Patrick Armstrong, MD

To the Editor:

The tongue is composed of 4 different types of papillae: fungiform, foliate, circumvallate, and filiform. Fungiform papillae, primarily located on the tip and sides of the tongue, are mushroom-shaped epithelial elevations composed of taste buds at the upper surface overlying a core of connective tissue.¹ Foliate and circumvallate papillae are likewise associated with taste buds, while the filiform papillae are hypothesized to exclusively provide a frictional surface for proper food manipulation. Pigmented fungiform papillae of the tongue (PFPT) was first reported by Leonard² in 1905, who described discrete hyperpigmentation present only on the surface of fungiform papillae, mainly in black patients. Although they have been primarily described in black individuals, PFPT also has been occasionally reported in Asian and Middle Eastern individuals as well as Indian women.^3-6

A 36-year-old Indian man initially presented to his primary care provider with brown discoloration of the dorsolateral aspects of the tongue that had been present since childhood. His primary care provider was concerned about a potential syndrome or systemic illness and referred the patient to dermatology for further evaluation. The patient denied any oral mucosal bleeding or discomfort, and a review of systems was unremarkable. His medical and family history were otherwise noncontributory, and he denied a history of tobacco use.

Physical examination of the tongue and oral mucosa revealed numerous 0.5- to 1.0-mm brown papillae in a symmetric distribution, primarily located on the tip and lateral aspects of the tongue (Figure). No hyperpigmentation was present on the posterior aspect of the tongue or on any other mucosal surface. Routine laboratory values were notable for mild elevations in aspartate aminotransferase and alanine aminotransferase (47 U/L [reference range, 10–30 U/L] and 64 U/L [reference range, 10–40 U/L], respectively) and mild hyperbilirubinemia (total bilirubin, 1.8 mg/dL [reference range, 0.3–1.2 mg/dL]). A complete blood cell count and electrolytes were within reference range. Based on the clinical appearance of the lesions and their presence since childhood, the patient was diagnosed with PFPT. No intervention was undertaken, and the patient was reassured of the benign nature of the lesions.

Pigmented fungiform papillae of the tongue presents in 3 variants. The first variant involves hyperpigmentation of all fungiform papillae located on the lateral and frontal aspects of the tongue and is the most common manifestation of PFPT.³ Our patient falls into this category. The second and third variants involve the dorsal surface, with the former involving only a few fungiform papillae on the dorsal aspect of the tongue and the latter variant involving all papillae.³ In 1974, Holzwanger et al³ conducted a survey of 300 random individuals, finding that 30% of black women and 25% of black men had some hyperpigmentation of the tongue, while only 1 white individual demonstrated lingual pigmentation. The physiology of PFPT remains largely unknown. Dermoscopic evaluation often demonstrates elevations with pigmented borders in a rose petal shape.⁷ Histopathologic evaluation reveals melanophages without inflammation that are positive for melanin on Fontana-Masson silver staining but negative for iron on Prussian blue staining.⁸

Despite the fact that PFPT is not a rare condition, the diagnosis remains notably missing from many standard dermatology textbooks and online dermatology resources, making it a potentially overlooked clinical entity.^4-6 The tongue has a number of normal variations that are unlikely to be fully appreciated or acknowledged by dermatologists on routine physical examination but may cause distress to patients and raise concerns from primary care providers. Given that PFPT are benign, physicians should be aware of this diagnosis so as to provide reassurance to patients and avoid unnecessary testing. However, because the tongue can represent a harbinger of systemic disease, the differential diagnosis for the hyperpigmented lesions must always be considered, including Peutz-Jeghers syndrome, hemochromatosis, Addison disease, and Laugier-Hunziker syndrome (a rarer condition causing pigmented lesions on the lips, palate, and tongue), particularly if the hyperpigmented lesions extend beyond the fungiform papillae and do not fit into the 3 categories of PFPT.⁹

To the Editor:

The tongue is composed of 4 different types of papillae: fungiform, foliate, circumvallate, and filiform. Fungiform papillae, primarily located on the tip and sides of the tongue, are mushroom-shaped epithelial elevations composed of taste buds at the upper surface overlying a core of connective tissue.¹ Foliate and circumvallate papillae are likewise associated with taste buds, while the filiform papillae are hypothesized to exclusively provide a frictional surface for proper food manipulation. Pigmented fungiform papillae of the tongue (PFPT) was first reported by Leonard² in 1905, who described discrete hyperpigmentation present only on the surface of fungiform papillae, mainly in black patients. Although they have been primarily described in black individuals, PFPT also has been occasionally reported in Asian and Middle Eastern individuals as well as Indian women.^3-6

