Next-generation sequencing as a potential diagnostic adjunct in distinguishing between desmoplastic melanocytic neoplasms Journal Article
| Authors: | Roth, A.; Boutko, A.; Lampley, N. 3rd; Dhillon, S.; Hagstrom, M.; Olivares, S.; Dittman, D.; Jennings, L.; Santana dos Santos, L.; Busam, K.; Gerami, P. |
| Article Title: | Next-generation sequencing as a potential diagnostic adjunct in distinguishing between desmoplastic melanocytic neoplasms |
| Abstract: | Desmoplastic melanomas (DMs) are often challenging to diagnose and ancillary tests, such as immunohistochemistry, have limitations. One challenge is distinguishing DM from benign desmoplastic melanocytic neoplasms. In this study, we explored the utility of next-generation sequencing data in the diagnosis of DMs versus desmoplastic Spitz nevi (DSN) and desmoplastic nevi (DN). We sequenced 47 cases and retrieved 12 additional previously sequenced clinical cases from our dermatopathology database. The 59 total cases were comprised of 21 DMs, 25 DSN, and 13 DN. The DMs had the highest tumor mutation burden at 22 mutations/megabase (m/Mb) versus the DSN (6 m/Mb) and DN (8 m/Mb). Truncating mutations in NF1 resulting in a loss-of-function were exclusive to the DM cohort, identified in 8/21 (38%) cases. Importantly, missense mutations in NF1 were nonspecific and seen with similar frequency in the different cohorts. Other mutations exclusive to the DMs included truncating mutations in TP53, CDKN2A, and ARID2. Among the DSN, 17/25 (68%) had an HRAS mutation or receptor tyrosine kinase fusion consistent with other Spitz tumors. Two cases in the DN cohort had missense mutations in BRAF without additional progression mutations and 2 other cases had mutations in GNAQ, supporting a diagnosis of a sclerosing blue nevus. The remainder of the DN had nonspecific mutations in various signaling pathways with few progression mutations. Overall, our study provides preliminary data that next-generation sequencing data may have the potential to serve as an ancillary diagnostic tool to help differentiate malignant and benign desmoplastic melanocytic neoplasms. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. |
| Keywords: | signal transduction; adult; clinical article; human tissue; aged; middle aged; unclassified drug; single nucleotide polymorphism; somatic mutation; missense mutation; mutation; janus kinase 2; histopathology; cancer diagnosis; melanoma; nevus; skin neoplasms; melanocyte; differential diagnosis; epidermal growth factor receptor; gene frequency; pathology; protein tyrosine kinase; phosphatidylinositol 3 kinase; protein p53; oncogene h ras; tumor suppressor gene; skin tumor; nevus, pigmented; microsatellite instability; mammalian target of rapamycin; tumor protein; telomerase reverse transcriptase; spindle cell; desmoplastic melanoma; spitz nevus; nevus, epithelioid and spindle cell; eosin; hematoxylin; cyclin dependent kinase inhibitor 2a; bioinformatics; loss of function mutation; b raf kinase; nonsense mutation; fibroblast growth factor receptor 2; sclerosis; xeroderma pigmentosum group c protein; axin; axin 2; epidermal growth factor receptor 4; canonical wnt signaling; fusion protein; blue nevus; oncogene n ras; pigmented nevus; pi3k/akt signaling; neurotropism; high throughput sequencing; spitz; high-throughput nucleotide sequencing; gain of function mutation; desmoplastic; next-generation sequencing; very elderly; dna sequencing; humans; human; male; female; article; nf1 protein; tumor mutational burden; jak-stat signaling; gnaq protein; ngs; arid2 protein |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 47 |
| Issue: | 3 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2023-03-01 |
| Start Page: | 318 |
| End Page: | 325 |
| Language: | English |
| DOI: | 10.1097/pas.0000000000001999 |
| PUBMED: | 36383901 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
