Endocrine Mucin-producing Sweat Gland Carcinoma Research Articles

An Enlarging Painless Eyelid Nodule.

A 50-year-old Asian man with a history of a kidney transplant presented with a painless enlarging lesion on his right lower eyelid that had been growing for two years. Biopsy revealed a low-grade neoplasm with cribiform architecture and mucin production, and subsequent immunohistochemistry was suggestive of Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC). This case highlights the importance of a high index of suspicion for malignancy in immunocompromised patients with non-resolving lesions, and the need for regular skin checks.

Recurrent GATA3 P409Afs*99 Frameshift Extension Mutations in Sweat-gland Carcinoma With Neuroendocrine Differentiation.

Sweat-gland carcinoma with neuroendocrine differentiation (SCAND) was recently proposed as a new cutaneous adnexal neoplasm with neuroendocrine differentiation; however, its genetics are not well known. Herein, we performed clinicopathologic and genetic analyses of 13 SCAND cases and 5 control cases of endocrine mucin-producing sweat gland carcinoma (EMPSGC). The SCAND group included 11 males and 2 females with a median age of 68 years (range, 50 to 80y). All SCAND lesions occurred in the ventral trunk or genital area. Of the 13 SCAND cases, 9 and 5 exhibited lymph node and distant metastases, respectively. Three (23.1%) patients with SCAND died of the disease. In contrast, neither metastasis nor mortality was confirmed in the EMPSGC cases. Immunoexpression of the androgen receptor, c-Myb, and MUC2 was limited in SCAND, whereas EMPSGC frequently expressed these immunomarkers. GATA3 P409Afs*99 extension mutations were detected in 7 (53.8%) of the 13 SCAND cases, using Sanger or panel sequencing. All 7 SCAND cases with GATA3 mutations were located in the genital, inguinal, or lower abdominal regions, whereas 5 of the other 6 SCAND cases were located in the anterior upper to mid-trunk. No GATA3 mutations were detected in the EMPSGC cases (0/5, 0%). These clinicopathologic and genetic findings support SCAND as a tumor entity distinguishable from EMPSGC. In addition, the characteristic frameshift extension mutations in GATA3 contribute to the establishment of the tumor-type concept of SCAND.

TRPS1 Expression in Endocrine Mucin-Producing Sweat Gland Carcinoma: Diagnostic Utility and Pitfalls.

TRPS1 Expression in Endocrine Mucin-Producing Sweat Gland Carcinoma: Diagnostic Utility and Pitfalls.

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.

Endocrine Mucin-Producing Sweat Gland Carcinoma and Primary Cutaneous Mucinous Carcinoma: A Case Series.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are rare low-grade neoplasms thought to arise from apocrine glands that share many histological features and are proposed to be on a single histopathologic continuum, with EMPSGC as the in situ form that may progress to the invasive PCMC. Management involves a metastatic workup and either wide local excision (WLE) with greater than 5 mm margins or Mohs micrographic surgery (MMS) in anatomically sensitive areas. We present 2 cases of EMPSGC and 3 cases of PCMC and review their clinical and histopathologic features, differential diagnoses, and treatment.

A Case of Endocrine Mucin-Producing Sweat Gland Carcinoma of the Eyelid

Purpose: We report an endocrine mucin-producing sweat gland carcinoma diagnosed by biopsy in a patient who presented with an eyelid mass.Case summary: A 64-year-old male presented with a 3 × 3 mm solitary, painless pinkish mass on the right lower eyelid that had developed over the past year. The mass was excised and a biopsy was performed. The pathological findings included basaloid nodules composed of cells with eosinophilic cytoplasm, focal mucin production, and occasional glandular structures. Immunohistochemical examination was positive for cytokeratin 7 (CK-7), tumor protein 63 (P63), and the androgen receptor (AR). The patient was thus diagnosed with an endocrine mucin-producing sweat gland carcinoma. The lesion healed, and there has been no sign of recurrence over 6 months of follow-up.Conclusions: An endocrine mucin-producing sweat gland carcinoma is a very rare low-grade glandular malignancy that has not been reported in Korea previously. The prognosis is good (i.e., there is no recurrence) when the lesion is completely surgically excised. We thought it would be useful to report this very rare case.

