Metastatic Melanoma with Rhabdomyosarcomatous Transdifferentiation: Two Tumors with Next-Generation Sequencing...

Area of Science:

• Oncology
• Pathology
• Genetics

Background:

• Metastatic melanoma poses diagnostic challenges due to differentiation loss and transdifferentiation, mimicking other cancers.
• Aberrant differentiation can lead to loss of melanocytic markers and expression of non-melanocytic markers.

Purpose of the Study:

• To report two cases of metastatic melanoma with rhabdomyosarcomatous transdifferentiation.
• To highlight the diagnostic utility of next-generation sequencing (NGS) in resolving ambiguous melanoma presentations.
• To underscore the importance of clinical suspicion in patients with a history of melanoma.

Main Methods:

• Case report analysis of two patients with metastatic melanoma exhibiting rhabdomyosarcomatous features.
• Immunohistochemistry (IHC) for melanocytic and muscle markers.
• Targeted next-generation sequencing (NGS) to identify genomic alterations.

Main Results:

• Both cases showed small round blue cell morphology with muscle marker expression (MYOD1, desmin, myogenin) and absent melanocytic markers.
• Histology and IHC were insufficient for diagnosis; NGS revealed melanoma-characteristic genomic alterations (UV signatures, mutations in *NF1*, *TERT* promoter, *NRAS*, *MITF*, *TP53*).
• Both patients responded well to immune checkpoint inhibitors, with 2 and 3 years of follow-up.

Conclusions:

• NGS is crucial for diagnosing metastatic melanoma with aberrant differentiation, especially when conventional methods fail.
• Rhabdomyosarcomatous transdifferentiation is a rare but important differential diagnosis in metastatic melanoma.
• Maintaining clinical suspicion and utilizing advanced genomic techniques are vital for managing challenging melanoma cases.