Endocrine mucin-producing sweat gland carcinoma of the peno-scrotum with systemic metastases: A rare case report

Milap Shah; Ambreen Aman; K Srinivaas; Archana Gudipati; Pooja Chavali

doi:10.4103/IJPM.IJPM_342_19

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CASE REPORT

Year : 2021 | Volume : 64 | Issue : 1 | Page : 180-182

Endocrine mucin-producing sweat gland carcinoma of the peno-scrotum with systemic metastases: A rare case report

Milap Shah¹, Ambreen Aman², K Srinivaas³, Archana Gudipati⁴, Pooja Chavali⁴
¹ Consultant Histopathologist, Yashoda Hospitals, Secunderabad, Telangana, India
² Department of Pathology, Yashoda Hospitals, Secunderabad, Telangana, India
³ Consultant Radiation Oncologist, Yashoda Hospitals, Secunderabad, Telangana, India
⁴ Consultant Pathologist, Yashoda Hospitals, Secunderabad, Telangana, India

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Date of Submission	03-May-2019
Date of Decision	07-Sep-2019
Date of Acceptance	23-Mar-2020
Date of Web Publication	8-Jan-2021

Abstract

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare adnexal tumor with a predilection for the skin of the eyelid. It has also been reported in other areas of the face. Extra facial location has rarely been reported. They are twice as common in the females as compared to men and frequently affect the elderly between 50 and 80 years of age. It is a low-grade carcinoma with no reported cases of metastases, although a few cases with recurrences have been reported. Since it was first described by Flieder et al. in 1997, fewer than 60 cases have been reported in the literature. We describe one such case of EMPSGC in an adult male occurring at an unusual location, the peno-scrotal junction with systemic metastases to bilateral inguinal and iliac lymph nodes, multiple bones, and pancreas. Unlike previously reported cases, our patient worsened rapidly and succumbed to the disease six months after initiation of chemotherapy and radiotherapy. To the best of our knowledge, this is the first reported case of its kind in modern published literature.

Keywords: Endocrine ductal carcinoma-in-situ, endocrine mucin-producing sweat gland carcinoma, solid papillary carcinoma

How to cite this article:
Shah M, Aman A, Srinivaas K, Gudipati A, Chavali P. Endocrine mucin-producing sweat gland carcinoma of the peno-scrotum with systemic metastases: A rare case report. Indian J Pathol Microbiol 2021;64:180-2

How to cite this URL:
Shah M, Aman A, Srinivaas K, Gudipati A, Chavali P. Endocrine mucin-producing sweat gland carcinoma of the peno-scrotum with systemic metastases: A rare case report. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 Apr 22];64:180-2. Available from: https://www.ijpmonline.org/text.asp?2021/64/1/180/306507

Introduction

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal tumor with a strong predilection to involve the eyelids of elderly women.^[3] It shows a striking morphological and immunophenotypical similarity to endocrine ductal carcinoma-in-situ (DCIS)/solid papillary carcinoma of the breast. EMPSGC is characterized by a relatively circumscribed, multinodular solid cystic mucinous tumor with immunoreactivity to neuroendocrine markers.^[3] This morphological similarity can be attributed to the close embryological relationship shared by the sweat glands and the mammary glands.

This tumor has rarely been reported at sites other than the eyelid with only a handful of cases involving the cheek. We report an unusual presentation of this neoplasm in an elderly male, at the peno-scrotal region with extensive systemic metastases and involvement of multiple inguinal and iliac lymph nodes.

Case Report

A 60-year-old male presented to our hospital with a non-healing ulcer over the scrotum. PET scan revealed a metabolically active subtle ill-defined enhancing lesion in the right scrotum and root of penis with multiple metabolically active bilateral common iliac, external iliac, and inguinal lymph nodes, a subtle metabolically active ill-defined enhancing lesion involving the body of pancreas and multiple skeletal lesions which were likely to be metastatic in nature. Based on a clinical suspicion of squamous cell carcinoma, an excision biopsy of the scrotal ulcer was performed. The pancreatic and bony lesions were not sampled for histopathological evaluation.

Figure 1: Light microscopy: hematoxyllin and eosin stain, 4× magnification

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Figure 2: Light microscoopy: Immunohistochemical stains, 4× magnification

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Light microscopy revealed a tumor in the dermis extending into the subcutaneous tissue. The tumor displayed a nodular architecture with solid, acinar, glandular, and cribriform patterns at places. The tumor cells had moderate amounts of eosinophilic cytoplasm with medium sized, monomorphic, round to oval nuclei displaying finely stippled ”salt and pepper chromatin,” minimal atypia, and rare mitotic figures. Intracellular mucin was noted throughout the tumor with small areas of extracellular mucin deposition. Numerous lymphatic and vascular emboli were seen. (Legend 1: Light Microscopy, hematoxylin and eosin stain, 4× magnification)

On immunohistochemistry, tumor cells showed strong immunopositivity for keratins (high molecular weight cytokeratin, CK7), Estrogen Receptor (ER) and GATA3. They also expressed neuroendocrine markers: Chromogranin A and Synaptophysin. However, they did not express CK20, CDX2, p40/DG3 cocktail. p63 was found to highlight the basal layer of the epidermis, while it was conspicuously negative in tumor cells. The Ki67 index was 2%– 3%. (Legend 2: Immunohistochemistry, 4× magnification)

The patient was administered radiation therapy directed at the scrotal ulcer and bone lesions. He was also administered systemic palliative chemotherapy to combat the extensive metastatic disease. He survived with disease for a period of 6 months after initiation of chemotherapy and radiation therapy. There was no remission in disease status, the lesions remained metabolically active during the course of treatment, and the patient succumbed to multiorgan dysfunction and septicemia 6 months later.

