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The other skin cancers (non-melanoma, non-basal cell carcinoma, non-squamous cell carcinoma)
The Other Skin Cancers (Non-Melanoma, Non–Basal Cell Carcinoma, Non–Squamous Cell Carcinoma) Henry W. Randle, MD, PhD
There are more than 1 million skin cancers diagnosed and treated in the United States each year. More than 30 different types of skin cancer have been described.1,2 Dermatologists are familiar with the common basal cell carcinomas, squamous cell carcinomas, and malignant melanomas. The diagnosis and treatment of these have been described elsewhere.3,4 With the evolution of Mohs micrographic surgery and dermatologic surgery, dermatologists have emerged as the experts for the other skin cancers. Although some of these cancers may be encountered only 1 to 2 times per year or less often, dermatologists need to know how to proceed with the evaluation, selection of treatment, and surgical margins and when it is appropriate to refer these patients for excision of their tumors by complete margin control (Mohs micrographic surgery), wide excision, sentinel node biopsy, elective lymph node dissection, or radiation therapy or oncologic treatment (or both). The purpose of this chapter is to provide guidelines for managing the other skin cancers and to provide a heightened awareness of them.3
Merkel Cell Carcinoma Trabecular Carcinoma, Primary Small Cell Carcinoma of the Skin, Primary Neuroepithelial Tumor of the Skin, Murky Cell Carcinoma, Cutaneous Apudoma, Neuroendocrine Carcinoma of the Skin Merkel cell carcinoma was first described in 1972 as a solitary, dome-shaped, painless, pink to violaceous nodule that may be shiny with telangiectasias and resembles a basal cell carcinoma (Fig 1). These occur more commonly on the head and neck of persons with actinically damaged fair skin, supporting a relationship to ultraviolet light damage. They are frequently misdiagnosed by light microscopy and therefore an adequate biopsy is needed. These may grow rapidly, extending into the fat and muscle, and are an extremely dangerous cutaneous tumor. Local recurrence is seen in one third of persons within 4 to 12 months after excision; regional nodal
Curr Probl Dermatol, March/April 2001
metastases develop in one half; distant metastases to the liver, bone, brain, lung, and skin develop in one third; and at least one third die of their disease. Therefore, patients with these tumors should be evaluated like those with a thick malignant melanoma, including a complete review of systems, physical examination with a total skin examination, and lymph node, liver, and spleen palpation. Baseline chest radiographs, chemistry group, and computed tomography of the chest should be considered.5 The aggressive behavior dictates an aggressive treatment plan, which usually consists of a wide excision (2 to 3 cm) of the primary tumor. Mohs micrographic surgery has been used with some success.6 The tumor is radiosensitive, and postoperative radiation to the primary site should be strongly considered. The status of the lymph nodes should be ascertained by palpation and, if palpable, consider lymph node dissection of the lymph node basin plus radiation. If not palpable, sentinel node biopsy or radiation to the lymph node bed may be considered. Sentinel node biopsy is feasible and can be used to stage patients, provide prognostic information, and may direct early regional lymphadenectomy.7 Sentinel node biopsy should be done before the definitive excision of the tumor. Because so few cases are available for a prospective trial (the incidence has been recorded at 0.16 per 100,000 patients), it is difficult to ascertain if this surgery prolongs life. Merkel cell carcinoma is sensitive to multiple chemotherapy agents, but the response is usually short-lived. Follow-up evaluation should be performed frequently.
Atypical Fibroxanthoma Paradoxical Fibrosarcoma of the Skin, Pseudosarcomatous Dermatofibroma, Pseudosarcoma, Pseudosarcomatous Reticulohistiocytosis First described in 1963, atypical fibroxanthoma is another solitary tumor that is often ulcerated and less than 2 cm in diameter, which usually involves the
123
FIG 1. Merkel cell carcinoma on the cheek of an 85-year-old man.
FIG 3. Atypical fibroxanthoma in a 68-year-old man.
