Cutaneous Non-Neural Granular Cell Tumors Harbor Recurrent ALK Gene Fusions

The American Journal of Surgical Pathology
Jarish N CohenPhilip E LeBoit

Abstract

Non-neural granular cell tumor (NNGCT; also known as primitive polypoid granular cell tumor) is a rare neoplasm composed of large ovoid cells with abundant granular cytoplasm, variable nuclear pleomorphism, and the potential for regional lymph node spread. In contrast to conventional granular cell tumor (GCT), NNGCT lacks S100 expression and can exhibit greater nuclear atypia and mitotic activity. Therefore, we investigated clinicopathologic features of 12 NNGCT, and also used next-generation sequencing to identify potential driver events in a subset of NNGCT and 6 GCT. NNGCT demonstrated mild-to-moderate nuclear pleomorphism, variable mitotic activity (0 to 10/10 high-power fields), and were S100. Genetic analysis of 5 cutaneous NNGCT revealed gene fusions involving the anaplastic lymphoma kinase gene (ALK) in 3 cases (60%). Specifically, an interstitial deletion of chromosome 2 resulting in an in-frame fusion of dyanactin 1 (DCTN1) to ALK was identified in 2 cases, and a translocation resulting in a fusion between sequestosome 1 (SQSTM1) on chromosome 5 and ALK was identified in one case. Two of 6 GCT (33%) showed gains of chromosome 7. No other molecular or chromosomal alterations were detected in NNGCT and GCT. ALK immunohi...Continue Reading

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Citations

Aug 25, 2020·Current Opinion in Neurology·Anders Meyer
Jul 10, 2020·Journal of Cutaneous Pathology·Juan Torre-CastroCarlos Santonja
Nov 11, 2019·Virchows Archiv : an International Journal of Pathology·Anders Meyer, Steven D Billings
Apr 23, 2020·Diagnostics·Joon Hyuk Choi, Jae Y Ro
Jan 5, 2022·Journal of Cutaneous Pathology·Landon K HobbsShyam S Raghavan

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Methods Mentioned

BETA
biopsies
biopsy

Software Mentioned

Nexus
Integrative Genomics Viewer
NNGCT
Samtools
Picard
Pindel
GATK
Integrated Genomics Viewer
Freebayes
BWA0

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