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Histopathology. 2019 Sep 6. doi: 10.1111/his.13986. [Epub ahead of print]

Mutation Profile of High-Grade Appendiceal Mucinous Neoplasm.

Author information

1
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY.
2
Departments of Pathology Molecular and Cell-Based Medicine and Department of Medicine, Icahn Medical Center at Mount Sinai, New York, NY.
3
Department of Pathology and Laboratory Medicine, University of California, San Diego Health System, San Diego, CA.
4
Department of Pathology and Laboratory Medicine, New York University, New York, NY.

Abstract

AIMS:

High-grade appendiceal mucinous neoplasm (HAMN) was recently proposed as a disease entity histologically analogous to low-grade appendiceal mucinous neoplasm (LAMN) but characterized by high-grade cytological atypia. The pathogenesis and clinical features of HAMN have not been fully elucidated.

METHODS AND RESULTS:

Nine cases of HAMN, 8 LAMN, 10 appendiceal mucinous adenocarcinomas (MACA) and 5 appendiceal serrated polyps resected between 2008 and 2017 contributed by three medical centers underwent targeted next generation sequencing of 50 cancer-related genes. The patients in each category had similar profiles with respect to gender, age, tumor stage, and follow-up intervals. Both LAMN and HAMN harbored mutations of KRAS (9/9 and 8/8 [100%], respectively) and GNAS (5/8 [63%] and 5/9 [56%], respectively) in significantly higher proportions than MACA (KRAS, 7/10 [70%, P=0.04]; GNAS: 1/10 [10%, P=0.02]) and serrated polyps (KRAS, 1/5 [20%, P=.0007]; GNAS: 0/5 [0%, P=0.04]). Four cases of HAMN, but none of LAMN, harbored mutations of TP53 (4/9 [44%]) and/or ATM (2/9 [22%]). Three cases of HAMN (33%) showed extraappendiceal spread with retention of the same mutational profiles in the intra- and extraappendiceal components. The 10 cases of MACA harbored a similar prevalence of TP53 mutations (n=5, 50%) as HAMN but, unlike LAMN and HAMN, some harbored mutations in PIK3CA, APC, FBXW7, PTEN, and SMAD4.

CONCLUSIONS:

HAMN and LAMN share high rates of KRAS and GNAS co-mutations supporting a common histogenesis and distinguishing them from MACA. Acquisition of TP53 or ATM mutations by HAMN may drive its progression to a more advanced phenotype. This article is protected by copyright. All rights reserved.

KEYWORDS:

Appendix; High-grade appendiceal mucinous neoplasm; Next-generation sequencing

PMID:
31491041
DOI:
10.1111/his.13986

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