Dermatopathology

THE DIAGNOSIS: Epithelioid Fibrous Histiocytoma

In our patient, immunohistochemical stains for Factor XIIIa, CD68, and anaplastic lymphoma kinase (ALK) 1 confirmed the diagnosis of epithelioid fibrous histiocytoma (EFH). The location and relatively large size of the lesion led to a joint decision by the patient and physician to perform a complete excision, which was done with no complications.

Once considered a rare variant of dermatofibroma, EFH most commonly manifests as a solitary, vascular-appearing or flesh-colored papule or nodule on the legs. It often develops in the fifth decade of life with greater prevalence in men.^1-5 Our patient is one of the few known cases of EFH in children that have been reported in the literature.^3,6 Although EFH is benign, complete excision typically is performed due to the rarity of the lesion.³

The overexpression of ALK distinguishes EFH from other fibrohistiocytic lesions (Figure 1).⁵ The most common fusion partners are sequestosome 1 and vinculin (VCL), which account for more than 70% of cases.^3,5,7 Interestingly, VCL-ALK fusions have been reported to occur in a subset of pediatric renal cell carcinomas and recently in an ovoid spindle cell neoplasm considered to be a low-grade sarcoma.^3,7-9 Further studies have identified less common fusion partners, including the dynactin subunit 1, ETS variant transcription factor 6, protein-tyrosine phosphatase, receptor-type, F polypeptide-interacting protein-binding protein 1, sperm antigen with calponin homology and coiled-coil domains 1, tropomyosin 3, protein kinase cAMP-dependent type II regulatory subunit alpha, melanophilin, and Echinoderm microtubule-associated protein-like 4 genes.^3,8

In contrast to benign fibrous histiocytomas, EFHs primarily consist of epithelioid cells, have well-defined borders, exhibit prominent vascularity, usually are situated close to the epidermis, and lack multinucleated cells or histiocytes laden with lipids or hemosiderin.² The characteristic histopathologic finding is rounded or angulated epithelioid cells, with eosinophilic cytoplasm accounting for more than 50% of the tumor cell population.^1-3,5 The nuclei of the epithelioid cells are rounded and vesicular with small eosinophilic nucleoli and low mitotic activity. Common clinical features include an exophytic nodule with a classic epidermal collarette and an epidermis that exhibits variable degrees of hyperplasia.^1-3,5 Epithelioid fibrous histiocytomas often are confined to the superficial dermis and rarely extend to the subcutaneous layer. The stroma is collagenous with prominent vascularity, although older lesions can become more hyalinized and sclerotic.³ Histopathologically, these tumors can be a diagnostic challenge, as they often are mistaken for other fibrohistiocytic or melanocytic lesions.

Atypical fibroxanthoma (AFX) manifests as a dome-shaped exophytic nodule that can rapidly grow to 1 to 2 cm. Historically, it was thought to be a pseudomalignancy, but most investigators consider it within the spectrum of pleomorphic dermal sarcoma and undifferentiated pleomorphic sarcoma. Atypical fibroxanthoma usually occurs on the head and neck in elderly patients with sun-damaged skin. Histopathologically, the neoplastic cells of AFX range from atypical spindle cells and pleomorphic round to polygonal epithelioid cells to large, irregularly shaped multinucleated cells, some with foamy cytoplasm (Figure 2). The atypical spindle cells stain diffusely positive for CD10 and vimentin, while small subpopulations stain positively for CD68 or CD163 and procollagen 1. Smooth muscle actin inconsistently stains the tumor, and when it does, the staining typically is faint and patchy. Atypical fibroxanthomas usually do not stain positively for melanocytic, skeletal muscle, or keratinocytic markers.

Cellular dermatofibroma typically manifests as small, dome-shaped papules on the arms and legs that normally range from a few millimeters to 1 cm but occasionally measure up to 2 cm. Histopathologically, there are interweaving fascicles of spindle cells with hyperchromatic nuclei and peripheral splaying of the plump spindle cells that wrap around collagen bundles, known as collagen trapping (Figure 3). Unlike EFH, multinucleated cells and histiocytes with abundant lipids and hemosiderin often accompany the spindle cells in cellular dermatofibromas, which stain strongly positive for CD10 and vimentin, similar to AFX and EFH. The smooth muscle actin–staining pattern usually is faint and patchy, and in some cases, cellular dermatofibroma may not stain at all. Factor XIIIa and CD68 highlight the 2 populations of cells—fibroblasts and histiocytes—that make up the lesion.⁴

Epithelioid sarcoma comprises 2 types: distal (or conventional) type occurring on the distal arms and legs, particularly the hands and fingers of young adults, and proximal type occurring on the trunk and proximal extremities, including the upper arms and thighs.¹⁰ Epithelioid sarcoma is a rare aggressive malignancy that usually manifests as a firm nodule, sometimes with ulceration depending on the size. Histopathologically, diffuse dermal proliferation of ovoid to polygonal epithelioid cells arranged in short fascicles and nodular aggregations is observed (Figure 4). Spindle cells may be observed at the periphery of the lesion. Areas of necrosis are a frequent finding and a helpful diagnostic clue. Nearly all cases stain positively for pancytokeratin, CAM5.2, epithelial membrane antigen, and vimentin, and approximately half stain positively for CD34; there are variable expressions of ERG and smooth muscle actin.¹⁰ In most cases, epithelioid sarcoma does not stain positively for S100 or CD68. The majority (90%) of cases harbor a mutation in the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 gene, resulting in the loss of INI1 protein expression, which can be demonstrated by immunohistochemistry. ¹⁰ As the cytologic atypia usually is minimal, epithelioid sarcoma may be misdiagnosed as a necrotizing granuloma and benign fibrous lesions, particularly when superficial or small partial biopsies are performed.

Intradermal Spitz nevi can measure from a few millimeters to more than 2 cm and can range from pink to brown to black. The most common locations are the lower extremities as well as the head and neck. Histopathologically, intradermal Spitz nevi have nests of large epithelioid melanocytes with large nuclei and abundant cytoplasm (eFigure). Nuclear pseudo-inclusions, which are cytoplasmic invaginations into the nucleus, are frequent. Unlike the other conditions in the differential, these entities stain positively for melanocytic markers—S100, SOX10, and Melan-A—but not CD68 or CD163.11 A variety of kinase fusions are observed in Spitz nevi, including the ALK gene, neurotrophic tyrosine receptor kinase, ROS proto-oncogene 1, megakaryocyte-erythroid progenitor, and v-raf murine sarcoma viral oncogene homolog B1 genes.¹²

THE DIAGNOSIS: Epithelioid Fibrous Histiocytoma

In our patient, immunohistochemical stains for Factor XIIIa, CD68, and anaplastic lymphoma kinase (ALK) 1 confirmed the diagnosis of epithelioid fibrous histiocytoma (EFH). The location and relatively large size of the lesion led to a joint decision by the patient and physician to perform a complete excision, which was done with no complications.

Once considered a rare variant of dermatofibroma, EFH most commonly manifests as a solitary, vascular-appearing or flesh-colored papule or nodule on the legs. It often develops in the fifth decade of life with greater prevalence in men.^1-5 Our patient is one of the few known cases of EFH in children that have been reported in the literature.^3,6 Although EFH is benign, complete excision typically is performed due to the rarity of the lesion.³

The overexpression of ALK distinguishes EFH from other fibrohistiocytic lesions (Figure 1).⁵ The most common fusion partners are sequestosome 1 and vinculin (VCL), which account for more than 70% of cases.^3,5,7 Interestingly, VCL-ALK fusions have been reported to occur in a subset of pediatric renal cell carcinomas and recently in an ovoid spindle cell neoplasm considered to be a low-grade sarcoma.^3,7-9 Further studies have identified less common fusion partners, including the dynactin subunit 1, ETS variant transcription factor 6, protein-tyrosine phosphatase, receptor-type, F polypeptide-interacting protein-binding protein 1, sperm antigen with calponin homology and coiled-coil domains 1, tropomyosin 3, protein kinase cAMP-dependent type II regulatory subunit alpha, melanophilin, and Echinoderm microtubule-associated protein-like 4 genes.^3,8

In contrast to benign fibrous histiocytomas, EFHs primarily consist of epithelioid cells, have well-defined borders, exhibit prominent vascularity, usually are situated close to the epidermis, and lack multinucleated cells or histiocytes laden with lipids or hemosiderin.² The characteristic histopathologic finding is rounded or angulated epithelioid cells, with eosinophilic cytoplasm accounting for more than 50% of the tumor cell population.^1-3,5 The nuclei of the epithelioid cells are rounded and vesicular with small eosinophilic nucleoli and low mitotic activity. Common clinical features include an exophytic nodule with a classic epidermal collarette and an epidermis that exhibits variable degrees of hyperplasia.^1-3,5 Epithelioid fibrous histiocytomas often are confined to the superficial dermis and rarely extend to the subcutaneous layer. The stroma is collagenous with prominent vascularity, although older lesions can become more hyalinized and sclerotic.³ Histopathologically, these tumors can be a diagnostic challenge, as they often are mistaken for other fibrohistiocytic or melanocytic lesions.

Atypical fibroxanthoma (AFX) manifests as a dome-shaped exophytic nodule that can rapidly grow to 1 to 2 cm. Historically, it was thought to be a pseudomalignancy, but most investigators consider it within the spectrum of pleomorphic dermal sarcoma and undifferentiated pleomorphic sarcoma. Atypical fibroxanthoma usually occurs on the head and neck in elderly patients with sun-damaged skin. Histopathologically, the neoplastic cells of AFX range from atypical spindle cells and pleomorphic round to polygonal epithelioid cells to large, irregularly shaped multinucleated cells, some with foamy cytoplasm (Figure 2). The atypical spindle cells stain diffusely positive for CD10 and vimentin, while small subpopulations stain positively for CD68 or CD163 and procollagen 1. Smooth muscle actin inconsistently stains the tumor, and when it does, the staining typically is faint and patchy. Atypical fibroxanthomas usually do not stain positively for melanocytic, skeletal muscle, or keratinocytic markers.

Cellular dermatofibroma typically manifests as small, dome-shaped papules on the arms and legs that normally range from a few millimeters to 1 cm but occasionally measure up to 2 cm. Histopathologically, there are interweaving fascicles of spindle cells with hyperchromatic nuclei and peripheral splaying of the plump spindle cells that wrap around collagen bundles, known as collagen trapping (Figure 3). Unlike EFH, multinucleated cells and histiocytes with abundant lipids and hemosiderin often accompany the spindle cells in cellular dermatofibromas, which stain strongly positive for CD10 and vimentin, similar to AFX and EFH. The smooth muscle actin–staining pattern usually is faint and patchy, and in some cases, cellular dermatofibroma may not stain at all. Factor XIIIa and CD68 highlight the 2 populations of cells—fibroblasts and histiocytes—that make up the lesion.⁴

Epithelioid sarcoma comprises 2 types: distal (or conventional) type occurring on the distal arms and legs, particularly the hands and fingers of young adults, and proximal type occurring on the trunk and proximal extremities, including the upper arms and thighs.¹⁰ Epithelioid sarcoma is a rare aggressive malignancy that usually manifests as a firm nodule, sometimes with ulceration depending on the size. Histopathologically, diffuse dermal proliferation of ovoid to polygonal epithelioid cells arranged in short fascicles and nodular aggregations is observed (Figure 4). Spindle cells may be observed at the periphery of the lesion. Areas of necrosis are a frequent finding and a helpful diagnostic clue. Nearly all cases stain positively for pancytokeratin, CAM5.2, epithelial membrane antigen, and vimentin, and approximately half stain positively for CD34; there are variable expressions of ERG and smooth muscle actin.¹⁰ In most cases, epithelioid sarcoma does not stain positively for S100 or CD68. The majority (90%) of cases harbor a mutation in the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 gene, resulting in the loss of INI1 protein expression, which can be demonstrated by immunohistochemistry. ¹⁰ As the cytologic atypia usually is minimal, epithelioid sarcoma may be misdiagnosed as a necrotizing granuloma and benign fibrous lesions, particularly when superficial or small partial biopsies are performed.

Intradermal Spitz nevi can measure from a few millimeters to more than 2 cm and can range from pink to brown to black. The most common locations are the lower extremities as well as the head and neck. Histopathologically, intradermal Spitz nevi have nests of large epithelioid melanocytes with large nuclei and abundant cytoplasm (eFigure). Nuclear pseudo-inclusions, which are cytoplasmic invaginations into the nucleus, are frequent. Unlike the other conditions in the differential, these entities stain positively for melanocytic markers—S100, SOX10, and Melan-A—but not CD68 or CD163.11 A variety of kinase fusions are observed in Spitz nevi, including the ALK gene, neurotrophic tyrosine receptor kinase, ROS proto-oncogene 1, megakaryocyte-erythroid progenitor, and v-raf murine sarcoma viral oncogene homolog B1 genes.¹²

THE DIAGNOSIS: Epithelioid Fibrous Histiocytoma

In our patient, immunohistochemical stains for Factor XIIIa, CD68, and anaplastic lymphoma kinase (ALK) 1 confirmed the diagnosis of epithelioid fibrous histiocytoma (EFH). The location and relatively large size of the lesion led to a joint decision by the patient and physician to perform a complete excision, which was done with no complications.

Once considered a rare variant of dermatofibroma, EFH most commonly manifests as a solitary, vascular-appearing or flesh-colored papule or nodule on the legs. It often develops in the fifth decade of life with greater prevalence in men.^1-5 Our patient is one of the few known cases of EFH in children that have been reported in the literature.^3,6 Although EFH is benign, complete excision typically is performed due to the rarity of the lesion.³

The overexpression of ALK distinguishes EFH from other fibrohistiocytic lesions (Figure 1).⁵ The most common fusion partners are sequestosome 1 and vinculin (VCL), which account for more than 70% of cases.^3,5,7 Interestingly, VCL-ALK fusions have been reported to occur in a subset of pediatric renal cell carcinomas and recently in an ovoid spindle cell neoplasm considered to be a low-grade sarcoma.^3,7-9 Further studies have identified less common fusion partners, including the dynactin subunit 1, ETS variant transcription factor 6, protein-tyrosine phosphatase, receptor-type, F polypeptide-interacting protein-binding protein 1, sperm antigen with calponin homology and coiled-coil domains 1, tropomyosin 3, protein kinase cAMP-dependent type II regulatory subunit alpha, melanophilin, and Echinoderm microtubule-associated protein-like 4 genes.^3,8

In contrast to benign fibrous histiocytomas, EFHs primarily consist of epithelioid cells, have well-defined borders, exhibit prominent vascularity, usually are situated close to the epidermis, and lack multinucleated cells or histiocytes laden with lipids or hemosiderin.² The characteristic histopathologic finding is rounded or angulated epithelioid cells, with eosinophilic cytoplasm accounting for more than 50% of the tumor cell population.^1-3,5 The nuclei of the epithelioid cells are rounded and vesicular with small eosinophilic nucleoli and low mitotic activity. Common clinical features include an exophytic nodule with a classic epidermal collarette and an epidermis that exhibits variable degrees of hyperplasia.^1-3,5 Epithelioid fibrous histiocytomas often are confined to the superficial dermis and rarely extend to the subcutaneous layer. The stroma is collagenous with prominent vascularity, although older lesions can become more hyalinized and sclerotic.³ Histopathologically, these tumors can be a diagnostic challenge, as they often are mistaken for other fibrohistiocytic or melanocytic lesions.

Atypical fibroxanthoma (AFX) manifests as a dome-shaped exophytic nodule that can rapidly grow to 1 to 2 cm. Historically, it was thought to be a pseudomalignancy, but most investigators consider it within the spectrum of pleomorphic dermal sarcoma and undifferentiated pleomorphic sarcoma. Atypical fibroxanthoma usually occurs on the head and neck in elderly patients with sun-damaged skin. Histopathologically, the neoplastic cells of AFX range from atypical spindle cells and pleomorphic round to polygonal epithelioid cells to large, irregularly shaped multinucleated cells, some with foamy cytoplasm (Figure 2). The atypical spindle cells stain diffusely positive for CD10 and vimentin, while small subpopulations stain positively for CD68 or CD163 and procollagen 1. Smooth muscle actin inconsistently stains the tumor, and when it does, the staining typically is faint and patchy. Atypical fibroxanthomas usually do not stain positively for melanocytic, skeletal muscle, or keratinocytic markers.

Cellular dermatofibroma typically manifests as small, dome-shaped papules on the arms and legs that normally range from a few millimeters to 1 cm but occasionally measure up to 2 cm. Histopathologically, there are interweaving fascicles of spindle cells with hyperchromatic nuclei and peripheral splaying of the plump spindle cells that wrap around collagen bundles, known as collagen trapping (Figure 3). Unlike EFH, multinucleated cells and histiocytes with abundant lipids and hemosiderin often accompany the spindle cells in cellular dermatofibromas, which stain strongly positive for CD10 and vimentin, similar to AFX and EFH. The smooth muscle actin–staining pattern usually is faint and patchy, and in some cases, cellular dermatofibroma may not stain at all. Factor XIIIa and CD68 highlight the 2 populations of cells—fibroblasts and histiocytes—that make up the lesion.⁴

Epithelioid sarcoma comprises 2 types: distal (or conventional) type occurring on the distal arms and legs, particularly the hands and fingers of young adults, and proximal type occurring on the trunk and proximal extremities, including the upper arms and thighs.¹⁰ Epithelioid sarcoma is a rare aggressive malignancy that usually manifests as a firm nodule, sometimes with ulceration depending on the size. Histopathologically, diffuse dermal proliferation of ovoid to polygonal epithelioid cells arranged in short fascicles and nodular aggregations is observed (Figure 4). Spindle cells may be observed at the periphery of the lesion. Areas of necrosis are a frequent finding and a helpful diagnostic clue. Nearly all cases stain positively for pancytokeratin, CAM5.2, epithelial membrane antigen, and vimentin, and approximately half stain positively for CD34; there are variable expressions of ERG and smooth muscle actin.¹⁰ In most cases, epithelioid sarcoma does not stain positively for S100 or CD68. The majority (90%) of cases harbor a mutation in the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 gene, resulting in the loss of INI1 protein expression, which can be demonstrated by immunohistochemistry. ¹⁰ As the cytologic atypia usually is minimal, epithelioid sarcoma may be misdiagnosed as a necrotizing granuloma and benign fibrous lesions, particularly when superficial or small partial biopsies are performed.

Intradermal Spitz nevi can measure from a few millimeters to more than 2 cm and can range from pink to brown to black. The most common locations are the lower extremities as well as the head and neck. Histopathologically, intradermal Spitz nevi have nests of large epithelioid melanocytes with large nuclei and abundant cytoplasm (eFigure). Nuclear pseudo-inclusions, which are cytoplasmic invaginations into the nucleus, are frequent. Unlike the other conditions in the differential, these entities stain positively for melanocytic markers—S100, SOX10, and Melan-A—but not CD68 or CD163.11 A variety of kinase fusions are observed in Spitz nevi, including the ALK gene, neurotrophic tyrosine receptor kinase, ROS proto-oncogene 1, megakaryocyte-erythroid progenitor, and v-raf murine sarcoma viral oncogene homolog B1 genes.¹²

THE DIAGNOSIS: Dermatofibrosarcoma Protuberans

The histologic findings showed fascicular proliferation of relatively monomorphic spindle cells with extensive entrapment of collagen and adipocytes. Immunohistochemical staining showed that the lesional cells were diffusely positive for CD34 and negative for SOX10, S100, desmin, and factor XIIIa. The decision was made to perform cytogenetic testing with fluorescence in situ hybridization to evaluate for the presence of platelet-derived growth factor receptor beta (PDGFB) polypeptide rearrangement, a key biomarker known to be positive in most patients with dermatofibrosarcoma protuberans (DFSP).¹ This rearrangement results in overproduction of PDGFB, continuous activation of platelet-derived growth factor receptor beta, cellular proliferation, and tumor formation.² In our patient, results were positive for the PDGFB polypeptide rearrangement, which confirmed suspected diagnosis of DFSP with fibrous histiocytoma like morphology. The patient was referred for Mohs micrographic surgery for proper management.

Dermatofibrosarcoma protuberans is a rare soft-tissue tumor that involves the dermis, subcutaneous fat, and sometimes muscle and fascia.² Dermatofibrosarcoma protuberans primarily affects young to middle-aged adults, with a slight predilection for individuals in the third to fifth decades of life.³ Lesions preferentially involve the trunk, particularly the shoulder and chest regions, and manifest as poorly circumscribed, locally aggressive mesenchymal neoplasms with a high local recurrence rate but low metastatic potential.^4,5 Clinically, the lesions appear as flesh-colored, rubbery plaques or nodules. A diagnosis of DFSP requires a high index of clinical suspicion, and histologic, immunohistochemical, and molecular testing usually are required for confirmation.

