Endocrine Mucin-Producing Sweat Gland Carcinoma: Case Presentation with a Comprehensive Review of the Literature.

(1) Background: Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) is a rare, low-grade, neuroendocrine-differentiated, cutaneous adnexal tumor, officially recognized by the World Health Organization (WHO) Skin Tumors Classification in 2018 as a separate entity and homologue of endocrine ductal carcinoma in situ (eDCIS)/solid papillary carcinoma of the breast. Although it is more frequent in the female sex, between 60 and 70 years old, in the peri-orbital region, EMPSGC has also been described in the male sex, in subjects under 60 and over 80, and in extra-eyelid localizations (cheek, temple, scalp), but also in extra-facial localizations (chest and scrotum). (2) Methods: We present the clinical case of a 71-year-old woman with an undated lesion of the scalp, which presented as a nodule, skin-colored, and 2.5 cm in maximum diameter. We also conduct a comprehensive literature review from 1997 to the end of 2022, consulting PubMed, Scopus, Web of Science (WoS), and Google Scholar using the following keywords: "Endocrine mucin-producing sweat gland carcinoma" and/or "EMPSGC" and/or "skin" and "cutaneous neoplasms". In addition, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 253 patients were recorded; 146 were females (57.7%) and 107 were males (42.2%). The vast majority of the lesions were in the eyelids (peri-ocular region), and only a minority of cases involved the cheeks, supra-auricular, retro-auricular, and occipital region, with very rare cases in the scalp, to which the present is also added. (4) Conclusions: The morphological and immunophenotypical features are essential both for the correct diagnosis and to be able to classify this lesion among the corresponding eDCIS/solid papillary carcinoma of the breast, with neuroendocrine differentiation. Recent papers have attempted to shed light on the molecular features of EMPSGC, and much remains to be conducted in the attempt to subtype the molecular profiles of these entities. Future studies with large case series, and especially with molecular biology techniques, will be needed to further add information about EMPSGC and its relationship in the PCMC spectrum.

Metastatic Endocrine Mucin-Producing Sweat Gland Carcinoma to the Lung: A Case Report.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade neuroendocrine neoplasm previously believed to be indolent in nature. There have only previously been six reported cases of metastases and none of thoracic structures. This case shows a metastatic EMPSGC in a 72-year-old male with a complex oncologic history and is the first reported case of metastases to the lung. As increased recognition of this entity continues to grow, it is important to consider it as part of the differential in mucinous and/or neuroendocrine neoplasms for appropriate management. This case adds to the oncologic literature by demonstrating a rare cutaneous neoplasm and emphasizing its metastatic potential.

Simultaneous presentation of orbital mantle cell lymphoma and endocrine mucin-producing sweat gland carcinoma.

Mantle cell lymphoma is a rare malignancy to present in the orbit, comprising only 1-5% adnexal lymphomas. Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an equally uncommon adnexal tumor of sweat gland origin that may present on the eyelid. Herein we present a case of a 77-year old man with no previous cancer history who presented with painless progressive left globe proptosis and an enlarging left upper lid margin lesion, ultimately determined upon biopsy to be simultaneous orbital mantle cell lymphoma with systemic involvement and isolated eyelid EMPSGC. The pathogenesis, clinical manifestation, and management for each rare disease entity are reviewed and concept of collision tumors is discussed.

A case of endocrine mucin-producing sweat gland carcinoma with distant metastasis.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal neoplasm typically arising on the face of older individuals, most commonly around the eyelids. Histopathologic features include a circumscribed proliferation of low-grade epithelioid cells with areas of cystic and cribriform growth, foci of intracytoplasmic and extracellular mucin, and coexpression of endocrine, neuroendocrine, and cytokeratin markers by immunohistochemistry. Given histopathologic and immunohistochemical similarities, EMPSGC is often likened to solid papillary carcinoma of the breast and endocrine ductal carcinoma in situ, and is thought by many to represent a forme fruste of mucinous carcinoma of the skin. To date, the vast majority of reported cases of EMPSGC have been described as having indolent behavior, with no cases of distant metastasis yet reported. Here we report a unique case of EMPSGC that recurred over several years following standard surgical excision and Mohs micrographic surgery, with subsequent metastasis to the parotid gland and axial skeleton.

