The morphologic spectrum of NF mutated desmoplastic melanocytic neoplasms Journal Article
| Authors: | Addo, A. K.; Beydoun, H. M.; Jeyakumar, J. E.; Olivares, S.; Busam, K. J.; Gerami, P. |
| Article Title: | The morphologic spectrum of NF mutated desmoplastic melanocytic neoplasms |
| Abstract: | Next generation sequencing is rapidly being integrated into diagnostic skin pathology. Critical components of this integration are studies to assist with the bioinformatic interpretation of genetic data. In this study, we characterize the morphologic and genomic spectrum of NF mutated desmoplastic melanomas (DMs) and compare them with DMs lacking pathogenic variants in NF and to NF mutated desmoplastic nevi. Relative to non-NF mutated DMs, NF mutated DMs were less likely to have an associated melanoma in situ (35% vs. 47%), less likely to have an epithelioid component (35% vs. 59%), and more likely to have prominent pigmentation (35% vs. 12%). Two distinct morphologic patterns were exclusive to the NF mutated subgroup, which included a pigmented DM mimicking blue nevi and a neurofibroma-like pattern of DM. The most common NF mutation in both specific morphologic subtypes was a truncating NF1 variant (4 of 8 and 6 of 8, respectively). Relative to NF mutated desmoplastic nevi, NF mutated DMs were more likely to have truncating variants in NF1, had a higher TMB (57.3 vs. 9.9, P < 0.05), and a higher number of pathogenic variants (19 vs. 3, P < 0.05). Pathogenic variants in p-TERT and TP53 were exclusive to the NF mutated DMs. Alternatively, truncating variants in NF2 were mostly seen in the NF-inactivated clonal nevus. We provide the first ever description including the genomic and morphologic features of this novel combined pattern nevus typically involving an activating mutation in BRAF or other oncogene accompanied by a truncating mutation in NF2. © 2025 Elsevier B.V., All rights reserved. |
| Keywords: | adult; clinical article; controlled study; human tissue; aged; middle aged; gene mutation; human cell; major clinical study; sequence analysis; frameshift mutation; missense mutation; follow up; diagnostic accuracy; genetic analysis; gene; melanoma; melanin; skin pigmentation; nevus; melanocyte; clinical assessment; cohort analysis; genetic variability; retrospective study; protein p53; morphology; questionnaire; oncogene; head and neck cancer; diagnosis; telomerase reverse transcriptase; surgery; spindle cell; desmoplastic melanoma; desmoplastic nevus; cyclin dependent kinase inhibitor 2a; bioinformatics; mediastinum; b raf kinase; neurofibroma; lymphadenopathy; nonsense mutation; nf2 gene; etiology; blue nevus; nf1; nf2; mitotic recombination; oncogene n ras; epithelioid; genotype phenotype correlation; neurofibromatosis type 1; melanocytic lesion; melanoma in situ; morphologic pattern; nf1 gene; high throughput sequencing; map2k1 gene; breslow thickness; melanocytic tumor; very elderly; human; male; female; article; swi/snf related matrix associated actin dependent regulator of chromatin subfamily b member 1; tumor mutational burden; splice site variant; pathogenic variant; spindle cell melanoma; microsoft excel; desmoplastic nevi; fascicular architecture; nodular epithelioid pattern; oncomine precision assay panel; spindle cell pattern |
| Journal Title: | American Journal of Dermatopathology |
| Volume: | 47 |
| Issue: | 9 |
| ISSN: | 0193-1091 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2025-09-01 |
| Start Page: | 692 |
| End Page: | 698 |
| Language: | English |
| DOI: | 10.1097/dad.0000000000003056 |
| PUBMED: | 40767457 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
