1. Whole exome sequencing of a gut-associated lymphoid tissue neoplasm points to precursor or early form of sporadic colon carcinoma.
- Author
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Yaseen A, Ladenheim A, Olson KA, Libertini SJ, McPherson JD, and Matsukuma K
- Subjects
- Adenocarcinoma immunology, Adenocarcinoma pathology, Adenocarcinoma surgery, Aged, Biomarkers, Tumor analysis, Colectomy, Colonic Neoplasms immunology, Colonic Neoplasms pathology, Colonic Neoplasms surgery, Female, Humans, Immunohistochemistry, Lymphoid Tissue immunology, Lymphoid Tissue surgery, Predictive Value of Tests, Adenocarcinoma genetics, Biomarkers, Tumor genetics, Colonic Neoplasms genetics, Genetic Variation, Lymphoid Tissue pathology, Exome Sequencing
- Abstract
Gut-associated lymphoid tissue (GALT) carcinoma is a colorectal neoplasm characterized by cystically dilated neoplastic glands that extend into prominent, well-circumscribed submucosal lymphoid tissue. Although often subtle, lamina propria between and around the neoplastic glands (identified by plasma cells, scattered eosinophils, etc.) is frequent in cases with classic morphology, arguing (at least in such cases) in favor of adenoma extending into lymphoglandular complexes rather than true invasive carcinoma. Some have postulated that the tumor arises from M-cells, specialized epithelial cells overlying GALT, and others have suggested it represents a unique pathway to carcinoma, specific to the environmental conditions of epithelium overlying lymphoid tissue. Although both hypotheses are intriguing, definitive phenotypic and genetic support is currently lacking. To address these possibilities, we undertook whole exome sequencing and immunohistochemical characterization of a GALT neoplasm recently identified on our clinical service. We discovered well-known mutations in both APC and KRAS, as well as mutations in several Wnt pathway components (MED12, BCL9L, RFX4, DACT3). No immunohistochemical expression of GP2, a marker of M-cell differentiation, was identified. Expression of CDX2, SATB2, and the DNA mismatch repair proteins was observed, while expression of both CK7 and CK20 was absent. No PD-L1 expression was present on tumor cells, but PD-L1 expression was noted in a subset of tumor-adjacent mononuclear cells. Overall, the findings suggest that GALT neoplasms, although morphologically distinct, may be a precursor or early form of typical sporadic colon carcinoma., (Copyright © 2021 Elsevier GmbH. All rights reserved.)
- Published
- 2021
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