It has been reported recently that LN-2, an antigen expressed by B cells, macrophages, and Reed-Sternberg cells, can be used to differentiate these tumors; the majority of malignant fibrous histiocytomas are positive for LN-2.9
Malignant Fibrous Histiocytoma Malignant Fibrous Xanthoma, Fibroxanthosarcoma
FIG 2. Atypical fibroxanthoma preoperatively in a 73-year-old man with renal transplant and receiving immunosuppressive medication.
actinically damaged skin of the head and neck of elderly persons with fair skin, most commonly men. In the majority of cases, the course is relatively benign, with a low recurrence rate of about 10% and rare metastases, usually to the parotid and regional lymph nodes. Atypical fibroxanthoma is best treated by Mohs micrographic surgery,8 although excision with an approximately 1-cm clinically tumor-free margin, including subcutaneous tissue, has been suggested. However, the subclinical extension is often greater than 1 cm (Figs 2 and 3). This fibrohistiocytic tumor may be considered a superficial form of malignant fibrous histiocytoma, which is histologically identical, but the latter penetrates much deeper, usually into the fat and muscle, is most common on the sun-protected lower extremities, and has a poor prognosis. 124
This tumor was first described in the 1960s and is now the most common sarcoma of adults, usually occurring between the ages of 50 and 70 years, and is twice as common in men. It typically appears as a painless, deep, smooth, enlarging tumor of the extremities or abdomen. It is usually located in the subcutaneous tissue and extends through fascia and muscle.10 Malignant fibrous histiocytoma is a locally destructive tumor with a 44% recurrence rate in the first 1 to 2 years after excision, with metastatic rates that approach 40%. Metastatic lesions are usually from a deep penetrating primary tumor. The 5-year survival rate is approximately 60%. Typically, these tumors extend far beyond the clinical mass and require wide local excision of 3 to 5 cm, including the subcutaneous tissue and fascia, or amputation (Fig 4). Mohs micrographic surgery has been used for the smaller more superficial lesions of the head and neck. Lymph node metastases are uncommon, and therefore elective lymph node dissection is usually not performed. Adjunct radiation therapy may reduce the chances of local recurrence, and chemotherapy is usually reserved for palliation. Curr Probl Dermatol, March/April 2001
FIG 5. Dermatofibrosarcoma protuberans.
FIG 4. Malignant fibrous histiocytoma on the leg of an 82-year-old man who died of an unrelated health problem 2 years after amputation.
Dermatofibrosarcoma Protuberans Dermatofibrosarcoma protuberans is a rare (less than 1 case per million persons per year), low-grade sarcoma first described in the 1920s. It differs from Merkel cell carcinoma and atypical fibroxanthoma in that it occurs in younger patients (3rd to 4th decade) on the non–sun-exposed skin. This generally presents as a slow-growing, indurated, multinodular plaque that may be skin-colored, red, reddish brown, or purple on the trunk or extremities of young to middle-aged adults (Figs 5 and 6). It is usually large, with extensive subclinical extension, averaging 5 cm in diameter at the time of diagnosis. This tumor is often associated with local recurrence. Metastasis is unusual (about 4%) but rapidly fatal if it occurs. Tumor recurrence usually occurs within 3 years, and preventing this is important, because recurrence is a strong predictor of metastasis. Standard excision of margins up to 5 cm results in a recurrence rate of 20% or higher. Mohs micrographic surgery has reduced the recurrence rate to less than 5%, Curr Probl Dermatol, March/April 2001
FIG 6. Dermatofibrosarcoma protuberans; local recurrence.
making it the treatment of choice.11,12 Elective lymph node dissection is not usually recommended unless the nodes are clinically palpable. This tumor is considered to be relatively radioresistant, although radiation has been reported as an adjunctive treatment for incompletely excised tumors. Chemotherapy is usually not effective. Those tumors with a fibrosarcomatous histology have a worse prognosis, but the pigmented variant, Bednar tumor, which occurs primarily in persons with dark skin, has the same clinical behavior as the nonpigmented types.
Extramammary Paget Disease This entity was first described in 1889 and is a rare cutaneous neoplasm that is sometimes (12%-25%) seen with an underlying adenocarcinoma. It typically appears in elderly patients as an asymptomatic or sometimes pruritic and painful, reddish brown, eroded patch in the 125
FIG 7. Extramammary Paget disease of the inguinal area; vulvar.
