Nonmelanoma Skin Cancer

Basaloid follicular hamartoma (BFH) is a benign adnexal tumor consisting of basaloid cells with follicular differentiation. BFH can occur as a solitary lesion, multiple lesions, or an autosomal dominant inherited syndrome—BFH syndrome (BFHS).1 In patients with BFHS, adnexal tumors predominantly occur on the head, neck, and torso. The syndrome often has coexisting hypotrichosis, hypohidrosis, and palmar/plantar pitting.1 A familial presentation of BFHS with palmar pitting is discussed with a review of BFHS, including the differential diagnosis of palmar pitting. 

Case Report
A 67-year-old white woman presented to dermatology with a 20-year history of several lesions on her face that started as flesh-colored papules and progressively darkened. Most lesions were 3 to 6 mm and located symmetrically around the nose, mouth, chin, and eyes. The woman presented with her 39-year-old daughter, who had a 2-year history of similar lesions around her eyes, none in a perioral distribution. The women reported that when the mother's lesions first appeared, they had the same appearance as the daughter's lesions. The persistent lesions were otherwise asymptomatic. Review of systems for both the mother and daughter were negative for other cutaneous lesions and for systemic symptoms such as fever; weight loss; and cardiovascular, respiratory, gastrointestinal, and genitourinary symptoms. The mother's medical history was significant for hypertension, diabetes mellitus, hypothyroidism, and hypercholesterolemia. The daughter's medical history was significant only for diabetes mellitus. Results of a physical examination of the mother revealed hundreds of soft flesh-colored to hyperpigmented papules, most less than 6 mm in diameter. The papules coalesced in the perioral distribution (Figure 1). Results of a physical examination of the daughter revealed similar symmetric distribution of small (most 1–2 mm but all <6 mm in diameter) flesh-colored papules in bilateral nasolabial and periorbital areas. Symmetric palmar pitting was present in both women (Figure 2). The patients had no other clinical manifestations such as frontoparietal bossing, high arched palates, jaw cysts, short fourth metacarpals, ocular hypertelorism, or narrow sloping shoulders to suggest nevoid basal cell carcinoma syndrome (NBCS). Histopathology results of both the mother and daughter revealed adnexal proliferation with follicular differentiation consistent with BFH (Figures 3–5).

Comment

BFH is a rare benign adnexal tumor that exhibits protean clinical manifestations. Despite the polymorphic clinical presentations, lesions exhibit similar histologic appearance, with only small variations.1,2 Lesions exist in both solitary and multiple forms.1-4 Multiple forms generally exhibit autosomal dominant inheritance, while solitary forms usually are not inherited.3 The solitary noninherited forms are more common than the multiple autosomal dominant inherited forms.3,5

Most reported solitary cases of BFH are in women, aged 20 to 88 years (median, 66 years; mean, 63 years).3 Patients with multiple familial disease may exhibit associated systemic diseases, though systemic disease is less likely in patients with solitary lesions.2,3 Systemic diseases that may be associated with BFHS include hypertension, cardiovascular disease, renal disease, obesity, carpal tunnel syndrome, and cancer of the breast and stomach.6 Generalized lesions also have been associated with cystic fibrosis,7 systemic lupus erythematosus,8 and myasthenia gravis.9

BFHS lesions have a predilection for the face and scalp but also have been reported on the neck, axillae, shoulders, and pubic regions.4 Wheeler et al6 examined 18 members in one family and found that dominantly-inherited generalized BFHS exhibits variability of disease. The patients exhibited lesions that ranged from hundreds of pigmented papules with associated hypotrichosis and palmar/ plantar pitting to minimal facial papules and a few milia involving only the face.6 Most papules are 1 to 2 mm.3 In mild forms, the lesions may go unnoticed or may be mistaken as normal.6 Lesions also may be present at birth or may develop in early childhood.6,10-12

Findings on physical examination most commonly associated with BFHS include milialike papules, comedonal-like papules, hypotrichosis, hypohidrosis, and palmar/plantar pitting (Table).6 Less common associated findings include atopic dermatitis, keratosis pilaris, lichen striatus, acrochordons, acanthosis nigricans—like changes, dermatosis papulosa nigra, acne vulgaris, café au lait spots, punctate palmar keratosis, and steatocystoma multiplex.6

The differential diagnoses of multiple facial papules include angiofibromas (tuberous sclerosis), multiple trichilemmomas (Cowden disease), multiple trichoepitheliomas, multiple syringomas, steatocystoma multiplex, seborrheic keratosis, melanocytic nevi, sebaceous hyperplasia, and NBCS or Gorlin syndrome.3 NBCS is believed to be caused by a lack of human homoloque patched (PTCH) tumor suppressor gene function, whereas BFHS is reported to be caused by a decrease in PTCH function.13 Girardi et al10 suggested that familial BFHS possibly is a forme fruste of NBCS (ie, since both entities involve the PTCH gene protein product or some member of its pathway).

Histologically, branching cords and thin strands of undifferentiated and anastomosing basaloid proliferations, which are surrounded by a loosely fibroblastic stroma, identify BFH.1 This histologic pattern may be found in a wide spectrum of clinically nevoid presentations, and individual lesions may be indistinguishable from infundibulocystic basal cell carcinoma (BCC). Occasional peripheral pallisading, papillary mesenchymal bodies, and connections to the epidermis also have been described.1

BFH is categorized within the spectrum of basaloid epithelial neoplasms associated with dysregulation of the PTCH signaling pathway.13 However, in general, BFH lesions show less mitotic figures and necrosis when compared with BCC.6,13 Immunohistochemistry results show CD34+ stromal cells in peritumoral distribution, resembling trichoepithelioma and distinguishing the condition from BCC, which lacks CD34 expression.14 Additional factors that distinguish BFH from BCC include BFH’s low proliferative index (ie, low Ki-67) and lack of bcl-2 expression.13,14

BFHS is a rare entity. It is a mainly histologic diagnosis with varied clinical presentations.6 Prognosis is good and treatment usually is cosmetic with shave, curette, or scissor methods most frequently reported.3 Because of the benign nature of this follicular tumor, observation without treatment is an option. It is important to be able to recognize this disease to avoid overaggressive surgical management and to closely monitor for any new tumors that may develop in these lesions.1 Monitoring and close follow-up of these lesions is necessary because some believe that familial BFHS is possibly a forme fruste of NBCS. Any indications of malignant changes in these lesions (eg, nonhealing and bleeding lesions, biopsy suggestive of BCC or other skin cancer) warrant surgical therapy. If lesions do not indicate malignant change, however, they may be removed for cosmetic reasons, but aggressive surgery, such as Mohs micrographic surgery, may put the patient at risk for unnecessary infection and increased morbidity.1

Basaloid follicular hamartoma (BFH) is a benign adnexal tumor consisting of basaloid cells with follicular differentiation. BFH can occur as a solitary lesion, multiple lesions, or an autosomal dominant inherited syndrome—BFH syndrome (BFHS).1 In patients with BFHS, adnexal tumors predominantly occur on the head, neck, and torso. The syndrome often has coexisting hypotrichosis, hypohidrosis, and palmar/plantar pitting.1 A familial presentation of BFHS with palmar pitting is discussed with a review of BFHS, including the differential diagnosis of palmar pitting. 