On histopathologic examination, DFSP classically demonstrates uniform, spindle-shaped cells that traditionally are arranged in an intersecting pattern and primarily are based in the dermis (Figure 1).⁵ Infiltration into the underlying tissue is a common feature, with neoplastic extensions causing a classic honeycomb pattern6 that also can be seen in diffuse neurofibroma and may cause diagnostic challenges; however, the immunohistology staining of neurofibroma differs from DFSP in that it stains positive for CD34, SOX-100, and S100, while DFSP has strong and diffuse CD34 immunoreactivity with negative immunostaining for SOX10, S100, desmin, and factor XIIIa.^2,6

Dermatofibrosarcoma protuberans can cause considerable fat infiltration compared to other soft-tissue neoplasms, making this finding suspicious for—if not characteristic of—DFSP. Collagen trapping also can be observed; however, this is more pathognomonic in cellular fibrous histiocytoma, which is a distinct clinical variant of dermatofibromas. Due to its similarity to other lesions, histopathologic examination along with immunostaining can assist in differentiating and accurately diagnosing DFSP.⁶

Cellular fibrous histiocytoma (CFH), a distinct clinical variant of dermatofibromas, is a benign tumor of mesenchymal origin that occurs more commonly on the trunk, arms, and legs. On histologic examination, CFH is composed of spindle-shaped cells with variable amounts of eosinophilic cytoplasm and small, oval-shaped eosinophilic nuclei and collagen trapping (Figure 2).^7,8 Most CFHs occupy the superficial dermis but can extend into the deep reticular dermis, thus mimicking the honeycomb pattern seen in DFSP. This neoplasm can show a similar architecture to DFSP, which is why further investigation including cytogenetics and immunohistochemical staining can help differentiate the two conditions. Cellular fibrous histiocytoma typically stains negative for CD34 and positive for factor XIIIa.⁹ However, CD34 can be positive in a subset of CFHs, with a considerable subset showing peripheral CD34 positivity and a smaller subset showing central CD34 the positivity.¹⁰ This suggests that CD34 cannot be the only factor differentiating these 2 lesions in making a proper dermatopathologic diagnosis.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor that can occur anywhere on the body and typically manifests as a deep, painless, enlarging mass in adults aged 50 to 60 years.¹¹ On histologic examination, SFT consists of randomly arranged cells with a spindle or ovoid shape within a collagenous stroma intermixed with blood vessels with a characteristic staghorn shape (Figure 3).¹¹ Low-grade SFT shows a patternless arrangement with spindle cells, a low number of mitotic figures, and vessels with a staghorn appearance compared to high-grade SFT, which shows hypercellularity with nuclear pleomorphism and a high number of mitotic figures.¹¹ Solitary fibrous tumors are positive for CD34 and STAT-6 and negative for CD31 and typically demonstrate NGFI-A binding protein 2 (NAB2)—signal transducer and activator of transcription 6 (STAT 6) gene fusion.¹¹

Spindle-cell lipomas are rare, benign, slow-growing, lipomatous tumors that typically manifest in men aged 40 to 70 years.¹² These lesions originate most frequently in the subcutaneous tissue of the upper back, posterior neck, and shoulders. The histologic growth pattern of spindle-cell lipomas can mimic other spindle-cell and myxoid tumors, which is why cytogenetic analysis is crucial for differentiating these lesions. On histologic examination, spindle-cell lipomas exhibit a mixture of mature adipocytes, uniform spindle cells, and collagen bundles (eFigure). Spindle-cell lipoma stains positive for CD34 but negative for S100.¹³ In addition, spindle-cell lipomas tend to show structural rearrangements (mainly deletions) of the long arm of chromosome 13 or even losses of whole chromosome 13, which contains the retinoblastoma (RB1) gene.¹³

Pleomorphic dermal sarcoma is a rare mesenchymal tumor that can appear clinically and histologically similar to atypical fibroxanthoma.¹⁴ This lesion often manifests in elderly patients and is strongly associated with chronic sun exposure.¹⁵ Pleomorphic dermal sarcoma is a locally aggressive tumor with metastatic potential to the skin or lymph nodes. On histologic examination, these tumors exhibit pleomorphic atypical epithelioid or spindle cells as well as multinucleated tumor giant cells with possible tumor necrosis, lymphovascular invasion, or perineural infiltration (Figure 4). Pleomorphic dermal sarcoma, typically a diagnosis of exclusion, requires immunohistochemistry to aid in proper identification.¹⁶ These lesions stain positive for CD10 and negative for cytokeratins, desmin, HMB45, CD34, p63, p40, SOX10, and S100.^15,16

THE DIAGNOSIS: Dermatofibrosarcoma Protuberans

The histologic findings showed fascicular proliferation of relatively monomorphic spindle cells with extensive entrapment of collagen and adipocytes. Immunohistochemical staining showed that the lesional cells were diffusely positive for CD34 and negative for SOX10, S100, desmin, and factor XIIIa. The decision was made to perform cytogenetic testing with fluorescence in situ hybridization to evaluate for the presence of platelet-derived growth factor receptor beta (PDGFB) polypeptide rearrangement, a key biomarker known to be positive in most patients with dermatofibrosarcoma protuberans (DFSP).¹ This rearrangement results in overproduction of PDGFB, continuous activation of platelet-derived growth factor receptor beta, cellular proliferation, and tumor formation.² In our patient, results were positive for the PDGFB polypeptide rearrangement, which confirmed suspected diagnosis of DFSP with fibrous histiocytoma like morphology. The patient was referred for Mohs micrographic surgery for proper management.

Dermatofibrosarcoma protuberans is a rare soft-tissue tumor that involves the dermis, subcutaneous fat, and sometimes muscle and fascia.² Dermatofibrosarcoma protuberans primarily affects young to middle-aged adults, with a slight predilection for individuals in the third to fifth decades of life.³ Lesions preferentially involve the trunk, particularly the shoulder and chest regions, and manifest as poorly circumscribed, locally aggressive mesenchymal neoplasms with a high local recurrence rate but low metastatic potential.^4,5 Clinically, the lesions appear as flesh-colored, rubbery plaques or nodules. A diagnosis of DFSP requires a high index of clinical suspicion, and histologic, immunohistochemical, and molecular testing usually are required for confirmation.

On histopathologic examination, DFSP classically demonstrates uniform, spindle-shaped cells that traditionally are arranged in an intersecting pattern and primarily are based in the dermis (Figure 1).⁵ Infiltration into the underlying tissue is a common feature, with neoplastic extensions causing a classic honeycomb pattern6 that also can be seen in diffuse neurofibroma and may cause diagnostic challenges; however, the immunohistology staining of neurofibroma differs from DFSP in that it stains positive for CD34, SOX-100, and S100, while DFSP has strong and diffuse CD34 immunoreactivity with negative immunostaining for SOX10, S100, desmin, and factor XIIIa.^2,6

Dermatofibrosarcoma protuberans can cause considerable fat infiltration compared to other soft-tissue neoplasms, making this finding suspicious for—if not characteristic of—DFSP. Collagen trapping also can be observed; however, this is more pathognomonic in cellular fibrous histiocytoma, which is a distinct clinical variant of dermatofibromas. Due to its similarity to other lesions, histopathologic examination along with immunostaining can assist in differentiating and accurately diagnosing DFSP.⁶

Cellular fibrous histiocytoma (CFH), a distinct clinical variant of dermatofibromas, is a benign tumor of mesenchymal origin that occurs more commonly on the trunk, arms, and legs. On histologic examination, CFH is composed of spindle-shaped cells with variable amounts of eosinophilic cytoplasm and small, oval-shaped eosinophilic nuclei and collagen trapping (Figure 2).^7,8 Most CFHs occupy the superficial dermis but can extend into the deep reticular dermis, thus mimicking the honeycomb pattern seen in DFSP. This neoplasm can show a similar architecture to DFSP, which is why further investigation including cytogenetics and immunohistochemical staining can help differentiate the two conditions. Cellular fibrous histiocytoma typically stains negative for CD34 and positive for factor XIIIa.⁹ However, CD34 can be positive in a subset of CFHs, with a considerable subset showing peripheral CD34 positivity and a smaller subset showing central CD34 the positivity.¹⁰ This suggests that CD34 cannot be the only factor differentiating these 2 lesions in making a proper dermatopathologic diagnosis.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor that can occur anywhere on the body and typically manifests as a deep, painless, enlarging mass in adults aged 50 to 60 years.¹¹ On histologic examination, SFT consists of randomly arranged cells with a spindle or ovoid shape within a collagenous stroma intermixed with blood vessels with a characteristic staghorn shape (Figure 3).¹¹ Low-grade SFT shows a patternless arrangement with spindle cells, a low number of mitotic figures, and vessels with a staghorn appearance compared to high-grade SFT, which shows hypercellularity with nuclear pleomorphism and a high number of mitotic figures.¹¹ Solitary fibrous tumors are positive for CD34 and STAT-6 and negative for CD31 and typically demonstrate NGFI-A binding protein 2 (NAB2)—signal transducer and activator of transcription 6 (STAT 6) gene fusion.¹¹

Spindle-cell lipomas are rare, benign, slow-growing, lipomatous tumors that typically manifest in men aged 40 to 70 years.¹² These lesions originate most frequently in the subcutaneous tissue of the upper back, posterior neck, and shoulders. The histologic growth pattern of spindle-cell lipomas can mimic other spindle-cell and myxoid tumors, which is why cytogenetic analysis is crucial for differentiating these lesions. On histologic examination, spindle-cell lipomas exhibit a mixture of mature adipocytes, uniform spindle cells, and collagen bundles (eFigure). Spindle-cell lipoma stains positive for CD34 but negative for S100.¹³ In addition, spindle-cell lipomas tend to show structural rearrangements (mainly deletions) of the long arm of chromosome 13 or even losses of whole chromosome 13, which contains the retinoblastoma (RB1) gene.¹³

Pleomorphic dermal sarcoma is a rare mesenchymal tumor that can appear clinically and histologically similar to atypical fibroxanthoma.¹⁴ This lesion often manifests in elderly patients and is strongly associated with chronic sun exposure.¹⁵ Pleomorphic dermal sarcoma is a locally aggressive tumor with metastatic potential to the skin or lymph nodes. On histologic examination, these tumors exhibit pleomorphic atypical epithelioid or spindle cells as well as multinucleated tumor giant cells with possible tumor necrosis, lymphovascular invasion, or perineural infiltration (Figure 4). Pleomorphic dermal sarcoma, typically a diagnosis of exclusion, requires immunohistochemistry to aid in proper identification.¹⁶ These lesions stain positive for CD10 and negative for cytokeratins, desmin, HMB45, CD34, p63, p40, SOX10, and S100.^15,16

THE DIAGNOSIS: Dermatofibrosarcoma Protuberans

The histologic findings showed fascicular proliferation of relatively monomorphic spindle cells with extensive entrapment of collagen and adipocytes. Immunohistochemical staining showed that the lesional cells were diffusely positive for CD34 and negative for SOX10, S100, desmin, and factor XIIIa. The decision was made to perform cytogenetic testing with fluorescence in situ hybridization to evaluate for the presence of platelet-derived growth factor receptor beta (PDGFB) polypeptide rearrangement, a key biomarker known to be positive in most patients with dermatofibrosarcoma protuberans (DFSP).¹ This rearrangement results in overproduction of PDGFB, continuous activation of platelet-derived growth factor receptor beta, cellular proliferation, and tumor formation.² In our patient, results were positive for the PDGFB polypeptide rearrangement, which confirmed suspected diagnosis of DFSP with fibrous histiocytoma like morphology. The patient was referred for Mohs micrographic surgery for proper management.

Dermatofibrosarcoma protuberans is a rare soft-tissue tumor that involves the dermis, subcutaneous fat, and sometimes muscle and fascia.² Dermatofibrosarcoma protuberans primarily affects young to middle-aged adults, with a slight predilection for individuals in the third to fifth decades of life.³ Lesions preferentially involve the trunk, particularly the shoulder and chest regions, and manifest as poorly circumscribed, locally aggressive mesenchymal neoplasms with a high local recurrence rate but low metastatic potential.^4,5 Clinically, the lesions appear as flesh-colored, rubbery plaques or nodules. A diagnosis of DFSP requires a high index of clinical suspicion, and histologic, immunohistochemical, and molecular testing usually are required for confirmation.

On histopathologic examination, DFSP classically demonstrates uniform, spindle-shaped cells that traditionally are arranged in an intersecting pattern and primarily are based in the dermis (Figure 1).⁵ Infiltration into the underlying tissue is a common feature, with neoplastic extensions causing a classic honeycomb pattern6 that also can be seen in diffuse neurofibroma and may cause diagnostic challenges; however, the immunohistology staining of neurofibroma differs from DFSP in that it stains positive for CD34, SOX-100, and S100, while DFSP has strong and diffuse CD34 immunoreactivity with negative immunostaining for SOX10, S100, desmin, and factor XIIIa.^2,6

Dermatofibrosarcoma protuberans can cause considerable fat infiltration compared to other soft-tissue neoplasms, making this finding suspicious for—if not characteristic of—DFSP. Collagen trapping also can be observed; however, this is more pathognomonic in cellular fibrous histiocytoma, which is a distinct clinical variant of dermatofibromas. Due to its similarity to other lesions, histopathologic examination along with immunostaining can assist in differentiating and accurately diagnosing DFSP.⁶

Cellular fibrous histiocytoma (CFH), a distinct clinical variant of dermatofibromas, is a benign tumor of mesenchymal origin that occurs more commonly on the trunk, arms, and legs. On histologic examination, CFH is composed of spindle-shaped cells with variable amounts of eosinophilic cytoplasm and small, oval-shaped eosinophilic nuclei and collagen trapping (Figure 2).^7,8 Most CFHs occupy the superficial dermis but can extend into the deep reticular dermis, thus mimicking the honeycomb pattern seen in DFSP. This neoplasm can show a similar architecture to DFSP, which is why further investigation including cytogenetics and immunohistochemical staining can help differentiate the two conditions. Cellular fibrous histiocytoma typically stains negative for CD34 and positive for factor XIIIa.⁹ However, CD34 can be positive in a subset of CFHs, with a considerable subset showing peripheral CD34 positivity and a smaller subset showing central CD34 the positivity.¹⁰ This suggests that CD34 cannot be the only factor differentiating these 2 lesions in making a proper dermatopathologic diagnosis.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor that can occur anywhere on the body and typically manifests as a deep, painless, enlarging mass in adults aged 50 to 60 years.¹¹ On histologic examination, SFT consists of randomly arranged cells with a spindle or ovoid shape within a collagenous stroma intermixed with blood vessels with a characteristic staghorn shape (Figure 3).¹¹ Low-grade SFT shows a patternless arrangement with spindle cells, a low number of mitotic figures, and vessels with a staghorn appearance compared to high-grade SFT, which shows hypercellularity with nuclear pleomorphism and a high number of mitotic figures.¹¹ Solitary fibrous tumors are positive for CD34 and STAT-6 and negative for CD31 and typically demonstrate NGFI-A binding protein 2 (NAB2)—signal transducer and activator of transcription 6 (STAT 6) gene fusion.¹¹

Spindle-cell lipomas are rare, benign, slow-growing, lipomatous tumors that typically manifest in men aged 40 to 70 years.¹² These lesions originate most frequently in the subcutaneous tissue of the upper back, posterior neck, and shoulders. The histologic growth pattern of spindle-cell lipomas can mimic other spindle-cell and myxoid tumors, which is why cytogenetic analysis is crucial for differentiating these lesions. On histologic examination, spindle-cell lipomas exhibit a mixture of mature adipocytes, uniform spindle cells, and collagen bundles (eFigure). Spindle-cell lipoma stains positive for CD34 but negative for S100.¹³ In addition, spindle-cell lipomas tend to show structural rearrangements (mainly deletions) of the long arm of chromosome 13 or even losses of whole chromosome 13, which contains the retinoblastoma (RB1) gene.¹³

Pleomorphic dermal sarcoma is a rare mesenchymal tumor that can appear clinically and histologically similar to atypical fibroxanthoma.¹⁴ This lesion often manifests in elderly patients and is strongly associated with chronic sun exposure.¹⁵ Pleomorphic dermal sarcoma is a locally aggressive tumor with metastatic potential to the skin or lymph nodes. On histologic examination, these tumors exhibit pleomorphic atypical epithelioid or spindle cells as well as multinucleated tumor giant cells with possible tumor necrosis, lymphovascular invasion, or perineural infiltration (Figure 4). Pleomorphic dermal sarcoma, typically a diagnosis of exclusion, requires immunohistochemistry to aid in proper identification.¹⁶ These lesions stain positive for CD10 and negative for cytokeratins, desmin, HMB45, CD34, p63, p40, SOX10, and S100.^15,16

THE DIAGNOSIS: Plaquelike Myofibroblastic Tumor

An incisional biopsy of the plaque demonstrated a hypercellular proliferation of bland spindle cells in the dermis that infiltrated the subcutis. The overlying epidermis was mildly acanthotic with both ulceration and follicular induction. There was trapping of individual adipocytes in a honeycomb pattern with foci of erythrocyte extravasation, microvesiculation, and widened fibrous septa (Figure 1). Immunohistochemistry was positive for vimentin, actin, and smooth muscle actin (SMA)(Figure 2A). Variable positivity for Factor XIIIa antibodies was noted. CD68 staining was focal positive, suggesting fibrohistiocytic lineage. Expression of CD31, CD34, S100, and anaplastic lymphoma kinase was negative, and Ki-67 was present in less than 10% of cells (Figure 2B).

We reviewed the case in conjunction with a soft-tissue pathologist (Y.L.), and based on the clinical and immunophenotypic features, a diagnosis of plaquelike myofibroblastic tumor (PLMT) was made. The patient’s parents refused further treatment, and there was no sign of disease progression at 6-month follow-up.

Plaquelike myofibroblastic tumor is an unusual pediatric dermal tumor that was first described by Clarke et al¹ in 2007. Clinical manifestation of PLMT on the right abdomen was unique in our patient, as the lesions typically present as indurated plaques on the lower back, but the central ulceration in our case resembled a report by Marqueling et al.² Ulceration and induration of PLMT developing at 8 months of age can suggest an aggressive disease course corresponding with deep infiltration and is seen mostly in children.

The histopathologic features of PLMT include an acanthotic epidermis and follicular induction, which also are characteristic of dermatofibroma (DF). The proliferation of spindle cells extended deep into the fat with foci of erythrocyte extravasation and microvesiculation of the stroma similar to nodular fasciitis and proliferative fasciitis. The presentation of infiltrating and expanding fibrous septae and trapping of individual adipocytes in a honeycomb pattern is similar to dermatofibrosarcoma protuberans (DFSP). Most cases of PLMT are positive for SMA. Factor XIIIa typically is variably positive, and in one report, 31% (4/13) of cases showed positive staining for calponin.³ Rapid growth, ulceration, and recurrence emphasize that PLMT can be locally aggressive, similar to DFSP.⁴

The main differential diagnoses include DF and its variants, dermatomyofibroma, DFSP, and proliferative fasciitis.^3,5 In the cases mentioned above, microscopic features were similar with a relatively well-circumscribed proliferation of spindle cells arranged in short fascicles through the entire reticular dermis, and the overlying epidermis was acanthotic.

Dermatofibroma commonly manifests in adults as a minor nodular lesion (commonly <1 cm), and usually is located on the legs. It has several clinical and histologic variants, including multiple clustered DF (MCDF)—a rare condition that has been reported in children and young adults and generally appears in the first and second decades of life. Of the reported cases of MCDF, immunohistochemical staining for SMA was performed in 8 cases. All these cases showed negative or minimal staining.^3-5 Smooth muscle actin staining in DFs is negative, or weak and patchy, unlike in PLMT where it is diffuse, uniform, and strong.

Dermatofibrosarcoma protuberans typically occurs in young adults and manifests as dermal and subcutaneous nodular/multinodular or plaquelike masses, with rare congenital cases. Immunohistochemical staining for CD34, which typically is firmly and diffusely positive, is the most reliable marker of DFSP.⁶ Factor XIIIA in DFSP typically is negative for focal staining, mainly at periphery or in scattered dendritic cells. The prognosis of DFSP generally is excellent, with local recurrences in up to 30% of cases and extremely low metastatic potential (essentially only in cases with fibrosarcomatous transformation).⁶ Dermatomyofibroma is another rare benign dermal myofibroblastic tumor that typically manifests with indurated hyperpigmented or erythematous plaques or nodules on the shoulders and torso.⁶ This condition occurs mainly in adolescents and young adults, unlike PLMT. The most striking features of dermatomyofibroma are the horizontal orientation of the spindle cell nuclei and the pattern of the proliferation concerning the adnexal structures, especially hair follicles. The hair follicles have a normal appearance, and the proliferation extends up to each follicle, then continues to the other side without any displacement of the follicle. Tumor cells are variably positive for SMA in dermatomyofibromas and are negative for muscle-specific actin, desmin, S100, CD34, and Factor XIIIA.⁶

Immunohistochemistry can be very useful in differentiating PLMT from other conditions. Neoplastic cells stain positively for CD34 but not for Factor XIIIa and SMA in cases of DFSP. Dermatofibroma and its variants always present with collagen trapping at the periphery of the lesions and may demonstrate foamy macrophages, hemosiderin, or plasma cells FXIIIA(+), CD34(-), and variable SMA reactivity. This positivity usually is less prominent in DF than in PLMT. Neoplastic cells in dermatomyofibroma often stain positive for calponin, but only focally for SMA. The clinical features of dermatomyofibroma include early onset, large size, multiple nodules, and plaquelike morphology. Moulonguet et al⁴ hypothesized that, although MCDF and PLMT appear to show some distinctive clinical and histologic features, they also show similarities that could suggest they form part of the myofibroblastic spectrum. Furthermore, Moradi et al⁷ also considered them as part of the same disease spectrum because of their overlapping clinical, histologic, and immunohistochemical features.

The microscopic features in our case are notable, as the lesion demonstrated overlying acanthosis and follicular induction, resembling DF. The stroma contained microvesicular changes and erythrocyte extravasation, characteristic of nodular or proliferative fasciitis. Additionally, densely packed spindle cells infiltrated deep into the subcutaneous adipose tissue, similar to DFSP.^2,3 Our findings expand on the reported histopathologic spectrum of this tumor to date.

THE DIAGNOSIS: Plaquelike Myofibroblastic Tumor

An incisional biopsy of the plaque demonstrated a hypercellular proliferation of bland spindle cells in the dermis that infiltrated the subcutis. The overlying epidermis was mildly acanthotic with both ulceration and follicular induction. There was trapping of individual adipocytes in a honeycomb pattern with foci of erythrocyte extravasation, microvesiculation, and widened fibrous septa (Figure 1). Immunohistochemistry was positive for vimentin, actin, and smooth muscle actin (SMA)(Figure 2A). Variable positivity for Factor XIIIa antibodies was noted. CD68 staining was focal positive, suggesting fibrohistiocytic lineage. Expression of CD31, CD34, S100, and anaplastic lymphoma kinase was negative, and Ki-67 was present in less than 10% of cells (Figure 2B).

