1. 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
- Author
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Anita S. Bowman, Joseph Mathew, Melissa Pulitzer, Klaus J. Busam, Jad Saab, and Kishwer S. Nehal
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,Adenoid cystic carcinoma ,Merkel cell polyomavirus ,Cell Cycle Proteins ,Dermatology ,Mucin 2 ,Protein Serine-Threonine Kinases ,Article ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Mucoepidermoid carcinoma ,Biomarkers, Tumor ,medicine ,Humans ,Basal cell carcinoma ,beta Catenin ,Aged ,Aged, 80 and over ,Mucin-2 ,Mucin-4 ,biology ,business.industry ,Tumor Suppressor Proteins ,Carcinoma, Skin Appendage ,Mucins ,High-Throughput Nucleotide Sequencing ,Nuclear Proteins ,Microsatellite instability ,Middle Aged ,medicine.disease ,biology.organism_classification ,Sweat Glands ,Pancreatic Neoplasms ,Repressor Proteins ,Sweat Gland Neoplasms ,Receptors, Androgen ,030220 oncology & carcinogenesis ,Mutation ,Immunohistochemistry ,Female ,Insulinoma ,DNA mismatch repair ,business ,Transcription Factors - 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.
- Published
- 2022