The Use of Molecular Studies for Diagnosis of Undifferentiated Tumors

Malignant melanoma (MM) is an aggressive heterogeneous skin cancer with phenotypic, immunoprofile, and molecular diversity. Some tumors may be undifferentiated, with loss of immunohistochemical markers and a less differentiated lesion status. These authors explored the immunoprofile and genetic landscape of 14 metastatic undifferentiated melanomas.

These melanomas were more frequent in males (median age, 67 years), one with an unknown primary. Metastasis was seen in one case at diagnosis of the primary tumor, in one was the presenting feature, and developed 3 months to 9 years after the primary diagnosis in the rest. The most frequent histology consists of undifferentiated pleomorphic or spindle cell tumors. Three cases showed heterologous elements. All were negative for S-100 protein, melanoma cocktail, HMB-45, Melan A, and SOX 10. Other markers seen were desmin (5/14), pancytokeratin (4/14), TP53 (2/12), smooth muscle, and p16 in (1/14). Tumors were negative for h-caldesmon, and MDM2/CDK4. Genotyping showed BRAF^V600E and NRAS mutations in 35%.