A 36-year-old Indian man initially presented to his primary care provider with brown discoloration of the dorsolateral aspects of the tongue that had been present since childhood. His primary care provider was concerned about a potential syndrome or systemic illness and referred the patient to dermatology for further evaluation. The patient denied any oral mucosal bleeding or discomfort, and a review of systems was unremarkable. His medical and family history were otherwise noncontributory, and he denied a history of tobacco use.

Physical examination of the tongue and oral mucosa revealed numerous 0.5- to 1.0-mm brown papillae in a symmetric distribution, primarily located on the tip and lateral aspects of the tongue (Figure). No hyperpigmentation was present on the posterior aspect of the tongue or on any other mucosal surface. Routine laboratory values were notable for mild elevations in aspartate aminotransferase and alanine aminotransferase (47 U/L [reference range, 10–30 U/L] and 64 U/L [reference range, 10–40 U/L], respectively) and mild hyperbilirubinemia (total bilirubin, 1.8 mg/dL [reference range, 0.3–1.2 mg/dL]). A complete blood cell count and electrolytes were within reference range. Based on the clinical appearance of the lesions and their presence since childhood, the patient was diagnosed with PFPT. No intervention was undertaken, and the patient was reassured of the benign nature of the lesions.

Pigmented fungiform papillae of the tongue presents in 3 variants. The first variant involves hyperpigmentation of all fungiform papillae located on the lateral and frontal aspects of the tongue and is the most common manifestation of PFPT.³ Our patient falls into this category. The second and third variants involve the dorsal surface, with the former involving only a few fungiform papillae on the dorsal aspect of the tongue and the latter variant involving all papillae.³ In 1974, Holzwanger et al³ conducted a survey of 300 random individuals, finding that 30% of black women and 25% of black men had some hyperpigmentation of the tongue, while only 1 white individual demonstrated lingual pigmentation. The physiology of PFPT remains largely unknown. Dermoscopic evaluation often demonstrates elevations with pigmented borders in a rose petal shape.⁷ Histopathologic evaluation reveals melanophages without inflammation that are positive for melanin on Fontana-Masson silver staining but negative for iron on Prussian blue staining.⁸

Despite the fact that PFPT is not a rare condition, the diagnosis remains notably missing from many standard dermatology textbooks and online dermatology resources, making it a potentially overlooked clinical entity.^4-6 The tongue has a number of normal variations that are unlikely to be fully appreciated or acknowledged by dermatologists on routine physical examination but may cause distress to patients and raise concerns from primary care providers. Given that PFPT are benign, physicians should be aware of this diagnosis so as to provide reassurance to patients and avoid unnecessary testing. However, because the tongue can represent a harbinger of systemic disease, the differential diagnosis for the hyperpigmented lesions must always be considered, including Peutz-Jeghers syndrome, hemochromatosis, Addison disease, and Laugier-Hunziker syndrome (a rarer condition causing pigmented lesions on the lips, palate, and tongue), particularly if the hyperpigmented lesions extend beyond the fungiform papillae and do not fit into the 3 categories of PFPT.⁹

To the Editor:

The tongue is composed of 4 different types of papillae: fungiform, foliate, circumvallate, and filiform. Fungiform papillae, primarily located on the tip and sides of the tongue, are mushroom-shaped epithelial elevations composed of taste buds at the upper surface overlying a core of connective tissue.¹ Foliate and circumvallate papillae are likewise associated with taste buds, while the filiform papillae are hypothesized to exclusively provide a frictional surface for proper food manipulation. Pigmented fungiform papillae of the tongue (PFPT) was first reported by Leonard² in 1905, who described discrete hyperpigmentation present only on the surface of fungiform papillae, mainly in black patients. Although they have been primarily described in black individuals, PFPT also has been occasionally reported in Asian and Middle Eastern individuals as well as Indian women.^3-6

A 36-year-old Indian man initially presented to his primary care provider with brown discoloration of the dorsolateral aspects of the tongue that had been present since childhood. His primary care provider was concerned about a potential syndrome or systemic illness and referred the patient to dermatology for further evaluation. The patient denied any oral mucosal bleeding or discomfort, and a review of systems was unremarkable. His medical and family history were otherwise noncontributory, and he denied a history of tobacco use.

