Mutational analysis valuable in diagnosing undifferentiated malignancy

March 3, 2020

Abstract

In recent years, the use of checkpoint inhibitors and targeted molecular therapy has dramatically improved survival in metastatic melanoma. Accurate and prompt diagnosis is essential to initiate appropriate management. Dedifferentiated tumours, i.e., those that have lost some or all morphologic and immunohistochemical features of melanoma, pose a major challenge to this endeavour. In these instances, identification of a melanomarelated mutation can be a useful ancillary investigation. The aims of this study were to describe the histological, immunochemical, and molecular features of undifferentiated melanomas. A search of our institutional database (2012–2019) identified 23 cases of undifferentiated malignant tumours that underwent subsequent mutational analysis. Of these, 15 tumours were found to harbour a melanoma-related mutation including BRAF V600E (3/15), BRAF V600K (3/15), and NRAS Q61R (5/15) among others. On the basis of the molecular findings, a diagnosis of melanoma was favoured. Sites of disease included lymph nodes (5/15), skin or subcutis (5/15), lung (2/15), small bowel (1/15), mediastinum (1/15), and epidural space (1/15). A prior history of melanoma was documented in 10 cases. This study illustrates the value of mutation testing in establishing a diagnosis in cases of undifferentiated malignancy, particularly when melanoma metastases are clinically suspected.

Source:

Aivazian, K., Rawson, R. V., Wilmott, J. S., Ferguson, P. M., Thompson, J. F., Long, G. V., & Scolyer, R. A. (2020). Mutational analysis of undifferentiated melanoma. Pathology, 52. doi: 10.1016/j.pathol.2020.01.203

https://www.pathologyjournal.rcpa.edu.au/article/S0031-3025(20)30203-8/pdf