PREDICTORS OF AGGRESSIVE DIFFERENTIATED THYROID CANCER. A REPORT OF A CASE OF PAPILLARY THYROID CANCER

Background. Differentiated thyroid cancer has a favorable prognosis in terms of relapse-free and overall survival. However, some cases of differentiated thyroid cancer (TC) are characterized by aggressive course with distant metastases and/or radioiodine refractoriness. 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. In this article, we present a case of PTC in a 76-year-old patient. The patient found a formation on the neck and complained of memory impairment. Upon examination, the patient was found to have a thyroid tumor with metastases in lungs, brain, and bones. The patient underwent thyroidectomy and started to receive suppressive doses of thyroxine. Stereotactic radiotherapy was performed to treat brain metastases. We observed a regression of small formations and partial response of larger metastatic foci. The patient received no radioiodine therapy due to his poor somatic status and extensive tumor spread. The patient received target therapy with sorafenib (800 mg/day) and bisphosphonates (BFT) for treatment of bone metastases. After the second cycle of target therapy, the dose of sorafenib was reduced by 50 % due to adverse events; during the next 10 month the patient received sorafenib at a dose of 400 mg/day. After the third cycle of target therapy we observed a stabilization of metastatic foci in the lungs and bones. However, during the treatment, the patient developed visceral metastases to the liver and the adrenal gland, a lytic metastasis in the right side of the mandible, and pain syndrome. A course of radiotherapy to the mandible was conducted along with BFT treatment. The patient received adequate analgesia and symptomatic therapy. The survival from the moment of diagnosis was 2 years. 

Results. We found that in some cases of differentiated TC, the disease has quite aggressive course with a rapid growth of the primary tumor and metastases into the brain and bones. Patients usually seek medical assistance at the advanced stages of the disease, when it is problematic to provide adequate therapy. The use of target therapy should be considered in such cases. There is a need to find new targets for the development of novel drugs for these patients.

Conclusion. 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. The following clinical prognostic factors are used to determine metastatic potential, probability of relapse, and mortality: age under 15 years or over 45 years, male gender, family history of TC, and exposure to ionizing radiation. Thus, in some cases these markers can help to predict the course of TC and to provide adequate and timely treatment.

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