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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.

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



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.


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.


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.


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


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