Case Report
A 67-year-old white woman presented to dermatology with a 20-year history of several lesions on her face that started as flesh-colored papules and progressively darkened. Most lesions were 3 to 6 mm and located symmetrically around the nose, mouth, chin, and eyes. The woman presented with her 39-year-old daughter, who had a 2-year history of similar lesions around her eyes, none in a perioral distribution. The women reported that when the mother's lesions first appeared, they had the same appearance as the daughter's lesions. The persistent lesions were otherwise asymptomatic. Review of systems for both the mother and daughter were negative for other cutaneous lesions and for systemic symptoms such as fever; weight loss; and cardiovascular, respiratory, gastrointestinal, and genitourinary symptoms. The mother's medical history was significant for hypertension, diabetes mellitus, hypothyroidism, and hypercholesterolemia. The daughter's medical history was significant only for diabetes mellitus. Results of a physical examination of the mother revealed hundreds of soft flesh-colored to hyperpigmented papules, most less than 6 mm in diameter. The papules coalesced in the perioral distribution (Figure 1). Results of a physical examination of the daughter revealed similar symmetric distribution of small (most 1–2 mm but all <6 mm in diameter) flesh-colored papules in bilateral nasolabial and periorbital areas. Symmetric palmar pitting was present in both women (Figure 2). The patients had no other clinical manifestations such as frontoparietal bossing, high arched palates, jaw cysts, short fourth metacarpals, ocular hypertelorism, or narrow sloping shoulders to suggest nevoid basal cell carcinoma syndrome (NBCS). Histopathology results of both the mother and daughter revealed adnexal proliferation with follicular differentiation consistent with BFH (Figures 3–5).

Comment

BFH is a rare benign adnexal tumor that exhibits protean clinical manifestations. Despite the polymorphic clinical presentations, lesions exhibit similar histologic appearance, with only small variations.1,2 Lesions exist in both solitary and multiple forms.1-4 Multiple forms generally exhibit autosomal dominant inheritance, while solitary forms usually are not inherited.3 The solitary noninherited forms are more common than the multiple autosomal dominant inherited forms.3,5

Most reported solitary cases of BFH are in women, aged 20 to 88 years (median, 66 years; mean, 63 years).3 Patients with multiple familial disease may exhibit associated systemic diseases, though systemic disease is less likely in patients with solitary lesions.2,3 Systemic diseases that may be associated with BFHS include hypertension, cardiovascular disease, renal disease, obesity, carpal tunnel syndrome, and cancer of the breast and stomach.6 Generalized lesions also have been associated with cystic fibrosis,7 systemic lupus erythematosus,8 and myasthenia gravis.9

BFHS lesions have a predilection for the face and scalp but also have been reported on the neck, axillae, shoulders, and pubic regions.4 Wheeler et al6 examined 18 members in one family and found that dominantly-inherited generalized BFHS exhibits variability of disease. The patients exhibited lesions that ranged from hundreds of pigmented papules with associated hypotrichosis and palmar/ plantar pitting to minimal facial papules and a few milia involving only the face.6 Most papules are 1 to 2 mm.3 In mild forms, the lesions may go unnoticed or may be mistaken as normal.6 Lesions also may be present at birth or may develop in early childhood.6,10-12

Findings on physical examination most commonly associated with BFHS include milialike papules, comedonal-like papules, hypotrichosis, hypohidrosis, and palmar/plantar pitting (Table).6 Less common associated findings include atopic dermatitis, keratosis pilaris, lichen striatus, acrochordons, acanthosis nigricans—like changes, dermatosis papulosa nigra, acne vulgaris, café au lait spots, punctate palmar keratosis, and steatocystoma multiplex.6

The differential diagnoses of multiple facial papules include angiofibromas (tuberous sclerosis), multiple trichilemmomas (Cowden disease), multiple trichoepitheliomas, multiple syringomas, steatocystoma multiplex, seborrheic keratosis, melanocytic nevi, sebaceous hyperplasia, and NBCS or Gorlin syndrome.3 NBCS is believed to be caused by a lack of human homoloque patched (PTCH) tumor suppressor gene function, whereas BFHS is reported to be caused by a decrease in PTCH function.13 Girardi et al10 suggested that familial BFHS possibly is a forme fruste of NBCS (ie, since both entities involve the PTCH gene protein product or some member of its pathway).

Histologically, branching cords and thin strands of undifferentiated and anastomosing basaloid proliferations, which are surrounded by a loosely fibroblastic stroma, identify BFH.1 This histologic pattern may be found in a wide spectrum of clinically nevoid presentations, and individual lesions may be indistinguishable from infundibulocystic basal cell carcinoma (BCC). Occasional peripheral pallisading, papillary mesenchymal bodies, and connections to the epidermis also have been described.1

BFH is categorized within the spectrum of basaloid epithelial neoplasms associated with dysregulation of the PTCH signaling pathway.13 However, in general, BFH lesions show less mitotic figures and necrosis when compared with BCC.6,13 Immunohistochemistry results show CD34+ stromal cells in peritumoral distribution, resembling trichoepithelioma and distinguishing the condition from BCC, which lacks CD34 expression.14 Additional factors that distinguish BFH from BCC include BFH’s low proliferative index (ie, low Ki-67) and lack of bcl-2 expression.13,14

BFHS is a rare entity. It is a mainly histologic diagnosis with varied clinical presentations.6 Prognosis is good and treatment usually is cosmetic with shave, curette, or scissor methods most frequently reported.3 Because of the benign nature of this follicular tumor, observation without treatment is an option. It is important to be able to recognize this disease to avoid overaggressive surgical management and to closely monitor for any new tumors that may develop in these lesions.1 Monitoring and close follow-up of these lesions is necessary because some believe that familial BFHS is possibly a forme fruste of NBCS. Any indications of malignant changes in these lesions (eg, nonhealing and bleeding lesions, biopsy suggestive of BCC or other skin cancer) warrant surgical therapy. If lesions do not indicate malignant change, however, they may be removed for cosmetic reasons, but aggressive surgery, such as Mohs micrographic surgery, may put the patient at risk for unnecessary infection and increased morbidity.1

Basaloid follicular hamartoma (BFH) is a benign adnexal tumor consisting of basaloid cells with follicular differentiation. BFH can occur as a solitary lesion, multiple lesions, or an autosomal dominant inherited syndrome—BFH syndrome (BFHS).1 In patients with BFHS, adnexal tumors predominantly occur on the head, neck, and torso. The syndrome often has coexisting hypotrichosis, hypohidrosis, and palmar/plantar pitting.1 A familial presentation of BFHS with palmar pitting is discussed with a review of BFHS, including the differential diagnosis of palmar pitting. 

Case Report
A 67-year-old white woman presented to dermatology with a 20-year history of several lesions on her face that started as flesh-colored papules and progressively darkened. Most lesions were 3 to 6 mm and located symmetrically around the nose, mouth, chin, and eyes. The woman presented with her 39-year-old daughter, who had a 2-year history of similar lesions around her eyes, none in a perioral distribution. The women reported that when the mother's lesions first appeared, they had the same appearance as the daughter's lesions. The persistent lesions were otherwise asymptomatic. Review of systems for both the mother and daughter were negative for other cutaneous lesions and for systemic symptoms such as fever; weight loss; and cardiovascular, respiratory, gastrointestinal, and genitourinary symptoms. The mother's medical history was significant for hypertension, diabetes mellitus, hypothyroidism, and hypercholesterolemia. The daughter's medical history was significant only for diabetes mellitus. Results of a physical examination of the mother revealed hundreds of soft flesh-colored to hyperpigmented papules, most less than 6 mm in diameter. The papules coalesced in the perioral distribution (Figure 1). Results of a physical examination of the daughter revealed similar symmetric distribution of small (most 1–2 mm but all <6 mm in diameter) flesh-colored papules in bilateral nasolabial and periorbital areas. Symmetric palmar pitting was present in both women (Figure 2). The patients had no other clinical manifestations such as frontoparietal bossing, high arched palates, jaw cysts, short fourth metacarpals, ocular hypertelorism, or narrow sloping shoulders to suggest nevoid basal cell carcinoma syndrome (NBCS). Histopathology results of both the mother and daughter revealed adnexal proliferation with follicular differentiation consistent with BFH (Figures 3–5).