Discussion

EMPSGC is a low-grade adnexal sweat gland carcinoma with neuroendocrine differentiation, and solid, papillary, and cystic growth pattern.^[2] This tumor has a predilection for the eyelids with few cases involving the cheek. It commonly affects the elderly and is twice as frequent in females as in males.

Since sweat glands and mammary glands share a common embryonical origin, it is not uncommon to find analogous tumors.^[1],[4] EMPSGC shares all the morphological and immunohistochemical features of solid papillary carcinoma/endocrine carcinoma-in-situ of the breast like overall low-grade cytology, a nodular, solid, papillary, and/or cribriforming architecture, neuroendocrine differentiation, and mucin production; some of which are only identifiable by immunohistochemistry and/or special stains. In the breast, solid papillary carcinoma/endocrine ductal carcinoma in situ is deemed the precursor lesion to mucinous (colloid) carcinoma. EMPSGC is believed to be the immediate precursor lesion to primary cutaneous mucinous (colloid) carcinoma (CMC). Although it would be exceedingly rare, clinicians and pathologists must rule out metastatic breast carcinoma to the skin before diagnosing EMPSGC. 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],[3]

Whether EMPSGC represents an in-situ or an invasive carcinoma largely rests on the presence or absence of a peripheral rim of myoepithelial cells.^[3] The loss of myoepithelial cells represents widely accepted evidence of invasion when observed in similar carcinomas in the breast. The expansile tumor nodules and nests of classic EMPSGC are typically devoid of myoepithelial cells. Thus, EMPSGC is best considered as an invasive carcinoma as an overwhelming majority of the cases demonstrate negative immunostaining for myoepithelial markers. The architectural complexity, size, and close apposition of the tumor cells to the reticular dermis in most cases also support the interpretation of EMPSGC as invasive carcinomas.^[2]

These morphologic observations suggest that EMPSGC is a precursor of some mucinous carcinomas similar to endocrine ductal carcinoma-in-situ (eDCIS)/solid? papillary carcinoma of the breast.^[2]

EMPSGC have been reported to stain positively with neuroendocrine markers such as synaptophysin, chromogranin, NSE, and CD 57 in most studies. They are also known to be immunopositive for cytokeratin 7, cytokeratin CAM 5.2, epithelial membrane antigen, estrogen receptor, and progesterone receptor. Expression of a specific neuroendocrine marker such as synaptophysin or chromogranin is required for the diagnosis of EMPSGC.

The treatment of choice for CMCs has been simple excision; however, a second excision may be needed if margins are positive. Such cases have high local recurrence rates. The prognosis of EMPSGC, even in cases associated with invasive mucinous carcinoma, is favorable. Yet, patients with EMPSGC should be closely followed clinically as mucinous carcinoma has a well-documented metastatic potential.

All previously reported cases involved the eyelid of elderly females aged between 53 and 79 years,^{[1],[2],[3],[4],[5],[6],[7]} with very few recurrences after surgical excision and none with systemic metastases. One case with EMPSGC co-existing with low-grade mucinous carcinoma of the breast has been reported, but the authors demonstrated that the EMPSGC was a synchronous malignancy and not a metastasis from the primary breast neoplasm.^[8] After an extensive search of published literature and PubMed indexed journals, we have come to the conclusion that this is the first reported case of EMPSGC presenting in an elderly male, involving an unusual site with extensive systemic and lymph node metastases.

Conclusion

EMPSGC is an uncommon malignant adnexal tumor which has analogous histological and immunohistochemical findings with solid papillary carcinoma of the breast. Therefore, it is pertinent to rule out a primary breast lesion with metastases. The mucinous nature of this tumor is often not obvious. Furthermore, many of these tumors can deceptively look like a benign or in-situ neoplasm. Demonstration of lack of myoepithelial cells supports the invasive nature of these tumors and aids in its distinction from benign neoplasms. A greater awareness of this neoplasm would prompt the pathologist to perform appropriate immunohistochemical stains to demonstrate neuroendocrine differentiation.^[3]

From published literature, the overall prognosis of EMPSGC is excellent, although there is a possibility of local recurrence. EMPSGC is best regarded as a precursor, with the transition to invasive carcinoma characterized by a loss of cell polarity and mucin secretion into the tissue stroma instead of the cystic spaces. When EMPSGC is associated with an invasive mucinous carcinomatous component, the risk of recurrence and that of direct extension into adjacent structures and lymph node metastases increases greatly.

This patient not only had an invasive mucinous carcinoma but also had extensive systemic metastases and responded poorly to treatment which makes it an exception from those reported previously in published literature.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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3.	Dhaliwal CA, Torgersen A, Ross JJ, Ironside JW, Biswas A. Endocrine mucin-producing sweat gland carcinoma: Report of two cases of an under-recognized malignant neoplasm and review of the literature. Am J Dermatopathol 2013;35:117-24.
4.	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;21:1501-6.
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8.	Jedrych J, Jones M, Seethala R, Ho J. Primary cutaneous endocrine mucin-producing sweat gland carcinoma co-occurring simultaneously with low-grade ductal mucinous breast cancer: A clinicopathologic conundrum. Am J Dermatopathol 2015;37:425-7.