FIG 8. Extramammary Paget disease of perianal skin.
anogenital skin, masquerading as tinea cruris or psoriasis (Figs 7 and 8). In addition, it may occur wherever there are apocrine glands (ie, axilla, chest, and external auditory canal). Recurrence rates are approximately 33% after conventional excision and as high as 23% after Mohs surgery, probably as a result of the pagetoid spread and multifocal nature of this tumor. About 25% of patients with this cancer die of their disease. Patients should be screened for lymph node involvement and underlying internal malignancies. Thorough gastrointestinal, urologic, and gynecologic examinations should be considered.13 Wide excision is the treatment of choice. Generally, several centimeters of normal tissue is included. Radiation therapy may be used in patients unable to undergo operation. Follow-up twice a year is important to detect early recurrence and associated malignancies.
is more frequent in males (2:1). Typically, there is a several-month history of bruised-like, red to purple plaques or nodules that increase in size (Fig 9). This is often a multifocal tumor with ill-defined margins and a poor prognosis. Recurrence and metastasis are frequent, with a 5-year survival rate of 10% to 20%. Average survival is about 20 months after diagnosis. Angiosarcoma is managed by wide local excision followed by adjunctive radiation therapy.14 However, this frequently does not alter the relentless course of this disease. Mohs surgery may be used in selected cases as a tissue-sparing technique, especially when the tumor approaches vital structures. Results with chemotherapy are disappointing. A workup for metastases should be done. Recent response of a patient with advanced disease to the combination of 13-cis-retinoic acid plus interferon alfa-2a may offer a glimmer of hope to patients with this cancer and its otherwise dismal prognosis.15
Angiosarcoma
Sebaceous Carcinoma
Cutaneous angiosarcoma of the face and scalp was first described in 1945, is an uncommon tumor (less than 0.1% of head and neck malignancies) of the elderly, and
First described in the 1800s, this is an uncommon, aggressive malignancy of older adults that is more frequent in women (2:1). It arises most often from periocu-
126
Curr Probl Dermatol, March/April 2001
FIG 10. Sebaceous carcinoma of the upper and lower eyelids; a poor prognosis.
both the upper and lower eyelids are involved (Fig 10), the mortality rate may be more than 80%, but if the lower eyelid alone is involved, mortality is less than 5%.
Leiomyosarcoma FIG 9. Angiosarcoma of the scalp.
lar sebaceous glands. It typically presents as an asymptomatic firm nodule on the inner surface of the eyelids and is frequently misdiagnosed clinically as blepharitis or conjunctivitis. Seventy-five percent of tumors occur on the eyelids, where they are more frequent on the upper than the lower eyelids. This cancer arises from the specialized sebaceous glands of Meibomian and Zeis. Twenty-five percent of tumors are extraocular. There is significant local recurrence of 25% to 30% and metastases 15% to 30% of the time to the regional lymph nodes, liver, lungs, brain, and bone. This tumor may also be associated with Muir-Torre syndrome, so a complete examination with palpation of lymph nodes and screening for colorectal malignancies is indicated, plus referral to an ocular plastic surgeon because exenteration is sometimes necessary. The primary treatment is surgical, usually with at least 0.5-cm margins. Examination of the margins is important; however, these may be multifocal and pagetoid, thus limiting the role of Mohs surgery.16 Cryosurgery is often used for conjunctival pagetoid spread at the same time as the excision. Lymph node dissection should be done if the nodes are palpable, and adjunctive radiation therapy should be considered. Chemotherapy is palliative. Mortality rate depends on the site of involvement. If Curr Probl Dermatol, March/April 2001
Leiomyosarcomas are soft tissue sarcomas that may occur in the retroperitoneum, gastrointestinal tract, uterus, and superficial dermis. The retroperitoneal and intra-abdominal leiomyosarcomas are aggressive, usually advanced, and unresectable at the time of diagnosis. Superficial leiomyosarcomas, on the other hand, which are restricted to the superficial soft tissue, are not aggressive tumors. Cure is difficult, with a 50% to 60% recurrence rate after standard excision. However, distant metastases are infrequent. The tumor tends to be infiltrative and locally aggressive and clinically may present as a discolored, ulcerated, or umbilicated tumor of the middle-aged or elderly; is usually painful; and occurs on the extensor surface of the extremities. These tumors generally present as a single nodule or occasionally grouped nodules with well-circumscribed borders. They grow slowly and are expansile. Traditional management has been with 2- to 5-cm margins. Mohs surgery has been reported recently to be a successful treatment in the majority of cases.17 Lymph node dissection is recommended only if nodal disease is documented. These tumors do not respond well to either radiation therapy or chemotherapy.
Malignant Sweat Gland Tumors Malignant sweat gland tumors (such as malignant eccrine poroma, malignant eccrine spiradenoma, malignant hidradenoma, malignant cylindroma, eccrine carci127
TABLE 1. All skin cancers are not the same Tumor Anatomic location Size Histology Adenopathy Stage Host Age, sex Immunosuppression Associated malignancies Environment Previous treatment Etiology
Recurrence Metastases Mortality Treatment Routine or Multidisciplinary Mohs Wide excision ELND Radiation Chemotherapy Sentinel node biopsy
ELND, Elective lymph node dissection.