Physical examination of the tongue and oral mucosa revealed numerous 0.5- to 1.0-mm brown papillae in a symmetric distribution, primarily located on the tip and lateral aspects of the tongue (Figure). No hyperpigmentation was present on the posterior aspect of the tongue or on any other mucosal surface. Routine laboratory values were notable for mild elevations in aspartate aminotransferase and alanine aminotransferase (47 U/L [reference range, 10–30 U/L] and 64 U/L [reference range, 10–40 U/L], respectively) and mild hyperbilirubinemia (total bilirubin, 1.8 mg/dL [reference range, 0.3–1.2 mg/dL]). A complete blood cell count and electrolytes were within reference range. Based on the clinical appearance of the lesions and their presence since childhood, the patient was diagnosed with PFPT. No intervention was undertaken, and the patient was reassured of the benign nature of the lesions.

Pigmented fungiform papillae of the tongue presents in 3 variants. The first variant involves hyperpigmentation of all fungiform papillae located on the lateral and frontal aspects of the tongue and is the most common manifestation of PFPT.³ Our patient falls into this category. The second and third variants involve the dorsal surface, with the former involving only a few fungiform papillae on the dorsal aspect of the tongue and the latter variant involving all papillae.³ In 1974, Holzwanger et al³ conducted a survey of 300 random individuals, finding that 30% of black women and 25% of black men had some hyperpigmentation of the tongue, while only 1 white individual demonstrated lingual pigmentation. The physiology of PFPT remains largely unknown. Dermoscopic evaluation often demonstrates elevations with pigmented borders in a rose petal shape.⁷ Histopathologic evaluation reveals melanophages without inflammation that are positive for melanin on Fontana-Masson silver staining but negative for iron on Prussian blue staining.⁸

Despite the fact that PFPT is not a rare condition, the diagnosis remains notably missing from many standard dermatology textbooks and online dermatology resources, making it a potentially overlooked clinical entity.^4-6 The tongue has a number of normal variations that are unlikely to be fully appreciated or acknowledged by dermatologists on routine physical examination but may cause distress to patients and raise concerns from primary care providers. Given that PFPT are benign, physicians should be aware of this diagnosis so as to provide reassurance to patients and avoid unnecessary testing. However, because the tongue can represent a harbinger of systemic disease, the differential diagnosis for the hyperpigmented lesions must always be considered, including Peutz-Jeghers syndrome, hemochromatosis, Addison disease, and Laugier-Hunziker syndrome (a rarer condition causing pigmented lesions on the lips, palate, and tongue), particularly if the hyperpigmented lesions extend beyond the fungiform papillae and do not fit into the 3 categories of PFPT.⁹

Cutaneous metastasis of internal malignancy is a relatively uncommon phenomenon, with an overall incidence of 5.3% in cancer patients.¹ Cutaneous involvement typically occurs late in the course of disease but can occasionally be the first extranodal sign of metastatic disease. Breast cancer has the highest rate of cutaneous metastasis, most often involving the chest wall¹; however, cutaneous metastasis to the acral sites is exceedingly rare. The hand is the site of 0.1% of all metastatic lesions, with only 10% of these being cutaneous lesions and the remaining 90% being osseous metastases.² Herein, we report a case of multiple cutaneous metastases to acral sites involving the palmar and plantar surfaces of the hands and feet.

Case Report

A 54-year-old black woman with a history of stage IV carcinoma of the breast was admitted to the university medical center with exquisitely painful cutaneous nodules on the hands and feet of 5 weeks’ duration that had started to cause difficulty with walking and daily activities. The patient reported that the breast carcinoma had initially been diagnosed in Nigeria 2 years prior, but she did not receive treatment until moving to the United States. She received a total of 4 cycles of chemotherapy with paclitaxel and bevacizumab, which was discontinued 6 weeks prior to admission due to pain in the lower extremities that was thought to be secondary to neuropathy. One week after discontinuation of chemotherapy, the patient reported increasing pain in the extremities and new-onset painful nodules on the hands and feet. Treatment with gabapentin as well as several courses of antibiotics failed to improve the condition.

