The Use of Molecular Studies for Diagnosis of Undifferentiated Tumors

Summary and Comment |
March 15, 2016

The Use of Molecular Studies for Diagnosis of Undifferentiated Tumors

  1. Angelica Selim, MD

Absent other diagnostic tools, BRAF/NRAS/KIT genotyping appears to provide viable surrogate markers for diagnosis of malignant melanoma in undifferentiated tumors.

  1. Angelica Selim, MD

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 BRAFV600E and NRAS mutations in 35%.

Comment

It's not uncommon to encounter tumors with a differential diagnosis of second neoplasia versus metastasis in patients with known MM history. Morphology of the tumor and immunohistochemical stains are most frequently used for clarification. Problems occur when a tumor fails to react to even the most sensitive melanocytic markers. These findings point to BRAF/NRAS/KIT not only as treatment targets but also as diagnostic tools. Inconsistencies between primary and metastatic melanoma in BRAF mutation (most frequently, loss of metastatic process seen in the primary tumor) have been reported in about 14% of cases. On the other hand, BRAFV600E is a rare oncogenic event in sarcoma. Absent any other diagnostic tool, BRAF/NRAS/KIT genotyping appears to provide viable surrogate markers for diagnosis of MM in undifferentiated tumors.

Editor Disclosures at Time of Publication

  • Disclosures for Angelica Selim, MD at time of publication Grant / Research support NIH/NCI, The Plastic Surgery Foundation

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