FIG 11. Malignant sweat gland tumor of the ear.
noma, and apocrine carcinoma) are rare tumors and poorly understood (Fig 11).18 The majority of these occur on the extremities. A pre-existing lesion that has been present for years may enter a stage of rapid growth and may be large at presentation—up to 5 to 10 cm in diameter. These have a marked tendency to metastasize widely in 40% to 50% of the cases. Wide local excision with control of margins with frozen sections (or Mohs micrographic surgery) is indicated, because these highly aggressive tumors may recur after excision and metastasize. Isotretinoin, interferon-alfa, and interleukin-2 may benefit patients with metastatic disease.
Microcystic Adnexal Carcinoma Sclerosing Sweat Duct Carcinoma, Malignant Syringoma, Sweat Gland Carcinoma With Syringomatous Features, Aggressive Trichofolliculoma, and Combined Adnexal Tumor of the Skin Microcystic adnexal carcinoma was first described in 1982. It is an aggressive, locally destructive cutaneous 128
carcinoma that frequently penetrates deep into the muscle and occasionally bone. Perineural invasion is seen up to 80% of the time. A deep biopsy is indicated because of these features. Typically, the lesion is a slow-growing, indurated, yellowish plaque with a nonulcerated surface on the central face, most commonly the upper lip, that has been present for several years in a person in the fourth decade of life. Although usually asymptomatic, the presence of pain, burning, stinging, anesthesia, or paresthesia suggests perineural involvement. Forty-seven percent of these tumors have been reported to recur after conventional surgical excision. Because of the potential for infiltrating growth with subclinical margins as great as 5 to 6 cm and common perineural involvement, Mohs micrographic surgery is the treatment of choice.19 Recurrence after Mohs surgery is uncommon. Typically, the tumor is deep rather than wide. I am aware of several cases in which superficial syringomatous changes have been pursued by Mohs surgeons more than 10 cm from the primary tumor. It is believed that these superficial syringomatous changes are benign and should not be excised. I am aware of only 1 or 2 cases of metastasis of this tumor, and there have been no deaths recorded. The tumor is radioresistant.
Conclusion Not all skin cancers are the same (Table 1). Some skin cancers are more likely to recur, metastasize, lead to disfigurement, or become fatal for the patient. Therefore, dermatologists must learn to recognize the various kinds of skin cancers so they can select treatments that offer the best possible outcome. As dermatologic surgery and Mohs micrographic surgery have evolved into prominent specialties, dermatologists have assumed the role of carCurr Probl Dermatol, March/April 2001
ing for patients with these unusual tumors. Dermatologists are now considered the experts and expected to have the answers for what constitutes the best therapy for the “other skin cancers.”
REFERENCES 1. Friedman R, Rigel D, Kopf A, Harris N, Baker D, editors. Cancer of the skin. Philadelphia: WB Saunders; 1991. 2. Miller SJ, Maloney ME, editors. Cutaneous oncology: pathophysiology, diagnosis, and management. Malden (MA): Blackwell Science; 1998. 3. Demetrius RW, Randle HW. High-risk nonmelanoma skin cancers. Dermatol Surg 1998;24:1272-92. 4. Randle HW. Basal cell carcinoma. Identification and treatment of the high-risk patient. Dermatol Surg 1996;22:255-61. 5. Ott MJ, Tanabe KK, Gadd MA, Stark P, Smith BL, Finkelstein DM, et al. Multimodality management of Merkel cell carcinoma. Arch Surg 1999;134:388-92. 6. O’Connor WJ, Brodland DG. Merkel cell carcinoma. Dermatol Surg 1996;22:262-7. 7. Hill AD, Brady MS, Coit DG. Intraoperative lymphatic mapping and sentinel lymph node biopsy for Merkel cell carcinoma. Br J Surg 1999;86:518-21. 8. Davis JL, Randle HW, Zalla MJ, Roenigk RK, Brodland DG. A comparison of Mohs micrographic surgery and wide excision for the treatment of atypical fibroxanthoma. Dermatol Surg 1997;23:105-10.