She was admitted for symptomatic pain control and a dermatology consultation. Physical examination revealed multiple firm, tender, subcutaneous nodules on the volar surfaces of the soles, toes, palms, and fingertips (Figure 1). A nodule also was noted on the scalp. A punch biopsy of a nodule on the right fourth finger revealed a dermal carcinoma (Figure 2). On immunohistochemistry, the tumor stained positive for cytokeratin 5/6, cytokeratin 7, and gross cystic disease fluid protein 15. It did not demonstrate connection to the epidermis or adnexal structures. Although the tumor did not express estrogen or progesterone receptors, the findings were compatible with metastasis from the patient’s primary breast carcinoma with poor differentiation. A biopsy of the primary breast carcinoma was not available for review from Nigeria.

Comment

The majority of cases reporting acral cutaneous metastasis from internal malignancies are unilateral, involving only one extremity. Several hypotheses have been provided, including spread from localized trauma, which causes disruption of blood vessels and consequent extravasation and localization of tumor cells into the extravascular space.³ The distal extremities are particularly vulnerable to trauma, making this hypothesis plausible.

Considering the overall rarity of metastases to acral sites, it is interesting that our patient developed multiple distal nodules on both the hands and feet. The rapid onset of cutaneous nodules shortly after a course of chemotherapy led the team to consider the physiologic effects of paclitaxel and bevacizumab in the etiology of the acral cutaneous metastases. Karamouzis et al³ described a similar case of multiple cutaneous metastases with a bilateral acral distribution. This case also was associated with chemotherapy in the treatment of breast cancer. The authors proposed hand-foot syndrome, a chemotherapy-related eruption localized to acral skin, as a possible mechanism for hematogenous spread of malignant cells.³ The pathogenesis of hand-foot syndrome is not well understood, but the unique anatomy and physiology of acral skin including temperature gradients, rapidly dividing epidermal cells, absence of hair follicles and sebaceous glands, wide dermal papillae, and exposure to high pressures from carrying body weight and repetitive minor trauma may contribute to the localization of signs and symptoms.^3,4 Our case supports a chemotherapy-related etiology of acral cutaneous metastasis of a primary breast cancer; however, our patient did not have apparent signs or symptoms of hand-foot syndrome during the course of treatment. We propose that effects of bevacizumab on acral skin may have contributed to the development of our patient’s metastatic pattern.

Bevacizumab, a monoclonal antibody to vascular endothelial growth factor A, has well-known vascular side effects. Unlike the inhibition of vascular endothelial growth factor A provided by the receptor tyrosine kinase inhibitors sorafenib and sunitinib, bevacizumab typically is not associated with hand-foot syndrome.⁵ However, several cases have been reported with chemotherapy-associated palmoplantar eruptions that resolved after withholding bevacizumab while continuing other chemotherapeutic agents, suggesting that bevacizumab-induced changes in acral skin contributed to the eruption.⁶ Specific factors that could contribute to acral metastasis in patients taking bevacizumab are endothelial dysfunction and capillary rarefaction of the acral skin, as well as hemorrhage, decreased wound healing, and changes in vascular permeability.^5,7

We present a rare case of acral cutaneous metastasis associated with bevacizumab, one of few reported cases associated with a taxane chemotherapeutic agent.³ More cases need to be identified and reported to establish a causative association, if indeed existent, between acral cutaneous metastasis of breast carcinoma and the use of bevacizumab as well as other chemotherapeutic drugs.

Cutaneous metastasis of internal malignancy is a relatively uncommon phenomenon, with an overall incidence of 5.3% in cancer patients.¹ Cutaneous involvement typically occurs late in the course of disease but can occasionally be the first extranodal sign of metastatic disease. Breast cancer has the highest rate of cutaneous metastasis, most often involving the chest wall¹; however, cutaneous metastasis to the acral sites is exceedingly rare. The hand is the site of 0.1% of all metastatic lesions, with only 10% of these being cutaneous lesions and the remaining 90% being osseous metastases.² Herein, we report a case of multiple cutaneous metastases to acral sites involving the palmar and plantar surfaces of the hands and feet.