Comment

BFH is a rare benign adnexal tumor that exhibits protean clinical manifestations. Despite the polymorphic clinical presentations, lesions exhibit similar histologic appearance, with only small variations.1,2 Lesions exist in both solitary and multiple forms.1-4 Multiple forms generally exhibit autosomal dominant inheritance, while solitary forms usually are not inherited.3 The solitary noninherited forms are more common than the multiple autosomal dominant inherited forms.3,5

Most reported solitary cases of BFH are in women, aged 20 to 88 years (median, 66 years; mean, 63 years).3 Patients with multiple familial disease may exhibit associated systemic diseases, though systemic disease is less likely in patients with solitary lesions.2,3 Systemic diseases that may be associated with BFHS include hypertension, cardiovascular disease, renal disease, obesity, carpal tunnel syndrome, and cancer of the breast and stomach.6 Generalized lesions also have been associated with cystic fibrosis,7 systemic lupus erythematosus,8 and myasthenia gravis.9

BFHS lesions have a predilection for the face and scalp but also have been reported on the neck, axillae, shoulders, and pubic regions.4 Wheeler et al6 examined 18 members in one family and found that dominantly-inherited generalized BFHS exhibits variability of disease. The patients exhibited lesions that ranged from hundreds of pigmented papules with associated hypotrichosis and palmar/ plantar pitting to minimal facial papules and a few milia involving only the face.6 Most papules are 1 to 2 mm.3 In mild forms, the lesions may go unnoticed or may be mistaken as normal.6 Lesions also may be present at birth or may develop in early childhood.6,10-12

Findings on physical examination most commonly associated with BFHS include milialike papules, comedonal-like papules, hypotrichosis, hypohidrosis, and palmar/plantar pitting (Table).6 Less common associated findings include atopic dermatitis, keratosis pilaris, lichen striatus, acrochordons, acanthosis nigricans—like changes, dermatosis papulosa nigra, acne vulgaris, café au lait spots, punctate palmar keratosis, and steatocystoma multiplex.6

The differential diagnoses of multiple facial papules include angiofibromas (tuberous sclerosis), multiple trichilemmomas (Cowden disease), multiple trichoepitheliomas, multiple syringomas, steatocystoma multiplex, seborrheic keratosis, melanocytic nevi, sebaceous hyperplasia, and NBCS or Gorlin syndrome.3 NBCS is believed to be caused by a lack of human homoloque patched (PTCH) tumor suppressor gene function, whereas BFHS is reported to be caused by a decrease in PTCH function.13 Girardi et al10 suggested that familial BFHS possibly is a forme fruste of NBCS (ie, since both entities involve the PTCH gene protein product or some member of its pathway).

Histologically, branching cords and thin strands of undifferentiated and anastomosing basaloid proliferations, which are surrounded by a loosely fibroblastic stroma, identify BFH.1 This histologic pattern may be found in a wide spectrum of clinically nevoid presentations, and individual lesions may be indistinguishable from infundibulocystic basal cell carcinoma (BCC). Occasional peripheral pallisading, papillary mesenchymal bodies, and connections to the epidermis also have been described.1

BFH is categorized within the spectrum of basaloid epithelial neoplasms associated with dysregulation of the PTCH signaling pathway.13 However, in general, BFH lesions show less mitotic figures and necrosis when compared with BCC.6,13 Immunohistochemistry results show CD34+ stromal cells in peritumoral distribution, resembling trichoepithelioma and distinguishing the condition from BCC, which lacks CD34 expression.14 Additional factors that distinguish BFH from BCC include BFH’s low proliferative index (ie, low Ki-67) and lack of bcl-2 expression.13,14

BFHS is a rare entity. It is a mainly histologic diagnosis with varied clinical presentations.6 Prognosis is good and treatment usually is cosmetic with shave, curette, or scissor methods most frequently reported.3 Because of the benign nature of this follicular tumor, observation without treatment is an option. It is important to be able to recognize this disease to avoid overaggressive surgical management and to closely monitor for any new tumors that may develop in these lesions.1 Monitoring and close follow-up of these lesions is necessary because some believe that familial BFHS is possibly a forme fruste of NBCS. Any indications of malignant changes in these lesions (eg, nonhealing and bleeding lesions, biopsy suggestive of BCC or other skin cancer) warrant surgical therapy. If lesions do not indicate malignant change, however, they may be removed for cosmetic reasons, but aggressive surgery, such as Mohs micrographic surgery, may put the patient at risk for unnecessary infection and increased morbidity.1

Adenoid cystic carcinoma (ACC) is a well-known tumor of the salivary glands and oral cavity that accounts for 10% to 15% of all head and neck tumors worldwide.1 In contrast, primary cutaneous ACC is a rare tumor, with less than 50 cases reported to date.2-10 We report an additional case of primary cutaneous ACC and describe the clinical presentation, histologic findings, and subsequent treatment. A brief review of the literature also is provided. 

Case Report
A 57-year-old white woman presented to her dermatologist with a one-year history of an enlarging flesh-colored nodule on the left side of the scalp. The patient's medical history was significant only for bradycardia and hypertension. The results of a biopsy of a tumor specimen revealed a large neoplasm composed of epithelial cells that filled the entire dermis (Figure). There was no connection between the tumor and the epidermis. The tumor cells were arranged in multiple lobules that varied in size and shape and that were separated by fibrous stroma. Some of the lobules showed cystic change and others showed ductal differentiation, imparting an overall cribriform appearance to the tumor. The tumor cells were small and basophilic in nature. Perineural invasion was not present. The findings were characteristic of ACC.

The patient underwent Mohs micrographic surgery for excision of the tumor. Clearance was achieved in 3 stages. The final defect measured 3.0x3.5 cm, extended through the periosteum, and primarily was closed. To rule out an extracutaneous primary site, computed tomography scans were obtained of the head, neck, chest, and abdomen. The scan results were unremarkable. The patient had no symptomatology of her head or neck. Results of an examination by an otolaryngologist revealed no abnormalities of the minor salivary glands, parotid glands, submandibular glands, tongue, oropharyngeal and nasal cavities, or ears. The patient then underwent 33 local radiation treatments to the scalp (total radiation dose of 5940 cGy) to decrease the possibility of recurrence. At 28 months postsurgery, she had no signs of recurrence. 

