Case of the Month: Dermatopathology
October 2013 Case of the Month authored by Dermatopathologist Wonwoo Shon, D.O., and UF Health Pathology Laboratories' Dermatopathology Unit Director Frederick L. Glavin, M.D.
A 59-year-old woman presented with a solitary and nontender lesion on her left upper eyelid that appeared six months earlier. She had no other significant medical history. Upon initial physical examination, the lesion was a firm 7 - 8 mm nodule. The initial clinical impression was chalazion. An excision biopsy was performed and submitted for histologic evaluation.
The overlying epidermis was unremarkable. Within the dermis, the lesion showed predominantly well-circumscribed, nonencapsulated, multiple dermal nodules with predominantly cystic growth pattern (Figures 1a and b).
The tumor nodules were composed of a relatively uniform population of round-to-oval cells with pale eosinophilic cytoplasm and centrally located round-to-elongated nuclei (Figure 2). There was at least mild-to-focal moderate cytologic atypia with occasional mitotic figures. Notably, tumor cells demonstrated intracytoplasmic and extracellular mucin.
The tumor peripherally exhibited discontinuous foci of atypical epithelial proliferation, forming stubby papillae (Figure 3).
Using immunohistochemistry, the tumor cells were found to be focally positive for synaptophysin, confirming their neuroendocrine differentiation (Figure 4a).
WT1 immunostain showed diffuse and strong nuclear reactivity in all tumor cells (Figure 4b).
The term endocrine mucin-producing sweat gland carcinoma (EMPSGC) was first documented in 1997 by Flieder and colleagues to describe a cutaneous adnexal neoplasm with similar morphologic and immunohistochemical features as endocrine ductal carcinoma in situ of the breast (1). EMPSGC is a rare type of low-grade sweat gland carcinoma with a predilection for the eyelids; approximately 20 cases have been reported in the literature. EMPSGC is often under-recognized by clinicians and pathologists, both because of its rarity and in addition to its clinical and histologic mimicry of other sweat gland tumors (both eccrine and apocrine).
Clinically, no specific features lead to the diagnosis of EMPSGC because most tumors present as nonspecific nodules. Microscopically, the hallmark of EMPSGC is a solid, cystic and/or papillary proliferation of uniform, medium-sized epithelial cells with pale eosinophilic abundant cytoplasm and round nuclei. Solid areas may also contain fibrovascular cores surrounded by the neoplastic cells, forming pseudorosettes. Both extracellular and intracellular mucin pools are seen, at least focally, in most EMPSGCs, whereas the lesions associated with mucinous carcinoma showed abundant mucin pools. The combination of neuroendocrine markers, including synaptophysin, chromogranin and neuron-specific enolase; and epithelial markers, such as keratin and carcinoembryonic antigen, are useful for establishing this diagnosis.
The relationship between EMPSGC and mucinous carcinoma was first proposed by Zembowicz and colleagues (2). Half of the cases reported in their series were closely associated with an area of invasive mucinous carcinoma. These authors also observed that, in addition to the association with mucinous carcinoma, EMPSGC demonstrated areas of eccrine cysts containing foci of atypical epithelial proliferation. Therefore, the authors hypothesized that these areas represented the earliest stage of EMPSGC tumor progression—so-called in situ areas—based on the presence of a myoepithelial layer. No immunohistochemical or molecular studies have yet been performed, however, to confirm their hypothesis of a continuing spectrum of tumor progression. Recently, our group further characterized the morphologic spectrum and the immunophenotype found in this group of EMPSGCs, emphasizing the expression of WT1 in different areas of these lesions (3).
Although there is significant overlap morphologically and immunohistochemically with cutaneous metastases, especially metastatic breast carcinoma, a known history of prior malignancy helps distinguish the diagnosis of metastasis. Considered a low-grade malignancy, EMPSGC can exhibit locally aggressive behavior with multiple recurrences if incompletely excised (4). To date, no distant metastases have been reported.
- Flieder A, Koerner FC, Pilch BZ, Maluf HM. Endocrine mucin-producing sweat gland carcinoma: a cutaneous neoplasm analogous to solid papillary carcinoma of breast. Am J Surg Pathol. 1997 Dec;21(12):1501-6.
- Zembowicz A, Garcia CF, Tannous ZS, Mihm MC, Koerner F, Pilch BZ. Endocrine mucin-producing sweat gland carcinoma: twelve new cases suggest that it is a precursor of some invasive mucinous carcinomas. Am J Surg Pathol. 2005 Oct;29(10):1330-9.
- Shon W, Salomao DR. WT-1 expression in endocrine mucin-producing sweat gland carcinoma: a study of 13 cases. Int J Dermatol. In press.
- Emanuel PO, de Vinck D, Waldorf HA, Phelps RG. Recurrent endocrine mucin-producing sweat gland carcinoma. Ann Diagn Pathol. 2007 Dec;11(6):448-52. Epub 2007 Jul