Case Report

A 54-year-old black woman with a history of stage IV carcinoma of the breast was admitted to the university medical center with exquisitely painful cutaneous nodules on the hands and feet of 5 weeks’ duration that had started to cause difficulty with walking and daily activities. The patient reported that the breast carcinoma had initially been diagnosed in Nigeria 2 years prior, but she did not receive treatment until moving to the United States. She received a total of 4 cycles of chemotherapy with paclitaxel and bevacizumab, which was discontinued 6 weeks prior to admission due to pain in the lower extremities that was thought to be secondary to neuropathy. One week after discontinuation of chemotherapy, the patient reported increasing pain in the extremities and new-onset painful nodules on the hands and feet. Treatment with gabapentin as well as several courses of antibiotics failed to improve the condition.

She was admitted for symptomatic pain control and a dermatology consultation. Physical examination revealed multiple firm, tender, subcutaneous nodules on the volar surfaces of the soles, toes, palms, and fingertips (Figure 1). A nodule also was noted on the scalp. A punch biopsy of a nodule on the right fourth finger revealed a dermal carcinoma (Figure 2). On immunohistochemistry, the tumor stained positive for cytokeratin 5/6, cytokeratin 7, and gross cystic disease fluid protein 15. It did not demonstrate connection to the epidermis or adnexal structures. Although the tumor did not express estrogen or progesterone receptors, the findings were compatible with metastasis from the patient’s primary breast carcinoma with poor differentiation. A biopsy of the primary breast carcinoma was not available for review from Nigeria.

Comment

The majority of cases reporting acral cutaneous metastasis from internal malignancies are unilateral, involving only one extremity. Several hypotheses have been provided, including spread from localized trauma, which causes disruption of blood vessels and consequent extravasation and localization of tumor cells into the extravascular space.³ The distal extremities are particularly vulnerable to trauma, making this hypothesis plausible.

Considering the overall rarity of metastases to acral sites, it is interesting that our patient developed multiple distal nodules on both the hands and feet. The rapid onset of cutaneous nodules shortly after a course of chemotherapy led the team to consider the physiologic effects of paclitaxel and bevacizumab in the etiology of the acral cutaneous metastases. Karamouzis et al³ described a similar case of multiple cutaneous metastases with a bilateral acral distribution. This case also was associated with chemotherapy in the treatment of breast cancer. The authors proposed hand-foot syndrome, a chemotherapy-related eruption localized to acral skin, as a possible mechanism for hematogenous spread of malignant cells.³ The pathogenesis of hand-foot syndrome is not well understood, but the unique anatomy and physiology of acral skin including temperature gradients, rapidly dividing epidermal cells, absence of hair follicles and sebaceous glands, wide dermal papillae, and exposure to high pressures from carrying body weight and repetitive minor trauma may contribute to the localization of signs and symptoms.^3,4 Our case supports a chemotherapy-related etiology of acral cutaneous metastasis of a primary breast cancer; however, our patient did not have apparent signs or symptoms of hand-foot syndrome during the course of treatment. We propose that effects of bevacizumab on acral skin may have contributed to the development of our patient’s metastatic pattern.

Bevacizumab, a monoclonal antibody to vascular endothelial growth factor A, has well-known vascular side effects. Unlike the inhibition of vascular endothelial growth factor A provided by the receptor tyrosine kinase inhibitors sorafenib and sunitinib, bevacizumab typically is not associated with hand-foot syndrome.⁵ However, several cases have been reported with chemotherapy-associated palmoplantar eruptions that resolved after withholding bevacizumab while continuing other chemotherapeutic agents, suggesting that bevacizumab-induced changes in acral skin contributed to the eruption.⁶ Specific factors that could contribute to acral metastasis in patients taking bevacizumab are endothelial dysfunction and capillary rarefaction of the acral skin, as well as hemorrhage, decreased wound healing, and changes in vascular permeability.^5,7

We present a rare case of acral cutaneous metastasis associated with bevacizumab, one of few reported cases associated with a taxane chemotherapeutic agent.³ More cases need to be identified and reported to establish a causative association, if indeed existent, between acral cutaneous metastasis of breast carcinoma and the use of bevacizumab as well as other chemotherapeutic drugs.

Cutaneous metastasis of internal malignancy is a relatively uncommon phenomenon, with an overall incidence of 5.3% in cancer patients.¹ Cutaneous involvement typically occurs late in the course of disease but can occasionally be the first extranodal sign of metastatic disease. Breast cancer has the highest rate of cutaneous metastasis, most often involving the chest wall¹; however, cutaneous metastasis to the acral sites is exceedingly rare. The hand is the site of 0.1% of all metastatic lesions, with only 10% of these being cutaneous lesions and the remaining 90% being osseous metastases.² Herein, we report a case of multiple cutaneous metastases to acral sites involving the palmar and plantar surfaces of the hands and feet.

