Subungual melanoma with cartilaginous differentiation: Molecular insights

• Published in: Journal of cutaneous pathology 2024-08, Vol.51 (8), p.576-582
• Main Authors: Shaikh, Umayr, Shah, Payal, Jones, Victoria, Ramos‐Rodriguez, Alvaro J., Sriharan, Aravindhan, Loo, Eric, Khan, Wahab A., Simmons, Brian, Cloutier, Jeffrey M.
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm; Cartilage - metabolism; Cartilage - pathology; cartilaginous differentiation; Cell Differentiation; chondrosarcoma; Chromosome deletion; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; DNA microarrays; DNA sequencing; Female; Gene deletion; Genomic analysis; heterologous differentiation; Humans; Male; Melanoma; Melanoma - diagnosis; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Molecular modelling; Nail Diseases - genetics; Nail Diseases - metabolism; Nail Diseases - pathology; Nucleotide sequence; S100 Proteins - metabolism; Single-nucleotide polymorphism; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Sox10 protein; SOXE Transcription Factors - genetics; SOXE Transcription Factors - metabolism; subungual; Tumor cells; Tumor suppressor genes; Tumors
• ISSN: 0303-6987; 1600-0560; 1600-0560
• DOI: 10.1111/cup.14630

Melanoma's rare capacity to undergo heterologous differentiation can create significant diagnostic challenges. The molecular mechanisms underlying this phenomenon are not well understood. We present an unusual case of subungual melanoma exhibiting extensive cartilaginous differentiation and provide insights into its molecular and cytogenomic features. Histopathologically, the tumor was predominantly composed of nodules of malignant cartilage in association with a smaller population of nested epithelioid to rhabdoid cells. Immunohistochemically, the tumor cells in both components were positive for S100, SOX10, and PRAME, and were negative for Melan‐A and HMB‐45. Molecular analysis by whole exome DNA sequence did not detect any pathogenic variants in genes commonly implicated in melanoma. Additional analysis by SNP chromosomal microarray revealed a complex genome characterized by numerous chromosomal losses and gains, including a homozygous deletion of the CDKN2A locus and a heterozygous deletion of the locus containing EXT2, a tumor suppressor implicated in hereditary multiple osteochondromas and secondary chondrosarcomas. This case underscores the importance of recognizing cartilaginous differentiation as a rare manifestation of melanoma, particularly at subungual sites, and suggests that at least some of these melanomas may be driven by non‐canonical molecular pathways.