Comment

ACC accounts for about 10% to 15% of head and neck tumors and most frequently occurs in the major and minor salivary glands; other sites that may be involved include the tracheobronchial tree, esophagus, lacrimal gland, ear canal, breast, uterine cervix, Bartholin glands, prostate, mucosal glands of the upper respiratory tract, and skin.1,4,11 ACC of the head and neck usually is a slow-growing tumor. Local recurrences are frequent; and metastasis, which occurs in 21% to 54% of cases, tends to involve the lung, liver, bone, and brain.12-14 Cutaneous metastasis from ACC of the head and neck is rare.15,16 Primary cutaneous ACC is a rare tumor that was first reported by Boggio in 1975.2 Primary cutaneous ACC most commonly involves the scalp and presents as a slow-growing nondescript nodule. The local recurrence rate after excision is approximately 50%.3,17 Nodal metastasis from primary cutaneous ACC is rare.3,4 To our knowledge, 5 cases of visceral metastasis from primary cutaneous ACC have been reported.^7,8 Histologically, the tumor is composed of epithelial cells arranged into multiple lobules, many of which show cystic change and therefore impart a cribriform appearance to the tumor. There is no connection between the tumor lobules and the epidermis. The tumor displays an infiltrating pattern that fills the entire dermis and that frequently invades the subcutaneous tissue. Perineural invasion is seen in approximately one half of cases; vascular invasion occurs less commonly.8,18,19 Basophilic mucinous material is present within the cystic lobules, and the stroma between the lobules is fibrous. The epithelial cells are small and basophilic with scant cytoplasm. Mitotic figures are rare. In addition to the cribriform areas, tubular foci sometimes are found.15,18 The main tumor that histologically may mimic primary cutaneous ACC is adenoid basal cell carcinoma. Both tumors are composed of small epithelial cells with minimal cytoplasm that are arranged into multiple cystic lobules, giving rise to an adenoid or cribriform appearance; additionally, both tumors contain abundant mucin. Adenoid basal cell carcinoma differs from primary cutaneous ACC in several ways: the tumor lobules may connect with the epidermis; perineural invasion is rare; peripheral palisading and retraction artifact may be present; and the stroma may be more cellular.5,19 Immunohistochemical staining may be useful in distinguishing tumors that are difficult to differentiate based on the results of histologic evaluations (Table).17,19

The cell of origin for primary cutaneous ACC is not known. Many authors believe that primary cutaneous ACC arises from the eccrine gland or duct; however, primary cutaneous ACC also occurs in the ear canal, which does not contain eccrine glands. Furthermore, ACC can arise in a variety of different organs. Therefore, ACC likely has a different cell of origin in different locations in the body, all of which give rise to tumors with a similar histologic appearance.5,8 Treatment recommendations for primary cutaneous ACC consist of either wide local excision or Mohs micrographic surgery.7-9,17,18 The high rate of perineural spread accounts for the large recurrence rate after local excision with minimal margins or without micrographic control. One group has used Mohs micrographic surgery using a toluidine blue stain (instead of the usual hematoxylin-eosin stain), which metachromatically stains the abundant mucin found within the tumor and may help to better delineate the tumor's margins.10 Some patients have had adjuvant local radiation therapy to decrease recurrence rates,7 but some clinicians find radiation to be ineffective.18,19 Visceral metastases from primary cutaneous ACC either have been treated with chemotherapy or have been monitored radiographically.7,8 In summary, primary cutaneous ACC is a rare tumor and is much less common than ACC arising in other sites. Therefore, a diagnosis of primary cutaneous ACC should be considered only after an extracutaneous origin has been ruled out. Because ACC most frequently arises from the salivary glands (and less commonly from other locations in the head and neck or elsewhere in the body), a complete physical examination of the head and neck region, preferably by an otolaryngologist, should be performed. Additional imaging studies may be useful. Because the risk of local recurrence is high, the authors recommend Mohs micrographic surgery for treatment of this tumor. Additionally, adjuvant radiation treatment may be helpful.

Adenoid cystic carcinoma (ACC) is a well-known tumor of the salivary glands and oral cavity that accounts for 10% to 15% of all head and neck tumors worldwide.1 In contrast, primary cutaneous ACC is a rare tumor, with less than 50 cases reported to date.2-10 We report an additional case of primary cutaneous ACC and describe the clinical presentation, histologic findings, and subsequent treatment. A brief review of the literature also is provided. 

Case Report
A 57-year-old white woman presented to her dermatologist with a one-year history of an enlarging flesh-colored nodule on the left side of the scalp. The patient's medical history was significant only for bradycardia and hypertension. The results of a biopsy of a tumor specimen revealed a large neoplasm composed of epithelial cells that filled the entire dermis (Figure). There was no connection between the tumor and the epidermis. The tumor cells were arranged in multiple lobules that varied in size and shape and that were separated by fibrous stroma. Some of the lobules showed cystic change and others showed ductal differentiation, imparting an overall cribriform appearance to the tumor. The tumor cells were small and basophilic in nature. Perineural invasion was not present. The findings were characteristic of ACC.

The patient underwent Mohs micrographic surgery for excision of the tumor. Clearance was achieved in 3 stages. The final defect measured 3.0x3.5 cm, extended through the periosteum, and primarily was closed. To rule out an extracutaneous primary site, computed tomography scans were obtained of the head, neck, chest, and abdomen. The scan results were unremarkable. The patient had no symptomatology of her head or neck. Results of an examination by an otolaryngologist revealed no abnormalities of the minor salivary glands, parotid glands, submandibular glands, tongue, oropharyngeal and nasal cavities, or ears. The patient then underwent 33 local radiation treatments to the scalp (total radiation dose of 5940 cGy) to decrease the possibility of recurrence. At 28 months postsurgery, she had no signs of recurrence. 

Comment

ACC accounts for about 10% to 15% of head and neck tumors and most frequently occurs in the major and minor salivary glands; other sites that may be involved include the tracheobronchial tree, esophagus, lacrimal gland, ear canal, breast, uterine cervix, Bartholin glands, prostate, mucosal glands of the upper respiratory tract, and skin.1,4,11 ACC of the head and neck usually is a slow-growing tumor. Local recurrences are frequent; and metastasis, which occurs in 21% to 54% of cases, tends to involve the lung, liver, bone, and brain.12-14 Cutaneous metastasis from ACC of the head and neck is rare.15,16 Primary cutaneous ACC is a rare tumor that was first reported by Boggio in 1975.2 Primary cutaneous ACC most commonly involves the scalp and presents as a slow-growing nondescript nodule. The local recurrence rate after excision is approximately 50%.3,17 Nodal metastasis from primary cutaneous ACC is rare.3,4 To our knowledge, 5 cases of visceral metastasis from primary cutaneous ACC have been reported.^7,8 Histologically, the tumor is composed of epithelial cells arranged into multiple lobules, many of which show cystic change and therefore impart a cribriform appearance to the tumor. There is no connection between the tumor lobules and the epidermis. The tumor displays an infiltrating pattern that fills the entire dermis and that frequently invades the subcutaneous tissue. Perineural invasion is seen in approximately one half of cases; vascular invasion occurs less commonly.8,18,19 Basophilic mucinous material is present within the cystic lobules, and the stroma between the lobules is fibrous. The epithelial cells are small and basophilic with scant cytoplasm. Mitotic figures are rare. In addition to the cribriform areas, tubular foci sometimes are found.15,18 The main tumor that histologically may mimic primary cutaneous ACC is adenoid basal cell carcinoma. Both tumors are composed of small epithelial cells with minimal cytoplasm that are arranged into multiple cystic lobules, giving rise to an adenoid or cribriform appearance; additionally, both tumors contain abundant mucin. Adenoid basal cell carcinoma differs from primary cutaneous ACC in several ways: the tumor lobules may connect with the epidermis; perineural invasion is rare; peripheral palisading and retraction artifact may be present; and the stroma may be more cellular.5,19 Immunohistochemical staining may be useful in distinguishing tumors that are difficult to differentiate based on the results of histologic evaluations (Table).17,19

