable summarizes all reported cases of GPPD.

Case Report

An 86-year-old white man with no remarkable medical history presented with an asymptomatic eruption over the bilateral shins extending up both thighs of 6 years’ duration (Figure 1). It began as a 15-cm patch on the right medial thigh that rapidly spread over 1 year to involve the majority of the legs. Physical examination revealed scattered 1- to 2-mm brown macules coalescing into patches on both legs. The patches increased in density distally and extended from the bilateral thighs to the ankles. Edema of the legs was absent, and lesions were nonblanchable and without scale or induration. The differential diagnoses included stasis dermatitis, vasculitis, and PPD. All laboratory values were within reference range, including complete blood cell count, comprehensive metabolic panel, urine analysis, and lipid profile.

A punch biopsy from the distal right thigh revealed a superficial to mid dermal perivascular lymphocyte-predominant infiltrate with associated siderophages and a focal granulomatous infiltrate comprised of histiocytes (Figure 2). Periodic acid–Schiff, acid-fast bacilli, and Fite stains were negative for microorganisms. No eosinophils or leukocytoclasia were seen. The patient applied betamethasone dipropionate cream 0.05% twice daily for several weeks without improvement. Because the lesions were asymptomatic, he discontinued the topical medication.

Comment

Pathogenesis/Etiology of GPPD
Granulomatous PPD is a rare histological variant of PPD, which was first reported in 1996 by Saito and Matsuoka.³ Originally, GPPD was mainly thought to affect individuals in the Far East and be associated with the hepatitis C virus, antinuclear antibodies, or rheumatoid factor.³ Since its initial description, GPPD continues to predominantly be seen on the distal legs. According to a PubMed search of articles indexed for MEDLINE and the Michigan State University library database using the terms granulomatous pigmented purpuric dermatosis and pigmented purpuric dermatosis, 26 known cases including the current case (Asian, n=13; white, n=13) have been reported. The mean age of onset was 54.5 years and the female to male ratio was 2.5 to 1.

Currently, the etiology of GPPD is unknown; however, 13 reported cases have been associated with hyperlipidemia,^{2,4,5,7,8,10,14-16} which has led to the speculation that they may be related. Previous investigators have postulated that the granulomatous infiltrate is a response to lipid deposition in the endothelial cells or that the elevated lipid levels launch an incompetent helper T cell (T_H1) response, leading to granuloma formation.^5,7,8 Currently, hyperlipidemia is present in 50% of patients and appears to be trending downward as more cases present in the literature.

Medications have been implicated in the pathogenesis of PPD and may have a possible role in the development of the granulomatous variant.⁹ One case report noted preceding medication changes, alluding to the possibility of aminosalicylates being the culprit.⁶

Another case described GPPD appearing after an upper respiratory tract infection.¹¹ Comorbidities are not uncommon in patients presenting with GPPD. Although the majority of cases are single reports, they include systemic derangements such as hepatitis C,^3,5 Sjögren syndrome,¹³ hypertension,^{2,4,5,8,10,14,15} seizure disorder,^9,14 ulcerative colitis,⁶ diabetes mellitus,^5,15 meningioma,³ renal calculi,¹⁵ thrombocytopenia,⁵ chronic obstructive pulmonary disease,⁴ thyroid goiter,⁸ obstructive sleep apnea,^2,15 osteoporosis,¹² asthma,¹⁵ gastroesophageal reflux disease/Barrett esophagus,^2,15 hypothyroidism,^2,14,15 and hyperuricemia.⁵

Clinical Presentation
Clinically, GPPD commonly presents as asymptomatic petechiae and bronze discoloration of the lower legs. The clinical presentation can vary from a solitary lesion to a localized eruption typically on the lower legs or rarely a widespread eruption. A review of the literature revealed 5 cases presenting on the upper arms^2,5,11,16 and 4 on the trunk.^2,11,16,17 Four patients presented with pruritus^3,8,13,16 and 1 described pain and photosensitive lesions.¹⁵ No other clinical signs of hyperlipidemia were described (eg, xanthomas). The duration of the disease has a wide spectrum, ranging from 3 weeks to 20 years.^4,16

Histopathology
With the increasing trend toward dermatoscopic evaluation, 2 reviews evaluated dermatoscopic features of GPPD. These reports described scattered, round to oval, red dots, globules, and patches with a diffuse red-brown or coppery background of pigmentation.^14,17

The granulomatous variant of PPD is characterized histopathologically by ill-defined, nonnecrotizing granulomas admixed with a lymphocytic infiltrate. Commonly, erythrocyte extravasation and hemosiderin are seen with granulomas superimposed on classic changes of PPD.¹⁵ Vasculitis features including endothelial swelling, fibrinoid necrosis, and leukocytoclasia are absent. Rarely, eosinophils are seen.⁶ Mild epidermal spongiosis and exocytosis of lymphocytes may be seen in all variants of PPD, except lichen aureus.¹ This exocytosis was observed focally in one case of GPPD.⁴ Although loosely formed granulomas in the papillary dermis are characteristic, 7 cases have had a concomitant lichenoid infiltrate.^2,9-11,15,16

Kaplan et al² reported granulomatous and nongranulomatous PPD occurring together in different areas of the body. A new granulomatous variant was proposed in a 2015 report that revealed 2 patients with granulomatous infiltrates in the mid to deep dermis rather than the classic superficial dermis.¹⁵ One case of GPPD was suspicious for progression into mycosis fungoides (MF) and described a lichenoid infiltrate with mild atypical and small lymphocytes migrating into the epidermis.¹¹ Follow-up biopsy lacked epidermotropism and quantitative representation of T-cell subsets. The diagnosis of early-phase MF was based on the progressive clinical course rather than immunohistologic and molecular findings.¹¹ One other case exhibited minimal epidermotropism.¹⁵

Management of GPPD should require a lipid profile with other tests to assess cardiovascular risk.¹⁰ A thorough medication review and a punch rather than a shave biopsy should be performed, especially because granulomatous infiltrates have been found in the mid to deep dermis.¹⁵ With the lack of rebiopsies documented, follow-up and rebiopsy has been suggested if there is suspicion of MF; however, we favor rebiopsy at a later time to help reveal the course of this disease and rule out progression into MF.

Therapy
Thus far, therapy has mostly been with oral and topical steroids. Five case reports noted improvement,^2,3,6,15,16 2 with oral and 3 with topical steroids. However, therapy has been discouraging, with clinical improvement being transient in most treatment-responsive patients. One case spontaneously resolved.³ Ten cases did not document therapy or follow-up.^{4,5,7,10,14,17} Only 1 case reported follow-up after treatment with simvastatin; unfortunately, the patient had no improvement.² Our case revealed no improvement with topical steroids.

Conclusion

The exact pathogenesis of GPPD is unknown. The initial impression that GPPD was a disease in Far East Asians and patients with hyperlipidemia is becoming less clear. Based on the current literature including the addition of our case, the prevalence appears to be equal among white individuals and Asians, possibly due to increased awareness of this condition and documentation in the literature. Correlation with systemic disorders such as hyperlipidemia and hypertensive medications needs further review. Eight cases reported a medical history of hypertension.^4,5,8,10,14 With antihypertensive medications being a potential culprit of PPD, this etiology should not be overlooked. A punch biopsy should be performed, especially because granulomatous infiltrates may be lurking in the mid to deep dermis.¹⁵ Granulomatous PPD has a chronic course with a disappointing response to therapy but appears to be benign in nature.¹² A rebiopsy is recommended if MF is suspected. Evaluation of GPPD following therapy for hyperlipidemia is not well documented and should be pursued. Clinicians and pathologists should be aware of the suspected associations and consider this variant when dermal granulomatous infiltrates are present with a background of PPD.

Take-Home Points

• Reconstruction of a torn ITB is important in restoration of native anatomy and function given its properties in anterolateral stabilization and resistance to varus stress and internal tibial rotation.
• Restoration of posterolateral instability primarily involves reconstructing the FCL, PLT, and popliteofibular ligament.
• For combined PLC injuries, concurrent reconstruction of the cruciate ligaments in one stage is highly recommended.
• Post-surgery, a 6-week non-weight-bearing, limited flexion rehab protocol utilizing a dynamic PCL brace, such as the PCL Rebound brace, is recommended to prevent posterior tibial sag.
• Arthrofibrosis and decreased ROM can be seen following a violent knee injury which requires extensive multiligament reconstruction surgeries, occasionally requiring a secondary surgery for further restoration of knee motion.

Tibiofemoral knee dislocations are uncommon injuries that have devastating complications and potentially result in complex surgeries.¹ Knee dislocations (KDs) can be classified with the Schenck system.² KD-I is a multiligament injury involving the anterior cruciate ligament (ACL) or the posterior cruciate ligament (PCL), and the scale increases in severity/number of ligaments involved, with KD-V being a multiligament injury with periarticular fracture.²

In this article, we report the case of a complex multiligament knee reconstruction performed with a midsubstance iliotibial band (ITB) repair. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 27-year-old man presented 12 days after a paraskiing crash in which he collided with a tree at 45 mph and fell 40 feet before hitting snow. Physical examination revealed a large hemarthrosis of the left lower extremity and ecchymosis about the posterolateral aspect of the knee and popliteal fossa. Range of motion (ROM) was limited from 5° of hyperextension to 90° of flexion. Additional motion was deferred secondary to pain. Varus stress testing at 0° and 30° of knee flexion demonstrated significant side-to-side differences. The Lachman test, posterior drawer test, and posterolateral drawer test were all 3+. The dial test was 3 to 4+ compared with the contralateral knee. Valgus stress testing at 0° and 30° of flexion did not reveal any side-to-side laxity. The calf was nontender, and all compartments were soft. The patient reported no neurovascular symptoms and had no neuromotor deficits other than mild common peroneal nerve dysesthesias.

Varus stress radiographs showed increased side-to-side gapping (8 mm) of the lateral compartment of the injured knee. Kneeling posterior stress radiographs, limited because of the patient’s inability to apply full stress on the injured knee secondary to pain, showed a difference of 6 mm in increased posterior translation on the uninjured leg (Figures 1A-1D).

First Surgery

1. PLC Approach. A lateral hockey-stick skin incision was made along the ITB and extended distally between the fibular head and the Gerdy tubercle. The subcutaneous tissue was then dissected, and a posteriorly based flap was developed for preservation of vascular support to the superficial tissues. The ITB and the lateral capsule had completely torn off of the femur, allowing exposure directly into the joint. The long and short heads of the biceps femoris were exposed, with about 50% of the biceps attachment torn. The FCL was torn midsubstance, and the PLT had no remnant attachment left on the femur.

2. ITB and Lateral Capsule Tag Stitched. The torn ends of the ITB were dissected and tag stitches placed in each end. Tag stitches were also placed in the lateral capsule in preparation for a direct repair.

3. Neurolysis. The common peroneal nerve was found encased in a significant amount of scar tissue, and extensive neurolysis was required. Slow, methodical dissection was performed under the partially torn long head of the biceps femoris and was continued through the scar tissue and adhesions. Distally, 5 mm to 7 mm of the peroneus longus fascia was incised as part of the neurolysis in order to prevent nerve irritation or foot drop caused by postoperative swelling.

4. PLC Tunnels. The margin between the lateral gastrocnemius tendon and the soleus muscle was identified by blunt dissection that allowed palpation of the posteromedial aspect of the fibular styloid and the popliteus musculotendinous junction. The underlying biceps bursa was incised in order to locate the midportion of the FCL remnant, which typically is tag-stitched with No. 2 FiberWire to help identify the femoral attachment (this was not done because of the complete tear at the midsubstance of the FCL).
Subperiosteal dissection of the lateral aspect of the fibular head was performed anterior to posterior and distally extended to the champagne-glass drop-off of the fibular head. Continuing the dissection distally beyond this point can endanger the common peroneal nerve. A small sulcus can be palpated where the distal FCL inserts on the fibular head. Posteriorly, a small elevator was used to dissect the soleus muscle off of the posteromedial aspect of the fibular head, where the fibular tunnel would later be created.

A Chandler retractor was placed posterior to the fibular head to protect the neurovascular bundle. With the aid of a collateral ligament aiming device, a guide pin was drilled from the lateral aspect of the fibular head (FCL attachment) to the posteromedial downslope of the fibular styloid (popliteofibular ligament attachment). The entry point of the guide pin was immediately above the champagne- glass drop-off, at the distal insertion site of the FCL, which was described as being 28.4 mm from the styloid tip and 8.2 mm posterior to the anterior margin of the fibular head.3 Care should be taken not to ream the tunnel too proximal, as doing so increases the risk of iatrogenic fracture. A 7-mm reamer was then used to drill the fibular tunnel. To facilitate later passage of the graft, a passing suture was placed through the tunnel, leaving the loop anterolateral.

Next, the starting point for the tibial tunnel was located on the flat spot of the anterolateral tibia distal and medial to the Gerdy tubercle, just lateral to the tibial tubercle. The tibial popliteal sulcus was identified by palpation of the posterolateral tibial plateau to localize the site of the popliteus musculotendinous junction, which is the ideal location of the posterior aperture of the tibial tunnel. This point is 1 cm proximal and 1 cm medial to the posteromedial exit of the fibular tunnel. A Chandler retractor was placed anterior to the lateral gastrocnemius to protect the neurovascular bundle. In the locations described earlier, a cruciate aiming device was used to place a guide pin anterior to posterior. A 9-mm tunnel was overreamed and a passing suture placed, leaving the loop posterior to facilitate graft passage.

The femoral insertions of the FCL and the PLT were then identified. ITB splitting was not necessary, given the complete midsubstance tear of this structure. The FCL attachment was identified 1.4 mm proximal and 3.1 mm posterior to the lateral epicondyle.3 Sharp dissection was performed in this location, proximal to distal, exposing the lateral epicondyle and the small sulcus at the FCL attachment site. A collateral ligament reconstruction aiming sleeve was used to drill a guide pin over the FCL femoral attachment site and out the medial aspect of the distal thigh, about 5 cm proximal and anterior to the adductor tubercle.

The femoral attachment of the PLT was reported located 18.5 mm anterior to the FCL insertion, in the anterior fifth of the popliteal sulcus.³ Although arthrotomy is usually required in order to access the PLT attachment, it was not necessary in this case, given the lateral capsule tear. A guide pin was inserted at the PLT attachment site, parallel to the FCL pin. After proper placement was verified, a 9-mm reamer was used to drill the FCL and PLT tunnels to a depth of 25 mm (socket), and a passing suture was placed into each tunnel to facilitate graft passage.

5. ACL Graft Harvest. The central third of the ipsilateral patellar tendon was harvested for use in the ACL reconstruction. Included were a 10-mm × 20-mm bone plug from the patella and a 10-mm × 25-mm bone plug from the tibial tubercle. The patella defect was then bone-grafted, and the patellar tendon closed side-to-side.

6. Graft Preparation. For the PLC, we used a split Achilles tendon allograft that had two 9-mm × 25-mm bone plugs proximally and were tubularized distally. For the PCL, we used an anterolateral bundle (ALB), which consisted of an Achilles tendon allograft that had an 11-mm × 25-mm bone plug proximally and was tubularized distally, and a posteromedial bundle (PMB), which consisted of a tibialis anterior allograft that was tubularized at both ends. For the ACL, we used a bone–patellar tendon–bone autograft 10 mm in diameter with a 20-mm femoral bone plug and a 25-mm tibial bone plug distally.

7. Arthroscopy. We created standard anterolateral and anteromedial parapatellar portals and performed arthroscopy, including lysis of adhesions. Cartilage and menisci were lesion-free.

8. PCL Femoral Tunnels. The ALB attachment was identified and outlined with a coagulator between the trochlear point and the medial arch point, adjacent to the edge of the articular cartilage. Similarly, the PMB attachment was marked about 8 mm or 9 mm posterior to the edge of the articular cartilage of the medial femoral condyle and slightly posterior to the ALB tunnel.⁴

In the anterolateral tunnel, an acorn reamer 11 mm in diameter was used to score the entry point of the ALB femoral tunnel. An eyelet pin was then drilled through the reamer anteromedially out the knee. Then a closed socket tunnel was reamed over the eyelet pin to a depth of 25 mm. A passing suture was pulled through the tunnel in preparation for graft passage. 

With use of the same technique, a 7-mm reamer was placed against the outline of the PMB attachment site, and an eyelet pin was drilled through this reamer and out the anteromedial aspect of the knee. Again, a 25-mm deep closed socket was reamed. A bone bridge distance of 2 mm was maintained between the 2 femoral PCL bundle tunnels.

9. ACL Femoral Tunnel. The femoral ACL attachment was identified and outlined. An over-the-top guide was used to determine proper placement of the 10-mm low-profile reamer. A guide pin was drilled through the center of the reamer. The reamer was used to create a 25-mm deep closed socket tunnel, and a passing stitch was placed. 

10. PCL Tibial Tunnel. With use of a 70° arthroscope for visualization, a posteromedial arthroscopic portal was created, and a shaver and a coagulator were used to identify the tibial PCL attachment, located distally along the PCL facet, until the proximal aspect of the popliteus muscle fibers were visualized. A guide pin was drilled starting at the anteromedial aspect of the tibia, about 6 cm distal to the joint line and centered between the anterior tibial crest and the medial tibial border. The pin exited posteriorly at the center of the PCL tibial attachment along the PCL bundle ridge, which was reported located between the ALB and the PMB on the tibia.5 Pin placement was verified with intraoperative lateral and anteroposterior radiographs. On the lateral radiograph, the pin should be about 6 mm or 7 mm proximal to the champagne-glass drop-off at the PCL facet on the posterior aspect of the tibia. On the anteroposterior radiograph, the pin should be 1 mm to 2 mm distal to the joint line and at the medial aspect of the lateral tibial eminence. A large curette was passed through the posteromedial arthroscopic portal both to retract the posterior tissues away from the reamer and to protect against guide-pin protrusion The guide pin was then overreamed with a 12-mm acorn reamer.

A large smoother was passed proximally up the tibial tunnel and then pulled out the anteromedial portal with a grasper. The smoother was gently cycled to smooth the intra-articular tibial tunnel aperture to remove any bony spicules that could interfere with graft passage. The smoother was then pulled back into the joint, passed out the anterolateral arthroscopic portal, and secured with a small clamp.⁴

11. ACL Tibial Tunnel. The ACL tibial attachment site was identified and cleaned of soft tissue. A guide pin was placed and then overreamed with a 10-mm acorn reamer.