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9. Lazova R, Moynes R, May D, Scott G: LN-2 (CD74). A marker to distinguish atypical fibroxanthoma from malignant fibrous histiocytoma. Cancer 1997;79:2115-24. 10. Enzinger FM, Weiss SW. Soft tissue tumors. 3rd ed. St Louis: Mosby; 1995. p. 351-5. 11. Gloster HM Jr. Dermatofibrosarcoma protuberans. J Am Acad Dermatol 1996;35:355-74. 12. Parker TL, Zitelli JA. Surgical margins for excision of dermatofibrosarcoma protuberans. J Am Acad Dermatol 1995;32: 233-6. 13. Heymann WR. Extramammary Paget disease. Clinical Dermatology 1993;11:83-7. 14. Morrison WH, Byers RM, Garden AS, Evans HL, Ang KK, Peters LJ. Cutaneous angiosarcoma of the head and neck. A therapeutic dilemma. Cancer 1995;76:319-27. 15. Spieth K, Gille J, Kaufmann R. Therapeutic efficacy of interferon alfa-2a and 13-cis-retinoic acid in recurrent angiosarcoma of the head. Arch Dermatol 1999;135:1035-7. 16. Nelson BR, Hamlet KR, Gillard M, Railan D, Johnson TM. Sebaceous carcinoma. J Am Acad Dermatol 1995;33:1-15. 17. Bernstein SC, Roenigk RK. Leiomyosarcoma of the skin. Treatment of 34 cases. Dermatol Surg 1996;22:631-5. 18. Arpey CJ, Argenyi ZB, Whitaker DC. Selected eccrine and apocrine tumors. In: Surgical dermatopathology. Maloney ME, Torres A, Hoffmann TJ, Helm KF, editors. Malden (MA): Blackwell Science; 1999. p. 313-70. 19. Burns MK, Chen SP, Goldberg LH. Microcystic adnexal carcinoma. Ten cases treated by Mohs micrographic surgery. J Dermatol Surg Oncol 1994;20:429-34.
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There are more than 1 million skin cancers diagnosed and treated in the United States each year. More than 30 different types of skin cancer have been described.1,2 Dermatologists are familiar with the common basal cell carcinomas, squamous cell carcinomas, and malignant melanomas. The diagnosis and treatment of these have been described elsewhere.3,4 With the evolution of Mohs micrographic surgery and dermatologic surgery, dermatologists have emerged as the experts for the other skin cancers. Although some of these cancers may be encountered only 1 to 2 times per year or less often, dermatologists need to know how to proceed with the evaluation, selection of treatment, and surgical margins and when it is appropriate to refer these patients for excision of their tumors by complete margin control (Mohs micrographic surgery), wide excision, sentinel node biopsy, elective lymph node dissection, or radiation therapy or oncologic treatment (or both). The purpose of this chapter is to provide guidelines for managing the other skin cancers and to provide a heightened awareness of them.3
Merkel Cell Carcinoma Trabecular Carcinoma, Primary Small Cell Carcinoma of the Skin, Primary Neuroepithelial Tumor of the Skin, Murky Cell Carcinoma, Cutaneous Apudoma, Neuroendocrine Carcinoma of the Skin Merkel cell carcinoma was first described in 1972 as a solitary, dome-shaped, painless, pink to violaceous nodule that may be shiny with telangiectasias and resembles a basal cell carcinoma (Fig 1). These occur more commonly on the head and neck of persons with actinically damaged fair skin, supporting a relationship to ultraviolet light damage. They are frequently misdiagnosed by light microscopy and therefore an adequate biopsy is needed. These may grow rapidly, extending into the fat and muscle, and are an extremely dangerous cutaneous tumor. Local recurrence is seen in one third of persons within 4 to 12 months after excision; regional nodal
Curr Probl Dermatol, March/April 2001
metastases develop in one half; distant metastases to the liver, bone, brain, lung, and skin develop in one third; and at least one third die of their disease. Therefore, patients with these tumors should be evaluated like those with a thick malignant melanoma, including a complete review of systems, physical examination with a total skin examination, and lymph node, liver, and spleen palpation. Baseline chest radiographs, chemistry group, and computed tomography of the chest should be considered.5 The aggressive behavior dictates an aggressive treatment plan, which usually consists of a wide excision (2 to 3 cm) of the primary tumor. Mohs micrographic surgery has been used with some success.6 The tumor is radiosensitive, and postoperative radiation to the primary site should be strongly considered. The status of the lymph nodes should be ascertained by palpation and, if palpable, consider lymph node dissection of the lymph node basin plus radiation. If not palpable, sentinel node biopsy or radiation to the lymph node bed may be considered. Sentinel node biopsy is feasible and can be used to stage patients, provide prognostic information, and may direct early regional lymphadenectomy.7 Sentinel node biopsy should be done before the definitive excision of the tumor. Because so few cases are available for a prospective trial (the incidence has been recorded at 0.16 per 100,000 patients), it is difficult to ascertain if this surgery prolongs life. Merkel cell carcinoma is sensitive to multiple chemotherapy agents, but the response is usually short-lived. Follow-up evaluation should be performed frequently.
