Endocrine mucin‐producing sweat gland carcinoma occurring on extra‐facial site: a case report

Cutaneous endocrine mucin‐producing sweat gland carcinoma (EMPSGC) is a very rare low‐grade malignant neoplasm analogous to the mammary solid‐papillary carcinoma. It frequently expresses neuroendocrine markers and may show mucinous differentiation. Although the nodules are circumscribed, myoepithelial cells cannot be showed in most cases and about half of the cases are associated with invasive mucinous carcinoma. Hence, it has been suggested to be invasive and the precursor lesion of some primary cutaneous mucinous carcinomas. After being recognized as a distinct entity, all cases reported to date occurred either in the periocular region or on the cheek. Two thirds of the patients were female. Herein we present an unusual case of in situ EMPSGC on the chest wall skin of a middle‐aged man.     

Recurrent endocrine mucin‐producing sweat gland carcinoma in the eyelid

Endocrine mucin‐producing sweat gland carcinoma (EMPSGC) has recently been recognised as a low‐grade carcinoma that almost always occurs on the eyelid. This carcinoma is very rare, with only 20 cases (including the present one) having been reported in the literature. EMPSGC is frequently found in association with invasive mucinous carcinoma. While EMPSGC treatments consist of a complete surgical removal, there has been no consensus regarding the surgical margin. Therefore, reports on surgical management of EMPSGC may potentially provide important therapeutic information. Here, we present a case of a 74‐year‐old man with EMPSGC of the eyelid that repeatedly recurred despite surgical treatments at another institution. After referral to our department, the patient underwent tumour excision. However, the specimen revealed a positive surgical margin and thus, he subsequently underwent a wider excision. There has been no sign of tumour recurrence or metastasis 6 months after his last operation. This article reviews the current literature and discusses the surgical management of EMPSGC.     

Endocrine mucin‐producing sweat gland carcinoma: a study of three cases and CK8, CK18 and CD5/6 immunoexpression

Endocrine mucin‐producing sweat gland carcinoma is a cutaneous adnexal tumor that is rarely reported in the literature. We identified only 29 previously reported cases. All these cases share some clinical morphologic and immunohistochemical features. Among the immunohistochemical markers, cytokeratins 5/6, 8 and 18 (CK5/6, CK8 and CK18) had not been previously studied in this tumor. Although studies with cytokeratin Cam5.2 exist, we know at present that this marker does not correspond to antibodies CK8/18, but rather to CK7 and CK8. We studied three examples of endocrine mucin‐producing sweat gland carcinoma with 18 immunostains. Our cases showed an immunoprofile CK8+, CK18+, CK5/6− (or only focally positive), CK7+, GCDFP‐15+ (2 cases), estrogen receptor+, progesterone receptor+, HER2‐, neuron‐specific enolase + (2 cases), anti‐synaptophysin+, chromogranin A +, CD56 variable (1 case +, 1 case−), CD57‐, anti‐human D2‐40‐ (two cases), p63‐ or focally positive, smooth muscle actin + with variable pattern of expression and smooth muscle myosin heavy chain expressed in a peripheral discontinuous layer in some nodules, but absent in most.     

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.     

Polymorphous sweat gland carcinoma: a report of two cases

Polymorphous sweat gland carcinoma (PSGC) is a rare adnexal neoplasm with characteristic variegated histopathologic findings and low‐grade clinical behavior. First described in 1994, only 11 cases have been reported in the literature. It is named for the multiplicity of architectural patterns that may be present: solid, tubular, trabecular, pseudopapillary and cylindromatous. Owing to the multiple architectural patterns, the differential diagnosis is broad, including metastatic adenocarcinoma and other adnexal neoplasms with ductular differentiation. We present two new cases of PSGC and review the literature on this rare tumor.     

