Clinicopathologic and molecular characteristics of acral melanomas harboring RARA fusions.
Mokhtar H Abdelhammed, Richard K Yang, Volha Lenskaya et al.
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Case in brief
The report describes two adults with acral cutaneous melanomas on the feet, both harboring RARA fusions. Tumors varied in spindle, epithelioid, and occasional rhabdoid morphology and had low tumor mutational burden. One was triple wild-type for BRAF, NRAS, and NF1; the other had an NF1 loss-of-function mutation and multiple gene amplifications. During a median follow-up of 23 months, one patient developed brain metastasis approximately 20 months after diagnosis. At last follow-up, one patient was alive with disease and the other had no clinical or radiological evidence of recurrence.
What made this case unusual
Both tumors were acral melanomas with RARA fusions, a molecular finding whose tumorigenic role in solid tumors remains largely unknown. The cases also showed distinct fusion partners and molecular profiles.
Diagnostic / clinical pearl
Acral melanoma can harbor RARA fusions across differing morphologic and molecular backgrounds; molecular profiling may identify these alterations even when common driver mutations are absent.
Why it matters
The findings add to the molecular characterization of acral melanoma and raise the possibility of targeted therapy against RARA fusions, although therapeutic utility in melanoma remains uncertain.