Atypical Fibroxanthoma Paradoxical Fibrosarcoma of the Skin, Pseudosarcomatous Dermatofibroma, Pseudosarcoma, Pseudosarcomatous Reticulohistiocytosis First described in 1963, atypical fibroxanthoma is another solitary tumor that is often ulcerated and less than 2 cm in diameter, which usually involves the
123
FIG 1. Merkel cell carcinoma on the cheek of an 85-year-old man.
FIG 3. Atypical fibroxanthoma in a 68-year-old man.
It has been reported recently that LN-2, an antigen expressed by B cells, macrophages, and Reed-Sternberg cells, can be used to differentiate these tumors; the majority of malignant fibrous histiocytomas are positive for LN-2.9
Malignant Fibrous Histiocytoma Malignant Fibrous Xanthoma, Fibroxanthosarcoma
FIG 2. Atypical fibroxanthoma preoperatively in a 73-year-old man with renal transplant and receiving immunosuppressive medication.
actinically damaged skin of the head and neck of elderly persons with fair skin, most commonly men. In the majority of cases, the course is relatively benign, with a low recurrence rate of about 10% and rare metastases, usually to the parotid and regional lymph nodes. Atypical fibroxanthoma is best treated by Mohs micrographic surgery,8 although excision with an approximately 1-cm clinically tumor-free margin, including subcutaneous tissue, has been suggested. However, the subclinical extension is often greater than 1 cm (Figs 2 and 3). This fibrohistiocytic tumor may be considered a superficial form of malignant fibrous histiocytoma, which is histologically identical, but the latter penetrates much deeper, usually into the fat and muscle, is most common on the sun-protected lower extremities, and has a poor prognosis. 124
This tumor was first described in the 1960s and is now the most common sarcoma of adults, usually occurring between the ages of 50 and 70 years, and is twice as common in men. It typically appears as a painless, deep, smooth, enlarging tumor of the extremities or abdomen. It is usually located in the subcutaneous tissue and extends through fascia and muscle.10 Malignant fibrous histiocytoma is a locally destructive tumor with a 44% recurrence rate in the first 1 to 2 years after excision, with metastatic rates that approach 40%. Metastatic lesions are usually from a deep penetrating primary tumor. The 5-year survival rate is approximately 60%. Typically, these tumors extend far beyond the clinical mass and require wide local excision of 3 to 5 cm, including the subcutaneous tissue and fascia, or amputation (Fig 4). Mohs micrographic surgery has been used for the smaller more superficial lesions of the head and neck. Lymph node metastases are uncommon, and therefore elective lymph node dissection is usually not performed. Adjunct radiation therapy may reduce the chances of local recurrence, and chemotherapy is usually reserved for palliation. Curr Probl Dermatol, March/April 2001
FIG 5. Dermatofibrosarcoma protuberans.
FIG 4. Malignant fibrous histiocytoma on the leg of an 82-year-old man who died of an unrelated health problem 2 years after amputation.
Dermatofibrosarcoma Protuberans Dermatofibrosarcoma protuberans is a rare (less than 1 case per million persons per year), low-grade sarcoma first described in the 1920s. It differs from Merkel cell carcinoma and atypical fibroxanthoma in that it occurs in younger patients (3rd to 4th decade) on the non–sun-exposed skin. This generally presents as a slow-growing, indurated, multinodular plaque that may be skin-colored, red, reddish brown, or purple on the trunk or extremities of young to middle-aged adults (Figs 5 and 6). It is usually large, with extensive subclinical extension, averaging 5 cm in diameter at the time of diagnosis. This tumor is often associated with local recurrence. Metastasis is unusual (about 4%) but rapidly fatal if it occurs. Tumor recurrence usually occurs within 3 years, and preventing this is important, because recurrence is a strong predictor of metastasis. Standard excision of margins up to 5 cm results in a recurrence rate of 20% or higher. Mohs micrographic surgery has reduced the recurrence rate to less than 5%, Curr Probl Dermatol, March/April 2001
FIG 6. Dermatofibrosarcoma protuberans; local recurrence.
making it the treatment of choice.11,12 Elective lymph node dissection is not usually recommended unless the nodes are clinically palpable. This tumor is considered to be relatively radioresistant, although radiation has been reported as an adjunctive treatment for incompletely excised tumors. Chemotherapy is usually not effective. Those tumors with a fibrosarcomatous histology have a worse prognosis, but the pigmented variant, Bednar tumor, which occurs primarily in persons with dark skin, has the same clinical behavior as the nonpigmented types.