The cell of origin for primary cutaneous ACC is not known. Many authors believe that primary cutaneous ACC arises from the eccrine gland or duct; however, primary cutaneous ACC also occurs in the ear canal, which does not contain eccrine glands. Furthermore, ACC can arise in a variety of different organs. Therefore, ACC likely has a different cell of origin in different locations in the body, all of which give rise to tumors with a similar histologic appearance.5,8 Treatment recommendations for primary cutaneous ACC consist of either wide local excision or Mohs micrographic surgery.7-9,17,18 The high rate of perineural spread accounts for the large recurrence rate after local excision with minimal margins or without micrographic control. One group has used Mohs micrographic surgery using a toluidine blue stain (instead of the usual hematoxylin-eosin stain), which metachromatically stains the abundant mucin found within the tumor and may help to better delineate the tumor's margins.10 Some patients have had adjuvant local radiation therapy to decrease recurrence rates,7 but some clinicians find radiation to be ineffective.18,19 Visceral metastases from primary cutaneous ACC either have been treated with chemotherapy or have been monitored radiographically.7,8 In summary, primary cutaneous ACC is a rare tumor and is much less common than ACC arising in other sites. Therefore, a diagnosis of primary cutaneous ACC should be considered only after an extracutaneous origin has been ruled out. Because ACC most frequently arises from the salivary glands (and less commonly from other locations in the head and neck or elsewhere in the body), a complete physical examination of the head and neck region, preferably by an otolaryngologist, should be performed. Additional imaging studies may be useful. Because the risk of local recurrence is high, the authors recommend Mohs micrographic surgery for treatment of this tumor. Additionally, adjuvant radiation treatment may be helpful.

Adenoid cystic carcinoma (ACC) is a well-known tumor of the salivary glands and oral cavity that accounts for 10% to 15% of all head and neck tumors worldwide.1 In contrast, primary cutaneous ACC is a rare tumor, with less than 50 cases reported to date.2-10 We report an additional case of primary cutaneous ACC and describe the clinical presentation, histologic findings, and subsequent treatment. A brief review of the literature also is provided. 

Case Report
A 57-year-old white woman presented to her dermatologist with a one-year history of an enlarging flesh-colored nodule on the left side of the scalp. The patient's medical history was significant only for bradycardia and hypertension. The results of a biopsy of a tumor specimen revealed a large neoplasm composed of epithelial cells that filled the entire dermis (Figure). There was no connection between the tumor and the epidermis. The tumor cells were arranged in multiple lobules that varied in size and shape and that were separated by fibrous stroma. Some of the lobules showed cystic change and others showed ductal differentiation, imparting an overall cribriform appearance to the tumor. The tumor cells were small and basophilic in nature. Perineural invasion was not present. The findings were characteristic of ACC.

The patient underwent Mohs micrographic surgery for excision of the tumor. Clearance was achieved in 3 stages. The final defect measured 3.0x3.5 cm, extended through the periosteum, and primarily was closed. To rule out an extracutaneous primary site, computed tomography scans were obtained of the head, neck, chest, and abdomen. The scan results were unremarkable. The patient had no symptomatology of her head or neck. Results of an examination by an otolaryngologist revealed no abnormalities of the minor salivary glands, parotid glands, submandibular glands, tongue, oropharyngeal and nasal cavities, or ears. The patient then underwent 33 local radiation treatments to the scalp (total radiation dose of 5940 cGy) to decrease the possibility of recurrence. At 28 months postsurgery, she had no signs of recurrence. 

Comment

ACC accounts for about 10% to 15% of head and neck tumors and most frequently occurs in the major and minor salivary glands; other sites that may be involved include the tracheobronchial tree, esophagus, lacrimal gland, ear canal, breast, uterine cervix, Bartholin glands, prostate, mucosal glands of the upper respiratory tract, and skin.1,4,11 ACC of the head and neck usually is a slow-growing tumor. Local recurrences are frequent; and metastasis, which occurs in 21% to 54% of cases, tends to involve the lung, liver, bone, and brain.12-14 Cutaneous metastasis from ACC of the head and neck is rare.15,16 Primary cutaneous ACC is a rare tumor that was first reported by Boggio in 1975.2 Primary cutaneous ACC most commonly involves the scalp and presents as a slow-growing nondescript nodule. The local recurrence rate after excision is approximately 50%.3,17 Nodal metastasis from primary cutaneous ACC is rare.3,4 To our knowledge, 5 cases of visceral metastasis from primary cutaneous ACC have been reported.^7,8 Histologically, the tumor is composed of epithelial cells arranged into multiple lobules, many of which show cystic change and therefore impart a cribriform appearance to the tumor. There is no connection between the tumor lobules and the epidermis. The tumor displays an infiltrating pattern that fills the entire dermis and that frequently invades the subcutaneous tissue. Perineural invasion is seen in approximately one half of cases; vascular invasion occurs less commonly.8,18,19 Basophilic mucinous material is present within the cystic lobules, and the stroma between the lobules is fibrous. The epithelial cells are small and basophilic with scant cytoplasm. Mitotic figures are rare. In addition to the cribriform areas, tubular foci sometimes are found.15,18 The main tumor that histologically may mimic primary cutaneous ACC is adenoid basal cell carcinoma. Both tumors are composed of small epithelial cells with minimal cytoplasm that are arranged into multiple cystic lobules, giving rise to an adenoid or cribriform appearance; additionally, both tumors contain abundant mucin. Adenoid basal cell carcinoma differs from primary cutaneous ACC in several ways: the tumor lobules may connect with the epidermis; perineural invasion is rare; peripheral palisading and retraction artifact may be present; and the stroma may be more cellular.5,19 Immunohistochemical staining may be useful in distinguishing tumors that are difficult to differentiate based on the results of histologic evaluations (Table).17,19

The cell of origin for primary cutaneous ACC is not known. Many authors believe that primary cutaneous ACC arises from the eccrine gland or duct; however, primary cutaneous ACC also occurs in the ear canal, which does not contain eccrine glands. Furthermore, ACC can arise in a variety of different organs. Therefore, ACC likely has a different cell of origin in different locations in the body, all of which give rise to tumors with a similar histologic appearance.5,8 Treatment recommendations for primary cutaneous ACC consist of either wide local excision or Mohs micrographic surgery.7-9,17,18 The high rate of perineural spread accounts for the large recurrence rate after local excision with minimal margins or without micrographic control. One group has used Mohs micrographic surgery using a toluidine blue stain (instead of the usual hematoxylin-eosin stain), which metachromatically stains the abundant mucin found within the tumor and may help to better delineate the tumor's margins.10 Some patients have had adjuvant local radiation therapy to decrease recurrence rates,7 but some clinicians find radiation to be ineffective.18,19 Visceral metastases from primary cutaneous ACC either have been treated with chemotherapy or have been monitored radiographically.7,8 In summary, primary cutaneous ACC is a rare tumor and is much less common than ACC arising in other sites. Therefore, a diagnosis of primary cutaneous ACC should be considered only after an extracutaneous origin has been ruled out. Because ACC most frequently arises from the salivary glands (and less commonly from other locations in the head and neck or elsewhere in the body), a complete physical examination of the head and neck region, preferably by an otolaryngologist, should be performed. Additional imaging studies may be useful. Because the risk of local recurrence is high, the authors recommend Mohs micrographic surgery for treatment of this tumor. Additionally, adjuvant radiation treatment may be helpful.

Angiosarcoma is an aggressive neoplasm that predominantly affects elderly patients. Most cases appear on the scalp and face de novo; however, trauma, longstanding lymphedema, and irradiation are predisposing factors. Management includes a multidisciplinary team and may involve a combination of surgery, radiation, and chemotherapy tailored to the patient’s age and associated comorbidities.

Bruiselike patches on the face and scalp of elderly patients should raise the index of suspicion for angiosarcoma. A biopsy of the lesion and a workup for other organ involvement should be considered. We present the case of an elderly patient with an angiosarcoma and discuss the management and follow-up along with a brief review of the current literature. 