Recurrent primary cutaneous mucinous carcinoma with neuroendocrine differentiation: case report and review of the literature

We report the case of a 60‐year‐old woman presenting with primary cutaneous mucinous carcinoma (PCMC) with neuroendocrine differentiation, revealed by neuroendocrine tumor lymph node metastasis 7 years before identification of the skin tumor. Only five cases of PCMC with neuroendocrine differentiation have been reported to date. The frequency of this neuroendocrine component may be underestimated, as it can require immunohistochemistry for identification, rather than being obvious on initial histopathologic examination. In the case presented here, the prominent neuroendocrine component displayed the morphological features of a well‐differentiated neuroendocrine tumor with expression of common neuroendocrine markers, strong expression of estrogen and progesterone receptors and low Ki67 proliferation index (5%). This case shows that not all primary cutaneous neuroendocrine carcinomas are Merkel cell carcinomas (MCCs). In addition to rare primary cutaneous carcinoid tumors, the diagnosis of PCMC with neuroendocrine differentiation must be considered, particularly when confronted by a mucinous tumor or lymph node metastases of neuroendocrine carcinoma of unknown origin. On the basis of this case, identification of a neuroendocrine component in a PCMC might be an adverse prognostic indicator of recurrence or of lymph node metastasis and should support wider excision margins of the tumor.     

Bowen disease with invasive mucin‐secreting sweat gland differentiation: Report of a case and review of the literature

Bowen disease (BD) with divergent adnexal differentiation is a rare composite cutaneous tumor featuring different phenotypic elements. Sebaceous, poroid and trichilemmal invasive components have been described in this setting and very infrequent reports of mucinous glandular differentiation are extant. Clinically, these tumors are not sufficiently distinctive to enable recognition without histopathological evaluation. From a microscopic perspective, care must be taken to exclude a collision tumor as well as other combined cutaneous neoplasms featuring squamous and glandular differentiation. Direct continuity between the two epithelial phenotypes helps to establish the correct diagnosis and generates interesting speculation about the pathogenesis of these and other epithelial skin tumors. We describe a case of BD in continuity with an invasive adenocarcinoma exhibiting mucinous sweat gland differentiation on the face of an elderly man. Details of the case are outlined with the objective of adding to a scant literature on this topic.     

Primary cutaneous adenoid cystic carcinoma with MYB aberrations: report of three cases and comprehensive review of the literature

Adenoid cystic carcinoma (ACC) is a relatively rare slow‐growing and often‐aggressive epithelial‐myoepithelial neoplasm that arises in multiple organs including the skin. The t(6;9) (q22‐23;p23‐24) translocation, resulting in a MYB‐NFIB gene fusion has been found in ACCs from the salivary glands and other organs. Recently, MYB aberrations occurring in a subset (40%) of primary cutaneous ACC (PCACC) examples was described. Herein, we report three additional cases of PCACC harboring MYB aberrations. The tumors presented in three males aged 43, 81 and 55 years old and affected the extremities in the first two patients and the scalp in the third one. None of the patients had history of prior or concurrent ACC elsewhere. Lesions exhibited the classic ACC morphology of nests of basaloid cells arranged in cribriform and adenoid patterns. Sentinel lymph node biopsy was performed in two cases with one case showing lymph node positivity. Fluorescence in situ hybridization with break‐apart probes for MYB and NFIB loci revealed that two cases showed MYB rearrangements while one case showed loss of one MYB signal. None of the cases showed NFIB rearrangements. We contribute with three additional cases of PCACC exhibiting MYB aberrations, the apparent driving genetic abnormality in these tumors.     

