To our knowledge, no case reports of patients with multiple primary cutaneous lesions existed prior to the presentation of this patient. Martin et al19 describe an 8-year-old patient with multiple carcinomas on the lower extremities arising within systemized compound epithelial lesions; however, only one of these lesions was MAC, and the remainder showed divergent differentiation. Multiple primary lesions in our current case are manifested by the stratified histologic appearance of the tumor at the primary sites and are supported by the lack of metastatic disease elsewhere, which was demonstrated by extensive clinical examination and the absence of additional clinical symptoms or suspicious lesions on computed tomography. Reports of metastasis in MACs also are infrequent and represent only 6 cases in the medical literature worldwide3-5,7-9; 4 of these cases possibly do not describe true metastases3-5,7—one in the axilla that arguably represented tumor extension.3 Two of the others showed metastatic disease in ipsilateral lymph nodes, with a primary lesion on the right posterior scalp4 and the upper forehead,7 respectively. The fourth case illustrated cutaneous metastases in transit, possibly representing recurrence and not metastasis.5 A recent report described a patient with lung metastases,8 and a single case exists in the literature of a patient with widely metastatic MAC of long-standing duration.6 For this reason, and despite its aggressive local behavior, MAC is considered to be a tumor with excellent overall prognosis. Of the more than 300 cases from the medical literature worldwide, only the group of aforementioned lesions demonstrated metastatic potential, which represents an incidence rate of only 2% (probably overrepresented because reported cases only are a fraction of cases in existence). The death rate of reported cases, 0.3%, is an overestimate for similar reasons.21 Because MAC demonstrates its greatest morbidity from local invasion and destruction with locoregional recurrence, the optimal therapeutic approach generally consists of Mohs micrographic surgery (MMS) or primary surgical excision (intraoperative frozen section).12 Local recurrence following surgical excision, however, is not uncommon. In a comprehensive study using MMS, it was found that the extent of these lesions generally is 4-fold larger than the initially clinically evident lesion. Hence, intraoperative assessment of marginal status is paramount.12 In a study of 48 cases, 22 cases were treated with MMS, 23 cases were treated with simple excision, and 3 cases were untreated.12 Only 2 of the cases treated with MMS recurred after a single procedure. In those cases treated with excision, 7 cases (30%) had to have at least one additional surgical procedure before excision was deemed complete, and 1 case experienced recurrence. The overall recurrence rate was similar between the 2 groups (1.98% per patient-year), but fewer procedures were required.12 Although a small number of cases have been treated with adjuvant modalities, including radiation and chemotherapy, the effectiveness of this protocol, in addition to surgical excision, is most likely minimal.22 Our case represents a therapeutic problem in that the number and size of the lesions would be a monumental task to undertake surgically. The indolent course of these lesions might require a conservative clinical approach, such as surgical therapy reserved for problematic or aesthetically displeasing lesions. Systemic therapy was proposed in this patient, possibly using currently known biologic adjunctive therapy such as tamoxifen citrate and trastuzumab. Given that this tumor tested negative for both estrogen and progesterone receptors, as well as HER2/neu, biologic therapy was not undertaken. In addition, the indolent nature and low proliferative rate of these neoplasms most likely would make them poorly responsive to radiation or chemotherapy. A recent case report by Eisen and Zloty21 described a 58-year-old woman with a 12X12-cm MAC involving a large portion of the face. Similar to our case, this patient presented a difficult therapeutic problem because surgical intervention would involve substantial facial disfigurement. The authors opted, as we did, for close clinical surveillance; 2 years after initial diagnosis, the patient continued to do well, with no reported evidence of metastatic disease.21 Radiation therapy has been advocated for palliation in elderly or debilitated individuals; however, this therapy is less than ideal because these lesions generally are radioresistant, and recurrence following this therapy is not infrequent. In addition, radiation has been implicated as a causative mechanism. Comparing treatment methods for a tumor for which no randomized prospective studies exist is difficult, but because the tumor can be locally aggressive, surgical therapy should be pursued if feasible.
Comment
Our case of multiple primary cutaneous MAC in a black patient appears to represent a unique presentation of MAC. Therapeutic options, particularly in a patient with multiple lesions, represent a difficult clinical problem; however, close clinical follow-up without surgical intervention, except for those cases in which MMS is feasible, remains a reasonable alternative.