Primary cutaneous endocrine mucin-producing sweat gland carcinoma: a rare case report

Background: Endocrine mucin-producing carcinoma is a rare adnexal tumour of the skin with low-grade cytological features and neuroendocrine differentiation. It has a predilection for skin of the eyelid, but has also been reported in the face and rarely extra-facial locations. The tumour is seen more frequently in women affecting the elderly. It is histologically and immunohistochemically analogous to solid papillary carcinoma of breast/ductal carcinoma in situ with nodular, solid, papillary, and /or cribriform architecture, neuroendocrine differentiation and mucin production with preserved myoepithelial cell layer.

Endocrine mucin-producing sweat gland carcinoma mimicking meibomian gland carcinoma

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare adnexal tumor of the skin with immunoexpression and neuroendocrine differentiation. It can be easily misdiagnosed as a meibomian gland tumor due to its prevalence in the Indian subcontinent over EMPSGC. It has a predilection for the skin of the eyelid and elderly females. It is histologically and immunohistochemically analogous to solid papillary carcinoma of the breast/endocrine ductal carcinoma in situ with a nodular, solid, papillary, and/or cribriform architecture, neuroendocrine differentiation, and mucin production. We describe a case of EMPSGC clinically mimicking meibomian gland carcinoma which was confirmed on immunohistochemistry and histopathological diagnosis.

Endocrine mucin-producing sweat gland carcinoma: a systematic review and meta-analysis

Background Endocrine mucin-producing sweat gland carcinoma is a rare, under-reported cutaneous adnexal tumor that is often misdiagnosed and has an unknown incidence of metastasis. Objective To determine the incidence of metastasis and tumor recurrence, as well as diagnostic accuracy and current trends in treatment modality. Methods A search was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Tumor pathology and clinical data concerning demographics, presentation, diagnosis, treatment and follow-up were assessed. Results A total of 36 publications with 110 cases were identified. Initial pathological diagnosis was incorrect in 45.5% of cases. One case of metastatic disease was reported. The incidence of locoregional recurrence was 10.6% over a mean follow-up period of 21.3 months. Of cases with known methods of resection, 34.6% were resected by excisional biopsy, 42.8% were resected by wide surgical excision, and 31.3% were cleared by Mohs micrographic surgery. Limitations The low reported incidence and level of evidence was suboptimal with only case reports and retrospective case studies being reported. Conclusion Reported cases of this pathology demonstrate poor diagnostic accuracy. High rates of misdiagnosis and inadequate definitive treatment suggest the need for more comprehensive work-up and management of lesions suspicious for this pathology.

Endocrine Mucin-Producing Sweat Gland Carcinoma: Emerging Evidence of Multicentric Cutaneous Origin and Occasional Concurrence With Analogous Breast Tumors.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a low-grade carcinoma with predilection for the eyelid. It is analogous to solid papillary carcinoma of the breast with both expressing neuroendocrine markers and the potential to progress to invasive mucinous carcinoma (IMC). Although over 80 cases of EMPSGC have been reported, few multicentric cases have been described in the literature. In this article, we report 9 cases of EMPSGC including 3 with multicentric disease. A computerized search was performed for EMPSGC and IMC of the eyelid from January 2000 to February 2021. Records were reviewed for age, sex, tumor location, and clinical impression. Eight EMPSGC (7 associated with IMC) and 1 IMC of the eyelid were identified. Lesions were slightly more common in men (55%) than women. The mean age of presentation was 76 years (range, 59-98 years). Lesions ranged from 2.5 to 12 mm. Three cases had multicentric synchronous lesions on the skin. Histologically, these were well-circumscribed dermal tumors with solid or partially cystic nodules. Tested tumors expressed at least 1 neuroendocrine marker and were positive for CK7, ER/PR, 1 or more of GCDFP-15, mammaglobin, and GATA-3. One case had an associated IMC of the breast, and another case was associated with an intraductal papilloma of the breast in a man. There was no evidence of metastasis. EMPSGC is a low-grade adnexal neoplasm, commonly affecting the eyelid of the elderly. Lesions often progress to IMC, metastases being exceptionally rare. EMPSGC can be bilateral and multicentric. Concurrence with breast neoplasms has been observed and deserves investigation.