Case Report
In February 2002, an 80-year-old white man presented with approximately a 3-month history of a growing raised area on the nose (Figure). The patient first noticed a sudden onset of redness on the right side of his nose in December 2001. The redness gradually darkened over the next 3 months.

Examination revealed a 30-X20-mm purplish red plaque on the right side of the patient's nose. Results of a 4-mm punch biopsy showed an angiosarcoma. The patient was referred to an ear, nose, and throat physician with a special interest in oncology. He also was evaluated by an oncologist. Results of the patient's physical examination were unremarkable except for the skin lesion on his nose. Results of a complete blood count, x-ray, and computed tomography of the chest, as well as an abdominal ultrasound and magnetic resonance imaging of the head and neck, were unremarkable for masses, lymphadenopathy, or other significant findings. In March 2002, the patient underwent excision of the tumor followed by skin grafting. Six weeks after the operation, the patient was started on external beam radiation therapy. He was treated with 98 Gy over 49 days (2.0 Gy daily). Results of follow-up physical examinations by the multidisciplinary team did not reveal any signs or symptoms of tumor recurrence. On the patient's last follow-up visit in April 2005, he showed no evidence of recurrence of the lesion or metastasis. No follow-up photographs were taken. 

Comment

Cutaneous angiosarcoma of the face and scalp is a distinct entity among the angiosarcomas. It was first described in detail by Jones1 in 1964 as malignant angioendothelioma of the skin.2 This aggressive vascular neoplasm predominantly affects elderly patients (average age, 70 years).3 Men are affected twice as frequently as women. Men also tend to develop the disease at an earlier age. The tumor is localized mostly to the upper half of the face and the scalp.3 Predisposing factors in the onset of angiosarcoma include trauma, longstanding lymphedema, and irradiation of benign vascular lesions; however, most cases present with no obvious etiology.4 The clinical presentation of angiosarcoma is variable. Ill-defined bruiselike areas or facial edema with minimal erythema are the initial signs. Progressively more indurated plaques appear with nodular or ulcerated components. The neoplasm spreads quickly, centrifugally, and transdermally.5,6 Multifocality also is possible. The original clinical size of the tumor rarely correlates to the degree of microscopic tissue invasion.7 Unusual presentations have included yellowish plaques over the upper eyelids that resemble xanthelasma and cause ptosis,8 rosacealike lesions,9 and lesions presenting with scarring alopecia.10 Angiosarcoma presenting with intermittent angioedema of the face that comes and goes is another uncommon manifestation.11 Rhinophymalike features also should be considered as an unusual clinical manifestation of cutaneous angiosarcoma.12 Diagnosis often is delayed by the variable presentation and the benign appearance of the lesion, which simulates a bruise or a hemangioma. Retrospective studies show that clinical diagnosis of cutaneous angiosarcomas often is difficult.13 Other lesions that may need to be differentiated from angiosarcoma on the face include hemangiomas, Kaposi sarcomas, malignant melanomas, metastases, and vascular venous malformations. A summary of the characteristic features is included in the Table.

Pathologically, 2 main patterns of angiomas are recognized: angiomatous and solid.9 The angiomatous pattern is characterized by irregular, anastomosing vascular channels that dissect through the collagen. The vessels are lined by endothelial cells with features that range from normal-appearing endothelial cells to pleomorphic, hyperchromatic cells that exhibit multi-layering. Papillary processes may be present within the lumen. Numerous normal or abnormal mitotic figures are present as well. A dense mononuclear cell infiltrate is present and correlates with a better prognosis. In the solid form of angiosarcoma, tumor cells may be spindle or polygonal shaped. Vascular architecture may not be identified in the poorly differentiated areas. Reticulin staining highlights the vascular channels.9 Possible immunohistochemical markers for angiosarcoma include ulex europaeus 1 lectin (sensitive marker; used in conjunction with epithelial membrane antigen and cytokeratin to exclude epithelial tumor); factor VIII antigen (highly specific; low detection sensitivity); CD34 cells (highly sensitive; stains dermal dendrocytes, sweat gland basement membrane, and hematopoietic progenitor cells); and CD31 cells (highly sensitive; good specificity).7,19 Several differential diagnoses should be considered on pathology.20 Unlike benign vascular lesions, the well-differentiated angiomatous areas in angiosarcoma display cytologic atypia; multilayering, papillary structures; and irregular anastomosing blood vessels. In Kaposi sarcoma, cytologic atypia is less prominent and there is no endothelial multilayering.20 The optimal treatment of cutaneous angiosarcoma has not been defined.21 Generally, radical surgery and postoperative radiotherapy are advocated to treat patients with these tumors. In many patients, surgery often is not feasible because of the tumor's multifocal nature and local spread pattern.21 Therefore, the results have been poor. In a study by Mark et al,22 only 1 of 12 patients had the disease locally controlled. Holden et al23 reported 1 cure in 7 patients treated with surgery alone. The surgical aim is to resect all clinically identifiable disease.24 In areas of doubt, microscopic control of surgical margins may have a role in guiding the extent of resection. Achieving a negative margin frequently is difficult in angiosarcoma patients because of the extensive microscopic spread that is so common in this disease. Therefore, in trying to achieve a negative margin, a wound is created that almost never can be closed primarily. The reconstructive surgeon has a number of options for initial temporary coverage, as well as definitive reconstruction, including homograft skin, autologous skin graft, rotation flaps, and free flaps.24 Angiosarcomas usually respond to radiotherapy to some degree and most studies suggest that a combination of surgery and radiotherapy offers the best chance for long-term control.3,21 In 1 series of 28 angiosarcomas of the head and neck, Mark et al22 reported better survival after a median 32 months with combined surgery and radiotherapy compared with surgery alone. In cases unsuited for surgery, radiotherapy alone may be considered; however, usually only partial responses are achieved. Morrison et al21 suggested that moderate doses of radiation could control subclinical disease. Because angiosarcoma is a systemic disease, chemotherapy may be useful in its management.25 The efficacy of chemotherapy is undefined, with some studies reporting a beneficial effect and others suggesting no survival benefit. Chemotherapeutic agents used have included doxorubicin, cyclophosphamide, dacarbazine, actinomycin D, methotrexate, and vincristine.25 Systemic paclitaxel therapy has been used with encouraging results in 3 patients with angiosarcoma with regression of the lesions.26 Spieth and colleagues27 reported the effectiveness of 13-cis-retinoic acid and interferon alfa-2a combination therapy in a patient with recurring cutaneous angiosarcoma of the head after radical radiation treatment. There is no optimal treatment for angiosarcoma and the search for effective systemic treatment is needed. The prognosis in angiosarcoma is poor because of its high potential for metastasis.28 The 5-year survival rate is about 12%. Prognostic factors include the size of the tumor and mitotic counts, with tumors less than 10 cm in diameter and those with low mitotic counts having a better prognosis.28

Conclusion

Angiosarcomas are rare, aggressive tumors of vascular origin. They occur most often in areas of long-term sun-exposed skin in elderly patients, patients with longstanding lymphedema, or patients who have completed radiation therapy. The prognosis is poor and radical surgery is often required. In addition, radiation or chemotherapy may be considered as therapeutic options.

Angiosarcoma is an aggressive neoplasm that predominantly affects elderly patients. Most cases appear on the scalp and face de novo; however, trauma, longstanding lymphedema, and irradiation are predisposing factors. Management includes a multidisciplinary team and may involve a combination of surgery, radiation, and chemotherapy tailored to the patient’s age and associated comorbidities.