12. PCL Femoral Fixation. The PMB graft was passed into its tunnel and secured with a 7-mm × 23-mm titanium screw. Next, the ALB was secured to the femur with a 7-mm × 20-mm titanium screw. The smoother was used to pull both grafts down through the tibial tunnel.

13. ACL Femoral Fixation. A 7-mm × 20-mm titanium screw was then used to fix the ACL autograft inside the femur. Traction was applied to the 3 cruciate grafts. There was no sign of impingement.

14. PLC Femoral Fixation. The FCL and the popliteus bone plugs were passed into their respective femoral sockets and secured with 7-mm × 20-mm titanium screws.

15. Lateral Capsule Femoral Anchors. Two suture anchors were placed into the femur, and the sutures were passed through the femoral portion of the lateral capsule for later repair.

16. PCL Tibial Fixation. Both grafts were fixed with a fully threaded bicortical 6.5-mm × 40-mm cannulated cancellous screw and an 18-mm spiked washer. The ALB was fixed first, with the knee flexed to 90°, traction on the graft, and the tibia in neutral rotation. Restoration of the normal tibiofemoral step-off was verified. The PMB was then fixed with the knee in full extension. A posterior drawer test was performed to verify restoration of stability.

17. PLC Fibula Fixation. The PLT graft was passed down the popliteal hiatus, and the FCL graft was passed under the remnant of the biceps bursa on the fibular head and then through the fibular head, anterolateral to posteromedial. The FCL graft was fixed in the fibular tunnel with the knee in 20° of flexion, a slight valgus reduction force, the tibia in neutral rotation, and traction on the graft. A 7-mm × 23-mm bioabsorbable screw was used.

18. Lateral Capsular Repair. The lateral capsule was directly repaired with the previously placed sutures. The sutures were tied with the knee in 20° of flexion.

19. PLC Tibial Fixation. The grafts were passed together, posterior to anterior, through the tibial tunnel. The knee was cycled several times through complete flexion/extension ROM. A 9-mm × 23-mm bioabsorbable screw was then used to fix the grafts to the tibia. During this fixation, the knee was kept in 60° of flexion and neutral rotation while traction was being applied to the distal end of both grafts.

20. ACL Tibial Fixation. A 9-mm × 20-mm titanium screw was used to fix the ACL graft with the knee in full extension. The graft was then viewed intra-articularly to confirm there was no impingement. The Lachman, posterior drawer, posterolateral drawer, dial, and varus stress tests were performed to ensure restoration of stability.

21. ITB Repair. A portion of the remaining Achilles tendon allograft was used to perform ITB reconstruction (reconstitution of the gaped portion of the ITB). Orthocord (DePuy Synthes) and Vicryl (Ethicon) sutures were used for this reconstruction. Knee stability was deemed restored, and the incisions were closed in standard layered fashion.

First Surgery: Postoperative Management

The patient remained non-weight-bearing the first 6 weeks after surgery, with prone knee flexion limited (0°-90°) the first 2 weeks. In addition, a PCL Jack brace (Albrecht) was placed 1 week after surgery and was to be worn at all times to decrease stress on the PCL grafts.

As ROM was not progressing as expected, the patient was instructed to use a continuous passive motion (CPM) machine 2 hours 3 times a day. About 4 weeks after surgery, with ROM still not progressing, the frequency of use of this machine was increased.

Despite continued physical therapy, use of the CPM machine, and pain management, ROM was limited (11°-90° of flexion) 5.5 months after left knee multiligament reconstruction. However, stress radiographs showed excellent stability. Varus stress radiographs showed a side-to-side difference of 0.3 mm less on the left (injured) knee, and kneeling PCL stress radiographs showed a side-to-side difference of 1.3 mm more on the left knee (Figures 3A-3D).

Second Surgery and Postoperative Management

As gentle manipulation under anesthesia was unsuccessful, the patient underwent knee arthroscopy, including 4-compartment lysis of adhesions, arthroscopically assisted posteromedial capsular release, and post-débridement manipulation under anesthesia. During manipulation, full extension and knee flexion up to 135° were achieved. ACL, PCL, and popliteus grafts were visualized and confirmed to be intact. 

After this second surgery, the patient was to resume physical therapy and begin weight- bearing as tolerated. Active ROM was prioritized in an attempt to reach full ROM. In addition, a CPM machine was to be used from 0° to 135° of knee flexion 4 hours 3 times a day for 6 weeks.

Two weeks after surgery, the patient had continued pain, and extracapsular swelling in the left knee. However, ROM (0°-115° of flexion) was improved relative to before surgery (11°-90° of flexion), though it remained below the range on the contralateral side. Of note, the patient reported having a flexion contracture (~10°) in the immediate postoperative period. He had woken up with it after sleeping with the CPM machine the night before. The contracture delayed his physical therapy for several hours and resulted in a redesign of his therapy protocol to emphasize full, active knee extension and patellar mobilization, as well as discontinuation of use of the CPM machine. Corticosteroids were initiated to help with the extracapsular swelling, and the new therapy regimen brought adequate progress in ROM. Four months after the second surgery, the patient had full extension and 135° of flexion and was transitioned into wearing the PCL Rebound brace.

Discussion

This case was unique because of the midsubstance ITB tear and simultaneous multiligament injury caused by a KD-IIIL, a KD involving the ACL, the PCL, and the PLC with the medial side intact. There is limited research on ITB repair generally, with or without KD involvement. In a retrospective review of acute knee trauma cases, ITB pathologies were seen on 45% of reviewed MRI scans, and only 3% of the injuries were grade III; in addition, only 9 (5%) of the 200 cases involved both ITB and multiligament (ACL, PCL) knee injuries.⁶

After our patient’s ACL, PCL, and PLC were reconstructed, a fan piece of the Achilles tendon allograft from the PLC reconstruction was used to repair the ITB. The graft was used to reconstitute the torn gapped portion of the band in multiple locations, and this repair helped restore stability. The literature has reported numerous surgical uses for a portion of the ITB but few studies on repairing this anatomical structure. Preservation of the ITB is important to restoration of native anatomy and function. The ITB helps with anterolateral stabilization of the knee and with resistance of varus stress and internal tibial rotation.

The PLC reconstruction used in this case has been biomechanically validated as restoring the knee to near native stability through anatomical reconstruction of the PLC’s 3 main static stabilizers: the FCL, the PLT, and the popliteofibular ligament.^7-9 First described in 2004,⁷ this anatomical PLC reconstruction technique has improved subjective and objective patient outcomes.^10,11 For combined PLC injuries (eg, our patient’s injuries), Geeslin and LaPrade¹⁰ recommended concurrent reconstruction of the cruciate ligaments. In addition to the PLC reconstruction, the anatomical double-bundle PCL reconstruction used in this case has demonstrated significant improvements in subjective and objective outcome scores and objective knee stability.¹²

Although the stability and anatomy of this patient’s injured knee were reestablished, his development of arthrofibrosis is important. Many have discussed the commonality of arthrofibrosis or decreased ROM after extensive multiligament reconstruction surgeries.^13,14 One study involving surgical management and outcomes of multiligament knee injuries found that, in more than half of its cases, restoration of full ROM required at least one operation after the initial one.¹³ Therefore, it is not unusual that our patient required a second operation for decreased ROM.

Conclusion

After surgery, excellent stabilization was achieved. Although the patient had setbacks related to pain and decreased ROM, his second surgery and continued physical therapy likely will help him return to his preoperative recreational activity levels.

Take-Home Points

• Reconstruction of a torn ITB is important in restoration of native anatomy and function given its properties in anterolateral stabilization and resistance to varus stress and internal tibial rotation.
• Restoration of posterolateral instability primarily involves reconstructing the FCL, PLT, and popliteofibular ligament.
• For combined PLC injuries, concurrent reconstruction of the cruciate ligaments in one stage is highly recommended.
• Post-surgery, a 6-week non-weight-bearing, limited flexion rehab protocol utilizing a dynamic PCL brace, such as the PCL Rebound brace, is recommended to prevent posterior tibial sag.
• Arthrofibrosis and decreased ROM can be seen following a violent knee injury which requires extensive multiligament reconstruction surgeries, occasionally requiring a secondary surgery for further restoration of knee motion.

Tibiofemoral knee dislocations are uncommon injuries that have devastating complications and potentially result in complex surgeries.¹ Knee dislocations (KDs) can be classified with the Schenck system.² KD-I is a multiligament injury involving the anterior cruciate ligament (ACL) or the posterior cruciate ligament (PCL), and the scale increases in severity/number of ligaments involved, with KD-V being a multiligament injury with periarticular fracture.²

In this article, we report the case of a complex multiligament knee reconstruction performed with a midsubstance iliotibial band (ITB) repair. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 27-year-old man presented 12 days after a paraskiing crash in which he collided with a tree at 45 mph and fell 40 feet before hitting snow. Physical examination revealed a large hemarthrosis of the left lower extremity and ecchymosis about the posterolateral aspect of the knee and popliteal fossa. Range of motion (ROM) was limited from 5° of hyperextension to 90° of flexion. Additional motion was deferred secondary to pain. Varus stress testing at 0° and 30° of knee flexion demonstrated significant side-to-side differences. The Lachman test, posterior drawer test, and posterolateral drawer test were all 3+. The dial test was 3 to 4+ compared with the contralateral knee. Valgus stress testing at 0° and 30° of flexion did not reveal any side-to-side laxity. The calf was nontender, and all compartments were soft. The patient reported no neurovascular symptoms and had no neuromotor deficits other than mild common peroneal nerve dysesthesias.

Varus stress radiographs showed increased side-to-side gapping (8 mm) of the lateral compartment of the injured knee. Kneeling posterior stress radiographs, limited because of the patient’s inability to apply full stress on the injured knee secondary to pain, showed a difference of 6 mm in increased posterior translation on the uninjured leg (Figures 1A-1D).

First Surgery

1. PLC Approach. A lateral hockey-stick skin incision was made along the ITB and extended distally between the fibular head and the Gerdy tubercle. The subcutaneous tissue was then dissected, and a posteriorly based flap was developed for preservation of vascular support to the superficial tissues. The ITB and the lateral capsule had completely torn off of the femur, allowing exposure directly into the joint. The long and short heads of the biceps femoris were exposed, with about 50% of the biceps attachment torn. The FCL was torn midsubstance, and the PLT had no remnant attachment left on the femur.

2. ITB and Lateral Capsule Tag Stitched. The torn ends of the ITB were dissected and tag stitches placed in each end. Tag stitches were also placed in the lateral capsule in preparation for a direct repair.

3. Neurolysis. The common peroneal nerve was found encased in a significant amount of scar tissue, and extensive neurolysis was required. Slow, methodical dissection was performed under the partially torn long head of the biceps femoris and was continued through the scar tissue and adhesions. Distally, 5 mm to 7 mm of the peroneus longus fascia was incised as part of the neurolysis in order to prevent nerve irritation or foot drop caused by postoperative swelling.

4. PLC Tunnels. The margin between the lateral gastrocnemius tendon and the soleus muscle was identified by blunt dissection that allowed palpation of the posteromedial aspect of the fibular styloid and the popliteus musculotendinous junction. The underlying biceps bursa was incised in order to locate the midportion of the FCL remnant, which typically is tag-stitched with No. 2 FiberWire to help identify the femoral attachment (this was not done because of the complete tear at the midsubstance of the FCL).
Subperiosteal dissection of the lateral aspect of the fibular head was performed anterior to posterior and distally extended to the champagne-glass drop-off of the fibular head. Continuing the dissection distally beyond this point can endanger the common peroneal nerve. A small sulcus can be palpated where the distal FCL inserts on the fibular head. Posteriorly, a small elevator was used to dissect the soleus muscle off of the posteromedial aspect of the fibular head, where the fibular tunnel would later be created.

A Chandler retractor was placed posterior to the fibular head to protect the neurovascular bundle. With the aid of a collateral ligament aiming device, a guide pin was drilled from the lateral aspect of the fibular head (FCL attachment) to the posteromedial downslope of the fibular styloid (popliteofibular ligament attachment). The entry point of the guide pin was immediately above the champagne- glass drop-off, at the distal insertion site of the FCL, which was described as being 28.4 mm from the styloid tip and 8.2 mm posterior to the anterior margin of the fibular head.3 Care should be taken not to ream the tunnel too proximal, as doing so increases the risk of iatrogenic fracture. A 7-mm reamer was then used to drill the fibular tunnel. To facilitate later passage of the graft, a passing suture was placed through the tunnel, leaving the loop anterolateral.

Next, the starting point for the tibial tunnel was located on the flat spot of the anterolateral tibia distal and medial to the Gerdy tubercle, just lateral to the tibial tubercle. The tibial popliteal sulcus was identified by palpation of the posterolateral tibial plateau to localize the site of the popliteus musculotendinous junction, which is the ideal location of the posterior aperture of the tibial tunnel. This point is 1 cm proximal and 1 cm medial to the posteromedial exit of the fibular tunnel. A Chandler retractor was placed anterior to the lateral gastrocnemius to protect the neurovascular bundle. In the locations described earlier, a cruciate aiming device was used to place a guide pin anterior to posterior. A 9-mm tunnel was overreamed and a passing suture placed, leaving the loop posterior to facilitate graft passage.

The femoral insertions of the FCL and the PLT were then identified. ITB splitting was not necessary, given the complete midsubstance tear of this structure. The FCL attachment was identified 1.4 mm proximal and 3.1 mm posterior to the lateral epicondyle.3 Sharp dissection was performed in this location, proximal to distal, exposing the lateral epicondyle and the small sulcus at the FCL attachment site. A collateral ligament reconstruction aiming sleeve was used to drill a guide pin over the FCL femoral attachment site and out the medial aspect of the distal thigh, about 5 cm proximal and anterior to the adductor tubercle.

The femoral attachment of the PLT was reported located 18.5 mm anterior to the FCL insertion, in the anterior fifth of the popliteal sulcus.³ Although arthrotomy is usually required in order to access the PLT attachment, it was not necessary in this case, given the lateral capsule tear. A guide pin was inserted at the PLT attachment site, parallel to the FCL pin. After proper placement was verified, a 9-mm reamer was used to drill the FCL and PLT tunnels to a depth of 25 mm (socket), and a passing suture was placed into each tunnel to facilitate graft passage.

5. ACL Graft Harvest. The central third of the ipsilateral patellar tendon was harvested for use in the ACL reconstruction. Included were a 10-mm × 20-mm bone plug from the patella and a 10-mm × 25-mm bone plug from the tibial tubercle. The patella defect was then bone-grafted, and the patellar tendon closed side-to-side.

6. Graft Preparation. For the PLC, we used a split Achilles tendon allograft that had two 9-mm × 25-mm bone plugs proximally and were tubularized distally. For the PCL, we used an anterolateral bundle (ALB), which consisted of an Achilles tendon allograft that had an 11-mm × 25-mm bone plug proximally and was tubularized distally, and a posteromedial bundle (PMB), which consisted of a tibialis anterior allograft that was tubularized at both ends. For the ACL, we used a bone–patellar tendon–bone autograft 10 mm in diameter with a 20-mm femoral bone plug and a 25-mm tibial bone plug distally.

7. Arthroscopy. We created standard anterolateral and anteromedial parapatellar portals and performed arthroscopy, including lysis of adhesions. Cartilage and menisci were lesion-free.

8. PCL Femoral Tunnels. The ALB attachment was identified and outlined with a coagulator between the trochlear point and the medial arch point, adjacent to the edge of the articular cartilage. Similarly, the PMB attachment was marked about 8 mm or 9 mm posterior to the edge of the articular cartilage of the medial femoral condyle and slightly posterior to the ALB tunnel.⁴

In the anterolateral tunnel, an acorn reamer 11 mm in diameter was used to score the entry point of the ALB femoral tunnel. An eyelet pin was then drilled through the reamer anteromedially out the knee. Then a closed socket tunnel was reamed over the eyelet pin to a depth of 25 mm. A passing suture was pulled through the tunnel in preparation for graft passage. 

With use of the same technique, a 7-mm reamer was placed against the outline of the PMB attachment site, and an eyelet pin was drilled through this reamer and out the anteromedial aspect of the knee. Again, a 25-mm deep closed socket was reamed. A bone bridge distance of 2 mm was maintained between the 2 femoral PCL bundle tunnels.

9. ACL Femoral Tunnel. The femoral ACL attachment was identified and outlined. An over-the-top guide was used to determine proper placement of the 10-mm low-profile reamer. A guide pin was drilled through the center of the reamer. The reamer was used to create a 25-mm deep closed socket tunnel, and a passing stitch was placed. 

10. PCL Tibial Tunnel. With use of a 70° arthroscope for visualization, a posteromedial arthroscopic portal was created, and a shaver and a coagulator were used to identify the tibial PCL attachment, located distally along the PCL facet, until the proximal aspect of the popliteus muscle fibers were visualized. A guide pin was drilled starting at the anteromedial aspect of the tibia, about 6 cm distal to the joint line and centered between the anterior tibial crest and the medial tibial border. The pin exited posteriorly at the center of the PCL tibial attachment along the PCL bundle ridge, which was reported located between the ALB and the PMB on the tibia.5 Pin placement was verified with intraoperative lateral and anteroposterior radiographs. On the lateral radiograph, the pin should be about 6 mm or 7 mm proximal to the champagne-glass drop-off at the PCL facet on the posterior aspect of the tibia. On the anteroposterior radiograph, the pin should be 1 mm to 2 mm distal to the joint line and at the medial aspect of the lateral tibial eminence. A large curette was passed through the posteromedial arthroscopic portal both to retract the posterior tissues away from the reamer and to protect against guide-pin protrusion The guide pin was then overreamed with a 12-mm acorn reamer.

A large smoother was passed proximally up the tibial tunnel and then pulled out the anteromedial portal with a grasper. The smoother was gently cycled to smooth the intra-articular tibial tunnel aperture to remove any bony spicules that could interfere with graft passage. The smoother was then pulled back into the joint, passed out the anterolateral arthroscopic portal, and secured with a small clamp.⁴

11. ACL Tibial Tunnel. The ACL tibial attachment site was identified and cleaned of soft tissue. A guide pin was placed and then overreamed with a 10-mm acorn reamer.

12. PCL Femoral Fixation. The PMB graft was passed into its tunnel and secured with a 7-mm × 23-mm titanium screw. Next, the ALB was secured to the femur with a 7-mm × 20-mm titanium screw. The smoother was used to pull both grafts down through the tibial tunnel.