We reviewed the case in conjunction with a soft-tissue pathologist (Y.L.), and based on the clinical and immunophenotypic features, a diagnosis of plaquelike myofibroblastic tumor (PLMT) was made. The patient’s parents refused further treatment, and there was no sign of disease progression at 6-month follow-up.

Plaquelike myofibroblastic tumor is an unusual pediatric dermal tumor that was first described by Clarke et al¹ in 2007. Clinical manifestation of PLMT on the right abdomen was unique in our patient, as the lesions typically present as indurated plaques on the lower back, but the central ulceration in our case resembled a report by Marqueling et al.² Ulceration and induration of PLMT developing at 8 months of age can suggest an aggressive disease course corresponding with deep infiltration and is seen mostly in children.

The histopathologic features of PLMT include an acanthotic epidermis and follicular induction, which also are characteristic of dermatofibroma (DF). The proliferation of spindle cells extended deep into the fat with foci of erythrocyte extravasation and microvesiculation of the stroma similar to nodular fasciitis and proliferative fasciitis. The presentation of infiltrating and expanding fibrous septae and trapping of individual adipocytes in a honeycomb pattern is similar to dermatofibrosarcoma protuberans (DFSP). Most cases of PLMT are positive for SMA. Factor XIIIa typically is variably positive, and in one report, 31% (4/13) of cases showed positive staining for calponin.³ Rapid growth, ulceration, and recurrence emphasize that PLMT can be locally aggressive, similar to DFSP.⁴

The main differential diagnoses include DF and its variants, dermatomyofibroma, DFSP, and proliferative fasciitis.^3,5 In the cases mentioned above, microscopic features were similar with a relatively well-circumscribed proliferation of spindle cells arranged in short fascicles through the entire reticular dermis, and the overlying epidermis was acanthotic.

Dermatofibroma commonly manifests in adults as a minor nodular lesion (commonly <1 cm), and usually is located on the legs. It has several clinical and histologic variants, including multiple clustered DF (MCDF)—a rare condition that has been reported in children and young adults and generally appears in the first and second decades of life. Of the reported cases of MCDF, immunohistochemical staining for SMA was performed in 8 cases. All these cases showed negative or minimal staining.^3-5 Smooth muscle actin staining in DFs is negative, or weak and patchy, unlike in PLMT where it is diffuse, uniform, and strong.

Dermatofibrosarcoma protuberans typically occurs in young adults and manifests as dermal and subcutaneous nodular/multinodular or plaquelike masses, with rare congenital cases. Immunohistochemical staining for CD34, which typically is firmly and diffusely positive, is the most reliable marker of DFSP.⁶ Factor XIIIA in DFSP typically is negative for focal staining, mainly at periphery or in scattered dendritic cells. The prognosis of DFSP generally is excellent, with local recurrences in up to 30% of cases and extremely low metastatic potential (essentially only in cases with fibrosarcomatous transformation).⁶ Dermatomyofibroma is another rare benign dermal myofibroblastic tumor that typically manifests with indurated hyperpigmented or erythematous plaques or nodules on the shoulders and torso.⁶ This condition occurs mainly in adolescents and young adults, unlike PLMT. The most striking features of dermatomyofibroma are the horizontal orientation of the spindle cell nuclei and the pattern of the proliferation concerning the adnexal structures, especially hair follicles. The hair follicles have a normal appearance, and the proliferation extends up to each follicle, then continues to the other side without any displacement of the follicle. Tumor cells are variably positive for SMA in dermatomyofibromas and are negative for muscle-specific actin, desmin, S100, CD34, and Factor XIIIA.⁶

Immunohistochemistry can be very useful in differentiating PLMT from other conditions. Neoplastic cells stain positively for CD34 but not for Factor XIIIa and SMA in cases of DFSP. Dermatofibroma and its variants always present with collagen trapping at the periphery of the lesions and may demonstrate foamy macrophages, hemosiderin, or plasma cells FXIIIA(+), CD34(-), and variable SMA reactivity. This positivity usually is less prominent in DF than in PLMT. Neoplastic cells in dermatomyofibroma often stain positive for calponin, but only focally for SMA. The clinical features of dermatomyofibroma include early onset, large size, multiple nodules, and plaquelike morphology. Moulonguet et al⁴ hypothesized that, although MCDF and PLMT appear to show some distinctive clinical and histologic features, they also show similarities that could suggest they form part of the myofibroblastic spectrum. Furthermore, Moradi et al⁷ also considered them as part of the same disease spectrum because of their overlapping clinical, histologic, and immunohistochemical features.

The microscopic features in our case are notable, as the lesion demonstrated overlying acanthosis and follicular induction, resembling DF. The stroma contained microvesicular changes and erythrocyte extravasation, characteristic of nodular or proliferative fasciitis. Additionally, densely packed spindle cells infiltrated deep into the subcutaneous adipose tissue, similar to DFSP.^2,3 Our findings expand on the reported histopathologic spectrum of this tumor to date.

THE DIAGNOSIS: Plaquelike Myofibroblastic Tumor

An incisional biopsy of the plaque demonstrated a hypercellular proliferation of bland spindle cells in the dermis that infiltrated the subcutis. The overlying epidermis was mildly acanthotic with both ulceration and follicular induction. There was trapping of individual adipocytes in a honeycomb pattern with foci of erythrocyte extravasation, microvesiculation, and widened fibrous septa (Figure 1). Immunohistochemistry was positive for vimentin, actin, and smooth muscle actin (SMA)(Figure 2A). Variable positivity for Factor XIIIa antibodies was noted. CD68 staining was focal positive, suggesting fibrohistiocytic lineage. Expression of CD31, CD34, S100, and anaplastic lymphoma kinase was negative, and Ki-67 was present in less than 10% of cells (Figure 2B).

We reviewed the case in conjunction with a soft-tissue pathologist (Y.L.), and based on the clinical and immunophenotypic features, a diagnosis of plaquelike myofibroblastic tumor (PLMT) was made. The patient’s parents refused further treatment, and there was no sign of disease progression at 6-month follow-up.

Plaquelike myofibroblastic tumor is an unusual pediatric dermal tumor that was first described by Clarke et al¹ in 2007. Clinical manifestation of PLMT on the right abdomen was unique in our patient, as the lesions typically present as indurated plaques on the lower back, but the central ulceration in our case resembled a report by Marqueling et al.² Ulceration and induration of PLMT developing at 8 months of age can suggest an aggressive disease course corresponding with deep infiltration and is seen mostly in children.

The histopathologic features of PLMT include an acanthotic epidermis and follicular induction, which also are characteristic of dermatofibroma (DF). The proliferation of spindle cells extended deep into the fat with foci of erythrocyte extravasation and microvesiculation of the stroma similar to nodular fasciitis and proliferative fasciitis. The presentation of infiltrating and expanding fibrous septae and trapping of individual adipocytes in a honeycomb pattern is similar to dermatofibrosarcoma protuberans (DFSP). Most cases of PLMT are positive for SMA. Factor XIIIa typically is variably positive, and in one report, 31% (4/13) of cases showed positive staining for calponin.³ Rapid growth, ulceration, and recurrence emphasize that PLMT can be locally aggressive, similar to DFSP.⁴

The main differential diagnoses include DF and its variants, dermatomyofibroma, DFSP, and proliferative fasciitis.^3,5 In the cases mentioned above, microscopic features were similar with a relatively well-circumscribed proliferation of spindle cells arranged in short fascicles through the entire reticular dermis, and the overlying epidermis was acanthotic.

Dermatofibroma commonly manifests in adults as a minor nodular lesion (commonly <1 cm), and usually is located on the legs. It has several clinical and histologic variants, including multiple clustered DF (MCDF)—a rare condition that has been reported in children and young adults and generally appears in the first and second decades of life. Of the reported cases of MCDF, immunohistochemical staining for SMA was performed in 8 cases. All these cases showed negative or minimal staining.^3-5 Smooth muscle actin staining in DFs is negative, or weak and patchy, unlike in PLMT where it is diffuse, uniform, and strong.

Dermatofibrosarcoma protuberans typically occurs in young adults and manifests as dermal and subcutaneous nodular/multinodular or plaquelike masses, with rare congenital cases. Immunohistochemical staining for CD34, which typically is firmly and diffusely positive, is the most reliable marker of DFSP.⁶ Factor XIIIA in DFSP typically is negative for focal staining, mainly at periphery or in scattered dendritic cells. The prognosis of DFSP generally is excellent, with local recurrences in up to 30% of cases and extremely low metastatic potential (essentially only in cases with fibrosarcomatous transformation).⁶ Dermatomyofibroma is another rare benign dermal myofibroblastic tumor that typically manifests with indurated hyperpigmented or erythematous plaques or nodules on the shoulders and torso.⁶ This condition occurs mainly in adolescents and young adults, unlike PLMT. The most striking features of dermatomyofibroma are the horizontal orientation of the spindle cell nuclei and the pattern of the proliferation concerning the adnexal structures, especially hair follicles. The hair follicles have a normal appearance, and the proliferation extends up to each follicle, then continues to the other side without any displacement of the follicle. Tumor cells are variably positive for SMA in dermatomyofibromas and are negative for muscle-specific actin, desmin, S100, CD34, and Factor XIIIA.⁶

Immunohistochemistry can be very useful in differentiating PLMT from other conditions. Neoplastic cells stain positively for CD34 but not for Factor XIIIa and SMA in cases of DFSP. Dermatofibroma and its variants always present with collagen trapping at the periphery of the lesions and may demonstrate foamy macrophages, hemosiderin, or plasma cells FXIIIA(+), CD34(-), and variable SMA reactivity. This positivity usually is less prominent in DF than in PLMT. Neoplastic cells in dermatomyofibroma often stain positive for calponin, but only focally for SMA. The clinical features of dermatomyofibroma include early onset, large size, multiple nodules, and plaquelike morphology. Moulonguet et al⁴ hypothesized that, although MCDF and PLMT appear to show some distinctive clinical and histologic features, they also show similarities that could suggest they form part of the myofibroblastic spectrum. Furthermore, Moradi et al⁷ also considered them as part of the same disease spectrum because of their overlapping clinical, histologic, and immunohistochemical features.

The microscopic features in our case are notable, as the lesion demonstrated overlying acanthosis and follicular induction, resembling DF. The stroma contained microvesicular changes and erythrocyte extravasation, characteristic of nodular or proliferative fasciitis. Additionally, densely packed spindle cells infiltrated deep into the subcutaneous adipose tissue, similar to DFSP.^2,3 Our findings expand on the reported histopathologic spectrum of this tumor to date.

To the Editor:

A 22-year-old man was referred to our dermatology outpatient department for wartlike growths that gradually developed around a postoperative enteroatmospheric fistula and stoma over the past 4 months. The patient presented for an emergency exploratory laparotomy with a history of perforation peritonitis 1.5 years prior to the current presentation. He also had a small bowel obstruction 5 months prior to the current presentation that resulted in the resection of a large segment of the small bowel. He underwent a diverting loop ileostomy when the abdominal closure was not achieved because of bowel edema, following which he developed a postoperative enteroatmospheric fistula. In addition, the stoma retracted and was followed by dermal dehiscence, which led to notable leakage and resulted in heavy fecal contamination of the midline wound.

At the current presentation, physical examination revealed multiple grayish-white, dome-shaped, moist papules coalescing to form a peristomal pseudoverrucous mass on the lower side of the stoma (Figure 1). The patient experienced mild itching. The lesion showed no signs of erosion, bleeding, or purulent discharge, and there were no nearby lumps or enlarged lymph nodes. The differential diagnosis included peristomal pyoderma gangrenosum, human papillomavirus (HPV) infection, pseudoverrucous papules and nodules (PPNs), squamous cell carcinoma, and exuberant granulation tissue. A skin biopsy was performed, and histopathology revealed hyperkeratosis, moderate papillomatosis, and marked acanthotic hyperplasia seen as downgrowths into the dermis (Figure 2). No koilocytes, atypia, or mitotic figures were present. Abundant neutrophils and few eosinophils were seen in the dermal infiltrate. A final diagnosis of PPN was made based on clinicopathologic correlation. The patient was advised to use a smaller stoma bag and to change the collection pouch frequently to reduce skin contact with fecal matter.

Peristomal skin conditions are reported in 18% to 55% of patients with stomas and include allergic contact dermatitis, mechanical dermatitis, infections, pyoderma gangrenosum, and irritant contact dermatitis.^1,2 Pseudoverrucous papules (also called chronic papillomatous dermatitis or pseudoverrucous lesions) is a rare dermatologic complication found on the skin around stomas,³ most commonly around urostomy stomas. The presence of PPNs around colostomy stomas and the perianal region is extremely rare.^2,4 This condition is the result of chronic irritant dermatitis from frequent exposure to urine or feces, leading to maceration and epidermal hyperplasia. It occurs because of improper sizing of the stoma bag or incorrect positioning or construction of the stoma.⁵

the overuse of topical benzocaine-resorcinol, leading to chronic irritation.⁶ It is clinically characterized by multiple grayish-white, wartlike, confluent papulonodules around areas chronically exposed to moisture. Differential diagnoses such as secondary neoplasms, HPV infection, exuberant granulation tissue, and candidal infections should be considered.³ Final diagnosis is based on clinicopathologic findings, similar to our case. Epidermal growth factor and transforming growth factor are thought to play a role in the pathophysiology of pseudoepitheliomatous hyperplasia. Increased expression of these mediators leads to proliferation of the epidermis into the dermis.⁷ The role of HPV in PPN remains unclear, as not all PPN lesions are positive for HPV and the cutaneous lesions resolve once the source of irritation is removed. Recommended treatment includes local skin care; stoma refitting; and, in severe cases, excision and revision of the stoma.² Dermatologists must be aware of this often-underdiagnosed condition.

To the Editor:

A 22-year-old man was referred to our dermatology outpatient department for wartlike growths that gradually developed around a postoperative enteroatmospheric fistula and stoma over the past 4 months. The patient presented for an emergency exploratory laparotomy with a history of perforation peritonitis 1.5 years prior to the current presentation. He also had a small bowel obstruction 5 months prior to the current presentation that resulted in the resection of a large segment of the small bowel. He underwent a diverting loop ileostomy when the abdominal closure was not achieved because of bowel edema, following which he developed a postoperative enteroatmospheric fistula. In addition, the stoma retracted and was followed by dermal dehiscence, which led to notable leakage and resulted in heavy fecal contamination of the midline wound.

At the current presentation, physical examination revealed multiple grayish-white, dome-shaped, moist papules coalescing to form a peristomal pseudoverrucous mass on the lower side of the stoma (Figure 1). The patient experienced mild itching. The lesion showed no signs of erosion, bleeding, or purulent discharge, and there were no nearby lumps or enlarged lymph nodes. The differential diagnosis included peristomal pyoderma gangrenosum, human papillomavirus (HPV) infection, pseudoverrucous papules and nodules (PPNs), squamous cell carcinoma, and exuberant granulation tissue. A skin biopsy was performed, and histopathology revealed hyperkeratosis, moderate papillomatosis, and marked acanthotic hyperplasia seen as downgrowths into the dermis (Figure 2). No koilocytes, atypia, or mitotic figures were present. Abundant neutrophils and few eosinophils were seen in the dermal infiltrate. A final diagnosis of PPN was made based on clinicopathologic correlation. The patient was advised to use a smaller stoma bag and to change the collection pouch frequently to reduce skin contact with fecal matter.

Peristomal skin conditions are reported in 18% to 55% of patients with stomas and include allergic contact dermatitis, mechanical dermatitis, infections, pyoderma gangrenosum, and irritant contact dermatitis.^1,2 Pseudoverrucous papules (also called chronic papillomatous dermatitis or pseudoverrucous lesions) is a rare dermatologic complication found on the skin around stomas,³ most commonly around urostomy stomas. The presence of PPNs around colostomy stomas and the perianal region is extremely rare.^2,4 This condition is the result of chronic irritant dermatitis from frequent exposure to urine or feces, leading to maceration and epidermal hyperplasia. It occurs because of improper sizing of the stoma bag or incorrect positioning or construction of the stoma.⁵

the overuse of topical benzocaine-resorcinol, leading to chronic irritation.⁶ It is clinically characterized by multiple grayish-white, wartlike, confluent papulonodules around areas chronically exposed to moisture. Differential diagnoses such as secondary neoplasms, HPV infection, exuberant granulation tissue, and candidal infections should be considered.³ Final diagnosis is based on clinicopathologic findings, similar to our case. Epidermal growth factor and transforming growth factor are thought to play a role in the pathophysiology of pseudoepitheliomatous hyperplasia. Increased expression of these mediators leads to proliferation of the epidermis into the dermis.⁷ The role of HPV in PPN remains unclear, as not all PPN lesions are positive for HPV and the cutaneous lesions resolve once the source of irritation is removed. Recommended treatment includes local skin care; stoma refitting; and, in severe cases, excision and revision of the stoma.² Dermatologists must be aware of this often-underdiagnosed condition.

To the Editor:

A 22-year-old man was referred to our dermatology outpatient department for wartlike growths that gradually developed around a postoperative enteroatmospheric fistula and stoma over the past 4 months. The patient presented for an emergency exploratory laparotomy with a history of perforation peritonitis 1.5 years prior to the current presentation. He also had a small bowel obstruction 5 months prior to the current presentation that resulted in the resection of a large segment of the small bowel. He underwent a diverting loop ileostomy when the abdominal closure was not achieved because of bowel edema, following which he developed a postoperative enteroatmospheric fistula. In addition, the stoma retracted and was followed by dermal dehiscence, which led to notable leakage and resulted in heavy fecal contamination of the midline wound.

At the current presentation, physical examination revealed multiple grayish-white, dome-shaped, moist papules coalescing to form a peristomal pseudoverrucous mass on the lower side of the stoma (Figure 1). The patient experienced mild itching. The lesion showed no signs of erosion, bleeding, or purulent discharge, and there were no nearby lumps or enlarged lymph nodes. The differential diagnosis included peristomal pyoderma gangrenosum, human papillomavirus (HPV) infection, pseudoverrucous papules and nodules (PPNs), squamous cell carcinoma, and exuberant granulation tissue. A skin biopsy was performed, and histopathology revealed hyperkeratosis, moderate papillomatosis, and marked acanthotic hyperplasia seen as downgrowths into the dermis (Figure 2). No koilocytes, atypia, or mitotic figures were present. Abundant neutrophils and few eosinophils were seen in the dermal infiltrate. A final diagnosis of PPN was made based on clinicopathologic correlation. The patient was advised to use a smaller stoma bag and to change the collection pouch frequently to reduce skin contact with fecal matter.

Peristomal skin conditions are reported in 18% to 55% of patients with stomas and include allergic contact dermatitis, mechanical dermatitis, infections, pyoderma gangrenosum, and irritant contact dermatitis.^1,2 Pseudoverrucous papules (also called chronic papillomatous dermatitis or pseudoverrucous lesions) is a rare dermatologic complication found on the skin around stomas,³ most commonly around urostomy stomas. The presence of PPNs around colostomy stomas and the perianal region is extremely rare.^2,4 This condition is the result of chronic irritant dermatitis from frequent exposure to urine or feces, leading to maceration and epidermal hyperplasia. It occurs because of improper sizing of the stoma bag or incorrect positioning or construction of the stoma.⁵

the overuse of topical benzocaine-resorcinol, leading to chronic irritation.⁶ It is clinically characterized by multiple grayish-white, wartlike, confluent papulonodules around areas chronically exposed to moisture. Differential diagnoses such as secondary neoplasms, HPV infection, exuberant granulation tissue, and candidal infections should be considered.³ Final diagnosis is based on clinicopathologic findings, similar to our case. Epidermal growth factor and transforming growth factor are thought to play a role in the pathophysiology of pseudoepitheliomatous hyperplasia. Increased expression of these mediators leads to proliferation of the epidermis into the dermis.⁷ The role of HPV in PPN remains unclear, as not all PPN lesions are positive for HPV and the cutaneous lesions resolve once the source of irritation is removed. Recommended treatment includes local skin care; stoma refitting; and, in severe cases, excision and revision of the stoma.² Dermatologists must be aware of this often-underdiagnosed condition.

Dermatopathology education, which comprises approximately 30% of the dermatology residency curriculum, is crucial for the holistic training of dermatology residents to diagnose and manage a range of dermatologic conditions.¹ Additionally, dermatopathology is the topic of one of the 4 American Board of Dermatology CORE Exam modules, further highlighting the need for comprehensive education in this area. A variety of resources including virtual dermatopathology and conventional microscopy training currently are used in residency programs for dermatopathology education.^2,3 Although used less frequently, social media platforms such as Instagram also are used to aid in dermatopathology education for a wider audience.⁴ Other online resources, including the American Society of Dermatopathology website (www.asdp.org) and DermpathAtlas.com, are excellent tools for medical students, residents, and fellows to develop their knowledge.⁵ While these resources are accessible, they must be directly sought out by the student and utilized on their own time. Additionally, if medical students do not have a strong understanding of the basics of dermatopathology, they may not have the foundation required to benefit from these resources.