Bruiselike patches on the face and scalp of elderly patients should raise the index of suspicion for angiosarcoma. A biopsy of the lesion and a workup for other organ involvement should be considered. We present the case of an elderly patient with an angiosarcoma and discuss the management and follow-up along with a brief review of the current literature. 

Case Report
In February 2002, an 80-year-old white man presented with approximately a 3-month history of a growing raised area on the nose (Figure). The patient first noticed a sudden onset of redness on the right side of his nose in December 2001. The redness gradually darkened over the next 3 months.

Examination revealed a 30-X20-mm purplish red plaque on the right side of the patient's nose. Results of a 4-mm punch biopsy showed an angiosarcoma. The patient was referred to an ear, nose, and throat physician with a special interest in oncology. He also was evaluated by an oncologist. Results of the patient's physical examination were unremarkable except for the skin lesion on his nose. Results of a complete blood count, x-ray, and computed tomography of the chest, as well as an abdominal ultrasound and magnetic resonance imaging of the head and neck, were unremarkable for masses, lymphadenopathy, or other significant findings. In March 2002, the patient underwent excision of the tumor followed by skin grafting. Six weeks after the operation, the patient was started on external beam radiation therapy. He was treated with 98 Gy over 49 days (2.0 Gy daily). Results of follow-up physical examinations by the multidisciplinary team did not reveal any signs or symptoms of tumor recurrence. On the patient's last follow-up visit in April 2005, he showed no evidence of recurrence of the lesion or metastasis. No follow-up photographs were taken. 

Comment

Cutaneous angiosarcoma of the face and scalp is a distinct entity among the angiosarcomas. It was first described in detail by Jones1 in 1964 as malignant angioendothelioma of the skin.2 This aggressive vascular neoplasm predominantly affects elderly patients (average age, 70 years).3 Men are affected twice as frequently as women. Men also tend to develop the disease at an earlier age. The tumor is localized mostly to the upper half of the face and the scalp.3 Predisposing factors in the onset of angiosarcoma include trauma, longstanding lymphedema, and irradiation of benign vascular lesions; however, most cases present with no obvious etiology.4 The clinical presentation of angiosarcoma is variable. Ill-defined bruiselike areas or facial edema with minimal erythema are the initial signs. Progressively more indurated plaques appear with nodular or ulcerated components. The neoplasm spreads quickly, centrifugally, and transdermally.5,6 Multifocality also is possible. The original clinical size of the tumor rarely correlates to the degree of microscopic tissue invasion.7 Unusual presentations have included yellowish plaques over the upper eyelids that resemble xanthelasma and cause ptosis,8 rosacealike lesions,9 and lesions presenting with scarring alopecia.10 Angiosarcoma presenting with intermittent angioedema of the face that comes and goes is another uncommon manifestation.11 Rhinophymalike features also should be considered as an unusual clinical manifestation of cutaneous angiosarcoma.12 Diagnosis often is delayed by the variable presentation and the benign appearance of the lesion, which simulates a bruise or a hemangioma. Retrospective studies show that clinical diagnosis of cutaneous angiosarcomas often is difficult.13 Other lesions that may need to be differentiated from angiosarcoma on the face include hemangiomas, Kaposi sarcomas, malignant melanomas, metastases, and vascular venous malformations. A summary of the characteristic features is included in the Table.

Pathologically, 2 main patterns of angiomas are recognized: angiomatous and solid.9 The angiomatous pattern is characterized by irregular, anastomosing vascular channels that dissect through the collagen. The vessels are lined by endothelial cells with features that range from normal-appearing endothelial cells to pleomorphic, hyperchromatic cells that exhibit multi-layering. Papillary processes may be present within the lumen. Numerous normal or abnormal mitotic figures are present as well. A dense mononuclear cell infiltrate is present and correlates with a better prognosis. In the solid form of angiosarcoma, tumor cells may be spindle or polygonal shaped. Vascular architecture may not be identified in the poorly differentiated areas. Reticulin staining highlights the vascular channels.9 Possible immunohistochemical markers for angiosarcoma include ulex europaeus 1 lectin (sensitive marker; used in conjunction with epithelial membrane antigen and cytokeratin to exclude epithelial tumor); factor VIII antigen (highly specific; low detection sensitivity); CD34 cells (highly sensitive; stains dermal dendrocytes, sweat gland basement membrane, and hematopoietic progenitor cells); and CD31 cells (highly sensitive; good specificity).7,19 Several differential diagnoses should be considered on pathology.20 Unlike benign vascular lesions, the well-differentiated angiomatous areas in angiosarcoma display cytologic atypia; multilayering, papillary structures; and irregular anastomosing blood vessels. In Kaposi sarcoma, cytologic atypia is less prominent and there is no endothelial multilayering.20 The optimal treatment of cutaneous angiosarcoma has not been defined.21 Generally, radical surgery and postoperative radiotherapy are advocated to treat patients with these tumors. In many patients, surgery often is not feasible because of the tumor's multifocal nature and local spread pattern.21 Therefore, the results have been poor. In a study by Mark et al,22 only 1 of 12 patients had the disease locally controlled. Holden et al23 reported 1 cure in 7 patients treated with surgery alone. The surgical aim is to resect all clinically identifiable disease.24 In areas of doubt, microscopic control of surgical margins may have a role in guiding the extent of resection. Achieving a negative margin frequently is difficult in angiosarcoma patients because of the extensive microscopic spread that is so common in this disease. Therefore, in trying to achieve a negative margin, a wound is created that almost never can be closed primarily. The reconstructive surgeon has a number of options for initial temporary coverage, as well as definitive reconstruction, including homograft skin, autologous skin graft, rotation flaps, and free flaps.24 Angiosarcomas usually respond to radiotherapy to some degree and most studies suggest that a combination of surgery and radiotherapy offers the best chance for long-term control.3,21 In 1 series of 28 angiosarcomas of the head and neck, Mark et al22 reported better survival after a median 32 months with combined surgery and radiotherapy compared with surgery alone. In cases unsuited for surgery, radiotherapy alone may be considered; however, usually only partial responses are achieved. Morrison et al21 suggested that moderate doses of radiation could control subclinical disease. Because angiosarcoma is a systemic disease, chemotherapy may be useful in its management.25 The efficacy of chemotherapy is undefined, with some studies reporting a beneficial effect and others suggesting no survival benefit. Chemotherapeutic agents used have included doxorubicin, cyclophosphamide, dacarbazine, actinomycin D, methotrexate, and vincristine.25 Systemic paclitaxel therapy has been used with encouraging results in 3 patients with angiosarcoma with regression of the lesions.26 Spieth and colleagues27 reported the effectiveness of 13-cis-retinoic acid and interferon alfa-2a combination therapy in a patient with recurring cutaneous angiosarcoma of the head after radical radiation treatment. There is no optimal treatment for angiosarcoma and the search for effective systemic treatment is needed. The prognosis in angiosarcoma is poor because of its high potential for metastasis.28 The 5-year survival rate is about 12%. Prognostic factors include the size of the tumor and mitotic counts, with tumors less than 10 cm in diameter and those with low mitotic counts having a better prognosis.28

Conclusion

Angiosarcomas are rare, aggressive tumors of vascular origin. They occur most often in areas of long-term sun-exposed skin in elderly patients, patients with longstanding lymphedema, or patients who have completed radiation therapy. The prognosis is poor and radical surgery is often required. In addition, radiation or chemotherapy may be considered as therapeutic options.

Angiosarcoma is an aggressive neoplasm that predominantly affects elderly patients. Most cases appear on the scalp and face de novo; however, trauma, longstanding lymphedema, and irradiation are predisposing factors. Management includes a multidisciplinary team and may involve a combination of surgery, radiation, and chemotherapy tailored to the patient’s age and associated comorbidities.