13. ACL Femoral Fixation. A 7-mm × 20-mm titanium screw was then used to fix the ACL autograft inside the femur. Traction was applied to the 3 cruciate grafts. There was no sign of impingement.

14. PLC Femoral Fixation. The FCL and the popliteus bone plugs were passed into their respective femoral sockets and secured with 7-mm × 20-mm titanium screws.

15. Lateral Capsule Femoral Anchors. Two suture anchors were placed into the femur, and the sutures were passed through the femoral portion of the lateral capsule for later repair.

16. PCL Tibial Fixation. Both grafts were fixed with a fully threaded bicortical 6.5-mm × 40-mm cannulated cancellous screw and an 18-mm spiked washer. The ALB was fixed first, with the knee flexed to 90°, traction on the graft, and the tibia in neutral rotation. Restoration of the normal tibiofemoral step-off was verified. The PMB was then fixed with the knee in full extension. A posterior drawer test was performed to verify restoration of stability.

17. PLC Fibula Fixation. The PLT graft was passed down the popliteal hiatus, and the FCL graft was passed under the remnant of the biceps bursa on the fibular head and then through the fibular head, anterolateral to posteromedial. The FCL graft was fixed in the fibular tunnel with the knee in 20° of flexion, a slight valgus reduction force, the tibia in neutral rotation, and traction on the graft. A 7-mm × 23-mm bioabsorbable screw was used.

18. Lateral Capsular Repair. The lateral capsule was directly repaired with the previously placed sutures. The sutures were tied with the knee in 20° of flexion.

19. PLC Tibial Fixation. The grafts were passed together, posterior to anterior, through the tibial tunnel. The knee was cycled several times through complete flexion/extension ROM. A 9-mm × 23-mm bioabsorbable screw was then used to fix the grafts to the tibia. During this fixation, the knee was kept in 60° of flexion and neutral rotation while traction was being applied to the distal end of both grafts.

20. ACL Tibial Fixation. A 9-mm × 20-mm titanium screw was used to fix the ACL graft with the knee in full extension. The graft was then viewed intra-articularly to confirm there was no impingement. The Lachman, posterior drawer, posterolateral drawer, dial, and varus stress tests were performed to ensure restoration of stability.

21. ITB Repair. A portion of the remaining Achilles tendon allograft was used to perform ITB reconstruction (reconstitution of the gaped portion of the ITB). Orthocord (DePuy Synthes) and Vicryl (Ethicon) sutures were used for this reconstruction. Knee stability was deemed restored, and the incisions were closed in standard layered fashion.

First Surgery: Postoperative Management

The patient remained non-weight-bearing the first 6 weeks after surgery, with prone knee flexion limited (0°-90°) the first 2 weeks. In addition, a PCL Jack brace (Albrecht) was placed 1 week after surgery and was to be worn at all times to decrease stress on the PCL grafts.

As ROM was not progressing as expected, the patient was instructed to use a continuous passive motion (CPM) machine 2 hours 3 times a day. About 4 weeks after surgery, with ROM still not progressing, the frequency of use of this machine was increased.

Despite continued physical therapy, use of the CPM machine, and pain management, ROM was limited (11°-90° of flexion) 5.5 months after left knee multiligament reconstruction. However, stress radiographs showed excellent stability. Varus stress radiographs showed a side-to-side difference of 0.3 mm less on the left (injured) knee, and kneeling PCL stress radiographs showed a side-to-side difference of 1.3 mm more on the left knee (Figures 3A-3D).

Second Surgery and Postoperative Management

As gentle manipulation under anesthesia was unsuccessful, the patient underwent knee arthroscopy, including 4-compartment lysis of adhesions, arthroscopically assisted posteromedial capsular release, and post-débridement manipulation under anesthesia. During manipulation, full extension and knee flexion up to 135° were achieved. ACL, PCL, and popliteus grafts were visualized and confirmed to be intact. 

After this second surgery, the patient was to resume physical therapy and begin weight- bearing as tolerated. Active ROM was prioritized in an attempt to reach full ROM. In addition, a CPM machine was to be used from 0° to 135° of knee flexion 4 hours 3 times a day for 6 weeks.

Two weeks after surgery, the patient had continued pain, and extracapsular swelling in the left knee. However, ROM (0°-115° of flexion) was improved relative to before surgery (11°-90° of flexion), though it remained below the range on the contralateral side. Of note, the patient reported having a flexion contracture (~10°) in the immediate postoperative period. He had woken up with it after sleeping with the CPM machine the night before. The contracture delayed his physical therapy for several hours and resulted in a redesign of his therapy protocol to emphasize full, active knee extension and patellar mobilization, as well as discontinuation of use of the CPM machine. Corticosteroids were initiated to help with the extracapsular swelling, and the new therapy regimen brought adequate progress in ROM. Four months after the second surgery, the patient had full extension and 135° of flexion and was transitioned into wearing the PCL Rebound brace.

Discussion

This case was unique because of the midsubstance ITB tear and simultaneous multiligament injury caused by a KD-IIIL, a KD involving the ACL, the PCL, and the PLC with the medial side intact. There is limited research on ITB repair generally, with or without KD involvement. In a retrospective review of acute knee trauma cases, ITB pathologies were seen on 45% of reviewed MRI scans, and only 3% of the injuries were grade III; in addition, only 9 (5%) of the 200 cases involved both ITB and multiligament (ACL, PCL) knee injuries.⁶

After our patient’s ACL, PCL, and PLC were reconstructed, a fan piece of the Achilles tendon allograft from the PLC reconstruction was used to repair the ITB. The graft was used to reconstitute the torn gapped portion of the band in multiple locations, and this repair helped restore stability. The literature has reported numerous surgical uses for a portion of the ITB but few studies on repairing this anatomical structure. Preservation of the ITB is important to restoration of native anatomy and function. The ITB helps with anterolateral stabilization of the knee and with resistance of varus stress and internal tibial rotation.

The PLC reconstruction used in this case has been biomechanically validated as restoring the knee to near native stability through anatomical reconstruction of the PLC’s 3 main static stabilizers: the FCL, the PLT, and the popliteofibular ligament.^7-9 First described in 2004,⁷ this anatomical PLC reconstruction technique has improved subjective and objective patient outcomes.^10,11 For combined PLC injuries (eg, our patient’s injuries), Geeslin and LaPrade¹⁰ recommended concurrent reconstruction of the cruciate ligaments. In addition to the PLC reconstruction, the anatomical double-bundle PCL reconstruction used in this case has demonstrated significant improvements in subjective and objective outcome scores and objective knee stability.¹²

Although the stability and anatomy of this patient’s injured knee were reestablished, his development of arthrofibrosis is important. Many have discussed the commonality of arthrofibrosis or decreased ROM after extensive multiligament reconstruction surgeries.^13,14 One study involving surgical management and outcomes of multiligament knee injuries found that, in more than half of its cases, restoration of full ROM required at least one operation after the initial one.¹³ Therefore, it is not unusual that our patient required a second operation for decreased ROM.

Conclusion

After surgery, excellent stabilization was achieved. Although the patient had setbacks related to pain and decreased ROM, his second surgery and continued physical therapy likely will help him return to his preoperative recreational activity levels.

Take-Home Points

• Reconstruction of a torn ITB is important in restoration of native anatomy and function given its properties in anterolateral stabilization and resistance to varus stress and internal tibial rotation.
• Restoration of posterolateral instability primarily involves reconstructing the FCL, PLT, and popliteofibular ligament.
• For combined PLC injuries, concurrent reconstruction of the cruciate ligaments in one stage is highly recommended.
• Post-surgery, a 6-week non-weight-bearing, limited flexion rehab protocol utilizing a dynamic PCL brace, such as the PCL Rebound brace, is recommended to prevent posterior tibial sag.
• Arthrofibrosis and decreased ROM can be seen following a violent knee injury which requires extensive multiligament reconstruction surgeries, occasionally requiring a secondary surgery for further restoration of knee motion.

Tibiofemoral knee dislocations are uncommon injuries that have devastating complications and potentially result in complex surgeries.¹ Knee dislocations (KDs) can be classified with the Schenck system.² KD-I is a multiligament injury involving the anterior cruciate ligament (ACL) or the posterior cruciate ligament (PCL), and the scale increases in severity/number of ligaments involved, with KD-V being a multiligament injury with periarticular fracture.²

In this article, we report the case of a complex multiligament knee reconstruction performed with a midsubstance iliotibial band (ITB) repair. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 27-year-old man presented 12 days after a paraskiing crash in which he collided with a tree at 45 mph and fell 40 feet before hitting snow. Physical examination revealed a large hemarthrosis of the left lower extremity and ecchymosis about the posterolateral aspect of the knee and popliteal fossa. Range of motion (ROM) was limited from 5° of hyperextension to 90° of flexion. Additional motion was deferred secondary to pain. Varus stress testing at 0° and 30° of knee flexion demonstrated significant side-to-side differences. The Lachman test, posterior drawer test, and posterolateral drawer test were all 3+. The dial test was 3 to 4+ compared with the contralateral knee. Valgus stress testing at 0° and 30° of flexion did not reveal any side-to-side laxity. The calf was nontender, and all compartments were soft. The patient reported no neurovascular symptoms and had no neuromotor deficits other than mild common peroneal nerve dysesthesias.

Varus stress radiographs showed increased side-to-side gapping (8 mm) of the lateral compartment of the injured knee. Kneeling posterior stress radiographs, limited because of the patient’s inability to apply full stress on the injured knee secondary to pain, showed a difference of 6 mm in increased posterior translation on the uninjured leg (Figures 1A-1D).

First Surgery

1. PLC Approach. A lateral hockey-stick skin incision was made along the ITB and extended distally between the fibular head and the Gerdy tubercle. The subcutaneous tissue was then dissected, and a posteriorly based flap was developed for preservation of vascular support to the superficial tissues. The ITB and the lateral capsule had completely torn off of the femur, allowing exposure directly into the joint. The long and short heads of the biceps femoris were exposed, with about 50% of the biceps attachment torn. The FCL was torn midsubstance, and the PLT had no remnant attachment left on the femur.

2. ITB and Lateral Capsule Tag Stitched. The torn ends of the ITB were dissected and tag stitches placed in each end. Tag stitches were also placed in the lateral capsule in preparation for a direct repair.

3. Neurolysis. The common peroneal nerve was found encased in a significant amount of scar tissue, and extensive neurolysis was required. Slow, methodical dissection was performed under the partially torn long head of the biceps femoris and was continued through the scar tissue and adhesions. Distally, 5 mm to 7 mm of the peroneus longus fascia was incised as part of the neurolysis in order to prevent nerve irritation or foot drop caused by postoperative swelling.

4. PLC Tunnels. The margin between the lateral gastrocnemius tendon and the soleus muscle was identified by blunt dissection that allowed palpation of the posteromedial aspect of the fibular styloid and the popliteus musculotendinous junction. The underlying biceps bursa was incised in order to locate the midportion of the FCL remnant, which typically is tag-stitched with No. 2 FiberWire to help identify the femoral attachment (this was not done because of the complete tear at the midsubstance of the FCL).
Subperiosteal dissection of the lateral aspect of the fibular head was performed anterior to posterior and distally extended to the champagne-glass drop-off of the fibular head. Continuing the dissection distally beyond this point can endanger the common peroneal nerve. A small sulcus can be palpated where the distal FCL inserts on the fibular head. Posteriorly, a small elevator was used to dissect the soleus muscle off of the posteromedial aspect of the fibular head, where the fibular tunnel would later be created.

A Chandler retractor was placed posterior to the fibular head to protect the neurovascular bundle. With the aid of a collateral ligament aiming device, a guide pin was drilled from the lateral aspect of the fibular head (FCL attachment) to the posteromedial downslope of the fibular styloid (popliteofibular ligament attachment). The entry point of the guide pin was immediately above the champagne- glass drop-off, at the distal insertion site of the FCL, which was described as being 28.4 mm from the styloid tip and 8.2 mm posterior to the anterior margin of the fibular head.3 Care should be taken not to ream the tunnel too proximal, as doing so increases the risk of iatrogenic fracture. A 7-mm reamer was then used to drill the fibular tunnel. To facilitate later passage of the graft, a passing suture was placed through the tunnel, leaving the loop anterolateral.

Next, the starting point for the tibial tunnel was located on the flat spot of the anterolateral tibia distal and medial to the Gerdy tubercle, just lateral to the tibial tubercle. The tibial popliteal sulcus was identified by palpation of the posterolateral tibial plateau to localize the site of the popliteus musculotendinous junction, which is the ideal location of the posterior aperture of the tibial tunnel. This point is 1 cm proximal and 1 cm medial to the posteromedial exit of the fibular tunnel. A Chandler retractor was placed anterior to the lateral gastrocnemius to protect the neurovascular bundle. In the locations described earlier, a cruciate aiming device was used to place a guide pin anterior to posterior. A 9-mm tunnel was overreamed and a passing suture placed, leaving the loop posterior to facilitate graft passage.

The femoral insertions of the FCL and the PLT were then identified. ITB splitting was not necessary, given the complete midsubstance tear of this structure. The FCL attachment was identified 1.4 mm proximal and 3.1 mm posterior to the lateral epicondyle.3 Sharp dissection was performed in this location, proximal to distal, exposing the lateral epicondyle and the small sulcus at the FCL attachment site. A collateral ligament reconstruction aiming sleeve was used to drill a guide pin over the FCL femoral attachment site and out the medial aspect of the distal thigh, about 5 cm proximal and anterior to the adductor tubercle.

The femoral attachment of the PLT was reported located 18.5 mm anterior to the FCL insertion, in the anterior fifth of the popliteal sulcus.³ Although arthrotomy is usually required in order to access the PLT attachment, it was not necessary in this case, given the lateral capsule tear. A guide pin was inserted at the PLT attachment site, parallel to the FCL pin. After proper placement was verified, a 9-mm reamer was used to drill the FCL and PLT tunnels to a depth of 25 mm (socket), and a passing suture was placed into each tunnel to facilitate graft passage.

5. ACL Graft Harvest. The central third of the ipsilateral patellar tendon was harvested for use in the ACL reconstruction. Included were a 10-mm × 20-mm bone plug from the patella and a 10-mm × 25-mm bone plug from the tibial tubercle. The patella defect was then bone-grafted, and the patellar tendon closed side-to-side.

6. Graft Preparation. For the PLC, we used a split Achilles tendon allograft that had two 9-mm × 25-mm bone plugs proximally and were tubularized distally. For the PCL, we used an anterolateral bundle (ALB), which consisted of an Achilles tendon allograft that had an 11-mm × 25-mm bone plug proximally and was tubularized distally, and a posteromedial bundle (PMB), which consisted of a tibialis anterior allograft that was tubularized at both ends. For the ACL, we used a bone–patellar tendon–bone autograft 10 mm in diameter with a 20-mm femoral bone plug and a 25-mm tibial bone plug distally.

7. Arthroscopy. We created standard anterolateral and anteromedial parapatellar portals and performed arthroscopy, including lysis of adhesions. Cartilage and menisci were lesion-free.

8. PCL Femoral Tunnels. The ALB attachment was identified and outlined with a coagulator between the trochlear point and the medial arch point, adjacent to the edge of the articular cartilage. Similarly, the PMB attachment was marked about 8 mm or 9 mm posterior to the edge of the articular cartilage of the medial femoral condyle and slightly posterior to the ALB tunnel.⁴

In the anterolateral tunnel, an acorn reamer 11 mm in diameter was used to score the entry point of the ALB femoral tunnel. An eyelet pin was then drilled through the reamer anteromedially out the knee. Then a closed socket tunnel was reamed over the eyelet pin to a depth of 25 mm. A passing suture was pulled through the tunnel in preparation for graft passage. 

With use of the same technique, a 7-mm reamer was placed against the outline of the PMB attachment site, and an eyelet pin was drilled through this reamer and out the anteromedial aspect of the knee. Again, a 25-mm deep closed socket was reamed. A bone bridge distance of 2 mm was maintained between the 2 femoral PCL bundle tunnels.

9. ACL Femoral Tunnel. The femoral ACL attachment was identified and outlined. An over-the-top guide was used to determine proper placement of the 10-mm low-profile reamer. A guide pin was drilled through the center of the reamer. The reamer was used to create a 25-mm deep closed socket tunnel, and a passing stitch was placed. 

10. PCL Tibial Tunnel. With use of a 70° arthroscope for visualization, a posteromedial arthroscopic portal was created, and a shaver and a coagulator were used to identify the tibial PCL attachment, located distally along the PCL facet, until the proximal aspect of the popliteus muscle fibers were visualized. A guide pin was drilled starting at the anteromedial aspect of the tibia, about 6 cm distal to the joint line and centered between the anterior tibial crest and the medial tibial border. The pin exited posteriorly at the center of the PCL tibial attachment along the PCL bundle ridge, which was reported located between the ALB and the PMB on the tibia.5 Pin placement was verified with intraoperative lateral and anteroposterior radiographs. On the lateral radiograph, the pin should be about 6 mm or 7 mm proximal to the champagne-glass drop-off at the PCL facet on the posterior aspect of the tibia. On the anteroposterior radiograph, the pin should be 1 mm to 2 mm distal to the joint line and at the medial aspect of the lateral tibial eminence. A large curette was passed through the posteromedial arthroscopic portal both to retract the posterior tissues away from the reamer and to protect against guide-pin protrusion The guide pin was then overreamed with a 12-mm acorn reamer.

A large smoother was passed proximally up the tibial tunnel and then pulled out the anteromedial portal with a grasper. The smoother was gently cycled to smooth the intra-articular tibial tunnel aperture to remove any bony spicules that could interfere with graft passage. The smoother was then pulled back into the joint, passed out the anterolateral arthroscopic portal, and secured with a small clamp.⁴

11. ACL Tibial Tunnel. The ACL tibial attachment site was identified and cleaned of soft tissue. A guide pin was placed and then overreamed with a 10-mm acorn reamer.

12. PCL Femoral Fixation. The PMB graft was passed into its tunnel and secured with a 7-mm × 23-mm titanium screw. Next, the ALB was secured to the femur with a 7-mm × 20-mm titanium screw. The smoother was used to pull both grafts down through the tibial tunnel.

13. ACL Femoral Fixation. A 7-mm × 20-mm titanium screw was then used to fix the ACL autograft inside the femur. Traction was applied to the 3 cruciate grafts. There was no sign of impingement.

14. PLC Femoral Fixation. The FCL and the popliteus bone plugs were passed into their respective femoral sockets and secured with 7-mm × 20-mm titanium screws.