Dermatopathology education is critical for the overall practice of dermatology, yet most dermatology residency programs may not be incorporating dermatopathology education early enough in training. One study evaluating the timing and length of dermatopathology education during residency reported that fewer than 40% (20/51) of dermatology residency programs allocate 3 or more weeks to dermatopathology education during the second postgraduate year.¹ Despite Ackerman6 advocating for early dermatopathology exposure to best prepare medical students to recognize and manage certain dermatologic conditions, the majority of exposure still seems to occur during postgraduate year 4.¹ Furthermore, current primary care residents feel that their medical school training did not sufficiently prepare them to diagnose and manage dermatologic conditions, with only 37% (93/252) reporting feeling adequately prepared.^7,8 Medical students also reported a lack of confidence in overall dermatology knowledge, with 89% (72/81) reporting they felt neutral, slightly confident, or not at all confident when asked to diagnose skin lesions.⁹ In the same study, the average score was 46.6% (7/15 questions answered correctly) when 74 participants were assessed via a multiple choice quiz on dermatologic diagnosis and treatment, further demonstrating the lack of general dermatology comfort among medical students.⁹ This likely stems from limited dermatology curriculum in medical schools, demonstrating the need for further dermatology education as a whole in medical school.¹⁰

Ensuring robust dermatopathology education in medical school and the first year of dermatology residency has the potential to better prepare medical students for the transition into dermatology residency and clinical practice. We created an introductory dermatopathology lecture and presented it to medical students and first year dermatology residents to improve dermatopathology knowledge and confidence in learners early in their dermatology training.

Structure of the Lecture

Participants included first-year dermatology residents and fourth-year medical students rotating with the Wayne State University Department of Dermatology (Detroit, Michigan). The same facilitator (H.O.) taught each of the lectures, and all lectures were conducted via Zoom at the beginning of the month from May 2024 through November 2024. A total of 7 lectures were given. The lecture was formatted so that a histologic image was shown, then learners expressed their thoughts about what the image was showing before the answer was given. This format allowed participants to view the images on their own device screen and allowed the facilitator to annotate the images. The lecture was divided into 3 sections: (1) cell types and basic structures, (2) anatomic slides, and (3) common diagnoses. Each session lasted approximately 45 minutes.

Section 1: Cell Types and Basic Structures—The first section covered the fundamental cell types (neutrophils, lymphocytes, plasma cells, melanocytes, and eosinophils) along with glandular structures (apocrine, eccrine, and sebaceous). The session was designed to follow a retention and allow learners to think through each slide. First, participants were shown histologic images of each cell type and were asked to identify what type of cell was being shown. On the following slide, key features of each cell type were highlighted. Next, participants similarly were shown images of the glandular structures followed by key features of each. The section concluded with a review of the layers of the skin (stratum corneum, stratum granulosum, stratum lucidum, stratum spinosum, and stratum basale). A histologic image was shown, and the facilitator discussed how to distinguish the layers.

Section 2: Anatomic Sites—This section focused on key pathologic features for differentiating body surfaces, including the scalp, face, eyelids, ears, areolae, palms and soles, and mucosae. Participants initially were shown an image of a hematoxylin and eosin–stained slide from a specific body surface and then were asked to identify structures that may serve as a clue to the anatomic location. If the participants were not sure, they were given hints; for example, when participants were shown an image of the ear and were unsure of the location, the facilitator circled cartilage and asked them to identify the structure. In most cases, once participants named this structure, they were able to recognize that the location was the ear.

Section 3: Common Diagnoses—This section addressed frequently encountered diagnoses in dermatopathology, including basal cell carcinoma, squamous cell carcinoma, squamous cell carcinoma in situ, epidermoid cyst, pilar cyst, seborrheic keratosis, solar lentigo, melanocytic nevus, melanoma, verruca vulgaris, spongiotic dermatitis, psoriasis, and lichen planus. It followed the same format of the first section: participants were shown an hemotoxyllin and eosin–stained image and then were asked to discuss what the diagnosis could be and why. Hints were given if participants struggled to come up with the correct diagnosis. A few slides also were dedicated to distinguishing benign nevi, dysplastic nevi, and melanoma.

Pretest and Posttest Results

Residents participated in the lecture as part of their first-year orientation, and medical students participated during their dermatology rotation. All participants were invited to complete a pretest and a posttest before and after the lecture, respectively. Both assessments were optional and anonymous. The pretest was completed electronically and consisted of 10 knowledge-based, multiple-choice questions that included a histopathologic image and asked, “What is the most likely diagnosis?,” “What is the predominant cell type?,” and “Where was this specimen taken from?” In addition to the knowledge-based questions, participants also were asked to rate their confidence in dermatopathology on a 5-point Likert scale ranging from 1 (not confident at all) to 5 (extremely confident). Participants completed the entire pretest before any information on the topic was provided. After the lecture, participants were asked to complete a posttest identical to the pretest and to rate their confidence in dermatopathology again on the same scale. The posttest included an additional question asking participants to rate the helpfulness of the lecture on a Likert scale ranging from 1 (not helpful at all) to 5 (extremely helpful). Participants completed the posttest within 48 hours of the lecture.

Overall, 15 learners participated in the pretest and 12 in the posttest. Of the 15 pretest participants, 3 were first-year residents and 12 were medical students. Similarly, in the posttest, 2 respondents were first-year residents and 10 were medical students. All responses contained complete pretests and posttests. The mean score on the pretest was 62%, whereas the mean score on the posttest was 75%. A paired t test indicated a statistically significant improvement (P=.017). In addition, the mean rating for confidence in dermatopathology knowledge before the lecture was 1.5 prior to the lecture and 2.6 after the lecture. A paired t test demonstrated statistical significance (P=.010). The mean rating of the helpfulness of the lecture was 4.67. The majority (91.7% [11/12]) of the participants gave a rating of 4 or 5.

Impact of the Lecture on Dermatopathology Knowledge

There is a gap in dermatopathology education early in medical training. Our introductory lecture led to higher post test scores and increased confidence in dermatopathology among medical students and dermatology residents, demonstrating the effectiveness of this kind of program in bridging this education gap. The majority of participants in our lecture said they found the session helpful. A previously published article called for early implementation of dermatology education as a whole in the medical curriculum due to lack of knowledge and confidence, and our introductory lecture may help to bridge this gap.⁸ Increasing dermatopathology content for medical students and first-year dermatology residents can expand knowledge, as shown by the increased scores on the posttest, and better supports learners transitioning to dermatology residency, where dermatopathology constitutes a large part of the overall curriculum.² More comprehensive knowledge of dermatopathology early in dermatology training also may help to better prepare residents to accurately diagnose and manage dermatologic conditions.

Pretest scores showed that the average confidence rating in dermatopathology among participants in our lecture was 1.5, which is rather low. This is consistent with prior studies that have found that residents feel that medical school inadequately prepared them for dermatology residency.^7,8 More than 87% (71/81) of medical students surveyed felt they received inadequate general dermatology training in medical school.⁹ This supports the proposed educational gap that is impacting confidence in overall dermatology knowledge, which includes dermatopathology. In our study, the average confidence rating increased by 1.1 points after the lecture, which was statistically significant (P=.010) and demonstrates that an introductory lecture serves as a feasible intervention to improve confidence in this area.

The feedback we received from participants in our lecture shows the benefits of an introductory interactive lecture with virtual dermatopathology images. Ngo et al2 highlighted how residents perceive virtual images to be superior to conventional microscopy for dermatopathology, which we utilized in our lecture. This method is not only cost effective but also provides a simple way for learners and facilitators to point out key findings on histopathology slides.²

Final Thoughts

Overall, implementing dermatopathology education early in training has a measurable impact on dermatopathology knowledge and confidence among medical students and first-year dermatology residents. An interactive lecture with virtual images similar to the one we describe here may better prepare learners for the transition to dermatology residency by addressing the educational gap in dermatopathology early in training.

Dermatopathology education, which comprises approximately 30% of the dermatology residency curriculum, is crucial for the holistic training of dermatology residents to diagnose and manage a range of dermatologic conditions.¹ Additionally, dermatopathology is the topic of one of the 4 American Board of Dermatology CORE Exam modules, further highlighting the need for comprehensive education in this area. A variety of resources including virtual dermatopathology and conventional microscopy training currently are used in residency programs for dermatopathology education.^2,3 Although used less frequently, social media platforms such as Instagram also are used to aid in dermatopathology education for a wider audience.⁴ Other online resources, including the American Society of Dermatopathology website (www.asdp.org) and DermpathAtlas.com, are excellent tools for medical students, residents, and fellows to develop their knowledge.⁵ While these resources are accessible, they must be directly sought out by the student and utilized on their own time. Additionally, if medical students do not have a strong understanding of the basics of dermatopathology, they may not have the foundation required to benefit from these resources.

Dermatopathology education is critical for the overall practice of dermatology, yet most dermatology residency programs may not be incorporating dermatopathology education early enough in training. One study evaluating the timing and length of dermatopathology education during residency reported that fewer than 40% (20/51) of dermatology residency programs allocate 3 or more weeks to dermatopathology education during the second postgraduate year.¹ Despite Ackerman6 advocating for early dermatopathology exposure to best prepare medical students to recognize and manage certain dermatologic conditions, the majority of exposure still seems to occur during postgraduate year 4.¹ Furthermore, current primary care residents feel that their medical school training did not sufficiently prepare them to diagnose and manage dermatologic conditions, with only 37% (93/252) reporting feeling adequately prepared.^7,8 Medical students also reported a lack of confidence in overall dermatology knowledge, with 89% (72/81) reporting they felt neutral, slightly confident, or not at all confident when asked to diagnose skin lesions.⁹ In the same study, the average score was 46.6% (7/15 questions answered correctly) when 74 participants were assessed via a multiple choice quiz on dermatologic diagnosis and treatment, further demonstrating the lack of general dermatology comfort among medical students.⁹ This likely stems from limited dermatology curriculum in medical schools, demonstrating the need for further dermatology education as a whole in medical school.¹⁰

Ensuring robust dermatopathology education in medical school and the first year of dermatology residency has the potential to better prepare medical students for the transition into dermatology residency and clinical practice. We created an introductory dermatopathology lecture and presented it to medical students and first year dermatology residents to improve dermatopathology knowledge and confidence in learners early in their dermatology training.

Structure of the Lecture

Participants included first-year dermatology residents and fourth-year medical students rotating with the Wayne State University Department of Dermatology (Detroit, Michigan). The same facilitator (H.O.) taught each of the lectures, and all lectures were conducted via Zoom at the beginning of the month from May 2024 through November 2024. A total of 7 lectures were given. The lecture was formatted so that a histologic image was shown, then learners expressed their thoughts about what the image was showing before the answer was given. This format allowed participants to view the images on their own device screen and allowed the facilitator to annotate the images. The lecture was divided into 3 sections: (1) cell types and basic structures, (2) anatomic slides, and (3) common diagnoses. Each session lasted approximately 45 minutes.

Section 1: Cell Types and Basic Structures—The first section covered the fundamental cell types (neutrophils, lymphocytes, plasma cells, melanocytes, and eosinophils) along with glandular structures (apocrine, eccrine, and sebaceous). The session was designed to follow a retention and allow learners to think through each slide. First, participants were shown histologic images of each cell type and were asked to identify what type of cell was being shown. On the following slide, key features of each cell type were highlighted. Next, participants similarly were shown images of the glandular structures followed by key features of each. The section concluded with a review of the layers of the skin (stratum corneum, stratum granulosum, stratum lucidum, stratum spinosum, and stratum basale). A histologic image was shown, and the facilitator discussed how to distinguish the layers.

Section 2: Anatomic Sites—This section focused on key pathologic features for differentiating body surfaces, including the scalp, face, eyelids, ears, areolae, palms and soles, and mucosae. Participants initially were shown an image of a hematoxylin and eosin–stained slide from a specific body surface and then were asked to identify structures that may serve as a clue to the anatomic location. If the participants were not sure, they were given hints; for example, when participants were shown an image of the ear and were unsure of the location, the facilitator circled cartilage and asked them to identify the structure. In most cases, once participants named this structure, they were able to recognize that the location was the ear.

Section 3: Common Diagnoses—This section addressed frequently encountered diagnoses in dermatopathology, including basal cell carcinoma, squamous cell carcinoma, squamous cell carcinoma in situ, epidermoid cyst, pilar cyst, seborrheic keratosis, solar lentigo, melanocytic nevus, melanoma, verruca vulgaris, spongiotic dermatitis, psoriasis, and lichen planus. It followed the same format of the first section: participants were shown an hemotoxyllin and eosin–stained image and then were asked to discuss what the diagnosis could be and why. Hints were given if participants struggled to come up with the correct diagnosis. A few slides also were dedicated to distinguishing benign nevi, dysplastic nevi, and melanoma.

Pretest and Posttest Results

Residents participated in the lecture as part of their first-year orientation, and medical students participated during their dermatology rotation. All participants were invited to complete a pretest and a posttest before and after the lecture, respectively. Both assessments were optional and anonymous. The pretest was completed electronically and consisted of 10 knowledge-based, multiple-choice questions that included a histopathologic image and asked, “What is the most likely diagnosis?,” “What is the predominant cell type?,” and “Where was this specimen taken from?” In addition to the knowledge-based questions, participants also were asked to rate their confidence in dermatopathology on a 5-point Likert scale ranging from 1 (not confident at all) to 5 (extremely confident). Participants completed the entire pretest before any information on the topic was provided. After the lecture, participants were asked to complete a posttest identical to the pretest and to rate their confidence in dermatopathology again on the same scale. The posttest included an additional question asking participants to rate the helpfulness of the lecture on a Likert scale ranging from 1 (not helpful at all) to 5 (extremely helpful). Participants completed the posttest within 48 hours of the lecture.

Overall, 15 learners participated in the pretest and 12 in the posttest. Of the 15 pretest participants, 3 were first-year residents and 12 were medical students. Similarly, in the posttest, 2 respondents were first-year residents and 10 were medical students. All responses contained complete pretests and posttests. The mean score on the pretest was 62%, whereas the mean score on the posttest was 75%. A paired t test indicated a statistically significant improvement (P=.017). In addition, the mean rating for confidence in dermatopathology knowledge before the lecture was 1.5 prior to the lecture and 2.6 after the lecture. A paired t test demonstrated statistical significance (P=.010). The mean rating of the helpfulness of the lecture was 4.67. The majority (91.7% [11/12]) of the participants gave a rating of 4 or 5.

Impact of the Lecture on Dermatopathology Knowledge

There is a gap in dermatopathology education early in medical training. Our introductory lecture led to higher post test scores and increased confidence in dermatopathology among medical students and dermatology residents, demonstrating the effectiveness of this kind of program in bridging this education gap. The majority of participants in our lecture said they found the session helpful. A previously published article called for early implementation of dermatology education as a whole in the medical curriculum due to lack of knowledge and confidence, and our introductory lecture may help to bridge this gap.⁸ Increasing dermatopathology content for medical students and first-year dermatology residents can expand knowledge, as shown by the increased scores on the posttest, and better supports learners transitioning to dermatology residency, where dermatopathology constitutes a large part of the overall curriculum.² More comprehensive knowledge of dermatopathology early in dermatology training also may help to better prepare residents to accurately diagnose and manage dermatologic conditions.

Pretest scores showed that the average confidence rating in dermatopathology among participants in our lecture was 1.5, which is rather low. This is consistent with prior studies that have found that residents feel that medical school inadequately prepared them for dermatology residency.^7,8 More than 87% (71/81) of medical students surveyed felt they received inadequate general dermatology training in medical school.⁹ This supports the proposed educational gap that is impacting confidence in overall dermatology knowledge, which includes dermatopathology. In our study, the average confidence rating increased by 1.1 points after the lecture, which was statistically significant (P=.010) and demonstrates that an introductory lecture serves as a feasible intervention to improve confidence in this area.

The feedback we received from participants in our lecture shows the benefits of an introductory interactive lecture with virtual dermatopathology images. Ngo et al2 highlighted how residents perceive virtual images to be superior to conventional microscopy for dermatopathology, which we utilized in our lecture. This method is not only cost effective but also provides a simple way for learners and facilitators to point out key findings on histopathology slides.²

Final Thoughts

Overall, implementing dermatopathology education early in training has a measurable impact on dermatopathology knowledge and confidence among medical students and first-year dermatology residents. An interactive lecture with virtual images similar to the one we describe here may better prepare learners for the transition to dermatology residency by addressing the educational gap in dermatopathology early in training.

Dermatopathology education, which comprises approximately 30% of the dermatology residency curriculum, is crucial for the holistic training of dermatology residents to diagnose and manage a range of dermatologic conditions.¹ Additionally, dermatopathology is the topic of one of the 4 American Board of Dermatology CORE Exam modules, further highlighting the need for comprehensive education in this area. A variety of resources including virtual dermatopathology and conventional microscopy training currently are used in residency programs for dermatopathology education.^2,3 Although used less frequently, social media platforms such as Instagram also are used to aid in dermatopathology education for a wider audience.⁴ Other online resources, including the American Society of Dermatopathology website (www.asdp.org) and DermpathAtlas.com, are excellent tools for medical students, residents, and fellows to develop their knowledge.⁵ While these resources are accessible, they must be directly sought out by the student and utilized on their own time. Additionally, if medical students do not have a strong understanding of the basics of dermatopathology, they may not have the foundation required to benefit from these resources.

Dermatopathology education is critical for the overall practice of dermatology, yet most dermatology residency programs may not be incorporating dermatopathology education early enough in training. One study evaluating the timing and length of dermatopathology education during residency reported that fewer than 40% (20/51) of dermatology residency programs allocate 3 or more weeks to dermatopathology education during the second postgraduate year.¹ Despite Ackerman6 advocating for early dermatopathology exposure to best prepare medical students to recognize and manage certain dermatologic conditions, the majority of exposure still seems to occur during postgraduate year 4.¹ Furthermore, current primary care residents feel that their medical school training did not sufficiently prepare them to diagnose and manage dermatologic conditions, with only 37% (93/252) reporting feeling adequately prepared.^7,8 Medical students also reported a lack of confidence in overall dermatology knowledge, with 89% (72/81) reporting they felt neutral, slightly confident, or not at all confident when asked to diagnose skin lesions.⁹ In the same study, the average score was 46.6% (7/15 questions answered correctly) when 74 participants were assessed via a multiple choice quiz on dermatologic diagnosis and treatment, further demonstrating the lack of general dermatology comfort among medical students.⁹ This likely stems from limited dermatology curriculum in medical schools, demonstrating the need for further dermatology education as a whole in medical school.¹⁰

Ensuring robust dermatopathology education in medical school and the first year of dermatology residency has the potential to better prepare medical students for the transition into dermatology residency and clinical practice. We created an introductory dermatopathology lecture and presented it to medical students and first year dermatology residents to improve dermatopathology knowledge and confidence in learners early in their dermatology training.

Structure of the Lecture

Participants included first-year dermatology residents and fourth-year medical students rotating with the Wayne State University Department of Dermatology (Detroit, Michigan). The same facilitator (H.O.) taught each of the lectures, and all lectures were conducted via Zoom at the beginning of the month from May 2024 through November 2024. A total of 7 lectures were given. The lecture was formatted so that a histologic image was shown, then learners expressed their thoughts about what the image was showing before the answer was given. This format allowed participants to view the images on their own device screen and allowed the facilitator to annotate the images. The lecture was divided into 3 sections: (1) cell types and basic structures, (2) anatomic slides, and (3) common diagnoses. Each session lasted approximately 45 minutes.

Section 1: Cell Types and Basic Structures—The first section covered the fundamental cell types (neutrophils, lymphocytes, plasma cells, melanocytes, and eosinophils) along with glandular structures (apocrine, eccrine, and sebaceous). The session was designed to follow a retention and allow learners to think through each slide. First, participants were shown histologic images of each cell type and were asked to identify what type of cell was being shown. On the following slide, key features of each cell type were highlighted. Next, participants similarly were shown images of the glandular structures followed by key features of each. The section concluded with a review of the layers of the skin (stratum corneum, stratum granulosum, stratum lucidum, stratum spinosum, and stratum basale). A histologic image was shown, and the facilitator discussed how to distinguish the layers.

Section 2: Anatomic Sites—This section focused on key pathologic features for differentiating body surfaces, including the scalp, face, eyelids, ears, areolae, palms and soles, and mucosae. Participants initially were shown an image of a hematoxylin and eosin–stained slide from a specific body surface and then were asked to identify structures that may serve as a clue to the anatomic location. If the participants were not sure, they were given hints; for example, when participants were shown an image of the ear and were unsure of the location, the facilitator circled cartilage and asked them to identify the structure. In most cases, once participants named this structure, they were able to recognize that the location was the ear.

Section 3: Common Diagnoses—This section addressed frequently encountered diagnoses in dermatopathology, including basal cell carcinoma, squamous cell carcinoma, squamous cell carcinoma in situ, epidermoid cyst, pilar cyst, seborrheic keratosis, solar lentigo, melanocytic nevus, melanoma, verruca vulgaris, spongiotic dermatitis, psoriasis, and lichen planus. It followed the same format of the first section: participants were shown an hemotoxyllin and eosin–stained image and then were asked to discuss what the diagnosis could be and why. Hints were given if participants struggled to come up with the correct diagnosis. A few slides also were dedicated to distinguishing benign nevi, dysplastic nevi, and melanoma.

Pretest and Posttest Results

Residents participated in the lecture as part of their first-year orientation, and medical students participated during their dermatology rotation. All participants were invited to complete a pretest and a posttest before and after the lecture, respectively. Both assessments were optional and anonymous. The pretest was completed electronically and consisted of 10 knowledge-based, multiple-choice questions that included a histopathologic image and asked, “What is the most likely diagnosis?,” “What is the predominant cell type?,” and “Where was this specimen taken from?” In addition to the knowledge-based questions, participants also were asked to rate their confidence in dermatopathology on a 5-point Likert scale ranging from 1 (not confident at all) to 5 (extremely confident). Participants completed the entire pretest before any information on the topic was provided. After the lecture, participants were asked to complete a posttest identical to the pretest and to rate their confidence in dermatopathology again on the same scale. The posttest included an additional question asking participants to rate the helpfulness of the lecture on a Likert scale ranging from 1 (not helpful at all) to 5 (extremely helpful). Participants completed the posttest within 48 hours of the lecture.

