TY - JOUR
T1 - Whole exome sequencing of a gut-associated lymphoid tissue neoplasm points to precursor or early form of sporadic colon carcinoma
AU - Yaseen, Alae
AU - Ladenheim, Alexander
AU - Olson, Kristin A.
AU - Libertini, Stephen J.
AU - McPherson, John D.
AU - Matsukuma, Karen
N1 - Funding Information:
Laser capture microdissection was performed at the Cellular and Molecular Imaging (CAMI) core facility at the University of California Davis Center for Health and the Environment (supported by NIHS10RR-023555). Whole exome sequencing was performed at the Vincent J. Coates Genomics Sequencing Laboratory at University of California Berkeley (supported by NIHS10OD-018174).
Publisher Copyright:
© 2021 Elsevier GmbH
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Colon cancer
KW - Colorectal carcinoma
KW - GALT
KW - Gut-associated lymphoid tissue
KW - Whole exome sequencing
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U2 - 10.1016/j.prp.2021.153406
DO - 10.1016/j.prp.2021.153406
M3 - Article
C2 - 33740545
AN - SCOPUS:85102565296
VL - 220
JO - Pathology Research and Practice
JF - Pathology Research and Practice
SN - 0344-0338
M1 - 153406
ER -