15. Lateral Capsule Femoral Anchors. Two suture anchors were placed into the femur, and the sutures were passed through the femoral portion of the lateral capsule for later repair.

16. PCL Tibial Fixation. Both grafts were fixed with a fully threaded bicortical 6.5-mm × 40-mm cannulated cancellous screw and an 18-mm spiked washer. The ALB was fixed first, with the knee flexed to 90°, traction on the graft, and the tibia in neutral rotation. Restoration of the normal tibiofemoral step-off was verified. The PMB was then fixed with the knee in full extension. A posterior drawer test was performed to verify restoration of stability.

17. PLC Fibula Fixation. The PLT graft was passed down the popliteal hiatus, and the FCL graft was passed under the remnant of the biceps bursa on the fibular head and then through the fibular head, anterolateral to posteromedial. The FCL graft was fixed in the fibular tunnel with the knee in 20° of flexion, a slight valgus reduction force, the tibia in neutral rotation, and traction on the graft. A 7-mm × 23-mm bioabsorbable screw was used.

18. Lateral Capsular Repair. The lateral capsule was directly repaired with the previously placed sutures. The sutures were tied with the knee in 20° of flexion.

19. PLC Tibial Fixation. The grafts were passed together, posterior to anterior, through the tibial tunnel. The knee was cycled several times through complete flexion/extension ROM. A 9-mm × 23-mm bioabsorbable screw was then used to fix the grafts to the tibia. During this fixation, the knee was kept in 60° of flexion and neutral rotation while traction was being applied to the distal end of both grafts.

20. ACL Tibial Fixation. A 9-mm × 20-mm titanium screw was used to fix the ACL graft with the knee in full extension. The graft was then viewed intra-articularly to confirm there was no impingement. The Lachman, posterior drawer, posterolateral drawer, dial, and varus stress tests were performed to ensure restoration of stability.

21. ITB Repair. A portion of the remaining Achilles tendon allograft was used to perform ITB reconstruction (reconstitution of the gaped portion of the ITB). Orthocord (DePuy Synthes) and Vicryl (Ethicon) sutures were used for this reconstruction. Knee stability was deemed restored, and the incisions were closed in standard layered fashion.

First Surgery: Postoperative Management

The patient remained non-weight-bearing the first 6 weeks after surgery, with prone knee flexion limited (0°-90°) the first 2 weeks. In addition, a PCL Jack brace (Albrecht) was placed 1 week after surgery and was to be worn at all times to decrease stress on the PCL grafts.

As ROM was not progressing as expected, the patient was instructed to use a continuous passive motion (CPM) machine 2 hours 3 times a day. About 4 weeks after surgery, with ROM still not progressing, the frequency of use of this machine was increased.

Despite continued physical therapy, use of the CPM machine, and pain management, ROM was limited (11°-90° of flexion) 5.5 months after left knee multiligament reconstruction. However, stress radiographs showed excellent stability. Varus stress radiographs showed a side-to-side difference of 0.3 mm less on the left (injured) knee, and kneeling PCL stress radiographs showed a side-to-side difference of 1.3 mm more on the left knee (Figures 3A-3D).

Second Surgery and Postoperative Management

As gentle manipulation under anesthesia was unsuccessful, the patient underwent knee arthroscopy, including 4-compartment lysis of adhesions, arthroscopically assisted posteromedial capsular release, and post-débridement manipulation under anesthesia. During manipulation, full extension and knee flexion up to 135° were achieved. ACL, PCL, and popliteus grafts were visualized and confirmed to be intact. 

After this second surgery, the patient was to resume physical therapy and begin weight- bearing as tolerated. Active ROM was prioritized in an attempt to reach full ROM. In addition, a CPM machine was to be used from 0° to 135° of knee flexion 4 hours 3 times a day for 6 weeks.

Two weeks after surgery, the patient had continued pain, and extracapsular swelling in the left knee. However, ROM (0°-115° of flexion) was improved relative to before surgery (11°-90° of flexion), though it remained below the range on the contralateral side. Of note, the patient reported having a flexion contracture (~10°) in the immediate postoperative period. He had woken up with it after sleeping with the CPM machine the night before. The contracture delayed his physical therapy for several hours and resulted in a redesign of his therapy protocol to emphasize full, active knee extension and patellar mobilization, as well as discontinuation of use of the CPM machine. Corticosteroids were initiated to help with the extracapsular swelling, and the new therapy regimen brought adequate progress in ROM. Four months after the second surgery, the patient had full extension and 135° of flexion and was transitioned into wearing the PCL Rebound brace.

Discussion

This case was unique because of the midsubstance ITB tear and simultaneous multiligament injury caused by a KD-IIIL, a KD involving the ACL, the PCL, and the PLC with the medial side intact. There is limited research on ITB repair generally, with or without KD involvement. In a retrospective review of acute knee trauma cases, ITB pathologies were seen on 45% of reviewed MRI scans, and only 3% of the injuries were grade III; in addition, only 9 (5%) of the 200 cases involved both ITB and multiligament (ACL, PCL) knee injuries.⁶

After our patient’s ACL, PCL, and PLC were reconstructed, a fan piece of the Achilles tendon allograft from the PLC reconstruction was used to repair the ITB. The graft was used to reconstitute the torn gapped portion of the band in multiple locations, and this repair helped restore stability. The literature has reported numerous surgical uses for a portion of the ITB but few studies on repairing this anatomical structure. Preservation of the ITB is important to restoration of native anatomy and function. The ITB helps with anterolateral stabilization of the knee and with resistance of varus stress and internal tibial rotation.

The PLC reconstruction used in this case has been biomechanically validated as restoring the knee to near native stability through anatomical reconstruction of the PLC’s 3 main static stabilizers: the FCL, the PLT, and the popliteofibular ligament.^7-9 First described in 2004,⁷ this anatomical PLC reconstruction technique has improved subjective and objective patient outcomes.^10,11 For combined PLC injuries (eg, our patient’s injuries), Geeslin and LaPrade¹⁰ recommended concurrent reconstruction of the cruciate ligaments. In addition to the PLC reconstruction, the anatomical double-bundle PCL reconstruction used in this case has demonstrated significant improvements in subjective and objective outcome scores and objective knee stability.¹²

Although the stability and anatomy of this patient’s injured knee were reestablished, his development of arthrofibrosis is important. Many have discussed the commonality of arthrofibrosis or decreased ROM after extensive multiligament reconstruction surgeries.^13,14 One study involving surgical management and outcomes of multiligament knee injuries found that, in more than half of its cases, restoration of full ROM required at least one operation after the initial one.¹³ Therefore, it is not unusual that our patient required a second operation for decreased ROM.

Conclusion

After surgery, excellent stabilization was achieved. Although the patient had setbacks related to pain and decreased ROM, his second surgery and continued physical therapy likely will help him return to his preoperative recreational activity levels.

THE CASE

A 32-year-old man was admitted to our hospital with fever, chills, malaise, leukopenia, and a rash. About 3 weeks earlier, he’d had oral maxillofacial surgery and started a 10-day course of prophylactic amoxicillin/clavulanic acid. Fifteen days after the surgery, he developed a fever (temperature, 103˚ F), chills, arthralgia, myalgia, cough, diarrhea, and malaise. He was seen by his physician, who obtained a chest x-ray showing a lingular infiltrate. The physician diagnosed influenza and pneumonia in this patient, and prescribed oseltamivir, azithromycin, and an additional course of amoxicillin/clavulanic acid.

Upon admission to the hospital, laboratory tests revealed a white blood cell count (WBC) of 3.1 k/mcL (normal: 3.2-10.8 k/mcL). The patient’s physical examination was notable for lip edema, white mucous membrane plaques, submandibular and inguinal lymphadenopathy, and a morbilliform rash across his chest (FIGURE 1). Broad-spectrum antibiotics were initiated for presumed sepsis.

On hospital day (HD) 1, tests revealed a WBC count of 1.8 k/mcL, an erythrocyte sedimentation rate of 53 mm/hr (normal: 20-30 mm/hr for women, 15-20 mm/hr for men), and a C-reactive protein level of 6.7 mg/dL (normal: <0.5 mg/dL). A repeat chest x-ray and orofacial computerized tomography scan were normal.

By HD 3, all bacterial cultures were negative, but the patient was positive for human herpesvirus (HHV)-6 on viral cultures. His leukopenia persisted and he had elevated levels of alanine transaminase ranging from 40 to 73 U/L (normal: 6-43 U/L) and aspartate aminotransferase ranging from 66 to 108 U/L (normal range: 10-40 U/L), both downtrending during his hospitalization. He also had elevated levels of antinuclear antibodies (ANAs) and anti-Smith (Sm) antibody titers.

A posterior-auricular biopsy was consistent with lymphocytic perivasculitis. The rash continued to progress, involving his chest, abdomen, and face (FIGURE 2). Bacterial and viral cultures remained negative and on HD 4, broad-spectrum antibiotics were discontinued.

THE DIAGNOSIS

We diagnosed the patient with DRESS (drug reaction with eosinophilia and systemic symptoms) based on persistent fever, onset of cutaneous manifestations (facial edema and morbilliform eruption), lymphadenopathy, increased liver function tests, and recent exposure to an offending drug. The patient did not have eosinophilia; however, atypical lymphocytes were present on his peripheral smear.

DISCUSSION

DRESS is typically characterized by fever, rash, eosinophilia, atypical lymphocytes, lymphadenopathy, and organ involvement (primarily liver, but multiple organ systems can be affected).¹ Patients with severe symptoms have renal involvement, anemia, respiratory and cardiac symptoms (chest pain, tachycardia, and myocarditis), and transaminase levels up to 5 times greater than normal.^1-3 Anticonvulsants and antibiotics are the most common offending classes among the medications that are associated with DRESS (TABLE 1).^2,4

The reported incidence of DRESS is between one in 1000 and one in 10,000 drug exposures.¹ Due to the broad presentation and a lack of established diagnostic criteria associated with DRESS, this number may be even higher. DRESS has a 10% mortality rate,¹ and hepatic necrosis is the most common cause of death.²

Certain people may be more prone to DRESS. People with certain gene mutations that code for drug detoxification enzymes have shown a greater incidence of DRESS.⁵ Viral reactivation, commonly of HHV-6, has also been shown to have an effect on the pathogenesis of DRESS. Additionally, genetic predisposition involving specific human leukocyte antigens (HLAs) makes certain people more prone to the development of DRESS (TABLE 2).^2,5

Case reports have demonstrated a link between certain autoimmune syndromes and DRESS, specifically Grave’s disease and type 1 diabetes mellitus.²

Patch testing and lymphocyte transformation tests can aid in the diagnosis of DRESS.

A unique finding of this case was the presence of elevated ANA and anti-Sm antibody titers at initial presentation, with spontaneous negative seroconversion 2 months later. Because of these 2 findings, as well as the patient’s leukopenia and rash, he briefly met 4 of the 11 criteria set forth by the American College of Rheumatology for a diagnosis of systemic lupus erythematosus (SLE).⁶ It is unclear whether the transiently elevated anti-Sm antibody titers were an acute phase reactant due to DRESS, a viral illness, or an evolving autoimmune process.

The false-positive rate for anti-Sm antibodies in association with DRESS has not been previously reported.

MAKING THE DIAGNOSIS

Distinguishing DRESS from other life-threatening cutaneous drug reactions, particularly Stevens-Johnson syndrome and toxic epidermal necrolysis, can be difficult. Likewise, acute bacterial/viral infections, autoimmune syndromes, vasculitis, and hematologic diseases can mimic DRESS.⁷ Exposure to an offending drug 2 to 6 weeks prior to the onset of symptoms is supportive of DRESS.

This scoring system can help. The RegiSCAR (Registry of Severe Cutaneous Adverse Reaction) has developed a scoring system to aid in the accurate diagnosis of DRESS.^1,8 The scoring consists of 8 categories: fever, eosinophilia, enlarged lymph nodes, atypical lymphocytes, skin involvement, organ involvement, time of resolution, and the evaluation of other potential causes.¹ Each category is graded a number from -1 (not supportive of DRESS) to 2 (highly supportive of DRESS) based on the patient’s presentation. The total score grades potential cases as “no,” “possible,” “probable,” or “definite.”^1,8 In one review, cases classified as “probable” or “definite” by the RegiSCAR scoring system constituted 88% of the cases reported in the literature.¹

Two tests that can also aid in the diagnosis of DRESS include patch testing (exposing the skin to a diluted version of the suspected offending drug and observing for a local reaction) and lymphocyte transformation tests. The latter are a better method of diagnosing drug-induced DRESS, with a sensitivity of 60% to 70%, and a specificity of 85%.⁹ However, this testing is not readily available.

Long-term sequelae, such as Grave's disease and diabetes mellitus, have been reported following DRESS.

Once DRESS is diagnosed, the offending drug should be immediately discontinued. For mild cases, supportive treatment is recommended. For more severe cases, the use of corticosteroids tapered over several months is the treatment of choice.¹⁰ Further studies are needed to determine the optimal type of corticosteroids, as well as the dose, route, and duration of therapy. Immunotherapy, plasmapheresis, and antivirals have been used with mixed results.^10,11

Our patient was started on topical and systemic oral corticosteroids. Within 24 hours, his fever resolved and his rash improved. By HD 7, his laboratory values were normal and he was discharged.

The patient was advised that in the future, he should avoid exposure to the penicillin class of medication.

THE TAKEAWAY

The presence of rash, fever, lymphadenopathy, eosinophilia, atypical lymphocytes, liver involvement, and HHV-6 reactivation in the absence of sepsis should raise suspicion for DRESS. Early diagnosis, discontinuation of the culprit drug, and timely treatment are imperative in the management of the condition. Due to a potential genetic predisposition to DRESS, clinicians should use caution when treating first-degree family members with the same class of medication that was problematic for their relative. Long-term sequelae, such as Grave’s disease and diabetes mellitus, have been reported following DRESS. Therefore, long-term monitoring with appropriate testing is recommended.

THE CASE

A 32-year-old man was admitted to our hospital with fever, chills, malaise, leukopenia, and a rash. About 3 weeks earlier, he’d had oral maxillofacial surgery and started a 10-day course of prophylactic amoxicillin/clavulanic acid. Fifteen days after the surgery, he developed a fever (temperature, 103˚ F), chills, arthralgia, myalgia, cough, diarrhea, and malaise. He was seen by his physician, who obtained a chest x-ray showing a lingular infiltrate. The physician diagnosed influenza and pneumonia in this patient, and prescribed oseltamivir, azithromycin, and an additional course of amoxicillin/clavulanic acid.

Upon admission to the hospital, laboratory tests revealed a white blood cell count (WBC) of 3.1 k/mcL (normal: 3.2-10.8 k/mcL). The patient’s physical examination was notable for lip edema, white mucous membrane plaques, submandibular and inguinal lymphadenopathy, and a morbilliform rash across his chest (FIGURE 1). Broad-spectrum antibiotics were initiated for presumed sepsis.

On hospital day (HD) 1, tests revealed a WBC count of 1.8 k/mcL, an erythrocyte sedimentation rate of 53 mm/hr (normal: 20-30 mm/hr for women, 15-20 mm/hr for men), and a C-reactive protein level of 6.7 mg/dL (normal: <0.5 mg/dL). A repeat chest x-ray and orofacial computerized tomography scan were normal.

By HD 3, all bacterial cultures were negative, but the patient was positive for human herpesvirus (HHV)-6 on viral cultures. His leukopenia persisted and he had elevated levels of alanine transaminase ranging from 40 to 73 U/L (normal: 6-43 U/L) and aspartate aminotransferase ranging from 66 to 108 U/L (normal range: 10-40 U/L), both downtrending during his hospitalization. He also had elevated levels of antinuclear antibodies (ANAs) and anti-Smith (Sm) antibody titers.

A posterior-auricular biopsy was consistent with lymphocytic perivasculitis. The rash continued to progress, involving his chest, abdomen, and face (FIGURE 2). Bacterial and viral cultures remained negative and on HD 4, broad-spectrum antibiotics were discontinued.

THE DIAGNOSIS

We diagnosed the patient with DRESS (drug reaction with eosinophilia and systemic symptoms) based on persistent fever, onset of cutaneous manifestations (facial edema and morbilliform eruption), lymphadenopathy, increased liver function tests, and recent exposure to an offending drug. The patient did not have eosinophilia; however, atypical lymphocytes were present on his peripheral smear.

DISCUSSION

DRESS is typically characterized by fever, rash, eosinophilia, atypical lymphocytes, lymphadenopathy, and organ involvement (primarily liver, but multiple organ systems can be affected).¹ Patients with severe symptoms have renal involvement, anemia, respiratory and cardiac symptoms (chest pain, tachycardia, and myocarditis), and transaminase levels up to 5 times greater than normal.^1-3 Anticonvulsants and antibiotics are the most common offending classes among the medications that are associated with DRESS (TABLE 1).^2,4

The reported incidence of DRESS is between one in 1000 and one in 10,000 drug exposures.¹ Due to the broad presentation and a lack of established diagnostic criteria associated with DRESS, this number may be even higher. DRESS has a 10% mortality rate,¹ and hepatic necrosis is the most common cause of death.²

Certain people may be more prone to DRESS. People with certain gene mutations that code for drug detoxification enzymes have shown a greater incidence of DRESS.⁵ Viral reactivation, commonly of HHV-6, has also been shown to have an effect on the pathogenesis of DRESS. Additionally, genetic predisposition involving specific human leukocyte antigens (HLAs) makes certain people more prone to the development of DRESS (TABLE 2).^2,5

Case reports have demonstrated a link between certain autoimmune syndromes and DRESS, specifically Grave’s disease and type 1 diabetes mellitus.²

Patch testing and lymphocyte transformation tests can aid in the diagnosis of DRESS.

A unique finding of this case was the presence of elevated ANA and anti-Sm antibody titers at initial presentation, with spontaneous negative seroconversion 2 months later. Because of these 2 findings, as well as the patient’s leukopenia and rash, he briefly met 4 of the 11 criteria set forth by the American College of Rheumatology for a diagnosis of systemic lupus erythematosus (SLE).⁶ It is unclear whether the transiently elevated anti-Sm antibody titers were an acute phase reactant due to DRESS, a viral illness, or an evolving autoimmune process.

The false-positive rate for anti-Sm antibodies in association with DRESS has not been previously reported.