Overall, 15 learners participated in the pretest and 12 in the posttest. Of the 15 pretest participants, 3 were first-year residents and 12 were medical students. Similarly, in the posttest, 2 respondents were first-year residents and 10 were medical students. All responses contained complete pretests and posttests. The mean score on the pretest was 62%, whereas the mean score on the posttest was 75%. A paired t test indicated a statistically significant improvement (P=.017). In addition, the mean rating for confidence in dermatopathology knowledge before the lecture was 1.5 prior to the lecture and 2.6 after the lecture. A paired t test demonstrated statistical significance (P=.010). The mean rating of the helpfulness of the lecture was 4.67. The majority (91.7% [11/12]) of the participants gave a rating of 4 or 5.

Impact of the Lecture on Dermatopathology Knowledge

There is a gap in dermatopathology education early in medical training. Our introductory lecture led to higher post test scores and increased confidence in dermatopathology among medical students and dermatology residents, demonstrating the effectiveness of this kind of program in bridging this education gap. The majority of participants in our lecture said they found the session helpful. A previously published article called for early implementation of dermatology education as a whole in the medical curriculum due to lack of knowledge and confidence, and our introductory lecture may help to bridge this gap.⁸ Increasing dermatopathology content for medical students and first-year dermatology residents can expand knowledge, as shown by the increased scores on the posttest, and better supports learners transitioning to dermatology residency, where dermatopathology constitutes a large part of the overall curriculum.² More comprehensive knowledge of dermatopathology early in dermatology training also may help to better prepare residents to accurately diagnose and manage dermatologic conditions.

Pretest scores showed that the average confidence rating in dermatopathology among participants in our lecture was 1.5, which is rather low. This is consistent with prior studies that have found that residents feel that medical school inadequately prepared them for dermatology residency.^7,8 More than 87% (71/81) of medical students surveyed felt they received inadequate general dermatology training in medical school.⁹ This supports the proposed educational gap that is impacting confidence in overall dermatology knowledge, which includes dermatopathology. In our study, the average confidence rating increased by 1.1 points after the lecture, which was statistically significant (P=.010) and demonstrates that an introductory lecture serves as a feasible intervention to improve confidence in this area.

The feedback we received from participants in our lecture shows the benefits of an introductory interactive lecture with virtual dermatopathology images. Ngo et al2 highlighted how residents perceive virtual images to be superior to conventional microscopy for dermatopathology, which we utilized in our lecture. This method is not only cost effective but also provides a simple way for learners and facilitators to point out key findings on histopathology slides.²

Final Thoughts

Overall, implementing dermatopathology education early in training has a measurable impact on dermatopathology knowledge and confidence among medical students and first-year dermatology residents. An interactive lecture with virtual images similar to the one we describe here may better prepare learners for the transition to dermatology residency by addressing the educational gap in dermatopathology early in training.

THE DIAGNOSIS: Cutaneous Endometriosis

Endometriosis is the ectopic presence of endometrial tissue and occurs in approximately 13% of women of childbearing age.¹ This non-neoplastic lesion can manifest on the skin in less than 5.5% of endometriosis cases worldwide. Historically, secondary cutaneous endometriosis (CE) most frequently has been associated with prior gynecologic surgery (often cesarean section)²; however, an increased incidence of primary CE in patients without prior surgical history recently has been documented in the literature.³ While secondary CE usually manifests at the site of a surgical scar, primary CE has a predilection for the umbilicus (Villar nodule). In both primary and secondary CE, patients present clinically with a solitary nodule and abdominal pain that may be exacerbated during menstruation. Bleeding without associated pain may be more common in primary CE, while bleeding with pain may be more common in secondary CE. Cutaneous endometriosis often is overlooked given its low incidence, leading to delayed diagnosis. Primary CE often is misdiagnosed clinically as a pyogenic granuloma, Sister Mary Joseph nodule, or keloid, while secondary CE may be mistaken for a fibroma, incisional hernia, or granuloma.²

Primary and secondary CE have identical histopathologic features. Glands of variable size consisting of a single epithelial layer of columnar cells are present in the reticular dermis or subcutis (quiz image).⁴ The accompanying periglandular stroma often is uniform, consisting of spindle-shaped basophilic cells with abundant vascular structures. The stroma may contain moderate numbers of mitotic figures, a chronic inflammatory infiltrate, and extravasated red blood cells. The ectopic tissue may be inactive or display morphologic changes resembling those of the endometrium in the normal menstrual cycle.⁴ As the ectopic tissue progresses through the stages of menstruation, the glandular morphology also transforms. The proliferative stage demonstrates increased epithelial mitotic figures, the secretory stage exhibits intraluminal secretion, and during menstruation there are degenerative epithelial cells and evidence of vascular congestion. A mixture of glandular stages may be seen in biopsy results. Robust immunohistochemical expression of CD10 in the endometrial stroma can aid in diagnosis (Figure 1). Estrogen and progesterone receptor immunostaining also shows strong nuclear positivity, except in decidualized tissue.⁴ Unlike intestinal glands, endometrial glands do not express CDX2 or CK20.⁵ Complete surgical excision of CE usually is curative; however, recurrence has been documented in 10% (3/30) of cases.²

Breast carcinoma is the most common internal malignancy associated with cutaneous metastasis and may develop prior to visceral diagnosis. It is possible that tumor cells travel through the communicating networks of the cutaneous lymphatic ducts and the mammary lymphatic plexus; however, cutaneous manifestation often is located on the ipsilateral breast, and therefore tumor expansion rather than true metastasis cannot always be ruled out. On histopathology, findings of breast adenocarcinoma include tumor cells that tend to show either interstitial, nodular, mixed, or intravascular growth patterns (Figure 2). Tumor cells may invade the stroma in clusters or as individual cells. Sites of distant metastasis may show an increased likelihood of vascular and lymphatic invasion.⁶

Nodular hidradenoma often manifests as a solitary nodule in the head or neck region, predominantly in women.⁷ Pathology shows well-demarcated intradermal aggregates of tumor cells within a hyalinized stroma; connection to the epidermis is not a feature of nodular hidradenoma. The epithelial component consists of polygonal cells with eosinophilic to amphophilic cytoplasm as well as large glycogenated cells with pale to clear cytoplasm (leading to the alternative term clear cell hidradenoma)(Figure 3). The cystic portion represents deterioration of tumor cells. Surgical excision usually is curative, although lesions may recur. Malignant transformation is rare.⁷

Sister Mary Joseph nodule is a cutaneous involvement of the umbilicus by a metastatic malignancy, often from an intra-abdominal primary malignancy (most commonly ovarian carcinoma in women and colonic carcinoma in men). Clinically, patients present with a solitary firm nodule or plaque within the umbilicus.^8,9 Histopathology recapitulates the primary tumor (Figure 4).⁹ Sister Mary Joseph nodule portends a poor prognosis, with a survival rate of less than 8 months from the time of diagnosis.¹⁰

Urachal duct cyst develops from a remnant of the urachus that closed appropriately at the umbilicus and bladder but did not completely regress. It may manifest as an extraperitoneal mass at the umbilicus. Clinically, urachal duct cysts may be asymptomatic until an inciting event (eg, inflammation, deposition of calculus, or malignancy) occurs.¹¹ Histopathology shows cystically dilated structures lined with a transitional epithelium (Figure 5).¹² Urachal duct cysts usually are diagnosed in children or young adults and subsequently are excised.¹¹

THE DIAGNOSIS: Cutaneous Endometriosis

Endometriosis is the ectopic presence of endometrial tissue and occurs in approximately 13% of women of childbearing age.¹ This non-neoplastic lesion can manifest on the skin in less than 5.5% of endometriosis cases worldwide. Historically, secondary cutaneous endometriosis (CE) most frequently has been associated with prior gynecologic surgery (often cesarean section)²; however, an increased incidence of primary CE in patients without prior surgical history recently has been documented in the literature.³ While secondary CE usually manifests at the site of a surgical scar, primary CE has a predilection for the umbilicus (Villar nodule). In both primary and secondary CE, patients present clinically with a solitary nodule and abdominal pain that may be exacerbated during menstruation. Bleeding without associated pain may be more common in primary CE, while bleeding with pain may be more common in secondary CE. Cutaneous endometriosis often is overlooked given its low incidence, leading to delayed diagnosis. Primary CE often is misdiagnosed clinically as a pyogenic granuloma, Sister Mary Joseph nodule, or keloid, while secondary CE may be mistaken for a fibroma, incisional hernia, or granuloma.²

Primary and secondary CE have identical histopathologic features. Glands of variable size consisting of a single epithelial layer of columnar cells are present in the reticular dermis or subcutis (quiz image).⁴ The accompanying periglandular stroma often is uniform, consisting of spindle-shaped basophilic cells with abundant vascular structures. The stroma may contain moderate numbers of mitotic figures, a chronic inflammatory infiltrate, and extravasated red blood cells. The ectopic tissue may be inactive or display morphologic changes resembling those of the endometrium in the normal menstrual cycle.⁴ As the ectopic tissue progresses through the stages of menstruation, the glandular morphology also transforms. The proliferative stage demonstrates increased epithelial mitotic figures, the secretory stage exhibits intraluminal secretion, and during menstruation there are degenerative epithelial cells and evidence of vascular congestion. A mixture of glandular stages may be seen in biopsy results. Robust immunohistochemical expression of CD10 in the endometrial stroma can aid in diagnosis (Figure 1). Estrogen and progesterone receptor immunostaining also shows strong nuclear positivity, except in decidualized tissue.⁴ Unlike intestinal glands, endometrial glands do not express CDX2 or CK20.⁵ Complete surgical excision of CE usually is curative; however, recurrence has been documented in 10% (3/30) of cases.²

Breast carcinoma is the most common internal malignancy associated with cutaneous metastasis and may develop prior to visceral diagnosis. It is possible that tumor cells travel through the communicating networks of the cutaneous lymphatic ducts and the mammary lymphatic plexus; however, cutaneous manifestation often is located on the ipsilateral breast, and therefore tumor expansion rather than true metastasis cannot always be ruled out. On histopathology, findings of breast adenocarcinoma include tumor cells that tend to show either interstitial, nodular, mixed, or intravascular growth patterns (Figure 2). Tumor cells may invade the stroma in clusters or as individual cells. Sites of distant metastasis may show an increased likelihood of vascular and lymphatic invasion.⁶

Nodular hidradenoma often manifests as a solitary nodule in the head or neck region, predominantly in women.⁷ Pathology shows well-demarcated intradermal aggregates of tumor cells within a hyalinized stroma; connection to the epidermis is not a feature of nodular hidradenoma. The epithelial component consists of polygonal cells with eosinophilic to amphophilic cytoplasm as well as large glycogenated cells with pale to clear cytoplasm (leading to the alternative term clear cell hidradenoma)(Figure 3). The cystic portion represents deterioration of tumor cells. Surgical excision usually is curative, although lesions may recur. Malignant transformation is rare.⁷

Sister Mary Joseph nodule is a cutaneous involvement of the umbilicus by a metastatic malignancy, often from an intra-abdominal primary malignancy (most commonly ovarian carcinoma in women and colonic carcinoma in men). Clinically, patients present with a solitary firm nodule or plaque within the umbilicus.^8,9 Histopathology recapitulates the primary tumor (Figure 4).⁹ Sister Mary Joseph nodule portends a poor prognosis, with a survival rate of less than 8 months from the time of diagnosis.¹⁰

Urachal duct cyst develops from a remnant of the urachus that closed appropriately at the umbilicus and bladder but did not completely regress. It may manifest as an extraperitoneal mass at the umbilicus. Clinically, urachal duct cysts may be asymptomatic until an inciting event (eg, inflammation, deposition of calculus, or malignancy) occurs.¹¹ Histopathology shows cystically dilated structures lined with a transitional epithelium (Figure 5).¹² Urachal duct cysts usually are diagnosed in children or young adults and subsequently are excised.¹¹

THE DIAGNOSIS: Cutaneous Endometriosis

Endometriosis is the ectopic presence of endometrial tissue and occurs in approximately 13% of women of childbearing age.¹ This non-neoplastic lesion can manifest on the skin in less than 5.5% of endometriosis cases worldwide. Historically, secondary cutaneous endometriosis (CE) most frequently has been associated with prior gynecologic surgery (often cesarean section)²; however, an increased incidence of primary CE in patients without prior surgical history recently has been documented in the literature.³ While secondary CE usually manifests at the site of a surgical scar, primary CE has a predilection for the umbilicus (Villar nodule). In both primary and secondary CE, patients present clinically with a solitary nodule and abdominal pain that may be exacerbated during menstruation. Bleeding without associated pain may be more common in primary CE, while bleeding with pain may be more common in secondary CE. Cutaneous endometriosis often is overlooked given its low incidence, leading to delayed diagnosis. Primary CE often is misdiagnosed clinically as a pyogenic granuloma, Sister Mary Joseph nodule, or keloid, while secondary CE may be mistaken for a fibroma, incisional hernia, or granuloma.²

Primary and secondary CE have identical histopathologic features. Glands of variable size consisting of a single epithelial layer of columnar cells are present in the reticular dermis or subcutis (quiz image).⁴ The accompanying periglandular stroma often is uniform, consisting of spindle-shaped basophilic cells with abundant vascular structures. The stroma may contain moderate numbers of mitotic figures, a chronic inflammatory infiltrate, and extravasated red blood cells. The ectopic tissue may be inactive or display morphologic changes resembling those of the endometrium in the normal menstrual cycle.⁴ As the ectopic tissue progresses through the stages of menstruation, the glandular morphology also transforms. The proliferative stage demonstrates increased epithelial mitotic figures, the secretory stage exhibits intraluminal secretion, and during menstruation there are degenerative epithelial cells and evidence of vascular congestion. A mixture of glandular stages may be seen in biopsy results. Robust immunohistochemical expression of CD10 in the endometrial stroma can aid in diagnosis (Figure 1). Estrogen and progesterone receptor immunostaining also shows strong nuclear positivity, except in decidualized tissue.⁴ Unlike intestinal glands, endometrial glands do not express CDX2 or CK20.⁵ Complete surgical excision of CE usually is curative; however, recurrence has been documented in 10% (3/30) of cases.²

Breast carcinoma is the most common internal malignancy associated with cutaneous metastasis and may develop prior to visceral diagnosis. It is possible that tumor cells travel through the communicating networks of the cutaneous lymphatic ducts and the mammary lymphatic plexus; however, cutaneous manifestation often is located on the ipsilateral breast, and therefore tumor expansion rather than true metastasis cannot always be ruled out. On histopathology, findings of breast adenocarcinoma include tumor cells that tend to show either interstitial, nodular, mixed, or intravascular growth patterns (Figure 2). Tumor cells may invade the stroma in clusters or as individual cells. Sites of distant metastasis may show an increased likelihood of vascular and lymphatic invasion.⁶

Nodular hidradenoma often manifests as a solitary nodule in the head or neck region, predominantly in women.⁷ Pathology shows well-demarcated intradermal aggregates of tumor cells within a hyalinized stroma; connection to the epidermis is not a feature of nodular hidradenoma. The epithelial component consists of polygonal cells with eosinophilic to amphophilic cytoplasm as well as large glycogenated cells with pale to clear cytoplasm (leading to the alternative term clear cell hidradenoma)(Figure 3). The cystic portion represents deterioration of tumor cells. Surgical excision usually is curative, although lesions may recur. Malignant transformation is rare.⁷

Sister Mary Joseph nodule is a cutaneous involvement of the umbilicus by a metastatic malignancy, often from an intra-abdominal primary malignancy (most commonly ovarian carcinoma in women and colonic carcinoma in men). Clinically, patients present with a solitary firm nodule or plaque within the umbilicus.^8,9 Histopathology recapitulates the primary tumor (Figure 4).⁹ Sister Mary Joseph nodule portends a poor prognosis, with a survival rate of less than 8 months from the time of diagnosis.¹⁰

Urachal duct cyst develops from a remnant of the urachus that closed appropriately at the umbilicus and bladder but did not completely regress. It may manifest as an extraperitoneal mass at the umbilicus. Clinically, urachal duct cysts may be asymptomatic until an inciting event (eg, inflammation, deposition of calculus, or malignancy) occurs.¹¹ Histopathology shows cystically dilated structures lined with a transitional epithelium (Figure 5).¹² Urachal duct cysts usually are diagnosed in children or young adults and subsequently are excised.¹¹

Alpha-gal syndrome (AGS), a tickborne disease commonly called “red meat allergy,” is a serious, potentially life-threatening allergy to the carbohydrate alpha-gal. The alpha-gal carbohydrate is found in most mammals, though it is not in humans, apes, or old-world monkeys. People with AGS can have allergic reactions when they consume mammalian meat, dairy products, or other products derived from mammals. People often live with this disease for years before receiving a correct diagnosis, greatly impacting their quality of life. The number of suspected cases is also rising. 

More than 110,000 suspected AGS cases were identified between 2010 and 2022, according to a Centers for Disease Control and Prevention (CDC) report.¹ However, because the diagnosis requires a positive test and a clinical exam and some people may not get tested, as many as 450,000 people might be affected by AGS in the United States. Additionally, a CDC survey found that nearly half (42%) of US healthcare providers had never heard of AGS.² Among those who had, less than one third (29%) knew how to diagnose the condition. 

Here are 5 things clinicians need to know about AGS.

 

1. People can develop AGS after being bitten by a tick, primarily the lone star tick (Amblyomma americanum), in the United States.

In the United States, AGS is primarily associated with the bite of a lone star tick, but other kinds of ticks have not been ruled out. The majority of suspected AGS cases in the United States were reported in parts of Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, Tennessee, and Virginia. The lone star tick is widely distributed with established populations in Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia. 

While AGS is associated with tick bites, more research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. Anyone can develop AGS, but most cases have been reported in adults. 

Know how to recognize the symptoms of AGS and be prepared to test, diagnose, and manage AGS, particularly in states where lone star ticks are found. 

 

2. Tick bites are only one risk factor for developing AGS. 

Many people are bitten by lone star ticks and will never develop AGS. Scientists are exploring the connection between other risk factors and developing AGS. A recent study has shown that people diagnosed with AGS may be more likely to have a family member who was also diagnosed with AGS, have another food allergy, have an allergy to stinging or biting insects, or have A or O blood types.³ 

Research has also shown that environmental risk factors could contribute to developing AGS,⁴ like living in an area with lone star ticks, remembering finding a tick on themselves, recalling multiple tick bites, living near a wooded forest, spending more time outside, or living in areas with deer, such as larger properties, wooded forests, and properties with shrubs and brush. 

Ask your patient questions about other allergies and history of recent tick bites or outdoor exposure to help determine if testing for AGS is appropriate.

 

3. Symptoms of AGS are consistently inconsistent.

There is a spectrum of how sensitive AGS patients are to alpha-gal, and reactions are often different from person to person, which can make it difficult to diagnose. The first allergic reaction to AGS typically occurs between 1-6 months after a tick bite. Symptoms commonly appear 2-6 hours after being in contact with products containing alpha-gal, like red meat (beef, pork, lamb, venison, rabbit, or other meat from mammals), dairy, and some medications. Symptoms can range from mild to severe and include hives or itchy rash; swelling of the lips, throat, tongue, or eyelids; gastrointestinal symptoms such as nausea, vomiting, or diarrhea; heartburn or indigestion; cough, shortness of breath, or difficulty breathing; dizziness or a drop in blood pressure; or anaphylaxis.

Consider AGS if a patient reports waking up in the middle of the night with allergic symptoms after eating alpha-gal containing products for dinner, if allergic reactions are delayed, or if a patient has anaphylaxis of unknown cause, adult-onset allergy, or allergic symptoms and reports a recent tick bite. 

 

4. Diagnosing AGS requires a combination of a blood test and a physical exam.

Diagnosing AGS requires a detailed patient history, physical exam, and a blood test to detect specific immunoglobulin E (IgE) antibodies specific to alpha-gal (alpha-gal sIgE). Tests for alpha-gal sIgE antibodies are available at several large commercial laboratories and some academic institutions. Skin tests to identify reactions to allergens like pork or beef may also be used to inform AGS diagnosis. However, a positive alpha-gal sIgE test or skin test does not mean a person has AGS. Many people, particularly those who live in regions with lone star ticks, have positive alpha-gal specific IgE tests without having AGS. 

Consider the test results along with your patient’s symptoms and risk factors.

 

5. There is no treatment for AGS, but people can take prevention steps and AGS can be managed.

People can protect themselves and their family from AGS by preventing tick bites. Encourage your patients to use an Environmental Protection Agency–registered insect repellent outdoors, wear permethrin-treated clothing, and conduct thorough tick checks after outdoor activities. 

Once a person is no longer exposed to alpha-gal containing products, they should no longer experience symptoms. People with AGS should also proactively prevent tick bites. Tick bites can trigger or reactivate AGS.

For patients who have AGS, help manage their symptoms and identify alpha-gal containing products to avoid.

Dr. Kersh is Chief of the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and disclosed no relevant conflicts of interest.

CDC resources:

About Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Testing and Diagnosis for Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Resources | Alpha-gal Syndrome | CDC 

References 

Thompson JM et al. MMWR Morb Mortal Wkly Rep. 2023;72:815-820. 

Carpenter A et al. MMWR Morb Mortal Wkly Rep. 2023;72:809-814. Taylor ML et al. Ann Allergy, Asthma & Immunol. 2024 Jun;132(6):759.e2-764.e2. Kersh GJ et al. Ann Allergy, Asthma & Immunol. 2023 Apr;130(4):472-478.

