Endocrine Mucin-Producing Sweat Gland Carcinoma

Abstract

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an underrecognized low-grade carcinoma with predilection to the eyelid. Only 4 cases of this entity have been described in the literature. Here, we describe 12 cases of EMPSGC. The lesions were twice as frequent in females than males with an average age of 70 years (range, 48-84 years). Clinically, they presented as a slowly growing cyst or swelling. The most common site of occurrence was the lower eyelid (8 cases). Two lesions occurred on the upper eyelid and 2 on the cheek. Histologically, they were well-circumscribed, typically multinodular tumors with solid or partially cystic nodules, frequently showing areas of papillary architecture. Focal cribriform arrangements were also present. The nodules were formed by uniform small- to medium-sized oval to polygonal epithelial cells with lightly eosinophilic to bluish cytoplasm. The nuclei were bland with diffusely stippled chromatin and inconspicuous nucleoli. Intracytoplasmic and extracellular mucin was usually present. Mitotic activity was present but never brisk. All tumors examined immunohistochemically expressed at least one neuroendocrine marker, synaptophysin or chromogranin. CD57 and neuron specific enolase, secondary markers of neuroendocrine differentiation, were expressed in most cases. All tumors tested expressed estrogen and progesterone receptors, cytokeratin 7, low molecular cytokeratin Cam5.2, and epithelial membrane antigen and were negative for cytokeratin 20 and S-100 protein. Calponin, smooth muscle actin, and p63 immunohistochemical stains did not disclose myoepithelial cells around larger tumor nests in most cases, supporting the notion that EMPSGC is an invasive carcinoma. In 10 cases, cystic areas lined by benign epithelium indistinguishable from eccrine ducts were present. In some foci, the benign ductal epithelium was undermined or replaced by carcinoma in situ with similar cytologic features to the solid or papillary areas of EMPSGC. Myoepithelial cells were preserved in the areas of in situ carcinoma. In 6 cases, EMPSGC was associated with invasive mucinous carcinoma. In situ carcinoma and mucinous carcinoma also expressed neuroendocrine markers. Clinical follow-up showed no recurrences or metastases, consistent with low-grade carcinoma. The series provides histologic evidence for a multistage progression of noninvasive sweat gland neuroendocrine carcinoma to EMPSGC and then to mucinous carcinoma of the eyelid. Although the data from this series support the notion that the prognosis of EMPSGC and mucinous carcinoma is good, longer follow-up is needed for better understanding of their pathogenesis and clinical behavior.

Endocrine Mucin-Producing Sweat Gland Carcinoma, a Histological Challenge

“…EMPSGC is a rare adnexal tumor that is twice as common in females [1–3, 6] and with a predilection for the face, particularly the eyelids [1–6]. It tends to occur in individuals in their 6th and 7th decades of life [1–3, 6].…”

“…It tends to occur in individuals in their 6th and 7th decades of life [1–3, 6]. The entity was first coined by Flieder et al in 1997 [7] and since then, less than 60 cases have been reported in the literature, making it an uncommon skin tumor that may pose diagnostic challenges to clinicians and pathologists.…”

“…Encapsulated papillary carcinoma of the breast may or may not have positive myoepithelial cells, and this could explain the discrepant staining seen amongst authors for EMPSGC. Zembowicz at al., on the other hand, state that the typical loss of myoepithelial cells seen in the large nodules of EMPSGC may best be regarded as an invasive carcinoma on its own [1]. Considering loss of myoepithelial cells in the breast is regarded as evidence for invasion, perhaps this notion should be used when evaluating sweat gland tumors as well [1].…”

“…Once the mass is deemed a primary skin adnexal tumor, the differential diagnosis for EMPSGC includes basal cell carcinoma (nodular subtype), nodular hidradenoma, hidradenocarcinoma, hidrocystoma, apocrine tubular adenoma, monomorphic adenoma, and dermal duct tumor [1, 2, 6, 8]. …”

“…It has a predilection for facial areas, most commonly being the eyelid [1–6], but is also known to affect the cheek and rarely extra-facial sites [1]. The tumor is seen more frequently in women and usually affects elderly patients [1–3, 6]. …”