HISTOLOGICAL AND MOLECULAR GENETIC CHARACTERISTICS OF CLINICALLY AGGRESSIVE VARIANTS OF PAPILLARY THYROID CARCINOMA: A LITERATURE REVIEW

Abstract

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer; this cancer presents relatively low malignancy, good prognosis, and a 10-year survival rate of over 90 %. However, the clinical behaviors of this cancer are complex and varied. PTC is easy to spread via lymphatic ducts, which results in recurrence, metastases, and even death [1]. Differentiated thyroid cancer has a favorable prognosis in terms of relapsefree and overall survival. However, some cases of differentiated thyroid cancer (TC) are characterized by aggressive course with distant metastases. Identification of histological subtypes of papillary thyroid cancer (PTC) and detection of specific mutations may have some prognostic value in the prediction of the disease course and clinical response to treatment. The severity of the disease depends on multiple clinical characteristics, morphological and molecular features of the tumor. Several histological variants of PTC with varying degrees of malignancy have been described so far: from well-differentiated PTC to radioiodine refractory undifferentiated anaplastic carcinoma with a high mitotic index and high probability of relapses. Recurrent PTC mainly refers to localized and distant recurrence, including recurrence of the primary tumor, lymph node metastases, invasion of the esophagus and trachea, invasion of muscles, soft tissues and nerves, and distant metastases. Many factors can affect the recurrence of thyroid cancer, and final conclusion has not yet been reached. Aim: to summarize the available literature data on the molecular genetic characteristics of aggressive variants of papillary thyroid carcinoma. Methods: We conducted a literature review of scientific papers over the past decade using PubMed search engine resources. In addition, a search was conducted using the data of the scientific electronic library eLIBRARY for the above keywords. For this meta-analysis, we used articles containing clinical evidence on the most recent issues regarding aggressive variants of papillary thyroid carcinoma. Results: The highest frequency of BRAF V600E among PTC is shown by the high-cell variant of PTC (90%), also significantly higher with «shoe nail» cells than in classical PTC and varies from 40-90%. In a columnar cell, PTC, mutations in the BRAF V600E gene are much less common than in classic PTC. The diffuse sclerosing type of PTC is characterized by the presence of a RET/PTC translocation, and the percentage of the BRAF V600E mutation is 0-60 in various studies. Conclusion: In the presented work, the morphological and clinical features of patients with prognostic unfavorable variants of PTC are considered. Correct recognition of these variants is an important component in the diagnosis of tumor pathology of the thyroid gland, except for accidentally detected microcarcinomas without signs of invasion into the tissues and into the capsule of the thyroid gland and into the lymphatic vessels. The most aggressive forms of PTC include diffuse sclerosing, tall cell, and insular variants of PTC. Various genetic abnormalities, such as BRAF mutation, can be detected in this case. Thus, in some cases these markers can help to predict the course of TC and to provide adequate and timely treatment.