Alpha-gal syndrome (AGS), a tickborne disease commonly called “red meat allergy,” is a serious, potentially life-threatening allergy to the carbohydrate alpha-gal. The alpha-gal carbohydrate is found in most mammals, though it is not in humans, apes, or old-world monkeys. People with AGS can have allergic reactions when they consume mammalian meat, dairy products, or other products derived from mammals. People often live with this disease for years before receiving a correct diagnosis, greatly impacting their quality of life. The number of suspected cases is also rising. 

More than 110,000 suspected AGS cases were identified between 2010 and 2022, according to a Centers for Disease Control and Prevention (CDC) report.¹ However, because the diagnosis requires a positive test and a clinical exam and some people may not get tested, as many as 450,000 people might be affected by AGS in the United States. Additionally, a CDC survey found that nearly half (42%) of US healthcare providers had never heard of AGS.² Among those who had, less than one third (29%) knew how to diagnose the condition. 

Here are 5 things clinicians need to know about AGS.

 

1. People can develop AGS after being bitten by a tick, primarily the lone star tick (Amblyomma americanum), in the United States.

In the United States, AGS is primarily associated with the bite of a lone star tick, but other kinds of ticks have not been ruled out. The majority of suspected AGS cases in the United States were reported in parts of Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, Tennessee, and Virginia. The lone star tick is widely distributed with established populations in Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia. 

While AGS is associated with tick bites, more research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. Anyone can develop AGS, but most cases have been reported in adults. 

Know how to recognize the symptoms of AGS and be prepared to test, diagnose, and manage AGS, particularly in states where lone star ticks are found. 

 

2. Tick bites are only one risk factor for developing AGS. 

Many people are bitten by lone star ticks and will never develop AGS. Scientists are exploring the connection between other risk factors and developing AGS. A recent study has shown that people diagnosed with AGS may be more likely to have a family member who was also diagnosed with AGS, have another food allergy, have an allergy to stinging or biting insects, or have A or O blood types.³ 

Research has also shown that environmental risk factors could contribute to developing AGS,⁴ like living in an area with lone star ticks, remembering finding a tick on themselves, recalling multiple tick bites, living near a wooded forest, spending more time outside, or living in areas with deer, such as larger properties, wooded forests, and properties with shrubs and brush. 

Ask your patient questions about other allergies and history of recent tick bites or outdoor exposure to help determine if testing for AGS is appropriate.

 

3. Symptoms of AGS are consistently inconsistent.

There is a spectrum of how sensitive AGS patients are to alpha-gal, and reactions are often different from person to person, which can make it difficult to diagnose. The first allergic reaction to AGS typically occurs between 1-6 months after a tick bite. Symptoms commonly appear 2-6 hours after being in contact with products containing alpha-gal, like red meat (beef, pork, lamb, venison, rabbit, or other meat from mammals), dairy, and some medications. Symptoms can range from mild to severe and include hives or itchy rash; swelling of the lips, throat, tongue, or eyelids; gastrointestinal symptoms such as nausea, vomiting, or diarrhea; heartburn or indigestion; cough, shortness of breath, or difficulty breathing; dizziness or a drop in blood pressure; or anaphylaxis.

Consider AGS if a patient reports waking up in the middle of the night with allergic symptoms after eating alpha-gal containing products for dinner, if allergic reactions are delayed, or if a patient has anaphylaxis of unknown cause, adult-onset allergy, or allergic symptoms and reports a recent tick bite. 

 

4. Diagnosing AGS requires a combination of a blood test and a physical exam.

Diagnosing AGS requires a detailed patient history, physical exam, and a blood test to detect specific immunoglobulin E (IgE) antibodies specific to alpha-gal (alpha-gal sIgE). Tests for alpha-gal sIgE antibodies are available at several large commercial laboratories and some academic institutions. Skin tests to identify reactions to allergens like pork or beef may also be used to inform AGS diagnosis. However, a positive alpha-gal sIgE test or skin test does not mean a person has AGS. Many people, particularly those who live in regions with lone star ticks, have positive alpha-gal specific IgE tests without having AGS. 

Consider the test results along with your patient’s symptoms and risk factors.

 

5. There is no treatment for AGS, but people can take prevention steps and AGS can be managed.

People can protect themselves and their family from AGS by preventing tick bites. Encourage your patients to use an Environmental Protection Agency–registered insect repellent outdoors, wear permethrin-treated clothing, and conduct thorough tick checks after outdoor activities. 

Once a person is no longer exposed to alpha-gal containing products, they should no longer experience symptoms. People with AGS should also proactively prevent tick bites. Tick bites can trigger or reactivate AGS.

For patients who have AGS, help manage their symptoms and identify alpha-gal containing products to avoid.

Dr. Kersh is Chief of the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and disclosed no relevant conflicts of interest.

CDC resources:

About Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Testing and Diagnosis for Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Resources | Alpha-gal Syndrome | CDC 

References 

Thompson JM et al. MMWR Morb Mortal Wkly Rep. 2023;72:815-820. 

Carpenter A et al. MMWR Morb Mortal Wkly Rep. 2023;72:809-814. Taylor ML et al. Ann Allergy, Asthma & Immunol. 2024 Jun;132(6):759.e2-764.e2. Kersh GJ et al. Ann Allergy, Asthma & Immunol. 2023 Apr;130(4):472-478.

Alpha-gal syndrome (AGS), a tickborne disease commonly called “red meat allergy,” is a serious, potentially life-threatening allergy to the carbohydrate alpha-gal. The alpha-gal carbohydrate is found in most mammals, though it is not in humans, apes, or old-world monkeys. People with AGS can have allergic reactions when they consume mammalian meat, dairy products, or other products derived from mammals. People often live with this disease for years before receiving a correct diagnosis, greatly impacting their quality of life. The number of suspected cases is also rising. 

More than 110,000 suspected AGS cases were identified between 2010 and 2022, according to a Centers for Disease Control and Prevention (CDC) report.¹ However, because the diagnosis requires a positive test and a clinical exam and some people may not get tested, as many as 450,000 people might be affected by AGS in the United States. Additionally, a CDC survey found that nearly half (42%) of US healthcare providers had never heard of AGS.² Among those who had, less than one third (29%) knew how to diagnose the condition. 

Here are 5 things clinicians need to know about AGS.

 

1. People can develop AGS after being bitten by a tick, primarily the lone star tick (Amblyomma americanum), in the United States.

In the United States, AGS is primarily associated with the bite of a lone star tick, but other kinds of ticks have not been ruled out. The majority of suspected AGS cases in the United States were reported in parts of Arkansas, Delaware, Illinois, Indiana, Kansas, Kentucky, Maryland, Mississippi, Missouri, North Carolina, Oklahoma, Tennessee, and Virginia. The lone star tick is widely distributed with established populations in Alabama, Arkansas, Connecticut, Delaware, Florida, Georgia, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New York, North Carolina, Ohio, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia, and West Virginia. 

While AGS is associated with tick bites, more research is needed to understand the role ticks play in starting this condition, and why certain people develop AGS. Anyone can develop AGS, but most cases have been reported in adults. 

Know how to recognize the symptoms of AGS and be prepared to test, diagnose, and manage AGS, particularly in states where lone star ticks are found. 

 

2. Tick bites are only one risk factor for developing AGS. 

Many people are bitten by lone star ticks and will never develop AGS. Scientists are exploring the connection between other risk factors and developing AGS. A recent study has shown that people diagnosed with AGS may be more likely to have a family member who was also diagnosed with AGS, have another food allergy, have an allergy to stinging or biting insects, or have A or O blood types.³ 

Research has also shown that environmental risk factors could contribute to developing AGS,⁴ like living in an area with lone star ticks, remembering finding a tick on themselves, recalling multiple tick bites, living near a wooded forest, spending more time outside, or living in areas with deer, such as larger properties, wooded forests, and properties with shrubs and brush. 

Ask your patient questions about other allergies and history of recent tick bites or outdoor exposure to help determine if testing for AGS is appropriate.

 

3. Symptoms of AGS are consistently inconsistent.

There is a spectrum of how sensitive AGS patients are to alpha-gal, and reactions are often different from person to person, which can make it difficult to diagnose. The first allergic reaction to AGS typically occurs between 1-6 months after a tick bite. Symptoms commonly appear 2-6 hours after being in contact with products containing alpha-gal, like red meat (beef, pork, lamb, venison, rabbit, or other meat from mammals), dairy, and some medications. Symptoms can range from mild to severe and include hives or itchy rash; swelling of the lips, throat, tongue, or eyelids; gastrointestinal symptoms such as nausea, vomiting, or diarrhea; heartburn or indigestion; cough, shortness of breath, or difficulty breathing; dizziness or a drop in blood pressure; or anaphylaxis.

Consider AGS if a patient reports waking up in the middle of the night with allergic symptoms after eating alpha-gal containing products for dinner, if allergic reactions are delayed, or if a patient has anaphylaxis of unknown cause, adult-onset allergy, or allergic symptoms and reports a recent tick bite. 

 

4. Diagnosing AGS requires a combination of a blood test and a physical exam.

Diagnosing AGS requires a detailed patient history, physical exam, and a blood test to detect specific immunoglobulin E (IgE) antibodies specific to alpha-gal (alpha-gal sIgE). Tests for alpha-gal sIgE antibodies are available at several large commercial laboratories and some academic institutions. Skin tests to identify reactions to allergens like pork or beef may also be used to inform AGS diagnosis. However, a positive alpha-gal sIgE test or skin test does not mean a person has AGS. Many people, particularly those who live in regions with lone star ticks, have positive alpha-gal specific IgE tests without having AGS. 

Consider the test results along with your patient’s symptoms and risk factors.

 

5. There is no treatment for AGS, but people can take prevention steps and AGS can be managed.

People can protect themselves and their family from AGS by preventing tick bites. Encourage your patients to use an Environmental Protection Agency–registered insect repellent outdoors, wear permethrin-treated clothing, and conduct thorough tick checks after outdoor activities. 

Once a person is no longer exposed to alpha-gal containing products, they should no longer experience symptoms. People with AGS should also proactively prevent tick bites. Tick bites can trigger or reactivate AGS.

For patients who have AGS, help manage their symptoms and identify alpha-gal containing products to avoid.

Dr. Kersh is Chief of the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and disclosed no relevant conflicts of interest.

CDC resources:

About Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Testing and Diagnosis for Alpha-gal Syndrome | Alpha-gal Syndrome | CDC 

Clinical Resources | Alpha-gal Syndrome | CDC 

References 

Thompson JM et al. MMWR Morb Mortal Wkly Rep. 2023;72:815-820. 

Carpenter A et al. MMWR Morb Mortal Wkly Rep. 2023;72:809-814. Taylor ML et al. Ann Allergy, Asthma & Immunol. 2024 Jun;132(6):759.e2-764.e2. Kersh GJ et al. Ann Allergy, Asthma & Immunol. 2023 Apr;130(4):472-478.

NEW YORK, NY — Work over the past several years has reframed hidradenitis suppurativa (HS) as a large-field inflammatory process, a recharacterization that has immediate relevance to treatment strategies and goals, according to two investigators intimately involved in much of the recent progress.

“Success is being achieved by targeting multiple inflammatory axes in HS, and therapeutics are evolving rapidly,” reported James G. Krueger, MD, PhD, head of the Laboratory of Investigative Dermatology, Rockefeller University, New York, NY.

The activity of targeted anti-inflammatory therapies — bimekizumab just joined adalimumab and secukinumab as a third approved biologic for HS — is not news, but the degree to which inflammation is upregulated systemically, not just at areas of skin involvement, has changed the conceptualization of HS.

HS Is a Systemic Inflammatory Disease

Relative to psoriasis, for which there are many parallels, “HS is hugely more inflammatory in the systemic circulation,” Krueger said at the 27th Annual Winter Symposium — Advances in Medical and Surgical Dermatology (MSWS) 2024. Yet, HS is also more complex involving additional pathways that appear to include dysbiosis. The concept of follicular occlusion, once a common explanation for HS, has been left far behind.

“Unlike psoriasis, which we can treat really well by inhibiting a single pathway target, HS is just not that simple,” Krueger said. Although largely an inflammatory process, the cascade of inflammatory factors for specific manifestations, such as tunnels, means that optimal therapy in one case might have little benefit in another.

The relatively new evidence that HS activity is not confined to lesional skin might be the most important recent step toward new strategies to target disease. These studies were performed by Kristina Navrazhina, MD, PhD, now a resident in dermatology at the Icahn School of Medicine at Mount Sinai, New York. She received her PhD while studying HS activity in non-lesional skin. Her work has led her to conclude that the best chance for better outcomes in HS is early diagnosis and treatment. Although this is generally true of any pathology, the changes in the HS phenotype once fistulae form includes a poor response to conventional therapies. 

In fact, based on her work in evaluating HS activity in non-lesional skin, Navrazhina has shown that “many patients with modest lesions already have advanced disease.” Consistent with the premise that HS is a deeply systemic inflammatory process, nodules, considered an early manifestation, turn out to be “the tip of the iceberg.”

 

Non-Lesional HS Skin Is Inflamed

When she has employed RNA sequencing based on tape strip sampling from completely normal skin away from nodules, interleukin (IL)-17 and a broad array of other inflammatory markers were found to be upregulated. When she performed ultrasound to look for disease activity under the normal skin, she has often found tunnels already formed. Doppler ultrasound showed some of these tunnels were actively draining.

This might provide a partial explanation for why therapies are not always effective even when clinical signs of disease are modest. 

“Are we missing the opportunity for intervening?” Navrazhina asked, noting that early intervention has been limited traditionally by extremely long diagnostic delays. Citing the literature, Navrazhina said the average delay is 7 years for HS versus 1 year for psoriasis. Patients often cycle through 3 or 4 providers before the diagnosis is made, she said.

Awakening first-line clinicians to the signs and symptoms of HS, whether in the emergency room or primary care, is a critical message because of the incrementally difficult task to control disease once fistulae have formed. 

Krueger made the same appeal. For the neutrophilic inflammation that characterizes nodules, targeted therapies are often effective, but he agreed that available therapies are generally far less so once tunnels form.

 

Role Seen for Bacteria in HS Pathogenesis

One reason might be an interaction between anaerobic bacteria and the keratinocytes that form the tunnel walls, according to Krueger. Although HS is not typically considered an infectious disease, he reported that the interaction of these bacteria with keratinocytes is associated with expression of approximately 1000 inflammatory gene products. The process of tunnel formation is traced to how factors recruited by upregulated inflammation, such as chemokines, coordinate.

He described recent work pursing novel strategies such as highly targeted antibiotics or inhibitors of complement factor C5a, which has been proposed as a biomarker for HS, to intervene in preventing or reversing HS tunnels. 

While this work progresses, one of the most Important unmet needs in HS is an accepted measure of clinically meaningful improvement in advanced disease, particularly the impact of therapy on HS tunnels, according to Krueger. 

“There is no measure of tunnel activity that the FDA accepts in evaluating drugs,” he noted, which will be essential for approving therapies that offer this benefit. 

A phase 3 trials program for one of the promising drugs, sonelokimab, was announced early in 2024. A nanobody that targets IL-17A/A, IL-17A/F, and IL-17F/F, the small size of this molecule permits exceptional tissue penetration while the broad anti-IL-17 activity has a high degree of theoretical potential in late-stage HS, according to Krueger. 

There are numerous pieces of the HS puzzle that are still missing, but both Krueger and Navrazhina are enthusiastic about new targets and opportunities for disease control that are stemming from a better understanding of the underlying pathophysiology. Not least, both indicated that testing for inflammatory phenotypes will allow for individualized therapeutic choices with a maximum likelihood of response, particularly if earlier diagnosis permits earlier treatment. 

“Due to the heterogeneity of HS, it is hard to know who will respond to which treatment or which treatment should be started first,” Navrazhina said. She thinks that early measures of the inflammatory profile in nodules or even non-lesional skin might provide that guidance. 

Both Krueger and Navrazhina reported no financial relationships relevant to this work. 

 

A version of this article appeared on Medscape.com.

NEW YORK, NY — Work over the past several years has reframed hidradenitis suppurativa (HS) as a large-field inflammatory process, a recharacterization that has immediate relevance to treatment strategies and goals, according to two investigators intimately involved in much of the recent progress.

“Success is being achieved by targeting multiple inflammatory axes in HS, and therapeutics are evolving rapidly,” reported James G. Krueger, MD, PhD, head of the Laboratory of Investigative Dermatology, Rockefeller University, New York, NY.

The activity of targeted anti-inflammatory therapies — bimekizumab just joined adalimumab and secukinumab as a third approved biologic for HS — is not news, but the degree to which inflammation is upregulated systemically, not just at areas of skin involvement, has changed the conceptualization of HS.

HS Is a Systemic Inflammatory Disease

Relative to psoriasis, for which there are many parallels, “HS is hugely more inflammatory in the systemic circulation,” Krueger said at the 27th Annual Winter Symposium — Advances in Medical and Surgical Dermatology (MSWS) 2024. Yet, HS is also more complex involving additional pathways that appear to include dysbiosis. The concept of follicular occlusion, once a common explanation for HS, has been left far behind.

“Unlike psoriasis, which we can treat really well by inhibiting a single pathway target, HS is just not that simple,” Krueger said. Although largely an inflammatory process, the cascade of inflammatory factors for specific manifestations, such as tunnels, means that optimal therapy in one case might have little benefit in another.

The relatively new evidence that HS activity is not confined to lesional skin might be the most important recent step toward new strategies to target disease. These studies were performed by Kristina Navrazhina, MD, PhD, now a resident in dermatology at the Icahn School of Medicine at Mount Sinai, New York. She received her PhD while studying HS activity in non-lesional skin. Her work has led her to conclude that the best chance for better outcomes in HS is early diagnosis and treatment. Although this is generally true of any pathology, the changes in the HS phenotype once fistulae form includes a poor response to conventional therapies. 

In fact, based on her work in evaluating HS activity in non-lesional skin, Navrazhina has shown that “many patients with modest lesions already have advanced disease.” Consistent with the premise that HS is a deeply systemic inflammatory process, nodules, considered an early manifestation, turn out to be “the tip of the iceberg.”

 

Non-Lesional HS Skin Is Inflamed

When she has employed RNA sequencing based on tape strip sampling from completely normal skin away from nodules, interleukin (IL)-17 and a broad array of other inflammatory markers were found to be upregulated. When she performed ultrasound to look for disease activity under the normal skin, she has often found tunnels already formed. Doppler ultrasound showed some of these tunnels were actively draining.

This might provide a partial explanation for why therapies are not always effective even when clinical signs of disease are modest. 

“Are we missing the opportunity for intervening?” Navrazhina asked, noting that early intervention has been limited traditionally by extremely long diagnostic delays. Citing the literature, Navrazhina said the average delay is 7 years for HS versus 1 year for psoriasis. Patients often cycle through 3 or 4 providers before the diagnosis is made, she said.

Awakening first-line clinicians to the signs and symptoms of HS, whether in the emergency room or primary care, is a critical message because of the incrementally difficult task to control disease once fistulae have formed. 

Krueger made the same appeal. For the neutrophilic inflammation that characterizes nodules, targeted therapies are often effective, but he agreed that available therapies are generally far less so once tunnels form.

 

Role Seen for Bacteria in HS Pathogenesis

One reason might be an interaction between anaerobic bacteria and the keratinocytes that form the tunnel walls, according to Krueger. Although HS is not typically considered an infectious disease, he reported that the interaction of these bacteria with keratinocytes is associated with expression of approximately 1000 inflammatory gene products. The process of tunnel formation is traced to how factors recruited by upregulated inflammation, such as chemokines, coordinate.

He described recent work pursing novel strategies such as highly targeted antibiotics or inhibitors of complement factor C5a, which has been proposed as a biomarker for HS, to intervene in preventing or reversing HS tunnels. 

While this work progresses, one of the most Important unmet needs in HS is an accepted measure of clinically meaningful improvement in advanced disease, particularly the impact of therapy on HS tunnels, according to Krueger. 

“There is no measure of tunnel activity that the FDA accepts in evaluating drugs,” he noted, which will be essential for approving therapies that offer this benefit. 

A phase 3 trials program for one of the promising drugs, sonelokimab, was announced early in 2024. A nanobody that targets IL-17A/A, IL-17A/F, and IL-17F/F, the small size of this molecule permits exceptional tissue penetration while the broad anti-IL-17 activity has a high degree of theoretical potential in late-stage HS, according to Krueger. 

There are numerous pieces of the HS puzzle that are still missing, but both Krueger and Navrazhina are enthusiastic about new targets and opportunities for disease control that are stemming from a better understanding of the underlying pathophysiology. Not least, both indicated that testing for inflammatory phenotypes will allow for individualized therapeutic choices with a maximum likelihood of response, particularly if earlier diagnosis permits earlier treatment. 

“Due to the heterogeneity of HS, it is hard to know who will respond to which treatment or which treatment should be started first,” Navrazhina said. She thinks that early measures of the inflammatory profile in nodules or even non-lesional skin might provide that guidance. 

Both Krueger and Navrazhina reported no financial relationships relevant to this work. 

 

A version of this article appeared on Medscape.com.

NEW YORK, NY — Work over the past several years has reframed hidradenitis suppurativa (HS) as a large-field inflammatory process, a recharacterization that has immediate relevance to treatment strategies and goals, according to two investigators intimately involved in much of the recent progress.

“Success is being achieved by targeting multiple inflammatory axes in HS, and therapeutics are evolving rapidly,” reported James G. Krueger, MD, PhD, head of the Laboratory of Investigative Dermatology, Rockefeller University, New York, NY.

The activity of targeted anti-inflammatory therapies — bimekizumab just joined adalimumab and secukinumab as a third approved biologic for HS — is not news, but the degree to which inflammation is upregulated systemically, not just at areas of skin involvement, has changed the conceptualization of HS.