Endocrine mucin-producing sweat gland carcinoma and associated primary cutaneous mucinous carcinoma: Review of the literature.

BACKGROUND: Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade, cutaneous adnexal carcinoma with neuroendocrine differentiation. It is considered to be a precursor of invasive neuroendocrine type primary cutaneous mucinous carcinoma (PCMC). OBJECTIVE: To review clinicopathological literature summary of EMPSGC and associated neuroendocrine PCMC from all reported cases and compare its behavior vs non-neuroendocrine PCMC data reported in the literature. METHODS: A review of English literature of all EMPSGC cases with and without associated PCMC was carried out. RESULTS: EMPSGC was associated with invasive neuroendocrine type PCMC in 35.7% of cases. We found the recurrence rate of PCMC associated with EMPSGC of about 12.3%, which is much less than the 30% recurrence rate reported for the non-neuroendocrine subtype of PCMC. The non-neuroendocrine subtype of PCMC shows a 4% and 11% rate of distant and lymph node metastasis, respectively, vs EMPSGC-associated neuroendocrine type of PCMC, which is very indolent and only one recent case of locoregional metastasis out of 190 EMPSGC cases has been reported so far. LIMITATION: Limitation of our study includes data derivation from case reports and case series in the literature. CONCLUSION: The prognostic benefits for this cohort of patients may be considered in their overall management.

Comparative performance of insulinoma-associated protein 1 (INSM1) and routine immunohistochemical markers of neuroendocrine differentiation in the diagnosis of endocrine mucin-producing sweat gland carcinoma.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal malignancy with predilection for the eyelids of older adults. It must be distinguished from metastatic adenocarcinomas of extracutaneous origin and from benign adnexal proliferations on partial samples when a solid growth component and mucin production are not evident. Thus, demonstration of neuroendocrine differentiation can help to ensure a correct diagnosis. Insulinoma-associated protein 1 (INSM1) is a novel neuroendocrine marker that has recently shown greater sensitivity than synaptophysin (SYN) and chromogranin (CHR) in the diagnosis of various neuroendocrine neoplasms. We compared the performance of these three markers across 10 examples of EMPSGC. All EMPSGCs expressed INSM1. Eight of ten were also immunoreactive for SYN; however, INSM1 staining was generally more intense and stained a greater proportion of the tumor cells. CHR staining was weak and focal in most cases. INSM1 staining was present in hidrocystoma-like components of cystic EMPSGC. These findings suggest that INSM1 may be more sensitive than SYN and CHR and thus valuable for establishing a diagnosis of EMPSGC.

Endocrine mucin-producing sweat gland carcinoma of the eyelid.

An elderly woman was incidentally noted to have a nodular mass on the upper eyelid, whilst under investigation for cataracts. Punch biopsy of this presumed basal cell carcinoma revealed it to be endocrine mucin-producing sweat gland carcinoma (EMPSGC). The tumour extended to the deep dermal layer and comprised solid nests with foci of cystic and papillary change, and additional cytoplasmic and focal extracellular mucin deposits. Immunohistochemistry confirmed epithelial lineage and neuroendocrine differentiation, and adjacent tissue invasion. The tumour was excised completely with Mohs micrographic surgery with no recurrence after 8 months. EMPSGC is a low-grade sweat gland carcinoma with variable neuroendocrine differentiation, a solid, papillary, or cystic growth pattern, and a predilection for the eyelid of elderly women [Am J Surg Pathol 29:1330-1339, 2005]. There have been 54 previously documented cases of EMPSCG. We report an additional case and review the literature.