To evaluate rare cutaneous tumors initially diagnosed as epithelioid or pleomorphic rhabdomyosarcoma and assess their potential reclassification as transdifferentiated melanoma.
Key Findings:
10 of the 13 tumors were reclassified as transdifferentiated melanoma.
All tumors expressed desmin and myogenin; S100 was negative in 12 of 12, SOX10 in 10 of 10, Melan A in 9 of 9, and HMB45 in 5 of 5.
DNA methylation profiling successfully clustered 7 tumors with desmoplastic melanoma.
All evaluable tumors had a DNA ultraviolet light signature.
TERT promoter mutations were identified in 5 of 7 sequenced cases.
Interpretation:
Melanoma can lose conventional markers and mimic sarcoma while retaining molecular evidence of melanocytic lineage, indicating the need for careful diagnostic consideration.
Limitations:
Small sample size and retrospective design.
Incomplete molecular testing across all cases.
Biopsy-heavy specimen set.
Mutational signature analysis not clinically validated.
Methylation profiling limitations, including inconclusive matches.
Conclusion:
The majority of cutaneous epithelioid/pleomorphic rhabdomyosarcomas in this study exhibit genetic/epigenetic phenotypes consistent with transdifferentiated melanoma, highlighting the importance of comprehensive molecular testing.