MAKING THE DIAGNOSIS

Distinguishing DRESS from other life-threatening cutaneous drug reactions, particularly Stevens-Johnson syndrome and toxic epidermal necrolysis, can be difficult. Likewise, acute bacterial/viral infections, autoimmune syndromes, vasculitis, and hematologic diseases can mimic DRESS.⁷ Exposure to an offending drug 2 to 6 weeks prior to the onset of symptoms is supportive of DRESS.

This scoring system can help. The RegiSCAR (Registry of Severe Cutaneous Adverse Reaction) has developed a scoring system to aid in the accurate diagnosis of DRESS.^1,8 The scoring consists of 8 categories: fever, eosinophilia, enlarged lymph nodes, atypical lymphocytes, skin involvement, organ involvement, time of resolution, and the evaluation of other potential causes.¹ Each category is graded a number from -1 (not supportive of DRESS) to 2 (highly supportive of DRESS) based on the patient’s presentation. The total score grades potential cases as “no,” “possible,” “probable,” or “definite.”^1,8 In one review, cases classified as “probable” or “definite” by the RegiSCAR scoring system constituted 88% of the cases reported in the literature.¹

Two tests that can also aid in the diagnosis of DRESS include patch testing (exposing the skin to a diluted version of the suspected offending drug and observing for a local reaction) and lymphocyte transformation tests. The latter are a better method of diagnosing drug-induced DRESS, with a sensitivity of 60% to 70%, and a specificity of 85%.⁹ However, this testing is not readily available.

Long-term sequelae, such as Grave's disease and diabetes mellitus, have been reported following DRESS.

Once DRESS is diagnosed, the offending drug should be immediately discontinued. For mild cases, supportive treatment is recommended. For more severe cases, the use of corticosteroids tapered over several months is the treatment of choice.¹⁰ Further studies are needed to determine the optimal type of corticosteroids, as well as the dose, route, and duration of therapy. Immunotherapy, plasmapheresis, and antivirals have been used with mixed results.^10,11

Our patient was started on topical and systemic oral corticosteroids. Within 24 hours, his fever resolved and his rash improved. By HD 7, his laboratory values were normal and he was discharged.

The patient was advised that in the future, he should avoid exposure to the penicillin class of medication.

THE TAKEAWAY

The presence of rash, fever, lymphadenopathy, eosinophilia, atypical lymphocytes, liver involvement, and HHV-6 reactivation in the absence of sepsis should raise suspicion for DRESS. Early diagnosis, discontinuation of the culprit drug, and timely treatment are imperative in the management of the condition. Due to a potential genetic predisposition to DRESS, clinicians should use caution when treating first-degree family members with the same class of medication that was problematic for their relative. Long-term sequelae, such as Grave’s disease and diabetes mellitus, have been reported following DRESS. Therefore, long-term monitoring with appropriate testing is recommended.

THE CASE

A 32-year-old man was admitted to our hospital with fever, chills, malaise, leukopenia, and a rash. About 3 weeks earlier, he’d had oral maxillofacial surgery and started a 10-day course of prophylactic amoxicillin/clavulanic acid. Fifteen days after the surgery, he developed a fever (temperature, 103˚ F), chills, arthralgia, myalgia, cough, diarrhea, and malaise. He was seen by his physician, who obtained a chest x-ray showing a lingular infiltrate. The physician diagnosed influenza and pneumonia in this patient, and prescribed oseltamivir, azithromycin, and an additional course of amoxicillin/clavulanic acid.

Upon admission to the hospital, laboratory tests revealed a white blood cell count (WBC) of 3.1 k/mcL (normal: 3.2-10.8 k/mcL). The patient’s physical examination was notable for lip edema, white mucous membrane plaques, submandibular and inguinal lymphadenopathy, and a morbilliform rash across his chest (FIGURE 1). Broad-spectrum antibiotics were initiated for presumed sepsis.

On hospital day (HD) 1, tests revealed a WBC count of 1.8 k/mcL, an erythrocyte sedimentation rate of 53 mm/hr (normal: 20-30 mm/hr for women, 15-20 mm/hr for men), and a C-reactive protein level of 6.7 mg/dL (normal: <0.5 mg/dL). A repeat chest x-ray and orofacial computerized tomography scan were normal.

By HD 3, all bacterial cultures were negative, but the patient was positive for human herpesvirus (HHV)-6 on viral cultures. His leukopenia persisted and he had elevated levels of alanine transaminase ranging from 40 to 73 U/L (normal: 6-43 U/L) and aspartate aminotransferase ranging from 66 to 108 U/L (normal range: 10-40 U/L), both downtrending during his hospitalization. He also had elevated levels of antinuclear antibodies (ANAs) and anti-Smith (Sm) antibody titers.

A posterior-auricular biopsy was consistent with lymphocytic perivasculitis. The rash continued to progress, involving his chest, abdomen, and face (FIGURE 2). Bacterial and viral cultures remained negative and on HD 4, broad-spectrum antibiotics were discontinued.

THE DIAGNOSIS

We diagnosed the patient with DRESS (drug reaction with eosinophilia and systemic symptoms) based on persistent fever, onset of cutaneous manifestations (facial edema and morbilliform eruption), lymphadenopathy, increased liver function tests, and recent exposure to an offending drug. The patient did not have eosinophilia; however, atypical lymphocytes were present on his peripheral smear.

DISCUSSION

DRESS is typically characterized by fever, rash, eosinophilia, atypical lymphocytes, lymphadenopathy, and organ involvement (primarily liver, but multiple organ systems can be affected).¹ Patients with severe symptoms have renal involvement, anemia, respiratory and cardiac symptoms (chest pain, tachycardia, and myocarditis), and transaminase levels up to 5 times greater than normal.^1-3 Anticonvulsants and antibiotics are the most common offending classes among the medications that are associated with DRESS (TABLE 1).^2,4

The reported incidence of DRESS is between one in 1000 and one in 10,000 drug exposures.¹ Due to the broad presentation and a lack of established diagnostic criteria associated with DRESS, this number may be even higher. DRESS has a 10% mortality rate,¹ and hepatic necrosis is the most common cause of death.²

Certain people may be more prone to DRESS. People with certain gene mutations that code for drug detoxification enzymes have shown a greater incidence of DRESS.⁵ Viral reactivation, commonly of HHV-6, has also been shown to have an effect on the pathogenesis of DRESS. Additionally, genetic predisposition involving specific human leukocyte antigens (HLAs) makes certain people more prone to the development of DRESS (TABLE 2).^2,5

Case reports have demonstrated a link between certain autoimmune syndromes and DRESS, specifically Grave’s disease and type 1 diabetes mellitus.²

Patch testing and lymphocyte transformation tests can aid in the diagnosis of DRESS.

A unique finding of this case was the presence of elevated ANA and anti-Sm antibody titers at initial presentation, with spontaneous negative seroconversion 2 months later. Because of these 2 findings, as well as the patient’s leukopenia and rash, he briefly met 4 of the 11 criteria set forth by the American College of Rheumatology for a diagnosis of systemic lupus erythematosus (SLE).⁶ It is unclear whether the transiently elevated anti-Sm antibody titers were an acute phase reactant due to DRESS, a viral illness, or an evolving autoimmune process.

The false-positive rate for anti-Sm antibodies in association with DRESS has not been previously reported.

MAKING THE DIAGNOSIS

Distinguishing DRESS from other life-threatening cutaneous drug reactions, particularly Stevens-Johnson syndrome and toxic epidermal necrolysis, can be difficult. Likewise, acute bacterial/viral infections, autoimmune syndromes, vasculitis, and hematologic diseases can mimic DRESS.⁷ Exposure to an offending drug 2 to 6 weeks prior to the onset of symptoms is supportive of DRESS.

This scoring system can help. The RegiSCAR (Registry of Severe Cutaneous Adverse Reaction) has developed a scoring system to aid in the accurate diagnosis of DRESS.^1,8 The scoring consists of 8 categories: fever, eosinophilia, enlarged lymph nodes, atypical lymphocytes, skin involvement, organ involvement, time of resolution, and the evaluation of other potential causes.¹ Each category is graded a number from -1 (not supportive of DRESS) to 2 (highly supportive of DRESS) based on the patient’s presentation. The total score grades potential cases as “no,” “possible,” “probable,” or “definite.”^1,8 In one review, cases classified as “probable” or “definite” by the RegiSCAR scoring system constituted 88% of the cases reported in the literature.¹

Two tests that can also aid in the diagnosis of DRESS include patch testing (exposing the skin to a diluted version of the suspected offending drug and observing for a local reaction) and lymphocyte transformation tests. The latter are a better method of diagnosing drug-induced DRESS, with a sensitivity of 60% to 70%, and a specificity of 85%.⁹ However, this testing is not readily available.

Long-term sequelae, such as Grave's disease and diabetes mellitus, have been reported following DRESS.

Once DRESS is diagnosed, the offending drug should be immediately discontinued. For mild cases, supportive treatment is recommended. For more severe cases, the use of corticosteroids tapered over several months is the treatment of choice.¹⁰ Further studies are needed to determine the optimal type of corticosteroids, as well as the dose, route, and duration of therapy. Immunotherapy, plasmapheresis, and antivirals have been used with mixed results.^10,11

Our patient was started on topical and systemic oral corticosteroids. Within 24 hours, his fever resolved and his rash improved. By HD 7, his laboratory values were normal and he was discharged.

The patient was advised that in the future, he should avoid exposure to the penicillin class of medication.

THE TAKEAWAY

The presence of rash, fever, lymphadenopathy, eosinophilia, atypical lymphocytes, liver involvement, and HHV-6 reactivation in the absence of sepsis should raise suspicion for DRESS. Early diagnosis, discontinuation of the culprit drug, and timely treatment are imperative in the management of the condition. Due to a potential genetic predisposition to DRESS, clinicians should use caution when treating first-degree family members with the same class of medication that was problematic for their relative. Long-term sequelae, such as Grave’s disease and diabetes mellitus, have been reported following DRESS. Therefore, long-term monitoring with appropriate testing is recommended.

THE CASE

A 56-year-old white man presented at our dental clinic for routine care. The intraoral examination revealed an asymptomatic red lesion with white vesicle-like areas on the right side of the soft palate (FIGURE). The extraoral examination was normal, and regional lymph nodes were nonpalpable. The patient’s medical history included liver cirrhosis and pancreatitis. He also had a 30-year history of alcohol misuse (1-5 drinks per day) and a 30-pack-year smoking history. (The patient had stopped drinking at the time of presentation, and had quit smoking 2 years earlier.) We instructed him to gargle with warm salt water at home and return in 2 weeks. At follow-up, the lesion was unresolved, so a biopsy was performed.

THE DIAGNOSIS

The clinical diagnosis was erythroplakia. Trauma from food burn and inflammation of the salivary gland were both considered, but ultimately ruled out due to lack of symptoms and persistence of the lesion after 14 days. The pathology report confirmed a diagnosis of squamous cell carcinoma (SCC) in situ. Based on the pathology report, we referred the patient to an oral surgeon for wide surgical excision with evaluation of the margins.

Because of its location and subtle presentation, the lesion could have been easily overlooked, underscoring the importance of routinely going beyond dentition to examine the soft tissues of the mouth.

DISCUSSION

SCC is the most common cancer found in the oral cavity, accounting for 90% of all oral malignancies.^1,2 Other malignancies include lymphomas, sarcomas, melanomas, salivary gland neoplasms, and metastasis from other sites.^3,4 Predisposing factors include tobacco use (namely inhaled methods and chewing tobacco), alcohol misuse, human papillomavirus infection, and chewing betel nut.^1,5 (Betel nuts grow on a species of palm tree mainly found in India, Pakistan, and Bangladesh. They are commonly chewed for their caffeine-like effect and are known to be carcinogenic.)

Presentation. SCC of the oral cavity can have various presentations. The lesion can appear as white, red, a mix of white and red, as a mass, or as a nonhealing ulcer. While some patients may be asymptomatic (as was ours), some may have signs and symptoms such as pain, bleeding, difficulty swallowing, difficulty wearing dentures, or a neck mass.⁶ A history of smoking and alcohol misuse, which was present in this case, should heighten suspicion and prompt further investigation of oral lesions.

Location. The most common intraoral site for oral cancer is the tongue (on the posterolateral border) followed by the floor of the mouth. Other common sites in descending order are the soft palate, gingiva, buccal mucosa, labial mucosa, and hard palate.¹ (Our patient’s lesion was on the border of the hard and soft palate).

Treatment of oral cancer is surgical. In some cases, depending on the stage and size of the tumor, radiation and chemotherapy may be considered.^3,5 Approximately two-thirds of oral cancers are detected in the later stages.⁷ The 5-year survival rate for people with oral SCC found at stages III or IV ranges from 32% to 45%, while the rate for those with SCC detected at stages I or II is 58% to 72%.¹ Patients with a history of oral cancer have a 20-fold increased risk of a recurrence in the oral cavity or of developing cancer in the surrounding areas, such as the larynx, esophagus, and lungs, underscoring the necessity of adequate follow-up in these patients.^2,3,5

Who is at risk?

In 2015, there were an estimated 45,780 new cases of oral cavity and pharyngeal cancer and 8650 deaths from these causes.⁸ Although oral cancer accounts for only 3% of all cancers in the United States, it is the eighth most common cancer in males and the 15^th most common in females.¹ Prevalence differs tremendously by location, however. In India, for example, oral cancer accounts for 30% of all cancers.⁹ Regardless of location, incidence increases with age; 62 is the average age at diagnosis.² Oral cancers are also more common among African Americans than among Caucasians.^1,3,5

Smokers are 2 to 3 times more likely to develop oral cancer than nonsmokers.¹ This risk increases with amount and duration of smoking.¹ The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.^1,3

Alcohol use. Among male patients with oral cancer, one-third are heavy alcohol users.¹ In fact, one study found that 20% of these patients have cirrhosis of the liver.¹ Thus, it makes good clinical sense to routinely examine the soft tissue of the oral cavity for abnormalities in patients with alcohol-induced cirrhosis of the liver.

The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.

Our patient. We placed our patient on a 3-month recall and stressed the importance of not smoking. The patient had surgery and a good outcome was documented. The patient indicated at follow-up that he’d started drinking again and was referred for counseling.

TAKEAWAY

It’s important to pay attention to color differences in the oral cavity on routine visits, particularly in patients with known risk factors for SCC. Patients with a lesion in the oral cavity should be seen again within 2 weeks. If the lesion is unresolved, the patient should be referred for further examination and/or biopsy. The possibility of recurrent oral cancer or cancer in the surrounding areas makes these patients good candidates for frequent follow-up examinations.

We strongly suggest that primary care physicians encourage their patients with the known predisposing risk factors of tobacco use and chronic alcohol misuse to quit these habits, visit their dentists for annual oral cancer screenings, and report any oral symptoms promptly to their medical and/or dental care providers. The asymptomatic nature of many of these lesions underscores the importance of following this advice. As is the case with most other cancers, survival rate is dependent on the stage of the disease at diagnosis.

THE CASE

A 56-year-old white man presented at our dental clinic for routine care. The intraoral examination revealed an asymptomatic red lesion with white vesicle-like areas on the right side of the soft palate (FIGURE). The extraoral examination was normal, and regional lymph nodes were nonpalpable. The patient’s medical history included liver cirrhosis and pancreatitis. He also had a 30-year history of alcohol misuse (1-5 drinks per day) and a 30-pack-year smoking history. (The patient had stopped drinking at the time of presentation, and had quit smoking 2 years earlier.) We instructed him to gargle with warm salt water at home and return in 2 weeks. At follow-up, the lesion was unresolved, so a biopsy was performed.

THE DIAGNOSIS

The clinical diagnosis was erythroplakia. Trauma from food burn and inflammation of the salivary gland were both considered, but ultimately ruled out due to lack of symptoms and persistence of the lesion after 14 days. The pathology report confirmed a diagnosis of squamous cell carcinoma (SCC) in situ. Based on the pathology report, we referred the patient to an oral surgeon for wide surgical excision with evaluation of the margins.

Because of its location and subtle presentation, the lesion could have been easily overlooked, underscoring the importance of routinely going beyond dentition to examine the soft tissues of the mouth.

DISCUSSION

SCC is the most common cancer found in the oral cavity, accounting for 90% of all oral malignancies.^1,2 Other malignancies include lymphomas, sarcomas, melanomas, salivary gland neoplasms, and metastasis from other sites.^3,4 Predisposing factors include tobacco use (namely inhaled methods and chewing tobacco), alcohol misuse, human papillomavirus infection, and chewing betel nut.^1,5 (Betel nuts grow on a species of palm tree mainly found in India, Pakistan, and Bangladesh. They are commonly chewed for their caffeine-like effect and are known to be carcinogenic.)

Presentation. SCC of the oral cavity can have various presentations. The lesion can appear as white, red, a mix of white and red, as a mass, or as a nonhealing ulcer. While some patients may be asymptomatic (as was ours), some may have signs and symptoms such as pain, bleeding, difficulty swallowing, difficulty wearing dentures, or a neck mass.⁶ A history of smoking and alcohol misuse, which was present in this case, should heighten suspicion and prompt further investigation of oral lesions.

Location. The most common intraoral site for oral cancer is the tongue (on the posterolateral border) followed by the floor of the mouth. Other common sites in descending order are the soft palate, gingiva, buccal mucosa, labial mucosa, and hard palate.¹ (Our patient’s lesion was on the border of the hard and soft palate).

Treatment of oral cancer is surgical. In some cases, depending on the stage and size of the tumor, radiation and chemotherapy may be considered.^3,5 Approximately two-thirds of oral cancers are detected in the later stages.⁷ The 5-year survival rate for people with oral SCC found at stages III or IV ranges from 32% to 45%, while the rate for those with SCC detected at stages I or II is 58% to 72%.¹ Patients with a history of oral cancer have a 20-fold increased risk of a recurrence in the oral cavity or of developing cancer in the surrounding areas, such as the larynx, esophagus, and lungs, underscoring the necessity of adequate follow-up in these patients.^2,3,5

Who is at risk?

In 2015, there were an estimated 45,780 new cases of oral cavity and pharyngeal cancer and 8650 deaths from these causes.⁸ Although oral cancer accounts for only 3% of all cancers in the United States, it is the eighth most common cancer in males and the 15^th most common in females.¹ Prevalence differs tremendously by location, however. In India, for example, oral cancer accounts for 30% of all cancers.⁹ Regardless of location, incidence increases with age; 62 is the average age at diagnosis.² Oral cancers are also more common among African Americans than among Caucasians.^1,3,5

Smokers are 2 to 3 times more likely to develop oral cancer than nonsmokers.¹ This risk increases with amount and duration of smoking.¹ The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.^1,3

Alcohol use. Among male patients with oral cancer, one-third are heavy alcohol users.¹ In fact, one study found that 20% of these patients have cirrhosis of the liver.¹ Thus, it makes good clinical sense to routinely examine the soft tissue of the oral cavity for abnormalities in patients with alcohol-induced cirrhosis of the liver.