HS Is a Systemic Inflammatory Disease

Relative to psoriasis, for which there are many parallels, “HS is hugely more inflammatory in the systemic circulation,” Krueger said at the 27th Annual Winter Symposium — Advances in Medical and Surgical Dermatology (MSWS) 2024. Yet, HS is also more complex involving additional pathways that appear to include dysbiosis. The concept of follicular occlusion, once a common explanation for HS, has been left far behind.

“Unlike psoriasis, which we can treat really well by inhibiting a single pathway target, HS is just not that simple,” Krueger said. Although largely an inflammatory process, the cascade of inflammatory factors for specific manifestations, such as tunnels, means that optimal therapy in one case might have little benefit in another.

The relatively new evidence that HS activity is not confined to lesional skin might be the most important recent step toward new strategies to target disease. These studies were performed by Kristina Navrazhina, MD, PhD, now a resident in dermatology at the Icahn School of Medicine at Mount Sinai, New York. She received her PhD while studying HS activity in non-lesional skin. Her work has led her to conclude that the best chance for better outcomes in HS is early diagnosis and treatment. Although this is generally true of any pathology, the changes in the HS phenotype once fistulae form includes a poor response to conventional therapies. 

In fact, based on her work in evaluating HS activity in non-lesional skin, Navrazhina has shown that “many patients with modest lesions already have advanced disease.” Consistent with the premise that HS is a deeply systemic inflammatory process, nodules, considered an early manifestation, turn out to be “the tip of the iceberg.”

 

Non-Lesional HS Skin Is Inflamed

When she has employed RNA sequencing based on tape strip sampling from completely normal skin away from nodules, interleukin (IL)-17 and a broad array of other inflammatory markers were found to be upregulated. When she performed ultrasound to look for disease activity under the normal skin, she has often found tunnels already formed. Doppler ultrasound showed some of these tunnels were actively draining.

This might provide a partial explanation for why therapies are not always effective even when clinical signs of disease are modest. 

“Are we missing the opportunity for intervening?” Navrazhina asked, noting that early intervention has been limited traditionally by extremely long diagnostic delays. Citing the literature, Navrazhina said the average delay is 7 years for HS versus 1 year for psoriasis. Patients often cycle through 3 or 4 providers before the diagnosis is made, she said.

Awakening first-line clinicians to the signs and symptoms of HS, whether in the emergency room or primary care, is a critical message because of the incrementally difficult task to control disease once fistulae have formed. 

Krueger made the same appeal. For the neutrophilic inflammation that characterizes nodules, targeted therapies are often effective, but he agreed that available therapies are generally far less so once tunnels form.

 

Role Seen for Bacteria in HS Pathogenesis

One reason might be an interaction between anaerobic bacteria and the keratinocytes that form the tunnel walls, according to Krueger. Although HS is not typically considered an infectious disease, he reported that the interaction of these bacteria with keratinocytes is associated with expression of approximately 1000 inflammatory gene products. The process of tunnel formation is traced to how factors recruited by upregulated inflammation, such as chemokines, coordinate.

He described recent work pursing novel strategies such as highly targeted antibiotics or inhibitors of complement factor C5a, which has been proposed as a biomarker for HS, to intervene in preventing or reversing HS tunnels. 

While this work progresses, one of the most Important unmet needs in HS is an accepted measure of clinically meaningful improvement in advanced disease, particularly the impact of therapy on HS tunnels, according to Krueger. 

“There is no measure of tunnel activity that the FDA accepts in evaluating drugs,” he noted, which will be essential for approving therapies that offer this benefit. 

A phase 3 trials program for one of the promising drugs, sonelokimab, was announced early in 2024. A nanobody that targets IL-17A/A, IL-17A/F, and IL-17F/F, the small size of this molecule permits exceptional tissue penetration while the broad anti-IL-17 activity has a high degree of theoretical potential in late-stage HS, according to Krueger. 

There are numerous pieces of the HS puzzle that are still missing, but both Krueger and Navrazhina are enthusiastic about new targets and opportunities for disease control that are stemming from a better understanding of the underlying pathophysiology. Not least, both indicated that testing for inflammatory phenotypes will allow for individualized therapeutic choices with a maximum likelihood of response, particularly if earlier diagnosis permits earlier treatment. 

“Due to the heterogeneity of HS, it is hard to know who will respond to which treatment or which treatment should be started first,” Navrazhina said. She thinks that early measures of the inflammatory profile in nodules or even non-lesional skin might provide that guidance. 

Both Krueger and Navrazhina reported no financial relationships relevant to this work. 

 

A version of this article appeared on Medscape.com.

Daniel C. Butler, MD, is associate professor of dermatology and director of the new Inflammatory and Aging Skin Research Program in the Division of Dermatology at the University of Arizona College of Medicine, Tucson, Arizona. Before returning to Arizona, where he had attended medical school, Butler practiced and was a researcher at the University of California, San Francisco, and its geriatric dermatology clinic. He is a co-founder and continues to co-lead the American Academy of Dermatology (AAD) Geriatric Dermatology Expert Resource Group (ERG).

Butler’s interest in geriatric dermatology is rooted in his experience growing up with four grandparents and witnessing their wisdom, relationships, moments with loved ones, and other unique and desirable parts of growing old. “When I looked later at how aging was perceived in dermatology, I found it was a lot about ‘antiaging,’” he told this news organization. “I thought there was a needed voice in dermatology for healthy aging, for all the desirable things that only growing old can provide, along with all the incredible ‘antiaging’ things we can do.”

In interviews, Butler spoke about research priorities in geriatric dermatology, how the “4M” model of geriatrics should be applied within dermatology, how dermatologists can best work with older complex patients, and more. The conversation was edited for clarity and length.

 

What is geriatric dermatology? It is described by the AAD’s Geriatric Dermatology ERG as “an emerging subspecialty.” Yet it’s also viewed more broadly. Please speak about its various identities and meanings and its importance for dermatology.

I’d describe geriatric dermatology as a “supra-specialty” in theory because it encapsulates a part of many practices. If you’re a general dermatologist, about 50% of your patients are over the age of 65. If you’re a Mohs surgeon, you’re seeing a strong majority of over 65 patients. And in various specialty clinics, such as inflammatory skin disease, geriatric dermatology pertains to you. In many ways, it can be viewed as a mindset.

From a framework standpoint, and as a field, geriatric dermatology is a basic science initiative, a clinical initiative, an educational initiative, and an advocacy initiative. The goal is to be able to influence, grow, and learn in each of these categories for our older patients. This is happening: Research in this field has progressed, and education has progressed, which has driven some progress in clinical care.

 

How has research progressed in the basic science of aging skin? What are key questions for dermatology?

There has been a lot of basic science research on aging skin and on how an aging immune system, for instance, is reflected in conditions such as bullous pemphigoid, atopic dermatitis (AD), and chronic itch. But aging involves more than immunosenescence. I think of aging skin as a three-headed monster that involves changes in the skin barrier and the microbiome as well. But is there a primary piece of aging in the skin? What comes first or influences the other? More research on these questions can potentially influence our treatments.

With respect to the immune system, what we’re finding in the skin is that age-related change is not a decline in the immune system per se, but rather aberrance in response. Parts of the system tend to become overactive, with a skew toward overexpression of type 2 inflammation. This can be problematic, driving conditions such as chronic itch.

With respect to the skin barrier, we lose essential fatty acids, and we lose a lot of our recovery ability and our ability to respond quickly to environmental stressors. But are barrier changes triggering the immune system? Or is it the other way around?

The microbiome, which is a big focus of research, involves similar chicken-and-egg discussions. Is it the microbiome that changes and alters the barrier, which then entices the immune system? Which one happens first? We have a lot to learn, and there’s probably not one answer for every patient.

 

Please speak about research more broadly. What questions and issues need to be answered and addressed to improve the dermatologic care of older adults?

In general, research in dermatology is very disease-specific and not particularly conducive to looking at the larger demographic populations. We have a huge opportunity, therefore, to break the mold and grow geriatric dermatology as an area of population-based research — so that geriatric dermatology research encompasses not only the melanoma researcher who’s trying to understand how aging influences the melanocytes but also the epidemiologic researcher looking at how our diagnoses and coding and prescription practices are different in the 65-plus age group.

Clinically speaking, researchers want to better understand how aging influences the clinical presentations of our diseases. And there’s research to be done on best practices. For example, what are the best practices for treating basal cell carcinomas in patients with mild cognitive impairment? How should we consider the use of topicals in a patient who has severe arthritis or who lives alone? And then how should we teach practical approaches to help providers meet people where they are?

Looking at it from a healthcare system standpoint, there are many care delivery and access issues — practical pieces — to research, and we’re getting a lot better with this. We’re also advocating not only for more inclusion of older adults in clinical trials of treatments but also for the use of evaluations and outcomes that are relevant and important for older adults.

One piece of good news is that we’re seeing safer treatment options with tremendous efficacy that target known pathways for diseases like AD and chronic itch that affect older adults. Again, now we must find ways to improve access to these novel, safe options.

Our research program at the University of Arizona College of Medicine, which we’re just getting off the ground, aims to be dual-sided, looking both at the basic science of aging skin and at access and care delivery issues, such as how to ensure that patients on Medicare have access to medications that are at least on par with others with private insurance.

 

What are the most common dermatologic problems experienced by older adults?

Based on my experience and on research that we expect to be published soon, it’s absolutely nonmelanoma skin cancers, precancers like actinic keratoses — and on the inflammatory disease side, itch, AD, and psoriasis. Of course, also common are the age-related changes to the skin that we put in the benign category, such as solar lentigines.

How does age influence dermatologic diseases from a pathophysiological and clinical standpoint?

Diseases overall are very similar and respond to the same treatments, but age in and of itself does influence little pieces. For example, there is more crossover in the presentation of psoriasis and AD in older adults, leading to delays in the diagnosis of psoriasis.

With AD, we’ve found that itch is the predominant symptom for older adults rather than the red rash. We see higher or more severe itch scores in older adults with AD with less visual changes on the skin than in younger cohorts. And rash occurs in different locations than in young patients. Older adults typically present with it on their chest, back, and across the trunk, rather than in folded areas. They’re also more likely to get it on their legs in a nummular pattern as opposed to the more traditional flexural area presentation.

 

What unique considerations need to be made in treating older adults? How should the 4M model of geriatrics be applied to dermatologic care?

Our care model pushes us to be very algorithmic, but at the end of the day, what’s really important are the 4Ms: Mobility, medication, mentation, and “what matters most.” As you’re having your shared decision-making conversations with your patients and their families, these should be your priorities.

A patient with physical limitations, for instance, may not be able to apply a topical cream twice a day all over the body. They may have comorbidities and treatments for these comorbidities that may conflict with medications you’re considering.

And then mentation is so important. For a long time, we used antihistamines for older adults, but this has been proven to be bad for their mentation and risky in other ways. We need to be sure we’re prioritizing their ability to be clear mentally when we’re prescribing medications and even when we’re considering surgical approaches. Do they show capacity for that procedure or treatment, and how will they respond to that treatment later on?

Using the 4M model to drive conversations is a way to get all of us to connect to the patient and learn about what’s most important for them. In many ways, geriatrics is about taking a step back from your specialist skills and thinking about how you would want a family member treated.

We want to avoid treating just the lesion or the pathologic diagnosis. We want to avoid the “conveyor belt” from a biopsy to Mohs. I have 95-year-olds who say, “Heck yeah, if Mohs is the best treatment, that’s what I want.” And I have 70-year-olds who say, “I think I’ll go with another option,” and that’s the right decision for them. It’s having the conversation that matters.

 

In practice, given time constraints and other confines, how can dermatologists best work with more complex older patients? What are your practical tips?

People talk about having 45-minute “golden year” conversations with their older patients, but it doesn’t have to be this way. In pursuing geriatric dermatology, I decided early on that I wanted to make sure it was practical, so I’ve focused on maximizing shorter visits and on embracing the concept that relationships can be developed over time. Each time we meet with someone, we’re building equity to have bigger conversations later on.

I can have a 15-minute conversation about whether my patient may want to have Mohs surgery, for instance, or escalate treatment to a systemic agent for their chronic inflammatory disease. If that time isn’t enough, I can encourage further thought about treatment options, acknowledge that decisions aren’t necessarily easy, and schedule a follow-up or offer to call the patient after clinic to continue the conversation.

Sometimes, when I’m at an impasse and my patient is unsure how to proceed, I’ll use clear metrics relevant to older adults — sleep, activity level, and caregiver burden — to help my patient. If someone is not sleeping because of their lesion — if they’re so itchy or their inflammatory disease is uncontrolled, for instance — I’ll point out that the side effects of not sleeping are worse than the medications or surgery we’d pursue. If someone removes themselves from an activity due to their skin condition, that’s a red flag. And if the caregiver in the room is overwhelmed or frustrated by having to put cream on twice a day, I’ll use this to advance treatment.

 

What resources are available for dermatologists interested in improving their geriatric dermatology skills or advancing the area?

For those interested in investigating these issues or improving their practices, the AAD’s Geriatric Dermatology ERG is always welcoming of new members. The ERG will have an all-inclusive meeting at the 2025 annual AAD meeting in March.

The AAD also has educational modules on geriatric dermatology that were recently published as an initiative of our ERG. More information is available on the website. Also valuable is the ElderDerm conference hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC; the second such conference takes place in May 2025.

Butler reported that he had no relevant financial disclosures.

 

A version of this article appeared on Medscape.com.

Daniel C. Butler, MD, is associate professor of dermatology and director of the new Inflammatory and Aging Skin Research Program in the Division of Dermatology at the University of Arizona College of Medicine, Tucson, Arizona. Before returning to Arizona, where he had attended medical school, Butler practiced and was a researcher at the University of California, San Francisco, and its geriatric dermatology clinic. He is a co-founder and continues to co-lead the American Academy of Dermatology (AAD) Geriatric Dermatology Expert Resource Group (ERG).

Butler’s interest in geriatric dermatology is rooted in his experience growing up with four grandparents and witnessing their wisdom, relationships, moments with loved ones, and other unique and desirable parts of growing old. “When I looked later at how aging was perceived in dermatology, I found it was a lot about ‘antiaging,’” he told this news organization. “I thought there was a needed voice in dermatology for healthy aging, for all the desirable things that only growing old can provide, along with all the incredible ‘antiaging’ things we can do.”

In interviews, Butler spoke about research priorities in geriatric dermatology, how the “4M” model of geriatrics should be applied within dermatology, how dermatologists can best work with older complex patients, and more. The conversation was edited for clarity and length.

 

What is geriatric dermatology? It is described by the AAD’s Geriatric Dermatology ERG as “an emerging subspecialty.” Yet it’s also viewed more broadly. Please speak about its various identities and meanings and its importance for dermatology.

I’d describe geriatric dermatology as a “supra-specialty” in theory because it encapsulates a part of many practices. If you’re a general dermatologist, about 50% of your patients are over the age of 65. If you’re a Mohs surgeon, you’re seeing a strong majority of over 65 patients. And in various specialty clinics, such as inflammatory skin disease, geriatric dermatology pertains to you. In many ways, it can be viewed as a mindset.

From a framework standpoint, and as a field, geriatric dermatology is a basic science initiative, a clinical initiative, an educational initiative, and an advocacy initiative. The goal is to be able to influence, grow, and learn in each of these categories for our older patients. This is happening: Research in this field has progressed, and education has progressed, which has driven some progress in clinical care.

 

How has research progressed in the basic science of aging skin? What are key questions for dermatology?

There has been a lot of basic science research on aging skin and on how an aging immune system, for instance, is reflected in conditions such as bullous pemphigoid, atopic dermatitis (AD), and chronic itch. But aging involves more than immunosenescence. I think of aging skin as a three-headed monster that involves changes in the skin barrier and the microbiome as well. But is there a primary piece of aging in the skin? What comes first or influences the other? More research on these questions can potentially influence our treatments.

With respect to the immune system, what we’re finding in the skin is that age-related change is not a decline in the immune system per se, but rather aberrance in response. Parts of the system tend to become overactive, with a skew toward overexpression of type 2 inflammation. This can be problematic, driving conditions such as chronic itch.

With respect to the skin barrier, we lose essential fatty acids, and we lose a lot of our recovery ability and our ability to respond quickly to environmental stressors. But are barrier changes triggering the immune system? Or is it the other way around?

The microbiome, which is a big focus of research, involves similar chicken-and-egg discussions. Is it the microbiome that changes and alters the barrier, which then entices the immune system? Which one happens first? We have a lot to learn, and there’s probably not one answer for every patient.

 

Please speak about research more broadly. What questions and issues need to be answered and addressed to improve the dermatologic care of older adults?

In general, research in dermatology is very disease-specific and not particularly conducive to looking at the larger demographic populations. We have a huge opportunity, therefore, to break the mold and grow geriatric dermatology as an area of population-based research — so that geriatric dermatology research encompasses not only the melanoma researcher who’s trying to understand how aging influences the melanocytes but also the epidemiologic researcher looking at how our diagnoses and coding and prescription practices are different in the 65-plus age group.

Clinically speaking, researchers want to better understand how aging influences the clinical presentations of our diseases. And there’s research to be done on best practices. For example, what are the best practices for treating basal cell carcinomas in patients with mild cognitive impairment? How should we consider the use of topicals in a patient who has severe arthritis or who lives alone? And then how should we teach practical approaches to help providers meet people where they are?

Looking at it from a healthcare system standpoint, there are many care delivery and access issues — practical pieces — to research, and we’re getting a lot better with this. We’re also advocating not only for more inclusion of older adults in clinical trials of treatments but also for the use of evaluations and outcomes that are relevant and important for older adults.

One piece of good news is that we’re seeing safer treatment options with tremendous efficacy that target known pathways for diseases like AD and chronic itch that affect older adults. Again, now we must find ways to improve access to these novel, safe options.

Our research program at the University of Arizona College of Medicine, which we’re just getting off the ground, aims to be dual-sided, looking both at the basic science of aging skin and at access and care delivery issues, such as how to ensure that patients on Medicare have access to medications that are at least on par with others with private insurance.

 

What are the most common dermatologic problems experienced by older adults?

Based on my experience and on research that we expect to be published soon, it’s absolutely nonmelanoma skin cancers, precancers like actinic keratoses — and on the inflammatory disease side, itch, AD, and psoriasis. Of course, also common are the age-related changes to the skin that we put in the benign category, such as solar lentigines.

How does age influence dermatologic diseases from a pathophysiological and clinical standpoint?

Diseases overall are very similar and respond to the same treatments, but age in and of itself does influence little pieces. For example, there is more crossover in the presentation of psoriasis and AD in older adults, leading to delays in the diagnosis of psoriasis.

With AD, we’ve found that itch is the predominant symptom for older adults rather than the red rash. We see higher or more severe itch scores in older adults with AD with less visual changes on the skin than in younger cohorts. And rash occurs in different locations than in young patients. Older adults typically present with it on their chest, back, and across the trunk, rather than in folded areas. They’re also more likely to get it on their legs in a nummular pattern as opposed to the more traditional flexural area presentation.

 

What unique considerations need to be made in treating older adults? How should the 4M model of geriatrics be applied to dermatologic care?

Our care model pushes us to be very algorithmic, but at the end of the day, what’s really important are the 4Ms: Mobility, medication, mentation, and “what matters most.” As you’re having your shared decision-making conversations with your patients and their families, these should be your priorities.

A patient with physical limitations, for instance, may not be able to apply a topical cream twice a day all over the body. They may have comorbidities and treatments for these comorbidities that may conflict with medications you’re considering.

And then mentation is so important. For a long time, we used antihistamines for older adults, but this has been proven to be bad for their mentation and risky in other ways. We need to be sure we’re prioritizing their ability to be clear mentally when we’re prescribing medications and even when we’re considering surgical approaches. Do they show capacity for that procedure or treatment, and how will they respond to that treatment later on?

Using the 4M model to drive conversations is a way to get all of us to connect to the patient and learn about what’s most important for them. In many ways, geriatrics is about taking a step back from your specialist skills and thinking about how you would want a family member treated.

We want to avoid treating just the lesion or the pathologic diagnosis. We want to avoid the “conveyor belt” from a biopsy to Mohs. I have 95-year-olds who say, “Heck yeah, if Mohs is the best treatment, that’s what I want.” And I have 70-year-olds who say, “I think I’ll go with another option,” and that’s the right decision for them. It’s having the conversation that matters.

 

In practice, given time constraints and other confines, how can dermatologists best work with more complex older patients? What are your practical tips?

People talk about having 45-minute “golden year” conversations with their older patients, but it doesn’t have to be this way. In pursuing geriatric dermatology, I decided early on that I wanted to make sure it was practical, so I’ve focused on maximizing shorter visits and on embracing the concept that relationships can be developed over time. Each time we meet with someone, we’re building equity to have bigger conversations later on.

I can have a 15-minute conversation about whether my patient may want to have Mohs surgery, for instance, or escalate treatment to a systemic agent for their chronic inflammatory disease. If that time isn’t enough, I can encourage further thought about treatment options, acknowledge that decisions aren’t necessarily easy, and schedule a follow-up or offer to call the patient after clinic to continue the conversation.

Sometimes, when I’m at an impasse and my patient is unsure how to proceed, I’ll use clear metrics relevant to older adults — sleep, activity level, and caregiver burden — to help my patient. If someone is not sleeping because of their lesion — if they’re so itchy or their inflammatory disease is uncontrolled, for instance — I’ll point out that the side effects of not sleeping are worse than the medications or surgery we’d pursue. If someone removes themselves from an activity due to their skin condition, that’s a red flag. And if the caregiver in the room is overwhelmed or frustrated by having to put cream on twice a day, I’ll use this to advance treatment.

 

What resources are available for dermatologists interested in improving their geriatric dermatology skills or advancing the area?

For those interested in investigating these issues or improving their practices, the AAD’s Geriatric Dermatology ERG is always welcoming of new members. The ERG will have an all-inclusive meeting at the 2025 annual AAD meeting in March.

