Clinical and morphological features of thyroid tumors with mutations in the <i>NTRK</i>, <i>RAS</i>, <i>BRAF</i>, <i>RET</i> genes

Abstract

Despite the rather favorable clinical course of thyroid tumors, the issue of timely and high-quality diagnosis is still relevant. Due to the development of personalized treatment in medicine and the emergence of drugs that target specific mutations, timely detection of these mutations is very important. The pathologist should be focused on the search for certain morphological markers that suggest the presence of certain mutations in tumor cells. To narrow the differential diagnostic search, it is important to know the mechanisms of development of key mutations, mutually exclusive mutations, to have information about the clinical course of the disease. Based on these data, the next step will be more specific diagnostics (IHC, molecular genetic methods). Based on the analysis of literature data, it was possible to identify some distinctive morphological signs that can help the pathologist to suspect the presence of a particular mutation in the tumor. For mutations in the NTRK genes, such signs are the follicular variant of papillary cancer, nuclear pseudo-inclusions, presence of an oncocytic component, metastases, and the absence of a solid component. For the assumption of RAS mutations, attention paid to tumors of the follicular structure with an aggressive clinical course. The young age of the patient, metastases to the lymph nodes, and cancer of the thyroid gland of the classic papillary structure will allow one to assume the presence of a mutation in the RET gene. The BRAF mutation is characterized by specific cellular changes (pseudo-inclusions in the nuclei, the presence of plump cells or cells with sickle-shaped nuclei) in a thyroid cancer with a classic papillary structure.