Syringomatous carcinoma (SC), considered by some to be a variant of microcystic adnexal carcinoma (MAC),1 is a rare malignant neoplasm of sweat gland origin. SC encompasses a range of neoplasms with different degrees of differentiation, and its nomenclature has varied over the years. SC also has been referred to as syringoid eccrine carcinoma,2 basal cell tumor with eccrine differentiation,3 malignant syringoma,4 and sclerosing sweat duct carcinoma.5 Its diagnosis has been a dilemma in a number of reported cases, probably due to the combination of its rarity and thus limited clinical and histopathologic information, microscopic similarities to other benign and malignant neoplasms, and characteristic histologic features that may only be apparent in surgical excisions containing deeper tissue. We report a case of SC that masqueraded as an epidermoid cyst in an unusually young patient.
Case Report
A 23-year-old Asian man, who was otherwise healthy, presented with an asymptomatic slowly enlarging nodule of one year's duration on the right medial eyebrow. Prior treatment with intralesional steroid injections resulted in minimal improvement. The patient had no personal or family history of skin cancers. Physical examination results demonstrated a well-demarcated, mobile, nontender subcutaneous nodule measuring 7 mm in diameter. The clinical presentation favored a diagnosis of an epidermal inclusion cyst, and the patient underwent surgical excision of the lesion. Results of the histopathologic examination revealed a neoplasm in the dermis consisting of bands and nests of pale staining basaloid cells extending between the collagen fibers (Figure 1). There were focal areas of ductal differentiation, scattered individual necrotic cells, moderate dermal fibrosis, and chronic inflammation with numerous eo-sinophils. Moderate nuclear atypia also was present (Figure 2). Perineural involvement was not seen. Results of immunohistochemical analysis revealed positive staining for high—and low—molecular-weight cytokeratins, as well as carcinoembryonic antigen (CEA)(Figure 3). There was scattered positivity with S-100 protein in occasional cells lining lumina and in dendritic cells (Figure 4). The histopathologic findings supported the diagnosis of SC. Because the neoplasm extended to the surgical margins of the specimen, repeat surgical excision with continuous microscopic control under the Mohs micrographic technique was performed to prevent local recurrence and spare normal tissue. At the 18-month follow-up visit, no local recurrence was seen.
Comment SC is a rare, malignant sweat gland neoplasm that usually occurs in the fourth and fifth decades of life.4-8 SC typically presents as a slow-growing, solitary, painless nodule or indurated plaque on the head or neck region.6-8 It has been frequently found on the upper and lower lips; however, it also has been reported to occur on the finger and breast.9,10 Predisposing factors for the development of SC are unclear11 but may include previous radiation to the face and history of receiving an organ transplant with immunosuppressive drug therapy.12-17 Histopathologically, SC is characterized by asymmetric and deep dermal invasion of tumor cells, perineural involvement, ductal formation, keratin-filled cysts, multiple nests of basaloid or squamous cells, and desmoplasia of the surrounding dermal stroma (Table 1).5,6 Some authors consider SC to be closely related to MAC but generally describe SC as more basaloid with larger tubules and a more sclerotic stroma than MAC.18-26 If histologic examination of SC is limited to the superficial dermis, SC demonstrates similarities to other neoplasms, including syringomas, trichoadenomas, trichoepitheliomas, basal cell carcinomas, or squamous cell carcinomas. In the reported cases in which SC was initially misdiagnosed as another benign or malignant neoplasm, many misdiagnoses were due to either a benign clinical appearance of the lesion or biopsy specimens that were too superficial to contain the deeper characteristic histologic features of SC.8,9,11,27-30
Immunohistochemical studies can facilitate the diagnosis of SC and differentiate it from other neoplasms. SC stains positively for CEA, S-100 protein, epithelial membrane antigen, cyto-keratin, and gross cystic disease fluid protein 15,31 all of which aid in the confirmation of a sweat gland neoplasm (Table 2).8,32,33,39 Positivity for CEA in the ductal lining cells and the luminal contents of tumor ducts confirms sweat gland differentiation.25,33,34 This ductal immunoreactivity to CEA appears to be one of the most reliable findings to differentiate SC and MAC from other adnexal tumors, especially desmoplastic trichoepithelioma, which may be one of the more challenging histo-pathologic differential diagnoses.35 In addition, epithelial membrane antigen positivity can be found in the areas showing glandular features.35 This can assist in distinguishing SC from a desmoplastic trichoepithelioma or sclerosing type basal cell carcinoma, both of which demonstrate negativity to epithelial membrane antigen.35 S-100 protein positivity in dendritic cells, as well as in some cords and ducts in SC, further verifies dendritic differentiation toward sweat gland structures and is useful as an adjunct in the confirmation of glandular differentiation.25,33,34,36