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 Journal Article
| Authors: | Mathew, J. G.; Bowman, A. S.; Saab, J.; Busam, K. J.; Nehal, K.; Pulitzer, M. |
| Article Title: | 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 |
| Abstract: | 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 71.8 years; range 53-88 years) 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 gland carcinoma. MUC2 positivity suggests conjunctival origin. Multistep pathogenesis involving DNA damage repair and tumor-suppressor pathways may be implicated. © 2021 American Academy of Dermatology, Inc. |
| Keywords: | aged; aged, 80 and over; middle aged; genetics; mutation; pancreatic neoplasms; cell cycle protein; metabolism; cell cycle proteins; skin neoplasms; nuclear protein; transcription factor; pathology; tumor marker; skin carcinoma; transcription factors; nuclear proteins; skin tumor; pancreas tumor; tumor suppressor proteins; merkel cell polyomavirus; androgen receptor; receptors, androgen; tumor suppressor protein; beta catenin; repressor protein; repressor proteins; insulinoma; mucin; mucins; mucin 2; mucin 4; sweat gland tumor; sweat gland neoplasms; mucin-2; sweat gland; sweat glands; high throughput sequencing; high-throughput nucleotide sequencing; very elderly; humans; human; male; female; brd4 protein, human; biomarkers, tumor; protein serine-threonine kinases; insm1 protein, human; lats2 protein, human; muc2 protein, human; carcinoma, skin appendage; mucin-4 |
| Journal Title: | Journal of the American Academy of Dermatology |
| Volume: | 86 |
| Issue: | 5 |
| ISSN: | 0190-9622 |
| Publisher: | Mosby Elsevier |
| Date Published: | 2022-05-01 |
| Start Page: | 1072 |
| End Page: | 1079 |
| Language: | English |
| DOI: | 10.1016/j.jaad.2020.11.073 |
| PUBMED: | 33515627 |
| PROVIDER: | scopus |
| PMCID: | PMC9627720 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2022 -- Source: Scopus |
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