Merkel Cell Carcinoma
Merkel cell carcinoma is an aggressive neoplasm of the skin that was originally described by Toker in 1972 as trabecular cell carcinoma. It is believed to be derived from the Merkel cell, which is a cell of neuroendocrine origin located in the basal layer of the epidermis involved in mediating the sensation of pressure. Merkel cell carcinoma is a rare neoplasm with an estimated annual incidence of 0.23 per 100,000 in Caucasians. It is primarily a tumor of older individuals, with an average age at presentation of 69 years and less than 5% of tumors occurring in patients younger than age 50. There is a slightly increased ratio of tumors in males compared to females (2.3:1).
Merkel cell carcinoma typically presents as an erythematous-to-violaceous subcutaneous nodule or plaque. The overlying skin usually remains intact but may exhibit central ulceration. It occurs predominantly in sun-exposed areas of skin, with 50% of tumors arising on the head and neck and 40% on the extremities. It is almost exclusively a disease of fair-skinned individuals. This, in combination with its usual anatomic presentation, has led investigators to presume that ultraviolet radiation is a primary factor in its etiology. Similar to SCC, Merkel cell carcinoma also appears to occur with increased frequency in patients who have undergone solid organ transplantation and those with other forms of immunosuppression.
Merkel cell carcinoma exhibits an aggressive biologic behavior with the potential for rapid spread through either lymphatic or hematogenous routes. Approximately 30% of patients have regional nodal mestastases at the time of presentation. Reported 5-year survival rates range from 30% to 81%. Due to the rarity of this tumor, no prospective randomized trials exist to guide surgical management. Currently, the most common approach to the patient with stage I disease (ie, tumor clinically localized to the skin) is wide local excision of the primary tumor with 2- to 3-cm margins of clinically uninvolved skin, with or without adjuvant radiation. Studies employing this approach have produced local recurrence rates ranging from 13% to 39%.[20,21] Complete resection of the primary tumor is of paramount importance, as two-thirds of those who develop local recurrences ultimately die of their disease.
With complete examination of the surgical margin, Mohs surgery was recognized as a possible alternative to wide local excision for optimizing resection of the primary tumor and minimizing local recurrence. The first series of patients with Merkel cell carcinoma treated with Mohs micrographic surgery was reported in 1997 by O'Connor et al. This retrospective study analyzed rates of local recurrence and regional metastasis in patients treated with either Mohs surgery (n = 12) or wide local excision (n = 41). Local recurrence was identified in 8.3% of patients treated with Mohs surgery vs 31.7% of those with wide local excision. Regional metastases developed in one-third of the Mohs surgery group and 48.8% of the wide local excision group.
Boyer et al reviewed 45 cases of Merkel cell carcinoma treated with Mohs surgery; 20 of the patients in this series also received adjuvant radiation therapy. A local recurrence, which the authors defined to include both marginal recurrence and in-transit metastases, was observed in 8.8% of patients-16% of those treated with Mohs alone but none of those treated with Mohs surgery plus radiation therapy. The overall 5-year survival estimate for both groups was 79% and 80%, respectively.
Thus, initial results of the treat treatment of Merkel cell carcinoma with Mohs surgery appear to demonstrate local recurrence and survival rates comparable to or better than those of wide local excision. That said, the experience with Mohs surgery in the management of Merkel cell carcinoma remains limited.
Dermatofibrosarcoma protuberans is an uncommon mesenchymal neoplasm that originates in the dermis. The tumor is characterized by a locally aggressive growth pattern in which ramifications of spindle cells infiltrate the dermis and surrounding tissues. With time, involvement of the subcutaneous fat, muscle, cartilage, and bone may occur. The potential for hematogenous or lymphatic dissemination does exist but is rare. Clinically, the tumor typically presents as an erythematous-to-violaceous nodule or plaque with poorly circumscribed clinical margins. It occurs primarily on the trunk and proximal extremities of individuals in their 30s and 40s.
With reported local recurrence rates of 30% to 50% for simple excision and 20% for wide local excision,[ 24] Mohs surgery has emerged as the treatment of choice for dermatofibrosarcoma protuberans. In a series of 29 cases with more than 5 years of follow-up, Snow et al experienced no recurrences in primary and recurrent tumors treated with Mohs surgery. Their review of 136 cases in the literature with similar follow-up documented 9 cases of recurrence, for a local recurrence rate of 6.6%. In a study of 22 patients with dermatofibrosarcoma protuberans treated with a modified Mohs technique utilizing rush paraffin(Drug information on paraffin) sections, no recurrences were observed.
Despite the absence of randomized controlled trials, Mohs surgery appears to offer lower recurrence rates than conventional surgical excision for the treatment of dermatofibrosarcoma protuberans. Experience in the treatment of other spindled cell tumors of the skin with Mohs surgery is more limited. However, Heuther et al reported local recurrence rates of 6.9% for atypical fibroxanthoma, 43% for malignant fibrous histiocytoma, and 14% for leiomyosarcoma. The role of Mohs surgery in the management of these other spindled neoplasms remains unclear and will become better defined with increased experience.