Bilateral Concurrent Endocrine Mucin-Producing Sweat Gland Carcinoma and Mucinous Carcinoma of the Eyelids

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is thought to be a precursor to mucinous carcinoma, both of which are rare. In this case report, the authors present a 55-year-old woman with concurrent EMPSGC and mucinous carcinoma manifesting with 2 distinct lesions on her left upper and lower eyelid and 1 lesion on her right lower eyelid. Biopsy and immunohistochemical staining supported primary cutaneous origin of the tumors. Systemic metastatic workup was initiated and thus far negative. The patient underwent staged slow Mohs micrographic surgery to remove one tumor at a time, with delayed reconstruction. This is the first reported case of EMPSGC and mucinous carcinoma presenting as distinct lesions both bilaterally and synchronously.

Endocrine Mucin-Producing Sweat Gland Carcinoma: A Case Report and Literature Review

Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) is a rare, low-grade, malignant tumor derived from sweat glands, arising preferentially in skin from the periorbital region. EMPSGC tumors are more frequently found in elderly female patients. To date, only around 70 cases have been reported in the literature [1-3]. Therefore, thorough immunohistochemical characterization of EMPSGC tumors is of pivotal importance to confirm its diagnosis [4-6].

Endocrine Mucin-Producing Sweat Gland Carcinoma Treated With Mohs Micrographic Surgery.

Endocrine Mucin-Producing Sweat Gland Carcinoma Treated With Mohs Micrographic Surgery.

28154 Endocrine mucin-producing sweat gland carcinoma in a patient with metastatic melanoma

A 55-year-old male with metastatic melanoma recently off immunotherapy presented with a 1-year history of an asymptomatic, slow growing mass on his right eyelid. Examination revealed a 3-mm well-circumscribed flesh-colored papule on the right upper eyelid margin. Excision performed by oculoplastics showed a multinodular superficial cystic and deep solid dermal neoplasm. The cystic component was comprised of an epithelial lining two layers thick. The deep solid component had foci of papillary change. Lesional cells had nuclear contours with small nuceloli and sparse pale granular eosinophilic cytoplasm. Scattered mitoses were present and high-grade atypia was absent. The tumor was positive for chromogranin A, CK7, EMA, BerEp4, synaptophysin (patchy), ER, and PR. MelanA, CK20, and CD56 were negative. P63 highlighted myoepithelial cells around the tumor. Based on the histopathologic and immunohistochemical features, endocrine mucin-producing sweat gland carcinoma (EMPSGC) was diagnosed. EMPSGC is an uncommon low-grade carcinoma with histopathologic and immunohistochemical features of solid, papillary breast carcinoma. Diagnosis can be difficult given its rarity and broad clinical differential diagnosis. The key immunohistochemical feature is neuroendocrine expression; tumors also often co-express estrogen and progesterone receptors. Elaboration of a myoepithelial layer surrounding the tumor is prudent to evaluate for invasive tumor. Although EMPSGC is a low-grade carcinoma with no reported cases of metastases, complete surgical excision is recommended given local recurrence and concern for progression to invasive mucinous carcinoma. Our patient’s tumor was completely excised via Mohs micrographic surgery with closure by oculoplastics. To our knowledge, there is no known association between EMPSGC and melanoma.

Cover Image

Journal of Cutaneous PathologyVolume 48, Issue 7 p. i-i COVER IMAGEFree Access Cover Image First published: 21 June 2021 https://doi.org/10.1111/cup.14081AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract The OBC cover image is based on the Case Report A case of endocrine mucin-producing sweat gland carcinoma with distant metastasis by Ata Moshiri et al., https://doi.org/10.1111/cup.13999. Volume48, Issue7July 2021Pages i-i RelatedInformation