Extramammary Paget Disease This entity was first described in 1889 and is a rare cutaneous neoplasm that is sometimes (12%-25%) seen with an underlying adenocarcinoma. It typically appears in elderly patients as an asymptomatic or sometimes pruritic and painful, reddish brown, eroded patch in the 125
FIG 7. Extramammary Paget disease of the inguinal area; vulvar.
FIG 8. Extramammary Paget disease of perianal skin.
anogenital skin, masquerading as tinea cruris or psoriasis (Figs 7 and 8). In addition, it may occur wherever there are apocrine glands (ie, axilla, chest, and external auditory canal). Recurrence rates are approximately 33% after conventional excision and as high as 23% after Mohs surgery, probably as a result of the pagetoid spread and multifocal nature of this tumor. About 25% of patients with this cancer die of their disease. Patients should be screened for lymph node involvement and underlying internal malignancies. Thorough gastrointestinal, urologic, and gynecologic examinations should be considered.13 Wide excision is the treatment of choice. Generally, several centimeters of normal tissue is included. Radiation therapy may be used in patients unable to undergo operation. Follow-up twice a year is important to detect early recurrence and associated malignancies.
is more frequent in males (2:1). Typically, there is a several-month history of bruised-like, red to purple plaques or nodules that increase in size (Fig 9). This is often a multifocal tumor with ill-defined margins and a poor prognosis. Recurrence and metastasis are frequent, with a 5-year survival rate of 10% to 20%. Average survival is about 20 months after diagnosis. Angiosarcoma is managed by wide local excision followed by adjunctive radiation therapy.14 However, this frequently does not alter the relentless course of this disease. Mohs surgery may be used in selected cases as a tissue-sparing technique, especially when the tumor approaches vital structures. Results with chemotherapy are disappointing. A workup for metastases should be done. Recent response of a patient with advanced disease to the combination of 13-cis-retinoic acid plus interferon alfa-2a may offer a glimmer of hope to patients with this cancer and its otherwise dismal prognosis.15
Angiosarcoma
Sebaceous Carcinoma
Cutaneous angiosarcoma of the face and scalp was first described in 1945, is an uncommon tumor (less than 0.1% of head and neck malignancies) of the elderly, and
First described in the 1800s, this is an uncommon, aggressive malignancy of older adults that is more frequent in women (2:1). It arises most often from periocu-
126
Curr Probl Dermatol, March/April 2001
FIG 10. Sebaceous carcinoma of the upper and lower eyelids; a poor prognosis.
both the upper and lower eyelids are involved (Fig 10), the mortality rate may be more than 80%, but if the lower eyelid alone is involved, mortality is less than 5%.
Leiomyosarcoma FIG 9. Angiosarcoma of the scalp.