Extramammary Paget's Disease
Extramammary Paget's disease is a rare cutaneous adenocarcinoma believed to be derived from apocrine cells. Cases primarily occur in regions of high apocrine gland distribution, namely the vulva, penis, scrotum, perianal region, and less frequently, the axilla. The precise histogenesis of this tumor is unknown, but 10% to 20% of cases have been observed in association with an internal malignancy, usually of the gastrointestinal or genitourinary system.[28,29]
Extramammary Paget's disease typically presents as an erythematous macerated patch of the anogenital region. A delay in diagnosis of 5 to 10 years is not uncommon, as the clinical presentation may be mistaken for other dermatoses such as tinea cruris, erythrasma, inverse psoriasis, or contact dermatitis. The growth of this neoplasm is usually intraepidermal in nature with involvement of adjacent adnexal structures; however, dermal invasive disease with subsequent regional and systemic metastases does occur in up to 10% of cases. The prognosis is poor once dissemination has begun.
Surgical management of the primary tumor of extramammary Paget's disease is confounded by the neoplasm's indistinct clinical margins and propensity for extensive subclinical spread. The literature reports local recurrence rates of 33% to 60% for standard surgical excision with frozen and/or fixed margin control.[30-34] In addition, for cases treated with wide local excision, reported local recurrence rates remain high at 20% to 50%.[31-34]
These high local recurrence rates, in addition to the known tendency of extramammary Paget's disease for broad subclinical extension, prompted several investigators to examine the use of Mohs surgery as an alternative treatment. The largest reported series of extramammary Paget's disease treated with Mohs surgery consisted of 27 cases (19 primary tumors, 8 recurrent tumors) with an average follow-up of 76 months. Their results revealed a local recurrence rate of 16% for primary extramammary Paget's disease and 50% for recurrent tumors (23% local recurrence rate for combined primary and recurrent tumors). Similar results, with a local recurrence rate of 23%, were reported by Coldiron et al in a survey of 48 cases of primary and recurrent extramammary Paget's disease treated with Mohs surgery.
In a retrospective review, O'Connor et al examined local recurrence rates in 83 patients treated with wide local excision as compared to 12 patients treated with Mohs micrographic surgery.[ 29] Locally recurrent disease was observed in 22% of the wide local excision group and 8% of the Mohs surgery group; however, it should be noted that the two groups had significantly different mean follow-up periods (65 vs 24 months).
Although the existing data regarding the use of Mohs surgery in the treatment of extramammary Paget's disease are limited, such results appear favorable in comparison with those of wide local excision. Regardless of whether Mohs surgery or wide local excision is utilized, several adjunct techniques have been identified to optimize complete surgical excision of extramammary Paget's disease. Identification of subclinical spread of tumor may be aided by the use of peripheral scouting biopsies, topical imiquimod(Drug information on imiquimod) (Aldara) or fluorouracil(Drug information on fluorouracil) cream, and photodynamic therapy. Histopathologic identification of residual tumor is aided by the use of immunohistochemical staining with cytokeratin-7 and carcinoembryonic antigen.
Microcystic Adnexal Carcinoma
Microcystic adnexal carcinoma is a locally aggressive neoplasm that was first described in 1982. Although the tumor does not appear to have the potential for metastasis, it is characterized by extensive subclinical spread of the malignancy beyond the identifiable tumor margins. Perineural invasion of tumor is not uncommon in the dermis, and invasion of deeper local structures such as the subcutaneous fat, muscle, and cartilage has been reported.
Microcystic adnexal carcinoma typically presents as a slightly indurated, flesh-colored plaque of the face (Figure 6). It occurs primarily in whites, but a single case has been reported in an African-American male. There appears to be a modestly increased incidence in females over males. It has been observed in all age groups, but highest incidence has occurred in patients in their 7th decade. There is often a prior history of x-ray irradiation of the site for the treatment of acne.
Given the indistinct nature of the clinical borders of microcystic adnexal carcinoma, Mohs surgery would appear ideal for surgical management of the tumor. Recurrence rates with conventional surgical excision have been estimated at 47%, based on review of the literature. In a series of 11 cases of microcystic adnexal carcinoma treated with Mohs surgery, Friedman et al observed no recurrences over a mean follow-up of 5 years. In a review of the Australian experience of the treatment of microcystic adnexal carcinoma with Mohs surgery, Lebovitch at al reported a 5% recurrence rate in the 20 patients with at least 5 years follow-up. The largest available series of patients with microcystic adnexal carcinoma treated with either Mohs surgery or traditional excision found a local recurrence rate of 12% for the Mohs group and 17% for the excision group. In addition, 30% of the group treated with standard excision required multiple additional procedures due to persistence of disease after initial excision.
The available data on the optimal therapy for microcystic adnexal carcinoma is sparse, and no prospective randomized controls exist due to the rarity of this tumor. Mohs micrographic surgery does appear to offer an advantage over traditional excision in the treatment of this locally aggressive neoplasm. The major challenge in the management of microcystic adnexal carcinoma with Mohs surgery is the accurate histopathologic interpretation of frozen sections of this tumor. This task is highly dependent upon both the quality of the sections produced by the histotechnician and the experience of the Mohs surgeon. Adjunctive measures to increase the sensitivity of this process include the use of immunohistochemical staining and a modified Mohs technique in which rush paraffin sections are used.
Fundamentally, Mohs micrographic surgery differs from conventional surgical excision by its ability to provide complete histologic examination of surgical margins. This technique allows the Mohs surgeon to maximize normal tissue conservation through narrower surgical margins while achieving the highest cure rates for the treatment of the most common cutaneous neoplasms.
Mohs surgery has been wellestablished as the gold standard for the treatment of BCCs and SCCs.[1-3] Preliminary reports suggest that it may play an equally important role in the management of several other cutaneous malignancies, as described above. Further experience will better define this role and provide additional insight into other uses.
Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.