The AAD also has educational modules on geriatric dermatology that were recently published as an initiative of our ERG. More information is available on the website. Also valuable is the ElderDerm conference hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC; the second such conference takes place in May 2025.

Butler reported that he had no relevant financial disclosures.

 

A version of this article appeared on Medscape.com.

Daniel C. Butler, MD, is associate professor of dermatology and director of the new Inflammatory and Aging Skin Research Program in the Division of Dermatology at the University of Arizona College of Medicine, Tucson, Arizona. Before returning to Arizona, where he had attended medical school, Butler practiced and was a researcher at the University of California, San Francisco, and its geriatric dermatology clinic. He is a co-founder and continues to co-lead the American Academy of Dermatology (AAD) Geriatric Dermatology Expert Resource Group (ERG).

Butler’s interest in geriatric dermatology is rooted in his experience growing up with four grandparents and witnessing their wisdom, relationships, moments with loved ones, and other unique and desirable parts of growing old. “When I looked later at how aging was perceived in dermatology, I found it was a lot about ‘antiaging,’” he told this news organization. “I thought there was a needed voice in dermatology for healthy aging, for all the desirable things that only growing old can provide, along with all the incredible ‘antiaging’ things we can do.”

In interviews, Butler spoke about research priorities in geriatric dermatology, how the “4M” model of geriatrics should be applied within dermatology, how dermatologists can best work with older complex patients, and more. The conversation was edited for clarity and length.

 

What is geriatric dermatology? It is described by the AAD’s Geriatric Dermatology ERG as “an emerging subspecialty.” Yet it’s also viewed more broadly. Please speak about its various identities and meanings and its importance for dermatology.

I’d describe geriatric dermatology as a “supra-specialty” in theory because it encapsulates a part of many practices. If you’re a general dermatologist, about 50% of your patients are over the age of 65. If you’re a Mohs surgeon, you’re seeing a strong majority of over 65 patients. And in various specialty clinics, such as inflammatory skin disease, geriatric dermatology pertains to you. In many ways, it can be viewed as a mindset.

From a framework standpoint, and as a field, geriatric dermatology is a basic science initiative, a clinical initiative, an educational initiative, and an advocacy initiative. The goal is to be able to influence, grow, and learn in each of these categories for our older patients. This is happening: Research in this field has progressed, and education has progressed, which has driven some progress in clinical care.

 

How has research progressed in the basic science of aging skin? What are key questions for dermatology?

There has been a lot of basic science research on aging skin and on how an aging immune system, for instance, is reflected in conditions such as bullous pemphigoid, atopic dermatitis (AD), and chronic itch. But aging involves more than immunosenescence. I think of aging skin as a three-headed monster that involves changes in the skin barrier and the microbiome as well. But is there a primary piece of aging in the skin? What comes first or influences the other? More research on these questions can potentially influence our treatments.

With respect to the immune system, what we’re finding in the skin is that age-related change is not a decline in the immune system per se, but rather aberrance in response. Parts of the system tend to become overactive, with a skew toward overexpression of type 2 inflammation. This can be problematic, driving conditions such as chronic itch.

With respect to the skin barrier, we lose essential fatty acids, and we lose a lot of our recovery ability and our ability to respond quickly to environmental stressors. But are barrier changes triggering the immune system? Or is it the other way around?

The microbiome, which is a big focus of research, involves similar chicken-and-egg discussions. Is it the microbiome that changes and alters the barrier, which then entices the immune system? Which one happens first? We have a lot to learn, and there’s probably not one answer for every patient.

 

Please speak about research more broadly. What questions and issues need to be answered and addressed to improve the dermatologic care of older adults?

In general, research in dermatology is very disease-specific and not particularly conducive to looking at the larger demographic populations. We have a huge opportunity, therefore, to break the mold and grow geriatric dermatology as an area of population-based research — so that geriatric dermatology research encompasses not only the melanoma researcher who’s trying to understand how aging influences the melanocytes but also the epidemiologic researcher looking at how our diagnoses and coding and prescription practices are different in the 65-plus age group.

Clinically speaking, researchers want to better understand how aging influences the clinical presentations of our diseases. And there’s research to be done on best practices. For example, what are the best practices for treating basal cell carcinomas in patients with mild cognitive impairment? How should we consider the use of topicals in a patient who has severe arthritis or who lives alone? And then how should we teach practical approaches to help providers meet people where they are?

Looking at it from a healthcare system standpoint, there are many care delivery and access issues — practical pieces — to research, and we’re getting a lot better with this. We’re also advocating not only for more inclusion of older adults in clinical trials of treatments but also for the use of evaluations and outcomes that are relevant and important for older adults.

One piece of good news is that we’re seeing safer treatment options with tremendous efficacy that target known pathways for diseases like AD and chronic itch that affect older adults. Again, now we must find ways to improve access to these novel, safe options.

Our research program at the University of Arizona College of Medicine, which we’re just getting off the ground, aims to be dual-sided, looking both at the basic science of aging skin and at access and care delivery issues, such as how to ensure that patients on Medicare have access to medications that are at least on par with others with private insurance.

 

What are the most common dermatologic problems experienced by older adults?

Based on my experience and on research that we expect to be published soon, it’s absolutely nonmelanoma skin cancers, precancers like actinic keratoses — and on the inflammatory disease side, itch, AD, and psoriasis. Of course, also common are the age-related changes to the skin that we put in the benign category, such as solar lentigines.

How does age influence dermatologic diseases from a pathophysiological and clinical standpoint?

Diseases overall are very similar and respond to the same treatments, but age in and of itself does influence little pieces. For example, there is more crossover in the presentation of psoriasis and AD in older adults, leading to delays in the diagnosis of psoriasis.

With AD, we’ve found that itch is the predominant symptom for older adults rather than the red rash. We see higher or more severe itch scores in older adults with AD with less visual changes on the skin than in younger cohorts. And rash occurs in different locations than in young patients. Older adults typically present with it on their chest, back, and across the trunk, rather than in folded areas. They’re also more likely to get it on their legs in a nummular pattern as opposed to the more traditional flexural area presentation.

 

What unique considerations need to be made in treating older adults? How should the 4M model of geriatrics be applied to dermatologic care?

Our care model pushes us to be very algorithmic, but at the end of the day, what’s really important are the 4Ms: Mobility, medication, mentation, and “what matters most.” As you’re having your shared decision-making conversations with your patients and their families, these should be your priorities.

A patient with physical limitations, for instance, may not be able to apply a topical cream twice a day all over the body. They may have comorbidities and treatments for these comorbidities that may conflict with medications you’re considering.

And then mentation is so important. For a long time, we used antihistamines for older adults, but this has been proven to be bad for their mentation and risky in other ways. We need to be sure we’re prioritizing their ability to be clear mentally when we’re prescribing medications and even when we’re considering surgical approaches. Do they show capacity for that procedure or treatment, and how will they respond to that treatment later on?

Using the 4M model to drive conversations is a way to get all of us to connect to the patient and learn about what’s most important for them. In many ways, geriatrics is about taking a step back from your specialist skills and thinking about how you would want a family member treated.

We want to avoid treating just the lesion or the pathologic diagnosis. We want to avoid the “conveyor belt” from a biopsy to Mohs. I have 95-year-olds who say, “Heck yeah, if Mohs is the best treatment, that’s what I want.” And I have 70-year-olds who say, “I think I’ll go with another option,” and that’s the right decision for them. It’s having the conversation that matters.

 

In practice, given time constraints and other confines, how can dermatologists best work with more complex older patients? What are your practical tips?

People talk about having 45-minute “golden year” conversations with their older patients, but it doesn’t have to be this way. In pursuing geriatric dermatology, I decided early on that I wanted to make sure it was practical, so I’ve focused on maximizing shorter visits and on embracing the concept that relationships can be developed over time. Each time we meet with someone, we’re building equity to have bigger conversations later on.

I can have a 15-minute conversation about whether my patient may want to have Mohs surgery, for instance, or escalate treatment to a systemic agent for their chronic inflammatory disease. If that time isn’t enough, I can encourage further thought about treatment options, acknowledge that decisions aren’t necessarily easy, and schedule a follow-up or offer to call the patient after clinic to continue the conversation.

Sometimes, when I’m at an impasse and my patient is unsure how to proceed, I’ll use clear metrics relevant to older adults — sleep, activity level, and caregiver burden — to help my patient. If someone is not sleeping because of their lesion — if they’re so itchy or their inflammatory disease is uncontrolled, for instance — I’ll point out that the side effects of not sleeping are worse than the medications or surgery we’d pursue. If someone removes themselves from an activity due to their skin condition, that’s a red flag. And if the caregiver in the room is overwhelmed or frustrated by having to put cream on twice a day, I’ll use this to advance treatment.

 

What resources are available for dermatologists interested in improving their geriatric dermatology skills or advancing the area?

For those interested in investigating these issues or improving their practices, the AAD’s Geriatric Dermatology ERG is always welcoming of new members. The ERG will have an all-inclusive meeting at the 2025 annual AAD meeting in March.

The AAD also has educational modules on geriatric dermatology that were recently published as an initiative of our ERG. More information is available on the website. Also valuable is the ElderDerm conference hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC; the second such conference takes place in May 2025.

Butler reported that he had no relevant financial disclosures.

 

A version of this article appeared on Medscape.com.

The Diagnosis: Apocrine Hidrocystoma

Histopathology of the excised nodule revealed a partially collapsed, multiloculated dermal cyst lined with apocrine cells, which was consistent with a diagnosis of apocrine hidrocystoma. Apocrine hidrocystomas are cysts that range from flesh-colored to blue-black and most commonly manifest as solitary lesions on the face, particularly near the eyelids.^1,2 Apocrine hidrocystomas typically range from 1 to 10 mm in diameter and contain fluid that can be colorless, yellow-brown, or blue-black.^1,2 Apocrine hidrocystomas usually are reported between the ages of 30 and 70 years and have no sex predilection.³ 

Apocrine hidrocystomas are thought to develop from adenomatous growth of apocrine sweat gland coils.⁴ The term apocrine hidrocystoma has been used interchangeably with apocrine cystadenoma, though some investigators have recommended using the latter term only for lesions with true papillary projections.⁵ Definitive diagnosis is obtained through histopathology, which typically shows unilocular or multilocular cystic spaces in the dermis lined by an apocrine secretory epithelium. These secretory cells often demonstrate decapitation secretion and apical snouting. The cyst wall may send pseudopapillary projections into the cystic cavity.^1,2 While apocrine and eccrine hidrocystomas previously were recognized as separate entities, it has been suggested that so-called eccrine hidrocystomas are truly apocrine in nature, with a cyst wall that is compressed by the cyst contents.⁴ 

Apocrine hidrocystomas are benign and do not require treatment; however, they may be removed for cosmetic purposes, most commonly via surgical excision. Lesions treated with needle puncture as monotherapy frequently recur. Other successful methods for removal include cyst puncture followed by hypertonic glucose sclerotherapy, trichloroacetic acid injection, botulinum toxin A injection, or CO₂ laser treatment.^3,6 

Several clinical and histopathologic findings can distinguish between apocrine hidrocystomas and other diagnoses in the differential. Lipomas are common benign tumors composed of mature fat that typically manifest as solitary, painless, soft nodules with a normal overlying epidermis. They frequently are distributed on the neck, arms, legs, and buttocks. While the differential for our patient initially included lipoma, these lesions do not contain or release fluid, which was present in our patient. On histopathology, lipoma shows a uniform population of mature fat cells with small, uniform, and eccentric nuclei (Figure 1).⁷ 

Epidermal inclusion cysts are derived from the follicular infundibulum and commonly are found on the face and upper trunk. They manifest as flesh-colored dermal nodules and may have a visible punctum. As opposed to the cystic cavities lined with apocrine cells seen in apocrine hidrocystomas, epidermal inclusion cysts are lined with a stratified squamous epithelium, are filled with laminated keratin, and have a visible granular layer (Figure 2).⁸ 

Pilar cysts, also known as trichilemmal cysts, clinically resemble epidermal inclusion cysts but are derived from the outer root sheath of hair follicles, manifesting as flesh-colored dermal nodules almost always found on the scalp. On histopathology, pilar cysts are lined with stratified squamous epithelial cells without a visible granular layer and are filled with compact eosinophilic keratin (Figure 3).⁸ 

Tubular apocrine adenomas are benign neoplasms of the apocrine glands that manifest as smooth nodules. They are within the same spectrum as papillary eccrine adenomas, appearing more frequently on the legs and less frequently on the face and scalp.⁹ Histopathology generally demonstrates well-circumscribed lobules of tubular structures in the dermis. Similar to apocrine hidrocystomas, tubular apocrine adenomas will demonstrate an inner layer of columnar apocrine cells with decapitation secretion, but the tubular architecture helps differentiate it from other adnexal tumors (Figure 4).¹⁰ 

The clinical manifestation of the apocrine hidrocystoma in our patient was unusual due to its size and location. Apocrine hidrocystomas rarely are found on the scalp, with few other cases found in the literature. To our knowledge, this is the largest apocrine hidrocystoma found on the scalp to date, although there is at least 1 other published case of an apocrine hidrocystoma on the scalp measuring at least 3 cm in diameter.¹¹ Our case highlights the importance of recognizing atypical manifestations of apocrine hidrocystomas, as a lesion on the midline scalp that discharges a thin fluid might raise initial concern for an intracranial connection. Awareness of atypical manifestations of common lesions can expand dermatologists’ differential diagnoses and help them to reassure patients. 

The Diagnosis: Apocrine Hidrocystoma

Histopathology of the excised nodule revealed a partially collapsed, multiloculated dermal cyst lined with apocrine cells, which was consistent with a diagnosis of apocrine hidrocystoma. Apocrine hidrocystomas are cysts that range from flesh-colored to blue-black and most commonly manifest as solitary lesions on the face, particularly near the eyelids.^1,2 Apocrine hidrocystomas typically range from 1 to 10 mm in diameter and contain fluid that can be colorless, yellow-brown, or blue-black.^1,2 Apocrine hidrocystomas usually are reported between the ages of 30 and 70 years and have no sex predilection.³ 

Apocrine hidrocystomas are thought to develop from adenomatous growth of apocrine sweat gland coils.⁴ The term apocrine hidrocystoma has been used interchangeably with apocrine cystadenoma, though some investigators have recommended using the latter term only for lesions with true papillary projections.⁵ Definitive diagnosis is obtained through histopathology, which typically shows unilocular or multilocular cystic spaces in the dermis lined by an apocrine secretory epithelium. These secretory cells often demonstrate decapitation secretion and apical snouting. The cyst wall may send pseudopapillary projections into the cystic cavity.^1,2 While apocrine and eccrine hidrocystomas previously were recognized as separate entities, it has been suggested that so-called eccrine hidrocystomas are truly apocrine in nature, with a cyst wall that is compressed by the cyst contents.⁴ 

Apocrine hidrocystomas are benign and do not require treatment; however, they may be removed for cosmetic purposes, most commonly via surgical excision. Lesions treated with needle puncture as monotherapy frequently recur. Other successful methods for removal include cyst puncture followed by hypertonic glucose sclerotherapy, trichloroacetic acid injection, botulinum toxin A injection, or CO₂ laser treatment.^3,6 

Several clinical and histopathologic findings can distinguish between apocrine hidrocystomas and other diagnoses in the differential. Lipomas are common benign tumors composed of mature fat that typically manifest as solitary, painless, soft nodules with a normal overlying epidermis. They frequently are distributed on the neck, arms, legs, and buttocks. While the differential for our patient initially included lipoma, these lesions do not contain or release fluid, which was present in our patient. On histopathology, lipoma shows a uniform population of mature fat cells with small, uniform, and eccentric nuclei (Figure 1).⁷ 

Epidermal inclusion cysts are derived from the follicular infundibulum and commonly are found on the face and upper trunk. They manifest as flesh-colored dermal nodules and may have a visible punctum. As opposed to the cystic cavities lined with apocrine cells seen in apocrine hidrocystomas, epidermal inclusion cysts are lined with a stratified squamous epithelium, are filled with laminated keratin, and have a visible granular layer (Figure 2).⁸ 

Pilar cysts, also known as trichilemmal cysts, clinically resemble epidermal inclusion cysts but are derived from the outer root sheath of hair follicles, manifesting as flesh-colored dermal nodules almost always found on the scalp. On histopathology, pilar cysts are lined with stratified squamous epithelial cells without a visible granular layer and are filled with compact eosinophilic keratin (Figure 3).⁸ 

Tubular apocrine adenomas are benign neoplasms of the apocrine glands that manifest as smooth nodules. They are within the same spectrum as papillary eccrine adenomas, appearing more frequently on the legs and less frequently on the face and scalp.⁹ Histopathology generally demonstrates well-circumscribed lobules of tubular structures in the dermis. Similar to apocrine hidrocystomas, tubular apocrine adenomas will demonstrate an inner layer of columnar apocrine cells with decapitation secretion, but the tubular architecture helps differentiate it from other adnexal tumors (Figure 4).¹⁰ 

The clinical manifestation of the apocrine hidrocystoma in our patient was unusual due to its size and location. Apocrine hidrocystomas rarely are found on the scalp, with few other cases found in the literature. To our knowledge, this is the largest apocrine hidrocystoma found on the scalp to date, although there is at least 1 other published case of an apocrine hidrocystoma on the scalp measuring at least 3 cm in diameter.¹¹ Our case highlights the importance of recognizing atypical manifestations of apocrine hidrocystomas, as a lesion on the midline scalp that discharges a thin fluid might raise initial concern for an intracranial connection. Awareness of atypical manifestations of common lesions can expand dermatologists’ differential diagnoses and help them to reassure patients. 

The Diagnosis: Apocrine Hidrocystoma

Histopathology of the excised nodule revealed a partially collapsed, multiloculated dermal cyst lined with apocrine cells, which was consistent with a diagnosis of apocrine hidrocystoma. Apocrine hidrocystomas are cysts that range from flesh-colored to blue-black and most commonly manifest as solitary lesions on the face, particularly near the eyelids.^1,2 Apocrine hidrocystomas typically range from 1 to 10 mm in diameter and contain fluid that can be colorless, yellow-brown, or blue-black.^1,2 Apocrine hidrocystomas usually are reported between the ages of 30 and 70 years and have no sex predilection.³ 

Apocrine hidrocystomas are thought to develop from adenomatous growth of apocrine sweat gland coils.⁴ The term apocrine hidrocystoma has been used interchangeably with apocrine cystadenoma, though some investigators have recommended using the latter term only for lesions with true papillary projections.⁵ Definitive diagnosis is obtained through histopathology, which typically shows unilocular or multilocular cystic spaces in the dermis lined by an apocrine secretory epithelium. These secretory cells often demonstrate decapitation secretion and apical snouting. The cyst wall may send pseudopapillary projections into the cystic cavity.^1,2 While apocrine and eccrine hidrocystomas previously were recognized as separate entities, it has been suggested that so-called eccrine hidrocystomas are truly apocrine in nature, with a cyst wall that is compressed by the cyst contents.⁴ 

Apocrine hidrocystomas are benign and do not require treatment; however, they may be removed for cosmetic purposes, most commonly via surgical excision. Lesions treated with needle puncture as monotherapy frequently recur. Other successful methods for removal include cyst puncture followed by hypertonic glucose sclerotherapy, trichloroacetic acid injection, botulinum toxin A injection, or CO₂ laser treatment.^3,6 

Several clinical and histopathologic findings can distinguish between apocrine hidrocystomas and other diagnoses in the differential. Lipomas are common benign tumors composed of mature fat that typically manifest as solitary, painless, soft nodules with a normal overlying epidermis. They frequently are distributed on the neck, arms, legs, and buttocks. While the differential for our patient initially included lipoma, these lesions do not contain or release fluid, which was present in our patient. On histopathology, lipoma shows a uniform population of mature fat cells with small, uniform, and eccentric nuclei (Figure 1).⁷ 

Epidermal inclusion cysts are derived from the follicular infundibulum and commonly are found on the face and upper trunk. They manifest as flesh-colored dermal nodules and may have a visible punctum. As opposed to the cystic cavities lined with apocrine cells seen in apocrine hidrocystomas, epidermal inclusion cysts are lined with a stratified squamous epithelium, are filled with laminated keratin, and have a visible granular layer (Figure 2).⁸ 

Pilar cysts, also known as trichilemmal cysts, clinically resemble epidermal inclusion cysts but are derived from the outer root sheath of hair follicles, manifesting as flesh-colored dermal nodules almost always found on the scalp. On histopathology, pilar cysts are lined with stratified squamous epithelial cells without a visible granular layer and are filled with compact eosinophilic keratin (Figure 3).⁸ 

Tubular apocrine adenomas are benign neoplasms of the apocrine glands that manifest as smooth nodules. They are within the same spectrum as papillary eccrine adenomas, appearing more frequently on the legs and less frequently on the face and scalp.⁹ Histopathology generally demonstrates well-circumscribed lobules of tubular structures in the dermis. Similar to apocrine hidrocystomas, tubular apocrine adenomas will demonstrate an inner layer of columnar apocrine cells with decapitation secretion, but the tubular architecture helps differentiate it from other adnexal tumors (Figure 4).¹⁰ 

The clinical manifestation of the apocrine hidrocystoma in our patient was unusual due to its size and location. Apocrine hidrocystomas rarely are found on the scalp, with few other cases found in the literature. To our knowledge, this is the largest apocrine hidrocystoma found on the scalp to date, although there is at least 1 other published case of an apocrine hidrocystoma on the scalp measuring at least 3 cm in diameter.¹¹ Our case highlights the importance of recognizing atypical manifestations of apocrine hidrocystomas, as a lesion on the midline scalp that discharges a thin fluid might raise initial concern for an intracranial connection. Awareness of atypical manifestations of common lesions can expand dermatologists’ differential diagnoses and help them to reassure patients.