The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.

Our patient. We placed our patient on a 3-month recall and stressed the importance of not smoking. The patient had surgery and a good outcome was documented. The patient indicated at follow-up that he’d started drinking again and was referred for counseling.

TAKEAWAY

It’s important to pay attention to color differences in the oral cavity on routine visits, particularly in patients with known risk factors for SCC. Patients with a lesion in the oral cavity should be seen again within 2 weeks. If the lesion is unresolved, the patient should be referred for further examination and/or biopsy. The possibility of recurrent oral cancer or cancer in the surrounding areas makes these patients good candidates for frequent follow-up examinations.

We strongly suggest that primary care physicians encourage their patients with the known predisposing risk factors of tobacco use and chronic alcohol misuse to quit these habits, visit their dentists for annual oral cancer screenings, and report any oral symptoms promptly to their medical and/or dental care providers. The asymptomatic nature of many of these lesions underscores the importance of following this advice. As is the case with most other cancers, survival rate is dependent on the stage of the disease at diagnosis.

THE CASE

A 56-year-old white man presented at our dental clinic for routine care. The intraoral examination revealed an asymptomatic red lesion with white vesicle-like areas on the right side of the soft palate (FIGURE). The extraoral examination was normal, and regional lymph nodes were nonpalpable. The patient’s medical history included liver cirrhosis and pancreatitis. He also had a 30-year history of alcohol misuse (1-5 drinks per day) and a 30-pack-year smoking history. (The patient had stopped drinking at the time of presentation, and had quit smoking 2 years earlier.) We instructed him to gargle with warm salt water at home and return in 2 weeks. At follow-up, the lesion was unresolved, so a biopsy was performed.

THE DIAGNOSIS

The clinical diagnosis was erythroplakia. Trauma from food burn and inflammation of the salivary gland were both considered, but ultimately ruled out due to lack of symptoms and persistence of the lesion after 14 days. The pathology report confirmed a diagnosis of squamous cell carcinoma (SCC) in situ. Based on the pathology report, we referred the patient to an oral surgeon for wide surgical excision with evaluation of the margins.

Because of its location and subtle presentation, the lesion could have been easily overlooked, underscoring the importance of routinely going beyond dentition to examine the soft tissues of the mouth.

DISCUSSION

SCC is the most common cancer found in the oral cavity, accounting for 90% of all oral malignancies.^1,2 Other malignancies include lymphomas, sarcomas, melanomas, salivary gland neoplasms, and metastasis from other sites.^3,4 Predisposing factors include tobacco use (namely inhaled methods and chewing tobacco), alcohol misuse, human papillomavirus infection, and chewing betel nut.^1,5 (Betel nuts grow on a species of palm tree mainly found in India, Pakistan, and Bangladesh. They are commonly chewed for their caffeine-like effect and are known to be carcinogenic.)

Presentation. SCC of the oral cavity can have various presentations. The lesion can appear as white, red, a mix of white and red, as a mass, or as a nonhealing ulcer. While some patients may be asymptomatic (as was ours), some may have signs and symptoms such as pain, bleeding, difficulty swallowing, difficulty wearing dentures, or a neck mass.⁶ A history of smoking and alcohol misuse, which was present in this case, should heighten suspicion and prompt further investigation of oral lesions.

Location. The most common intraoral site for oral cancer is the tongue (on the posterolateral border) followed by the floor of the mouth. Other common sites in descending order are the soft palate, gingiva, buccal mucosa, labial mucosa, and hard palate.¹ (Our patient’s lesion was on the border of the hard and soft palate).

Treatment of oral cancer is surgical. In some cases, depending on the stage and size of the tumor, radiation and chemotherapy may be considered.^3,5 Approximately two-thirds of oral cancers are detected in the later stages.⁷ The 5-year survival rate for people with oral SCC found at stages III or IV ranges from 32% to 45%, while the rate for those with SCC detected at stages I or II is 58% to 72%.¹ Patients with a history of oral cancer have a 20-fold increased risk of a recurrence in the oral cavity or of developing cancer in the surrounding areas, such as the larynx, esophagus, and lungs, underscoring the necessity of adequate follow-up in these patients.^2,3,5

Who is at risk?

In 2015, there were an estimated 45,780 new cases of oral cavity and pharyngeal cancer and 8650 deaths from these causes.⁸ Although oral cancer accounts for only 3% of all cancers in the United States, it is the eighth most common cancer in males and the 15^th most common in females.¹ Prevalence differs tremendously by location, however. In India, for example, oral cancer accounts for 30% of all cancers.⁹ Regardless of location, incidence increases with age; 62 is the average age at diagnosis.² Oral cancers are also more common among African Americans than among Caucasians.^1,3,5

Smokers are 2 to 3 times more likely to develop oral cancer than nonsmokers.¹ This risk increases with amount and duration of smoking.¹ The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.^1,3

Alcohol use. Among male patients with oral cancer, one-third are heavy alcohol users.¹ In fact, one study found that 20% of these patients have cirrhosis of the liver.¹ Thus, it makes good clinical sense to routinely examine the soft tissue of the oral cavity for abnormalities in patients with alcohol-induced cirrhosis of the liver.

The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.

Our patient. We placed our patient on a 3-month recall and stressed the importance of not smoking. The patient had surgery and a good outcome was documented. The patient indicated at follow-up that he’d started drinking again and was referred for counseling.

TAKEAWAY

It’s important to pay attention to color differences in the oral cavity on routine visits, particularly in patients with known risk factors for SCC. Patients with a lesion in the oral cavity should be seen again within 2 weeks. If the lesion is unresolved, the patient should be referred for further examination and/or biopsy. The possibility of recurrent oral cancer or cancer in the surrounding areas makes these patients good candidates for frequent follow-up examinations.

We strongly suggest that primary care physicians encourage their patients with the known predisposing risk factors of tobacco use and chronic alcohol misuse to quit these habits, visit their dentists for annual oral cancer screenings, and report any oral symptoms promptly to their medical and/or dental care providers. The asymptomatic nature of many of these lesions underscores the importance of following this advice. As is the case with most other cancers, survival rate is dependent on the stage of the disease at diagnosis.

Atypical fibroxanthoma (AFX) is a low-grade dermal malignancy comprised of atypical spindle cells.¹ Classified as a superficial fibrohistiocytic tumor with intermediate malignant potential, AFX has an incidence of approximately 0.24% worldwide.² The tumor appears mainly on the head and neck in sun-exposed areas but can occur less frequently on the trunk and limbs in non–sun-exposed areas. There is a 70% to 80% predominance in men aged 69 to 77 years, with lesions primarily occurring in sun-exposed areas of the head and neck.³ A median period of 4 months between time of onset and time of diagnosis has been previously established.⁴

When AFX does occur in non–sun-exposed areas, it tends to be in a younger patient population. Clinically, it presents as a rather nondescript, firm, erythematous papule or nodule less than 2 cm in diameter. Atypical fibroxanthoma most often presents asymptomatically, but the tumor may ulcerate and bleed, though pain and pruritus are uncommon.5 Findings are nonspecific, and the diagnosis must be confirmed with biopsy, as it can resemble other common dermatological lesions. The pathogenesis of AFX has been controversial. Two different studies looked at AFX using electron microscopy and concluded that the tumor most closely resembled a myofibroblast,^6,7 which is consistent with current thinking today.

Atypical fibroxanthoma is believed to be associated with p53 mutation and is closely linked with exposure to UV radiation due to its predominance in sun-exposed areas. Other predisposing factors may include prior exposure to UV radiation, history of organ transplantation, immunosuppression, advanced age in men, and xeroderma pigmentosum. The differential diagnosis for AFX encompasses basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, adnexal tumor, and pyogenic granuloma.

Case Report

A 93-year-old man was referred to our clinic for treatment of erosive pustular dermatosis of the scalp with photodynamic therapy (PDT). He had a more than 20-year history of multiple skin lesions including basal cell carcinoma, squamous cell carcinoma, and actinic keratoses (AKs). For one year prior to the current presentation the patient had concerns of pustules, scaling, itching, and scabbing on the scalp. The patient admitted that the pruritus caused him to pick at the scabs on the scalp. He had previously been treated with lactic acid 12% neutralized with ammonium hydroxide, tacrolimus, and halobetasol, all to no avail.

On physical examination, the lesions appeared erosive with crusting and granulation tissue (Figure 1A). The presentation was consistent with erosive pustular dermatosis of the scalp. Biopsy revealed granulation tissue. The patient underwent PDT and prednisone treatment with improvement. Additional biopsies revealed AKs. His condition improved with 2 PDT sessions but never fully cleared. During the PDT sessions, the patient reported intense unilateral headaches without visual changes. The headaches were intermittent and not apparently related to the treatments. He was referred for a temporal artery biopsy and rebiopsy of the remaining lesion on the scalp. The temporal artery biopsy was negative. The lesion that remained was a large nodule on the vertex scalp, and biopsy revealed AFX.

Immunohistochemical marker studies for S-100 and cytokeratin were negative. Invasion into subcutaneous fat was encountered (Figure 2A). Highly atypical spindle cells and mitoses were present (Figure 2B). Neoplastic cells were noted adjacent to nerve (Figure 2C). Excision of the lesion was curative, and his symptoms of pain and erosive pustular dermatosis resolved weeks thereafter (Figure 1B). The area of erosive pustular dermatosis was not excised, but symptoms resolved weeks following excision of the AFX.

Comment

Our case of AFX is unique due to the patient’s atypical presentation of severe pain. Because AFX usually presents asymptomatically, pain is an uncommon symptom. Based on the histologic findings in our case, we suspected that neural involvement of the tumor most likely explained the intense pain that our patient experienced.

The presence of erosive pustular dermatosis of the scalp also is interesting in our case. This elderly man had an extensive history of actinic damage and had reported pustules, scaling, itching, and scabbing of the scalp. It is possible that erosive pustular dermatosis was superimposed over the tumor and could have been the reason that multiple biopsies were needed to eventually arrive at a diagnosis. The coexistence of the 2 entities suggests that the chronic actinic damage played a role in the etiology of both.

Classification
There is a question regarding nomenclature when discussing AFX. Atypical fibroxanthoma has been referred to as a variant of undifferentiated pleomorphic sarcoma, which is a type of soft tissue sarcoma. Atypical fibroxanthoma can be referred to as undifferentiated pleomorphic sarcoma if it is more than 2 cm in diameter, if it involves the fascia or subcutaneous tissue, or if there is evidence of necrosis.³ Atypical fibroxanthoma generally is confined to the head and neck region and usually is less than 2 cm in diameter. In this patient, the presentation was consistent with AFX, as there was evidence of necrosis and invasion into the subcutaneous fat. The fact that the lesion also appeared on the scalp further supported the diagnosis of AFX.

Pathology
Biopsy of AFX typically reveals a spindle cell proliferation that usually arises in the setting of profound actinic damage. The epidermis may or may not be ulcerated, and in most cases, it is seen in close proximity to the overlying epidermis but not arising from it.8 Classic AFX is composed of highly atypical histiocytelike (epithelioid) cells admixed with pleomorphic spindle cells and giant cells, all showing frequent mitoses including atypical ones.9 Several histologic subtypes of AFX have been described, including clear cell, granular cell, pigmented cell, chondroid, osteoid, osteoclastic, and the most common spindle cell subtype.9 Features that indicate potential aggressive behavior include infiltration into the subcutaneous tissue, vascular invasion, and presence of necrosis. A diagnosis of AFX is made by exclusion of other malignant neoplasms with similar morphology, namely spindle cell squamous cell carcinoma, spindle cell melanoma, and leiomyoscarcoma.9 As such, immunohistochemistry plays a critical role in distinguishing these lesions, as they arise as part of the differential diagnosis. A panel of immunohistochemical stains is helpful for diagnosis and commonly includes but is not limited to S-100, Melan-A, smooth muscle actin, desmin, and cytokeratin.

Sampling error is an inherent flaw in any biopsy specimen. The eventual diagnosis of AFX in our case supports the argument for multiple biopsies of an unknown lesion, seeing as the affected area was interpreted as both granulation tissue and AK prior to the eventual diagnosis. Repeat biopsies, especially if a lesion is nonhealing, often can help clinicians arrive at a definitive diagnosis.

Treatment
Different treatment options have been used to manage AFX. Mohs micrographic surgery is most often used because of its tissue-sparing potential, often giving the most cosmetically appealing result. Wide local excision is another surgical technique utilized, generally with fixed margins of at least 1 cm.¹⁰ Radiation at the tumor site is used as a treatment method but most often during cases of reoccurrence. Cryotherapy as well as electrodesiccation and curettage are possible treatment options but are not the standard of care.

Atypical fibroxanthoma (AFX) is a low-grade dermal malignancy comprised of atypical spindle cells.¹ Classified as a superficial fibrohistiocytic tumor with intermediate malignant potential, AFX has an incidence of approximately 0.24% worldwide.² The tumor appears mainly on the head and neck in sun-exposed areas but can occur less frequently on the trunk and limbs in non–sun-exposed areas. There is a 70% to 80% predominance in men aged 69 to 77 years, with lesions primarily occurring in sun-exposed areas of the head and neck.³ A median period of 4 months between time of onset and time of diagnosis has been previously established.⁴

When AFX does occur in non–sun-exposed areas, it tends to be in a younger patient population. Clinically, it presents as a rather nondescript, firm, erythematous papule or nodule less than 2 cm in diameter. Atypical fibroxanthoma most often presents asymptomatically, but the tumor may ulcerate and bleed, though pain and pruritus are uncommon.5 Findings are nonspecific, and the diagnosis must be confirmed with biopsy, as it can resemble other common dermatological lesions. The pathogenesis of AFX has been controversial. Two different studies looked at AFX using electron microscopy and concluded that the tumor most closely resembled a myofibroblast,^6,7 which is consistent with current thinking today.

Atypical fibroxanthoma is believed to be associated with p53 mutation and is closely linked with exposure to UV radiation due to its predominance in sun-exposed areas. Other predisposing factors may include prior exposure to UV radiation, history of organ transplantation, immunosuppression, advanced age in men, and xeroderma pigmentosum. The differential diagnosis for AFX encompasses basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, adnexal tumor, and pyogenic granuloma.

Case Report

A 93-year-old man was referred to our clinic for treatment of erosive pustular dermatosis of the scalp with photodynamic therapy (PDT). He had a more than 20-year history of multiple skin lesions including basal cell carcinoma, squamous cell carcinoma, and actinic keratoses (AKs). For one year prior to the current presentation the patient had concerns of pustules, scaling, itching, and scabbing on the scalp. The patient admitted that the pruritus caused him to pick at the scabs on the scalp. He had previously been treated with lactic acid 12% neutralized with ammonium hydroxide, tacrolimus, and halobetasol, all to no avail.

On physical examination, the lesions appeared erosive with crusting and granulation tissue (Figure 1A). The presentation was consistent with erosive pustular dermatosis of the scalp. Biopsy revealed granulation tissue. The patient underwent PDT and prednisone treatment with improvement. Additional biopsies revealed AKs. His condition improved with 2 PDT sessions but never fully cleared. During the PDT sessions, the patient reported intense unilateral headaches without visual changes. The headaches were intermittent and not apparently related to the treatments. He was referred for a temporal artery biopsy and rebiopsy of the remaining lesion on the scalp. The temporal artery biopsy was negative. The lesion that remained was a large nodule on the vertex scalp, and biopsy revealed AFX.

Immunohistochemical marker studies for S-100 and cytokeratin were negative. Invasion into subcutaneous fat was encountered (Figure 2A). Highly atypical spindle cells and mitoses were present (Figure 2B). Neoplastic cells were noted adjacent to nerve (Figure 2C). Excision of the lesion was curative, and his symptoms of pain and erosive pustular dermatosis resolved weeks thereafter (Figure 1B). The area of erosive pustular dermatosis was not excised, but symptoms resolved weeks following excision of the AFX.

Comment

Our case of AFX is unique due to the patient’s atypical presentation of severe pain. Because AFX usually presents asymptomatically, pain is an uncommon symptom. Based on the histologic findings in our case, we suspected that neural involvement of the tumor most likely explained the intense pain that our patient experienced.

The presence of erosive pustular dermatosis of the scalp also is interesting in our case. This elderly man had an extensive history of actinic damage and had reported pustules, scaling, itching, and scabbing of the scalp. It is possible that erosive pustular dermatosis was superimposed over the tumor and could have been the reason that multiple biopsies were needed to eventually arrive at a diagnosis. The coexistence of the 2 entities suggests that the chronic actinic damage played a role in the etiology of both.

Classification
There is a question regarding nomenclature when discussing AFX. Atypical fibroxanthoma has been referred to as a variant of undifferentiated pleomorphic sarcoma, which is a type of soft tissue sarcoma. Atypical fibroxanthoma can be referred to as undifferentiated pleomorphic sarcoma if it is more than 2 cm in diameter, if it involves the fascia or subcutaneous tissue, or if there is evidence of necrosis.³ Atypical fibroxanthoma generally is confined to the head and neck region and usually is less than 2 cm in diameter. In this patient, the presentation was consistent with AFX, as there was evidence of necrosis and invasion into the subcutaneous fat. The fact that the lesion also appeared on the scalp further supported the diagnosis of AFX.

Pathology
Biopsy of AFX typically reveals a spindle cell proliferation that usually arises in the setting of profound actinic damage. The epidermis may or may not be ulcerated, and in most cases, it is seen in close proximity to the overlying epidermis but not arising from it.8 Classic AFX is composed of highly atypical histiocytelike (epithelioid) cells admixed with pleomorphic spindle cells and giant cells, all showing frequent mitoses including atypical ones.9 Several histologic subtypes of AFX have been described, including clear cell, granular cell, pigmented cell, chondroid, osteoid, osteoclastic, and the most common spindle cell subtype.9 Features that indicate potential aggressive behavior include infiltration into the subcutaneous tissue, vascular invasion, and presence of necrosis. A diagnosis of AFX is made by exclusion of other malignant neoplasms with similar morphology, namely spindle cell squamous cell carcinoma, spindle cell melanoma, and leiomyoscarcoma.9 As such, immunohistochemistry plays a critical role in distinguishing these lesions, as they arise as part of the differential diagnosis. A panel of immunohistochemical stains is helpful for diagnosis and commonly includes but is not limited to S-100, Melan-A, smooth muscle actin, desmin, and cytokeratin.