lar sebaceous glands. It typically presents as an asymptomatic firm nodule on the inner surface of the eyelids and is frequently misdiagnosed clinically as blepharitis or conjunctivitis. Seventy-five percent of tumors occur on the eyelids, where they are more frequent on the upper than the lower eyelids. This cancer arises from the specialized sebaceous glands of Meibomian and Zeis. Twenty-five percent of tumors are extraocular. There is significant local recurrence of 25% to 30% and metastases 15% to 30% of the time to the regional lymph nodes, liver, lungs, brain, and bone. This tumor may also be associated with Muir-Torre syndrome, so a complete examination with palpation of lymph nodes and screening for colorectal malignancies is indicated, plus referral to an ocular plastic surgeon because exenteration is sometimes necessary. The primary treatment is surgical, usually with at least 0.5-cm margins. Examination of the margins is important; however, these may be multifocal and pagetoid, thus limiting the role of Mohs surgery.16 Cryosurgery is often used for conjunctival pagetoid spread at the same time as the excision. Lymph node dissection should be done if the nodes are palpable, and adjunctive radiation therapy should be considered. Chemotherapy is palliative. Mortality rate depends on the site of involvement. If Curr Probl Dermatol, March/April 2001
Leiomyosarcomas are soft tissue sarcomas that may occur in the retroperitoneum, gastrointestinal tract, uterus, and superficial dermis. The retroperitoneal and intra-abdominal leiomyosarcomas are aggressive, usually advanced, and unresectable at the time of diagnosis. Superficial leiomyosarcomas, on the other hand, which are restricted to the superficial soft tissue, are not aggressive tumors. Cure is difficult, with a 50% to 60% recurrence rate after standard excision. However, distant metastases are infrequent. The tumor tends to be infiltrative and locally aggressive and clinically may present as a discolored, ulcerated, or umbilicated tumor of the middle-aged or elderly; is usually painful; and occurs on the extensor surface of the extremities. These tumors generally present as a single nodule or occasionally grouped nodules with well-circumscribed borders. They grow slowly and are expansile. Traditional management has been with 2- to 5-cm margins. Mohs surgery has been reported recently to be a successful treatment in the majority of cases.17 Lymph node dissection is recommended only if nodal disease is documented. These tumors do not respond well to either radiation therapy or chemotherapy.
Malignant Sweat Gland Tumors Malignant sweat gland tumors (such as malignant eccrine poroma, malignant eccrine spiradenoma, malignant hidradenoma, malignant cylindroma, eccrine carci127
TABLE 1. All skin cancers are not the same Tumor Anatomic location Size Histology Adenopathy Stage Host Age, sex Immunosuppression Associated malignancies Environment Previous treatment Etiology
Recurrence Metastases Mortality Treatment Routine or Multidisciplinary Mohs Wide excision ELND Radiation Chemotherapy Sentinel node biopsy
ELND, Elective lymph node dissection.
FIG 11. Malignant sweat gland tumor of the ear.
noma, and apocrine carcinoma) are rare tumors and poorly understood (Fig 11).18 The majority of these occur on the extremities. A pre-existing lesion that has been present for years may enter a stage of rapid growth and may be large at presentation—up to 5 to 10 cm in diameter. These have a marked tendency to metastasize widely in 40% to 50% of the cases. Wide local excision with control of margins with frozen sections (or Mohs micrographic surgery) is indicated, because these highly aggressive tumors may recur after excision and metastasize. Isotretinoin, interferon-alfa, and interleukin-2 may benefit patients with metastatic disease.
Microcystic Adnexal Carcinoma Sclerosing Sweat Duct Carcinoma, Malignant Syringoma, Sweat Gland Carcinoma With Syringomatous Features, Aggressive Trichofolliculoma, and Combined Adnexal Tumor of the Skin Microcystic adnexal carcinoma was first described in 1982. It is an aggressive, locally destructive cutaneous 128
carcinoma that frequently penetrates deep into the muscle and occasionally bone. Perineural invasion is seen up to 80% of the time. A deep biopsy is indicated because of these features. Typically, the lesion is a slow-growing, indurated, yellowish plaque with a nonulcerated surface on the central face, most commonly the upper lip, that has been present for several years in a person in the fourth decade of life. Although usually asymptomatic, the presence of pain, burning, stinging, anesthesia, or paresthesia suggests perineural involvement. Forty-seven percent of these tumors have been reported to recur after conventional surgical excision. Because of the potential for infiltrating growth with subclinical margins as great as 5 to 6 cm and common perineural involvement, Mohs micrographic surgery is the treatment of choice.19 Recurrence after Mohs surgery is uncommon. Typically, the tumor is deep rather than wide. I am aware of several cases in which superficial syringomatous changes have been pursued by Mohs surgeons more than 10 cm from the primary tumor. It is believed that these superficial syringomatous changes are benign and should not be excised. I am aware of only 1 or 2 cases of metastasis of this tumor, and there have been no deaths recorded. The tumor is radioresistant.
Conclusion Not all skin cancers are the same (Table 1). Some skin cancers are more likely to recur, metastasize, lead to disfigurement, or become fatal for the patient. Therefore, dermatologists must learn to recognize the various kinds of skin cancers so they can select treatments that offer the best possible outcome. As dermatologic surgery and Mohs micrographic surgery have evolved into prominent specialties, dermatologists have assumed the role of carCurr Probl Dermatol, March/April 2001
ing for patients with these unusual tumors. Dermatologists are now considered the experts and expected to have the answers for what constitutes the best therapy for the “other skin cancers.”
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