Abstract
Introduction Differentiating desmoplastic/spindle cell melanoma (DSCM) and malignant peripheral nerve sheath tumor (MPNST), especially the superficial variant, can become very challenging as they share many overlapping histological and immunohistochemical (IHC) features including loss of H3K27me3. Loss of function NF1 & CDKN2A mutations are also common among both tumors complicating the use of genetic studies in differentiating them. Case report 83-year-old male presented with a submental swelling and biopsy evaluated at two outside institutions reported MPNST and DSCM as their diagnosis. Upon our examination, slide sections showed a dermal and subcutis based SOX-10 positive malignant spindle cell neoplasm without any epidermal component. Past medical history revealed multiple surgically removed melanoma involving left chest (1.47 mm), right posterior neck & left temporal region, both 0.3 mm in thickness, 9 years back. Tumor was analyzed using next generation DNA sequencing using a targeted panel (Oncomine V3, 0.29 MB size) and showed high number of mutations including NF1 p.R440*, TERT promoter mutation C228T, KNSTRN p.S24F, ARID1A p.Q1458*, TP53 p.L194R, TP53 copy number loss and CDKN2A/CDKN2B copy number loss. Unfortunately, none of these mutations are specific to these two entities. However, the tumor mutation burden (TMB) was very high (53.1 Mutations/Mb) with predominant C>T transitions. These findings favored a DSCM as cutaneous melanomas are well known to harbor high number of mutations specifically with high C>T transitions due to their UV related pathogenesis. Conclusion Distinguishing DSCM and MPNST is critical due to their differences in treatment and prognosis. Recent study has shown molecular markers such as TMB and UV specific signature C>T fraction are significantly different among these two tumors owing to their etiopathogenetic differences. Our case demonstrates the usefulness of targeted NGS panel based results in the diagnosis of DSCM over MPNST.Financial Disclosure: No current or relevant financial relationships exist.