Sampling error is an inherent flaw in any biopsy specimen. The eventual diagnosis of AFX in our case supports the argument for multiple biopsies of an unknown lesion, seeing as the affected area was interpreted as both granulation tissue and AK prior to the eventual diagnosis. Repeat biopsies, especially if a lesion is nonhealing, often can help clinicians arrive at a definitive diagnosis.

Treatment
Different treatment options have been used to manage AFX. Mohs micrographic surgery is most often used because of its tissue-sparing potential, often giving the most cosmetically appealing result. Wide local excision is another surgical technique utilized, generally with fixed margins of at least 1 cm.¹⁰ Radiation at the tumor site is used as a treatment method but most often during cases of reoccurrence. Cryotherapy as well as electrodesiccation and curettage are possible treatment options but are not the standard of care.

Atypical fibroxanthoma (AFX) is a low-grade dermal malignancy comprised of atypical spindle cells.¹ Classified as a superficial fibrohistiocytic tumor with intermediate malignant potential, AFX has an incidence of approximately 0.24% worldwide.² The tumor appears mainly on the head and neck in sun-exposed areas but can occur less frequently on the trunk and limbs in non–sun-exposed areas. There is a 70% to 80% predominance in men aged 69 to 77 years, with lesions primarily occurring in sun-exposed areas of the head and neck.³ A median period of 4 months between time of onset and time of diagnosis has been previously established.⁴

When AFX does occur in non–sun-exposed areas, it tends to be in a younger patient population. Clinically, it presents as a rather nondescript, firm, erythematous papule or nodule less than 2 cm in diameter. Atypical fibroxanthoma most often presents asymptomatically, but the tumor may ulcerate and bleed, though pain and pruritus are uncommon.5 Findings are nonspecific, and the diagnosis must be confirmed with biopsy, as it can resemble other common dermatological lesions. The pathogenesis of AFX has been controversial. Two different studies looked at AFX using electron microscopy and concluded that the tumor most closely resembled a myofibroblast,^6,7 which is consistent with current thinking today.

Atypical fibroxanthoma is believed to be associated with p53 mutation and is closely linked with exposure to UV radiation due to its predominance in sun-exposed areas. Other predisposing factors may include prior exposure to UV radiation, history of organ transplantation, immunosuppression, advanced age in men, and xeroderma pigmentosum. The differential diagnosis for AFX encompasses basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, adnexal tumor, and pyogenic granuloma.

Case Report

A 93-year-old man was referred to our clinic for treatment of erosive pustular dermatosis of the scalp with photodynamic therapy (PDT). He had a more than 20-year history of multiple skin lesions including basal cell carcinoma, squamous cell carcinoma, and actinic keratoses (AKs). For one year prior to the current presentation the patient had concerns of pustules, scaling, itching, and scabbing on the scalp. The patient admitted that the pruritus caused him to pick at the scabs on the scalp. He had previously been treated with lactic acid 12% neutralized with ammonium hydroxide, tacrolimus, and halobetasol, all to no avail.

On physical examination, the lesions appeared erosive with crusting and granulation tissue (Figure 1A). The presentation was consistent with erosive pustular dermatosis of the scalp. Biopsy revealed granulation tissue. The patient underwent PDT and prednisone treatment with improvement. Additional biopsies revealed AKs. His condition improved with 2 PDT sessions but never fully cleared. During the PDT sessions, the patient reported intense unilateral headaches without visual changes. The headaches were intermittent and not apparently related to the treatments. He was referred for a temporal artery biopsy and rebiopsy of the remaining lesion on the scalp. The temporal artery biopsy was negative. The lesion that remained was a large nodule on the vertex scalp, and biopsy revealed AFX.

Immunohistochemical marker studies for S-100 and cytokeratin were negative. Invasion into subcutaneous fat was encountered (Figure 2A). Highly atypical spindle cells and mitoses were present (Figure 2B). Neoplastic cells were noted adjacent to nerve (Figure 2C). Excision of the lesion was curative, and his symptoms of pain and erosive pustular dermatosis resolved weeks thereafter (Figure 1B). The area of erosive pustular dermatosis was not excised, but symptoms resolved weeks following excision of the AFX.

Comment

Our case of AFX is unique due to the patient’s atypical presentation of severe pain. Because AFX usually presents asymptomatically, pain is an uncommon symptom. Based on the histologic findings in our case, we suspected that neural involvement of the tumor most likely explained the intense pain that our patient experienced.

The presence of erosive pustular dermatosis of the scalp also is interesting in our case. This elderly man had an extensive history of actinic damage and had reported pustules, scaling, itching, and scabbing of the scalp. It is possible that erosive pustular dermatosis was superimposed over the tumor and could have been the reason that multiple biopsies were needed to eventually arrive at a diagnosis. The coexistence of the 2 entities suggests that the chronic actinic damage played a role in the etiology of both.

Classification
There is a question regarding nomenclature when discussing AFX. Atypical fibroxanthoma has been referred to as a variant of undifferentiated pleomorphic sarcoma, which is a type of soft tissue sarcoma. Atypical fibroxanthoma can be referred to as undifferentiated pleomorphic sarcoma if it is more than 2 cm in diameter, if it involves the fascia or subcutaneous tissue, or if there is evidence of necrosis.³ Atypical fibroxanthoma generally is confined to the head and neck region and usually is less than 2 cm in diameter. In this patient, the presentation was consistent with AFX, as there was evidence of necrosis and invasion into the subcutaneous fat. The fact that the lesion also appeared on the scalp further supported the diagnosis of AFX.

Pathology
Biopsy of AFX typically reveals a spindle cell proliferation that usually arises in the setting of profound actinic damage. The epidermis may or may not be ulcerated, and in most cases, it is seen in close proximity to the overlying epidermis but not arising from it.8 Classic AFX is composed of highly atypical histiocytelike (epithelioid) cells admixed with pleomorphic spindle cells and giant cells, all showing frequent mitoses including atypical ones.9 Several histologic subtypes of AFX have been described, including clear cell, granular cell, pigmented cell, chondroid, osteoid, osteoclastic, and the most common spindle cell subtype.9 Features that indicate potential aggressive behavior include infiltration into the subcutaneous tissue, vascular invasion, and presence of necrosis. A diagnosis of AFX is made by exclusion of other malignant neoplasms with similar morphology, namely spindle cell squamous cell carcinoma, spindle cell melanoma, and leiomyoscarcoma.9 As such, immunohistochemistry plays a critical role in distinguishing these lesions, as they arise as part of the differential diagnosis. A panel of immunohistochemical stains is helpful for diagnosis and commonly includes but is not limited to S-100, Melan-A, smooth muscle actin, desmin, and cytokeratin.

Sampling error is an inherent flaw in any biopsy specimen. The eventual diagnosis of AFX in our case supports the argument for multiple biopsies of an unknown lesion, seeing as the affected area was interpreted as both granulation tissue and AK prior to the eventual diagnosis. Repeat biopsies, especially if a lesion is nonhealing, often can help clinicians arrive at a definitive diagnosis.

Treatment
Different treatment options have been used to manage AFX. Mohs micrographic surgery is most often used because of its tissue-sparing potential, often giving the most cosmetically appealing result. Wide local excision is another surgical technique utilized, generally with fixed margins of at least 1 cm.¹⁰ Radiation at the tumor site is used as a treatment method but most often during cases of reoccurrence. Cryotherapy as well as electrodesiccation and curettage are possible treatment options but are not the standard of care.

Take-Home Points

• Prevalence of the medial oblique meniscomeniscal ligament is 1% to 4%.
• It is important to distinguish this ligament from a meniscus tear on MRI.
• The functional characteristics of this ligament are not well understood.
• What may appear to be a meniscal tear in a younger patient could be a medial oblique meniscomeniscal ligament.
• Dr. Flanigan recommends leaving the ligament intact unless resection is needed to provide better visualization.

We report a case of aberrant meniscus attachment in the setting of anterior cruciate ligament (ACL) injury. An anomalous cordlike attachment ran from the anterior horn of the medial meniscus to the posterior horn of the lateral meniscus through the intercondylar notch. This attachment was previously named the medial oblique meniscomeniscal ligament1 but has seldom been reported in the literature. Prevalence is 1% to 4%.^1,2 This case was treated at Ohio State University Wexner Medical Center in Columbus. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An 18-year-old man presented with left knee pain after sustaining 2 injuries to the knee. The first injury occurred during a dodgeball game—when the knee buckled on landing from a jump. A “pop” was felt, and the knee swelled immediately. The second injury occurred about 3 months later, during soccer play. The patient was running when his foot slipped and caused the knee to buckle. Again, a “pop” was felt, and there was swelling. Mechanical symptoms of clicking then started. The patient reported no instability episodes. His medical history and family history were otherwise unremarkable. The patient was healthy and had a body mass index of 23.05 kg/m2.

Physical examination revealed no effusion, erythema, or warmth in the left knee. Range of motion was 0° to 135° in the left knee and 0° to 140° in the right knee. There was no pain on hyperextension of the knee or medial or lateral joint-line tenderness, but there was pain on hyperflexion, and the McMurray test was positive. Ligament examination was negative except for positive anterior drawer, Lachman, and pivot-shift tests.

Radiographs taken the day of the first clinic visit showed no acute osseous abnormality. Magnetic resonance imaging (MRI) showed complete disruption of the proximal fibers of the ACL (Figures 1, 2). 

Also observed was a small oblique tear of the body of the lateral meniscus with slight blunting of the anterior horn of the medial meniscus, which may have been related to a small tear. A pivot-shift contusion pattern with impaction fracture of the lateral femoral condyle was also appreciated. There were no definite cartilage defects identified.

Discussion

The medial and lateral menisci typically are separate fibrocartilaginous structures acting as a cushion for the knee, but normal variant connections between the structures have been described. These connections include the anterior transverse meniscal ligament, the posterior transverse meniscal ligament, and the medial and lateral oblique meniscomeniscal ligaments.³ In the present case, a medial oblique meniscomeniscal ligament was identified. Its path between menisci was traceable on coronal and axial views. Video taken during arthroscopy also clearly showed its path and its relationship to other structures in the knee. To Dr. Flanigan’s knowledge, this ligament was not previously described with video. It is important to distinguish this ligament from a horizontal tear of the meniscus, given the potential for misinterpretation on MRI. A horizontal tear is a degenerative change that often occurs in older patients. Our patient was 18 years old at time of injury. In addition, the surface of his lower meniscus was smooth, whereas in a tear the edge is irregular and discontinuous. Dr. Flanigan prefers to leave this ligament intact unless resection would provide better visualization during arthroscopy. His reasoning is that the functional characteristics of the ligament are not well understood.

There are few reports on the medial oblique meniscomeniscal ligament.¹ Sanders and colleagues¹ found 3 cases of this normal variant. In the first, the ligament was interpreted as a flap tear on MRI; in the other 2 cases, the ligament was correctly identified. Kim and Laor² and Dervin and Paterson⁴ also described this variant in case reports.

There are many abnormalities of the meniscus. In our literature review, we found reports on various anomalies, including discoid meniscus,⁵ ring-shape meniscus,^6,7 accessory meniscus,⁸ double-layer meniscus,^9-12 abnormal band formation,^13,14 hypoplasia,¹⁵ Wrisberg meniscus,⁶ and congenital absence of meniscus.¹⁶ These variations have multifactorial causes, including congenital and developmental influences.

In a recent case report, Giordano and Goldblatt¹⁴ described an abnormal band of lateral meniscus extending from the posterior horn to the anterior-mid portion of the same meniscus. Lee and Min¹³ described the same band earlier, in a 2-patient case report.¹³ One patient presented symptomatically, nontraumatically, and the other with a posterior cruciate ligament tear. Each case was deemed congenital given the characteristic appearance and bilaterality of the anomaly.

In an 11-patient case series in Finland, Rainio and colleagues¹⁷ described an attachment from the anterior horn of the medial meniscus inserting into the ACL—a crescent band from the upper surface of the anterior horn that attached along the upper two thirds of the ACL.

At 2-year follow-up, our patient was doing well with rehabilitation and experienced only minimal symptoms. Radiologists and surgeons should be able to identify such variants. Knowing the common and rare variants, radiologists can help surgeons by identifying normal anatomy from pathology and providing a more clinically relevant report. Surgeons should be aware of the anatomical variability in the knee in order to provide the best care for their patients. 

Take-Home Points

• Prevalence of the medial oblique meniscomeniscal ligament is 1% to 4%.
• It is important to distinguish this ligament from a meniscus tear on MRI.
• The functional characteristics of this ligament are not well understood.
• What may appear to be a meniscal tear in a younger patient could be a medial oblique meniscomeniscal ligament.
• Dr. Flanigan recommends leaving the ligament intact unless resection is needed to provide better visualization.

We report a case of aberrant meniscus attachment in the setting of anterior cruciate ligament (ACL) injury. An anomalous cordlike attachment ran from the anterior horn of the medial meniscus to the posterior horn of the lateral meniscus through the intercondylar notch. This attachment was previously named the medial oblique meniscomeniscal ligament1 but has seldom been reported in the literature. Prevalence is 1% to 4%.^1,2 This case was treated at Ohio State University Wexner Medical Center in Columbus. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An 18-year-old man presented with left knee pain after sustaining 2 injuries to the knee. The first injury occurred during a dodgeball game—when the knee buckled on landing from a jump. A “pop” was felt, and the knee swelled immediately. The second injury occurred about 3 months later, during soccer play. The patient was running when his foot slipped and caused the knee to buckle. Again, a “pop” was felt, and there was swelling. Mechanical symptoms of clicking then started. The patient reported no instability episodes. His medical history and family history were otherwise unremarkable. The patient was healthy and had a body mass index of 23.05 kg/m2.

Physical examination revealed no effusion, erythema, or warmth in the left knee. Range of motion was 0° to 135° in the left knee and 0° to 140° in the right knee. There was no pain on hyperextension of the knee or medial or lateral joint-line tenderness, but there was pain on hyperflexion, and the McMurray test was positive. Ligament examination was negative except for positive anterior drawer, Lachman, and pivot-shift tests.

Radiographs taken the day of the first clinic visit showed no acute osseous abnormality. Magnetic resonance imaging (MRI) showed complete disruption of the proximal fibers of the ACL (Figures 1, 2). 

Also observed was a small oblique tear of the body of the lateral meniscus with slight blunting of the anterior horn of the medial meniscus, which may have been related to a small tear. A pivot-shift contusion pattern with impaction fracture of the lateral femoral condyle was also appreciated. There were no definite cartilage defects identified.

Discussion

The medial and lateral menisci typically are separate fibrocartilaginous structures acting as a cushion for the knee, but normal variant connections between the structures have been described. These connections include the anterior transverse meniscal ligament, the posterior transverse meniscal ligament, and the medial and lateral oblique meniscomeniscal ligaments.³ In the present case, a medial oblique meniscomeniscal ligament was identified. Its path between menisci was traceable on coronal and axial views. Video taken during arthroscopy also clearly showed its path and its relationship to other structures in the knee. To Dr. Flanigan’s knowledge, this ligament was not previously described with video. It is important to distinguish this ligament from a horizontal tear of the meniscus, given the potential for misinterpretation on MRI. A horizontal tear is a degenerative change that often occurs in older patients. Our patient was 18 years old at time of injury. In addition, the surface of his lower meniscus was smooth, whereas in a tear the edge is irregular and discontinuous. Dr. Flanigan prefers to leave this ligament intact unless resection would provide better visualization during arthroscopy. His reasoning is that the functional characteristics of the ligament are not well understood.

There are few reports on the medial oblique meniscomeniscal ligament.¹ Sanders and colleagues¹ found 3 cases of this normal variant. In the first, the ligament was interpreted as a flap tear on MRI; in the other 2 cases, the ligament was correctly identified. Kim and Laor² and Dervin and Paterson⁴ also described this variant in case reports.

There are many abnormalities of the meniscus. In our literature review, we found reports on various anomalies, including discoid meniscus,⁵ ring-shape meniscus,^6,7 accessory meniscus,⁸ double-layer meniscus,^9-12 abnormal band formation,^13,14 hypoplasia,¹⁵ Wrisberg meniscus,⁶ and congenital absence of meniscus.¹⁶ These variations have multifactorial causes, including congenital and developmental influences.

In a recent case report, Giordano and Goldblatt¹⁴ described an abnormal band of lateral meniscus extending from the posterior horn to the anterior-mid portion of the same meniscus. Lee and Min¹³ described the same band earlier, in a 2-patient case report.¹³ One patient presented symptomatically, nontraumatically, and the other with a posterior cruciate ligament tear. Each case was deemed congenital given the characteristic appearance and bilaterality of the anomaly.

In an 11-patient case series in Finland, Rainio and colleagues¹⁷ described an attachment from the anterior horn of the medial meniscus inserting into the ACL—a crescent band from the upper surface of the anterior horn that attached along the upper two thirds of the ACL.

At 2-year follow-up, our patient was doing well with rehabilitation and experienced only minimal symptoms. Radiologists and surgeons should be able to identify such variants. Knowing the common and rare variants, radiologists can help surgeons by identifying normal anatomy from pathology and providing a more clinically relevant report. Surgeons should be aware of the anatomical variability in the knee in order to provide the best care for their patients. 

Take-Home Points

• Prevalence of the medial oblique meniscomeniscal ligament is 1% to 4%.
• It is important to distinguish this ligament from a meniscus tear on MRI.
• The functional characteristics of this ligament are not well understood.
• What may appear to be a meniscal tear in a younger patient could be a medial oblique meniscomeniscal ligament.
• Dr. Flanigan recommends leaving the ligament intact unless resection is needed to provide better visualization.

We report a case of aberrant meniscus attachment in the setting of anterior cruciate ligament (ACL) injury. An anomalous cordlike attachment ran from the anterior horn of the medial meniscus to the posterior horn of the lateral meniscus through the intercondylar notch. This attachment was previously named the medial oblique meniscomeniscal ligament1 but has seldom been reported in the literature. Prevalence is 1% to 4%.^1,2 This case was treated at Ohio State University Wexner Medical Center in Columbus. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

An 18-year-old man presented with left knee pain after sustaining 2 injuries to the knee. The first injury occurred during a dodgeball game—when the knee buckled on landing from a jump. A “pop” was felt, and the knee swelled immediately. The second injury occurred about 3 months later, during soccer play. The patient was running when his foot slipped and caused the knee to buckle. Again, a “pop” was felt, and there was swelling. Mechanical symptoms of clicking then started. The patient reported no instability episodes. His medical history and family history were otherwise unremarkable. The patient was healthy and had a body mass index of 23.05 kg/m2.