Bruiselike patches on the face and scalp of elderly patients should raise the index of suspicion for angiosarcoma. A biopsy of the lesion and a workup for other organ involvement should be considered. We present the case of an elderly patient with an angiosarcoma and discuss the management and follow-up along with a brief review of the current literature. 

Case Report
In February 2002, an 80-year-old white man presented with approximately a 3-month history of a growing raised area on the nose (Figure). The patient first noticed a sudden onset of redness on the right side of his nose in December 2001. The redness gradually darkened over the next 3 months.

Examination revealed a 30-X20-mm purplish red plaque on the right side of the patient's nose. Results of a 4-mm punch biopsy showed an angiosarcoma. The patient was referred to an ear, nose, and throat physician with a special interest in oncology. He also was evaluated by an oncologist. Results of the patient's physical examination were unremarkable except for the skin lesion on his nose. Results of a complete blood count, x-ray, and computed tomography of the chest, as well as an abdominal ultrasound and magnetic resonance imaging of the head and neck, were unremarkable for masses, lymphadenopathy, or other significant findings. In March 2002, the patient underwent excision of the tumor followed by skin grafting. Six weeks after the operation, the patient was started on external beam radiation therapy. He was treated with 98 Gy over 49 days (2.0 Gy daily). Results of follow-up physical examinations by the multidisciplinary team did not reveal any signs or symptoms of tumor recurrence. On the patient's last follow-up visit in April 2005, he showed no evidence of recurrence of the lesion or metastasis. No follow-up photographs were taken. 

Comment

Cutaneous angiosarcoma of the face and scalp is a distinct entity among the angiosarcomas. It was first described in detail by Jones1 in 1964 as malignant angioendothelioma of the skin.2 This aggressive vascular neoplasm predominantly affects elderly patients (average age, 70 years).3 Men are affected twice as frequently as women. Men also tend to develop the disease at an earlier age. The tumor is localized mostly to the upper half of the face and the scalp.3 Predisposing factors in the onset of angiosarcoma include trauma, longstanding lymphedema, and irradiation of benign vascular lesions; however, most cases present with no obvious etiology.4 The clinical presentation of angiosarcoma is variable. Ill-defined bruiselike areas or facial edema with minimal erythema are the initial signs. Progressively more indurated plaques appear with nodular or ulcerated components. The neoplasm spreads quickly, centrifugally, and transdermally.5,6 Multifocality also is possible. The original clinical size of the tumor rarely correlates to the degree of microscopic tissue invasion.7 Unusual presentations have included yellowish plaques over the upper eyelids that resemble xanthelasma and cause ptosis,8 rosacealike lesions,9 and lesions presenting with scarring alopecia.10 Angiosarcoma presenting with intermittent angioedema of the face that comes and goes is another uncommon manifestation.11 Rhinophymalike features also should be considered as an unusual clinical manifestation of cutaneous angiosarcoma.12 Diagnosis often is delayed by the variable presentation and the benign appearance of the lesion, which simulates a bruise or a hemangioma. Retrospective studies show that clinical diagnosis of cutaneous angiosarcomas often is difficult.13 Other lesions that may need to be differentiated from angiosarcoma on the face include hemangiomas, Kaposi sarcomas, malignant melanomas, metastases, and vascular venous malformations. A summary of the characteristic features is included in the Table.

Pathologically, 2 main patterns of angiomas are recognized: angiomatous and solid.9 The angiomatous pattern is characterized by irregular, anastomosing vascular channels that dissect through the collagen. The vessels are lined by endothelial cells with features that range from normal-appearing endothelial cells to pleomorphic, hyperchromatic cells that exhibit multi-layering. Papillary processes may be present within the lumen. Numerous normal or abnormal mitotic figures are present as well. A dense mononuclear cell infiltrate is present and correlates with a better prognosis. In the solid form of angiosarcoma, tumor cells may be spindle or polygonal shaped. Vascular architecture may not be identified in the poorly differentiated areas. Reticulin staining highlights the vascular channels.9 Possible immunohistochemical markers for angiosarcoma include ulex europaeus 1 lectin (sensitive marker; used in conjunction with epithelial membrane antigen and cytokeratin to exclude epithelial tumor); factor VIII antigen (highly specific; low detection sensitivity); CD34 cells (highly sensitive; stains dermal dendrocytes, sweat gland basement membrane, and hematopoietic progenitor cells); and CD31 cells (highly sensitive; good specificity).7,19 Several differential diagnoses should be considered on pathology.20 Unlike benign vascular lesions, the well-differentiated angiomatous areas in angiosarcoma display cytologic atypia; multilayering, papillary structures; and irregular anastomosing blood vessels. In Kaposi sarcoma, cytologic atypia is less prominent and there is no endothelial multilayering.20 The optimal treatment of cutaneous angiosarcoma has not been defined.21 Generally, radical surgery and postoperative radiotherapy are advocated to treat patients with these tumors. In many patients, surgery often is not feasible because of the tumor's multifocal nature and local spread pattern.21 Therefore, the results have been poor. In a study by Mark et al,22 only 1 of 12 patients had the disease locally controlled. Holden et al23 reported 1 cure in 7 patients treated with surgery alone. The surgical aim is to resect all clinically identifiable disease.24 In areas of doubt, microscopic control of surgical margins may have a role in guiding the extent of resection. Achieving a negative margin frequently is difficult in angiosarcoma patients because of the extensive microscopic spread that is so common in this disease. Therefore, in trying to achieve a negative margin, a wound is created that almost never can be closed primarily. The reconstructive surgeon has a number of options for initial temporary coverage, as well as definitive reconstruction, including homograft skin, autologous skin graft, rotation flaps, and free flaps.24 Angiosarcomas usually respond to radiotherapy to some degree and most studies suggest that a combination of surgery and radiotherapy offers the best chance for long-term control.3,21 In 1 series of 28 angiosarcomas of the head and neck, Mark et al22 reported better survival after a median 32 months with combined surgery and radiotherapy compared with surgery alone. In cases unsuited for surgery, radiotherapy alone may be considered; however, usually only partial responses are achieved. Morrison et al21 suggested that moderate doses of radiation could control subclinical disease. Because angiosarcoma is a systemic disease, chemotherapy may be useful in its management.25 The efficacy of chemotherapy is undefined, with some studies reporting a beneficial effect and others suggesting no survival benefit. Chemotherapeutic agents used have included doxorubicin, cyclophosphamide, dacarbazine, actinomycin D, methotrexate, and vincristine.25 Systemic paclitaxel therapy has been used with encouraging results in 3 patients with angiosarcoma with regression of the lesions.26 Spieth and colleagues27 reported the effectiveness of 13-cis-retinoic acid and interferon alfa-2a combination therapy in a patient with recurring cutaneous angiosarcoma of the head after radical radiation treatment. There is no optimal treatment for angiosarcoma and the search for effective systemic treatment is needed. The prognosis in angiosarcoma is poor because of its high potential for metastasis.28 The 5-year survival rate is about 12%. Prognostic factors include the size of the tumor and mitotic counts, with tumors less than 10 cm in diameter and those with low mitotic counts having a better prognosis.28

Conclusion

Angiosarcomas are rare, aggressive tumors of vascular origin. They occur most often in areas of long-term sun-exposed skin in elderly patients, patients with longstanding lymphedema, or patients who have completed radiation therapy. The prognosis is poor and radical surgery is often required. In addition, radiation or chemotherapy may be considered as therapeutic options.