Large‐cell neuroendocrine carcinoma of the skin: ultrastructural and immunohistochemical findings

Large‐cell neuroendocrine carcinoma (LCNEC) is an uncommon and aggressive neuroendocrine tumor, found mainly in the lung. Although LCNEC has been reported in various organs, LCNEC of the skin is extremely rare, poorly recognized and probably underestimated. Here we report a case of LCNEC of the skin, focusing on the histopathological and ultrastructural findings in detail. The patient was an 85‐year‐old Japanese woman presented with a mass on her right upper eyelid. Biopsy specimen showed an infiltrative mass with extension into the subcutis. Tumor cells were arranged in organoid and trabecular patterns with sheets, nests and trabecular cords. Extensive necrotic areas were observed. Most of the tumor cells were characterized by large cell size, polygonal shape, low nuclear‐cytoplasmic ratio, coarse nuclear chromatin and frequent nucleoli. They were positive for CD56, NSE, AE1/AE3, CK7, and negative for CK20, TTF‐1, synaptophysin and chromogranin A. A systematic radiographic examination revealed no additional neoplastic lesions other than the right upper eyelid mass. These findings suggest that the present case is a LCNEC of the skin. The existence of LCNEC in the skin should be recognized, as it is a rare variant of carcinoma that can potentially be misconstrued as a metastasis or as Merkel cell carcinoma.     

Low‐grade cylindromatous adnexal carcinoma with unusual histopathological features: report of a case with comparative immunohistochemical study and meta‐analysis of the literature

We present an extremely rare case of low‐grade cylindromatous adnexal carcinoma (CAC) on the right chest wall of a 77‐year‐old man. Histopathologically, the neoplasm was initially diagnosed as a cylindroma that developed over the course of 13 years. A diagnosis of low‐grade CAC was rendered after the documentation of a local recurrence and histopathology of the recurrent tumor. To further assess the evolution of low‐grade CAC over time, we compared the morphology, mitotic account, proliferative markers and adhesion molecule immunoreactivity among paired primary and recurrent tumors. Unlike those earlier reported, our case showed the maintenance of tumor morphology after a recurrence without areas of obvious malignant transformation or metaplastic change. We showed here for the first time the expression of adhesion molecules of CAC/spiradenoma and a comparison of proliferation indices between a primary tumor and its local recurrence. This peculiar tumor differs from previously reported cases and harbors a malignant potential although the histopathological features of malignancy are subtle. Our meta‐analysis of the literature provided background information regarding this rare entity. Alterations of E‐cadherin and GCDFP‐15 expression may provide additional helpful clues in differential diagnosis and determining the clinical behavior of this unusual neoplasm. Further studies are warranted to confirm the potential discriminative role of these markers.     

Glutathione‐conjugated sulfanylalkanols are substrates for ABCC11 and γ‐glutamyl transferase 1: a potential new pathway for the formation of odorant precursors in the apocrine sweat gland

We have previously shown that precursors of odorous components characteristic of axillary sweat are hardly detectable or undetectable in individuals carrying the 538G > A SNP in the ABCC11 transporter gene. However, it is unclear, whether ABCC11 is directly involved in the transport of these compounds. To approach this question, transport of peptide‐conjugated potential precursors of 3‐methyl‐3‐sulfanylhexanol (3M3SH), a key determinant of axillary malodour, was measured using membrane vesicles of Sf9 insect cells overexpressing human ABCC11. Whilst no ABCC11‐mediated transport was detected for the dipeptide precursor Cys‐Gly‐3M3SH, the glutathione conjugate of 3M3SH (SG‐3M3SH) was robustly taken up by ABCC11 at a transport rate of 0.47 pmol/mg/min. Collectively, these results illuminate SG‐3M3SH as a putative precursor of 3M3SH, which then may undergo intra‐vesicular maturation to generate Cys‐Gly‐3M3SH. Critically, the apocrine sweat gland was demonstrated to express γ‐glutamyl transferase 1 (GGT1) protein, which is known to catalyse the deglutamylation of glutathionyl conjugates. Additionally, we provide evidence that recombinant and isolated hepatic human GGT1 is capable of transforming SG‐3M3SH to Cys‐Gly‐3M3SH in vitro. To sum up, we demonstrate that the functionality of ABCC11 is likely to play an important role in the generation of axillary malodour. Furthermore, we identify GGT1 as a key enzyme involved in the biosynthesis of Cys‐Gly‐3M3SH.