Utility of Insulinoma-Associated Protein 1 (INSM1) and Mucin 2 (MUC2) Immunohistochemistry in the Distinction of Endocrine Mucin-Producing Sweat Gland Carcinoma From Morphologic Mimics.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare low-grade adnexal malignancy with a predilection for the eyelids of elderly White women, which is associated with invasive mucinous carcinoma with endocrine features in one-third of cases. EMPSGC is characterized by the presence of neuroendocrine differentiation and mucin production. However, EMPSGC displays a variety of architectural patterns including solid, cribriform, papillary, and cystic growth. In addition, EMPSGC may also display nonendocrine cytologic features, such as apocrine change. Because of their variable appearance, EMPSGC can show significant morphologic overlap with certain histologic mimics, namely basal cell carcinoma, hidrocystoma, apocrine hidradenoma, and tubular adenoma. In addition, the often limited sampling of this anatomically delicate area can make the diagnosis of EMPSGC challenging. EMPSGC expresses neuroendocrine markers, including synaptophysin and chromogranin, often in a focal distribution. However, insulinoma-associated protein 1 (INSM1) has been found to be a more sensitive marker for EMPSGC. Recent studies have also demonstrated the expression of the gel-forming mucin 2 (MUC2) in EMPSGC, possibly signifying a lacrimal or conjunctival origin of these neoplasms. In this article, we discuss EMPSGC in the context of its histologic mimics (BCC, hidrocystoma, apocrine hidradenoma, and tubular adenoma) and we investigate the utility of the immunohistochemical expression of INSM1 and MUC2 in the distinction of EMPSGC from them. We demonstrate that INSM1 and MUC2 can reliably distinguish EMPSGC from these histologic mimics.

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

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). 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. A review of English literature of all EMPSGC cases with and without associated PCMC was carried out. 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% and is much less than that 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 of our study includes data derivation from case reports and case series in the literature. The prognostic benefits for this cohort of patients may be considered in their overall management.

Next-generation sequencing analysis suggests varied multistep mutational pathogenesis for endocrine mucin-producing sweat gland carcinoma with comments on INSM1 and MUC2 suggesting a conjunctival origin

Endocrine mucin-producing sweat gland carcinoma is a low-grade eyelid tumor. Small biopsies and insensitive immunohistochemistry predispose to misdiagnosis. We aimed to identify clarifying immunohistochemical markers, molecular markers, or both. Clinicopathologic data (22 cases) were reviewed. Immunohistochemistry (insulinoma-associated protein 1, BCL-2, mucin 2 [MUC2], mucin 4, androgen receptor, β-catenin, and Merkel cell polyomavirus) and next-generation sequencing (Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets, 468 genes) were performed (3 cases). Female patients (n=15) and male patients (n=7) (mean age 71.8years; range 53-88years) had eyelid or periorbital tumors (>90%) with mucin-containing solid or cystic neuroendocrine pathology. Immunohistochemistry (insulinoma-associated protein 1, BCL2, androgen receptor, retinoblastoma-associated protein 1, and β-catenin) was diffusely positive (5/5), MUC2 partial, mucin 4 focal, and Merkel cell polyomavirus negative. Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets identified 12 single-nucleotide variants and 1 in-frame deletion in 3 cases, each with DNA damage response or repair (BRD4, PPP4R2, and RTEL1) and tumor-suppressor pathway (BRD4, TP53, TSC1, and LATS2) mutations. Microsatellite instability, copy number alterations, and structural alterations were absent. Insulinoma-associated protein 1 and MUC2 are positive in endocrine mucin-producing sweat glandcarcinoma. MUC2 positivity suggests conjunctival origin. Multistep pathogenesis involving DNAdamage repair and tumor-suppressor pathways may be implicated.

15713 Endocrine mucin-producing sweat gland carcinoma: Expanding the differential of eyelid tumors

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an uncommon low-grade adnexal neoplasm that most commonly occurs on the eyelid of elderly women. Clinically, this neoplasm presents as a flesh-colored to bluish or pink papule, nodule or swelling, often with overlying telangiectasias. It is often mistaken for basal cell carcinoma. Histopathologically, EMPSGC is positive for one or more neuroendocrine markers: synaptophysin, chromogranin, or neuron-specific enolase. It is often also positive for cytokeratin 7 (CK7), estrogen receptor (ER), and progesterone receptor (PR). Although EMPSGC is uncommon, it is being increasingly reported in the literature. This is likely due to an increase in diagnosis, not necessarily an increase in incidence. EMPSGC can be locally aggressive and can recur, but it is not known to metastasize. Treatment options include excision with wide margins or Mohs micrographic surgery. We present a case series of three biopsy proven EMPSGCs at our institution that demonstrated classic histopathologic and immunohistochemical patterns. We hope to increase awareness of this entity in the clinical and histopathologic differential diagnosis of eyelid tumors. We also hope to stress the importance of using immunohistochemistry to aid in the diagnosis of basaloid neoplasms.

Local invasion in endocrine mucin-producing sweat gland carcinoma: Still an open issue.

Local invasion in endocrine mucin-producing sweat gland carcinoma: Still an open issue.