Physical examination revealed no effusion, erythema, or warmth in the left knee. Range of motion was 0° to 135° in the left knee and 0° to 140° in the right knee. There was no pain on hyperextension of the knee or medial or lateral joint-line tenderness, but there was pain on hyperflexion, and the McMurray test was positive. Ligament examination was negative except for positive anterior drawer, Lachman, and pivot-shift tests.

Radiographs taken the day of the first clinic visit showed no acute osseous abnormality. Magnetic resonance imaging (MRI) showed complete disruption of the proximal fibers of the ACL (Figures 1, 2). 

Also observed was a small oblique tear of the body of the lateral meniscus with slight blunting of the anterior horn of the medial meniscus, which may have been related to a small tear. A pivot-shift contusion pattern with impaction fracture of the lateral femoral condyle was also appreciated. There were no definite cartilage defects identified.

Discussion

The medial and lateral menisci typically are separate fibrocartilaginous structures acting as a cushion for the knee, but normal variant connections between the structures have been described. These connections include the anterior transverse meniscal ligament, the posterior transverse meniscal ligament, and the medial and lateral oblique meniscomeniscal ligaments.³ In the present case, a medial oblique meniscomeniscal ligament was identified. Its path between menisci was traceable on coronal and axial views. Video taken during arthroscopy also clearly showed its path and its relationship to other structures in the knee. To Dr. Flanigan’s knowledge, this ligament was not previously described with video. It is important to distinguish this ligament from a horizontal tear of the meniscus, given the potential for misinterpretation on MRI. A horizontal tear is a degenerative change that often occurs in older patients. Our patient was 18 years old at time of injury. In addition, the surface of his lower meniscus was smooth, whereas in a tear the edge is irregular and discontinuous. Dr. Flanigan prefers to leave this ligament intact unless resection would provide better visualization during arthroscopy. His reasoning is that the functional characteristics of the ligament are not well understood.

There are few reports on the medial oblique meniscomeniscal ligament.¹ Sanders and colleagues¹ found 3 cases of this normal variant. In the first, the ligament was interpreted as a flap tear on MRI; in the other 2 cases, the ligament was correctly identified. Kim and Laor² and Dervin and Paterson⁴ also described this variant in case reports.

There are many abnormalities of the meniscus. In our literature review, we found reports on various anomalies, including discoid meniscus,⁵ ring-shape meniscus,^6,7 accessory meniscus,⁸ double-layer meniscus,^9-12 abnormal band formation,^13,14 hypoplasia,¹⁵ Wrisberg meniscus,⁶ and congenital absence of meniscus.¹⁶ These variations have multifactorial causes, including congenital and developmental influences.

In a recent case report, Giordano and Goldblatt¹⁴ described an abnormal band of lateral meniscus extending from the posterior horn to the anterior-mid portion of the same meniscus. Lee and Min¹³ described the same band earlier, in a 2-patient case report.¹³ One patient presented symptomatically, nontraumatically, and the other with a posterior cruciate ligament tear. Each case was deemed congenital given the characteristic appearance and bilaterality of the anomaly.

In an 11-patient case series in Finland, Rainio and colleagues¹⁷ described an attachment from the anterior horn of the medial meniscus inserting into the ACL—a crescent band from the upper surface of the anterior horn that attached along the upper two thirds of the ACL.

At 2-year follow-up, our patient was doing well with rehabilitation and experienced only minimal symptoms. Radiologists and surgeons should be able to identify such variants. Knowing the common and rare variants, radiologists can help surgeons by identifying normal anatomy from pathology and providing a more clinically relevant report. Surgeons should be aware of the anatomical variability in the knee in order to provide the best care for their patients. 

Imipramine is a tricyclic medication uncommonly used to treat depression, anxiety, and other psychiatric illnesses. Although relatively rare, it has been associated with hyperpigmentation of the skin including slate gray discoloration of sun-exposed areas.

We present the case of a 63-year-old woman who had been taking imipramine for more than 20 years when she developed bluish gray discoloration on the face and neck. Histopathology of biopsy specimens showed numerous perivascular and interstitial brown globules in the dermis that were composed of melanin only, as evidenced by positive Fontana-Masson staining and negative Perls Prussian blue staining. A diagnosis of imipramine-induced hyperpigmentation was made based on histopathology and clinical history.

In addition to the case presentation, we provide a review of drugs that commonly cause hyperpigmentation as well as their associated histopathologic staining characteristics.

Case Report

A 63-year-old woman presented with blue-gray discoloration on the face and neck. She first noted the discoloration on the left side of the forehead 3 years prior; it then spread to the right side of the forehead, cheeks, and neck. She denied pruritus, pain, redness, and scaling of the involved areas; any recent changes in medications; or the use of any topical products on the affected areas. Her medical history was remarkable for hypertension, which was inconsistently controlled with lisinopril and hydrochlorothiazide, and depression, which had been managed with oral imipramine.

Physical examination disclosed blue-gray hyperpigmented patches with irregular borders on the bilateral forehead, temples, and periorbital skin (Figure 1). Reticulated brown patches were noted on the bilateral cheeks, and the neck displayed diffuse muddy brown patches with sparing of the submental areas.

Punch biopsies obtained from the lateral forehead showed an unremarkable epidermis with deposition of numerous golden brown granules in the upper and mid dermis and in perivascular macrophages (Figure 2). The pigmented granules showed positive staining with Fontana-Masson (Figure 3), and a Perls Prussian blue stain for hemosiderin was negative. Based on the clinical history, a diagnosis of imipramine-induced hyperpigmentation was made.

The patient revealed that she had taken imipramine for more than 20 years for depression as prescribed by her mental health professional. She had tried several other antidepressants but none were as effective as imipramine. Therefore, she was not willing to discontinue it despite the likelihood that the hyperpigmentation would persist and could worsen with continued use of the medication. Diligent photoprotection was advised. Additionally, she started taking lisinopril some time after the appearance of the hyperpigmentation presented and had not taken hydrochlorothiazide consistently for several years. Although these drugs are known to cause various cutaneous reactions, it was not considered likely in this case.

Comment

Drug-induced hyperpigmentation accounts for 10% to 20% of all cases of acquired hyperpigmentation.¹ Common causative drugs include amiodarone, antimalarials, minocycline, and rarely psychotropics including phenothiazines and tricyclic antidepressants such as imipramine.^1-4 Although amiodarone-induced hyperpigmentation is associated with lipofuscin in addition to melanin, most other medications, including imipramine, induce cutaneous effects through deposition of melanin and/or hemosiderin. A review of the histopathologic staining characteristics in pigment anomalies caused by these drugs is summarized in the Table.

Imipramine-induced hyperpigmentation presents as slate gray discrete macules and patches on sun-exposed skin that may appear anywhere from 2 to 22 years after initiating the medication.^1-4 Affected areas include the malar cheeks, temples, periorbital areas, hands, forearms, and seldom the iris and sclera.^2-4 Although the blue to slate gray coloring is classic, other colors have been described including brown, golden brown, and purple.²

Histopathology of imipramine-induced hyperpigmentation shows golden brown, round to oval granules in the superficial dermis and within dermal macrophages.^1,3 Generally, Fontana-Masson staining is positive for melanin and Perls Prussian blue staining is negative for iron.^1,2,4

Imipramine-induced hyperpigmentation likely results from photoexcitation of imipramine or one of its metabolites. These compounds activate tyrosinase, increasing melanogenesis and leading to formation of melanin-imipramine or melanin-metabolite complexes.^1-3 Complexes are deposited in the dermis and basal layer or are engulfed by dermal macrophages and darkened on sun exposure due to their high melanin content.¹ Other possible mechanisms of hyperpigmentation include nonspecific inflammation caused by the drug in the skin, hemosiderin deposition from vessel damage and subsequent erythrocyte extravasation, or deposition of newly formed pigments related to the drug.¹

Most patients report satisfactory resolution of imipramine-induced discoloration within 1 year of stopping imipramine or switching to a different antidepressant.^1,4 Patients who are unwilling to discontinue imipramine may achieve resolution with alexandrite or Q-switched ruby laser therapy.^1,4 Strict sun protective measures are necessary, both to prevent new deposition of melanin and to prevent darkening of existing pigment.

Despite the advent of new psychotropic medications, imipramine remains the antidepressant of choice for many patients. Although rare, it is important to be able to recognize imipramine-induced hyperpigmentation and to encourage patient-psychiatrist communication to determine an antidepressant regimen that avoids unnecessary cutaneous side effects.

Imipramine is a tricyclic medication uncommonly used to treat depression, anxiety, and other psychiatric illnesses. Although relatively rare, it has been associated with hyperpigmentation of the skin including slate gray discoloration of sun-exposed areas.

We present the case of a 63-year-old woman who had been taking imipramine for more than 20 years when she developed bluish gray discoloration on the face and neck. Histopathology of biopsy specimens showed numerous perivascular and interstitial brown globules in the dermis that were composed of melanin only, as evidenced by positive Fontana-Masson staining and negative Perls Prussian blue staining. A diagnosis of imipramine-induced hyperpigmentation was made based on histopathology and clinical history.

In addition to the case presentation, we provide a review of drugs that commonly cause hyperpigmentation as well as their associated histopathologic staining characteristics.

Case Report

A 63-year-old woman presented with blue-gray discoloration on the face and neck. She first noted the discoloration on the left side of the forehead 3 years prior; it then spread to the right side of the forehead, cheeks, and neck. She denied pruritus, pain, redness, and scaling of the involved areas; any recent changes in medications; or the use of any topical products on the affected areas. Her medical history was remarkable for hypertension, which was inconsistently controlled with lisinopril and hydrochlorothiazide, and depression, which had been managed with oral imipramine.

Physical examination disclosed blue-gray hyperpigmented patches with irregular borders on the bilateral forehead, temples, and periorbital skin (Figure 1). Reticulated brown patches were noted on the bilateral cheeks, and the neck displayed diffuse muddy brown patches with sparing of the submental areas.

Punch biopsies obtained from the lateral forehead showed an unremarkable epidermis with deposition of numerous golden brown granules in the upper and mid dermis and in perivascular macrophages (Figure 2). The pigmented granules showed positive staining with Fontana-Masson (Figure 3), and a Perls Prussian blue stain for hemosiderin was negative. Based on the clinical history, a diagnosis of imipramine-induced hyperpigmentation was made.

The patient revealed that she had taken imipramine for more than 20 years for depression as prescribed by her mental health professional. She had tried several other antidepressants but none were as effective as imipramine. Therefore, she was not willing to discontinue it despite the likelihood that the hyperpigmentation would persist and could worsen with continued use of the medication. Diligent photoprotection was advised. Additionally, she started taking lisinopril some time after the appearance of the hyperpigmentation presented and had not taken hydrochlorothiazide consistently for several years. Although these drugs are known to cause various cutaneous reactions, it was not considered likely in this case.

Comment

Drug-induced hyperpigmentation accounts for 10% to 20% of all cases of acquired hyperpigmentation.¹ Common causative drugs include amiodarone, antimalarials, minocycline, and rarely psychotropics including phenothiazines and tricyclic antidepressants such as imipramine.^1-4 Although amiodarone-induced hyperpigmentation is associated with lipofuscin in addition to melanin, most other medications, including imipramine, induce cutaneous effects through deposition of melanin and/or hemosiderin. A review of the histopathologic staining characteristics in pigment anomalies caused by these drugs is summarized in the Table.

Imipramine-induced hyperpigmentation presents as slate gray discrete macules and patches on sun-exposed skin that may appear anywhere from 2 to 22 years after initiating the medication.^1-4 Affected areas include the malar cheeks, temples, periorbital areas, hands, forearms, and seldom the iris and sclera.^2-4 Although the blue to slate gray coloring is classic, other colors have been described including brown, golden brown, and purple.²

Histopathology of imipramine-induced hyperpigmentation shows golden brown, round to oval granules in the superficial dermis and within dermal macrophages.^1,3 Generally, Fontana-Masson staining is positive for melanin and Perls Prussian blue staining is negative for iron.^1,2,4

Imipramine-induced hyperpigmentation likely results from photoexcitation of imipramine or one of its metabolites. These compounds activate tyrosinase, increasing melanogenesis and leading to formation of melanin-imipramine or melanin-metabolite complexes.^1-3 Complexes are deposited in the dermis and basal layer or are engulfed by dermal macrophages and darkened on sun exposure due to their high melanin content.¹ Other possible mechanisms of hyperpigmentation include nonspecific inflammation caused by the drug in the skin, hemosiderin deposition from vessel damage and subsequent erythrocyte extravasation, or deposition of newly formed pigments related to the drug.¹

Most patients report satisfactory resolution of imipramine-induced discoloration within 1 year of stopping imipramine or switching to a different antidepressant.^1,4 Patients who are unwilling to discontinue imipramine may achieve resolution with alexandrite or Q-switched ruby laser therapy.^1,4 Strict sun protective measures are necessary, both to prevent new deposition of melanin and to prevent darkening of existing pigment.

Despite the advent of new psychotropic medications, imipramine remains the antidepressant of choice for many patients. Although rare, it is important to be able to recognize imipramine-induced hyperpigmentation and to encourage patient-psychiatrist communication to determine an antidepressant regimen that avoids unnecessary cutaneous side effects.

Imipramine is a tricyclic medication uncommonly used to treat depression, anxiety, and other psychiatric illnesses. Although relatively rare, it has been associated with hyperpigmentation of the skin including slate gray discoloration of sun-exposed areas.

We present the case of a 63-year-old woman who had been taking imipramine for more than 20 years when she developed bluish gray discoloration on the face and neck. Histopathology of biopsy specimens showed numerous perivascular and interstitial brown globules in the dermis that were composed of melanin only, as evidenced by positive Fontana-Masson staining and negative Perls Prussian blue staining. A diagnosis of imipramine-induced hyperpigmentation was made based on histopathology and clinical history.

In addition to the case presentation, we provide a review of drugs that commonly cause hyperpigmentation as well as their associated histopathologic staining characteristics.

Case Report

A 63-year-old woman presented with blue-gray discoloration on the face and neck. She first noted the discoloration on the left side of the forehead 3 years prior; it then spread to the right side of the forehead, cheeks, and neck. She denied pruritus, pain, redness, and scaling of the involved areas; any recent changes in medications; or the use of any topical products on the affected areas. Her medical history was remarkable for hypertension, which was inconsistently controlled with lisinopril and hydrochlorothiazide, and depression, which had been managed with oral imipramine.

Physical examination disclosed blue-gray hyperpigmented patches with irregular borders on the bilateral forehead, temples, and periorbital skin (Figure 1). Reticulated brown patches were noted on the bilateral cheeks, and the neck displayed diffuse muddy brown patches with sparing of the submental areas.

Punch biopsies obtained from the lateral forehead showed an unremarkable epidermis with deposition of numerous golden brown granules in the upper and mid dermis and in perivascular macrophages (Figure 2). The pigmented granules showed positive staining with Fontana-Masson (Figure 3), and a Perls Prussian blue stain for hemosiderin was negative. Based on the clinical history, a diagnosis of imipramine-induced hyperpigmentation was made.

The patient revealed that she had taken imipramine for more than 20 years for depression as prescribed by her mental health professional. She had tried several other antidepressants but none were as effective as imipramine. Therefore, she was not willing to discontinue it despite the likelihood that the hyperpigmentation would persist and could worsen with continued use of the medication. Diligent photoprotection was advised. Additionally, she started taking lisinopril some time after the appearance of the hyperpigmentation presented and had not taken hydrochlorothiazide consistently for several years. Although these drugs are known to cause various cutaneous reactions, it was not considered likely in this case.

Comment

Drug-induced hyperpigmentation accounts for 10% to 20% of all cases of acquired hyperpigmentation.¹ Common causative drugs include amiodarone, antimalarials, minocycline, and rarely psychotropics including phenothiazines and tricyclic antidepressants such as imipramine.^1-4 Although amiodarone-induced hyperpigmentation is associated with lipofuscin in addition to melanin, most other medications, including imipramine, induce cutaneous effects through deposition of melanin and/or hemosiderin. A review of the histopathologic staining characteristics in pigment anomalies caused by these drugs is summarized in the Table.

Imipramine-induced hyperpigmentation presents as slate gray discrete macules and patches on sun-exposed skin that may appear anywhere from 2 to 22 years after initiating the medication.^1-4 Affected areas include the malar cheeks, temples, periorbital areas, hands, forearms, and seldom the iris and sclera.^2-4 Although the blue to slate gray coloring is classic, other colors have been described including brown, golden brown, and purple.²

Histopathology of imipramine-induced hyperpigmentation shows golden brown, round to oval granules in the superficial dermis and within dermal macrophages.^1,3 Generally, Fontana-Masson staining is positive for melanin and Perls Prussian blue staining is negative for iron.^1,2,4

Imipramine-induced hyperpigmentation likely results from photoexcitation of imipramine or one of its metabolites. These compounds activate tyrosinase, increasing melanogenesis and leading to formation of melanin-imipramine or melanin-metabolite complexes.^1-3 Complexes are deposited in the dermis and basal layer or are engulfed by dermal macrophages and darkened on sun exposure due to their high melanin content.¹ Other possible mechanisms of hyperpigmentation include nonspecific inflammation caused by the drug in the skin, hemosiderin deposition from vessel damage and subsequent erythrocyte extravasation, or deposition of newly formed pigments related to the drug.¹

Most patients report satisfactory resolution of imipramine-induced discoloration within 1 year of stopping imipramine or switching to a different antidepressant.^1,4 Patients who are unwilling to discontinue imipramine may achieve resolution with alexandrite or Q-switched ruby laser therapy.^1,4 Strict sun protective measures are necessary, both to prevent new deposition of melanin and to prevent darkening of existing pigment.

Despite the advent of new psychotropic medications, imipramine remains the antidepressant of choice for many patients. Although rare, it is important to be able to recognize imipramine-induced hyperpigmentation and to encourage patient-psychiatrist communication to determine an antidepressant regimen that avoids unnecessary cutaneous side effects.