Case Report

A 54-year-old black woman with a history of stage IV carcinoma of the breast was admitted to the university medical center with exquisitely painful cutaneous nodules on the hands and feet of 5 weeks’ duration that had started to cause difficulty with walking and daily activities. The patient reported that the breast carcinoma had initially been diagnosed in Nigeria 2 years prior, but she did not receive treatment until moving to the United States. She received a total of 4 cycles of chemotherapy with paclitaxel and bevacizumab, which was discontinued 6 weeks prior to admission due to pain in the lower extremities that was thought to be secondary to neuropathy. One week after discontinuation of chemotherapy, the patient reported increasing pain in the extremities and new-onset painful nodules on the hands and feet. Treatment with gabapentin as well as several courses of antibiotics failed to improve the condition.

She was admitted for symptomatic pain control and a dermatology consultation. Physical examination revealed multiple firm, tender, subcutaneous nodules on the volar surfaces of the soles, toes, palms, and fingertips (Figure 1). A nodule also was noted on the scalp. A punch biopsy of a nodule on the right fourth finger revealed a dermal carcinoma (Figure 2). On immunohistochemistry, the tumor stained positive for cytokeratin 5/6, cytokeratin 7, and gross cystic disease fluid protein 15. It did not demonstrate connection to the epidermis or adnexal structures. Although the tumor did not express estrogen or progesterone receptors, the findings were compatible with metastasis from the patient’s primary breast carcinoma with poor differentiation. A biopsy of the primary breast carcinoma was not available for review from Nigeria.

Comment

The majority of cases reporting acral cutaneous metastasis from internal malignancies are unilateral, involving only one extremity. Several hypotheses have been provided, including spread from localized trauma, which causes disruption of blood vessels and consequent extravasation and localization of tumor cells into the extravascular space.³ The distal extremities are particularly vulnerable to trauma, making this hypothesis plausible.

Considering the overall rarity of metastases to acral sites, it is interesting that our patient developed multiple distal nodules on both the hands and feet. The rapid onset of cutaneous nodules shortly after a course of chemotherapy led the team to consider the physiologic effects of paclitaxel and bevacizumab in the etiology of the acral cutaneous metastases. Karamouzis et al³ described a similar case of multiple cutaneous metastases with a bilateral acral distribution. This case also was associated with chemotherapy in the treatment of breast cancer. The authors proposed hand-foot syndrome, a chemotherapy-related eruption localized to acral skin, as a possible mechanism for hematogenous spread of malignant cells.³ The pathogenesis of hand-foot syndrome is not well understood, but the unique anatomy and physiology of acral skin including temperature gradients, rapidly dividing epidermal cells, absence of hair follicles and sebaceous glands, wide dermal papillae, and exposure to high pressures from carrying body weight and repetitive minor trauma may contribute to the localization of signs and symptoms.^3,4 Our case supports a chemotherapy-related etiology of acral cutaneous metastasis of a primary breast cancer; however, our patient did not have apparent signs or symptoms of hand-foot syndrome during the course of treatment. We propose that effects of bevacizumab on acral skin may have contributed to the development of our patient’s metastatic pattern.

Bevacizumab, a monoclonal antibody to vascular endothelial growth factor A, has well-known vascular side effects. Unlike the inhibition of vascular endothelial growth factor A provided by the receptor tyrosine kinase inhibitors sorafenib and sunitinib, bevacizumab typically is not associated with hand-foot syndrome.⁵ However, several cases have been reported with chemotherapy-associated palmoplantar eruptions that resolved after withholding bevacizumab while continuing other chemotherapeutic agents, suggesting that bevacizumab-induced changes in acral skin contributed to the eruption.⁶ Specific factors that could contribute to acral metastasis in patients taking bevacizumab are endothelial dysfunction and capillary rarefaction of the acral skin, as well as hemorrhage, decreased wound healing, and changes in vascular permeability.^5,7

We present a rare case of acral cutaneous metastasis associated with bevacizumab, one of few reported cases associated with a taxane chemotherapeutic agent.³ More cases need to be identified and reported to establish a causative association, if indeed existent, between acral cutaneous metastasis of breast carcinoma and the use of bevacizumab as well as other chemotherapeutic drugs.