Clinical and oncological characteristics of sporadic medullary thyroid carcinoma in patients of different sexes

Abstract

Abstract. Sporadic medullary thyroid carcinoma (MTC) is a heterogeneous orphan disease with a variable and unpredictable course associated with heterogeneous genetic disorders, in particular the different role of somatic mutations of the RET, RAS genes, as well as mutated variants of other genes, which are the causes of carcinomas. The clinical course of MTC varies from an extremely indolent tumor, which can remain unchanged for years, to an aggressive variant with a high mortality rate. One of the reasons for such features is considered to be the difference in the frequency of gene mutations among women and men and, therefore, the influence of gender on the aggressiveness of MTC.

The aim is to determine the oncological and clinical characteristics of the disease in patients of different sexes with sporadic thyroid cancer.

Material and methods. Clinical data of 66 patients with sporadic MTC were analyzed retrospectively. Patient data included age, sex, tumor size
and TNM classification, presence of aggressive characteristics, concomitant chronic autoimmune thyroiditis (CAIT), extent of surgical intervention, preoperative and postoperative serum calcitonin (Ctn) levels, number of relapses, repeated operations, and as well as postoperative health status (healthy, prolongatio morbi, deceased).

Results. The peak incidence in women occurs at the age of 51-60 years, in men – 10 years earlier. In male patients, the size of carcinomas is significantly larger than in females, which is also confirmed by a higher proportion of men in the cohort who had tumors of the T3 and T4 categories. In men, MCs metastasize simultaneously to the central and lateral lymph nodes of the neck (N1ab) three times more often than in women and are removed 18.5 times more often (most often to the liver). The frequency of multifocal sporadic MCs does not differ among men and women, as well as the frequency of MC invasion into the tumor capsule and the presence of CAIT, whereas intra- and extrathyroidal invasion was more common in male patients. In all patients the preoperative serum Ctn level was above the upper limit of normal; in men it was almost three times higher than in women. Almost all patients, regardless of gender, underwent total thyroidectomy simultaneously with central and lateral lymph node dissection, however, in in one fifth of female patients, lymph node dissection was limited to the central neck compartment only (in men, such an operation was not performed). In the postoperative period, relapses were noted in one third of male patients, which necessitated repeated operations; the need for them in women was five times lower. Incomplete biochemical remission was recorded in 14.6% of women and 27.7% of men during follow-up examinations, as evidenced by the results of determining the Ctn concentration in the blood serum. In women, the postoperative concentration of Ctn decreased by 21 times, in men by 3.7 times. At the same time, normalization of the postoperative concentration of Ctn depended on the presence of distant metastases or incomplete biochemical remission. This dependence was manifested more significantly in male patients. Six out of 18 male patients with sporadic medullary carcinoma died; among women, the mortality rate is 4 times lower. The average time between carcinoma removal and death of male patients was 3 years less than that of female patients. At the same time, the average age of the latter was 20 years older than that of the deceased male patients.

Conclusions. The more aggressive behavior of MTC in men (than in women) includes larger tumor size, more frequent intra- and extrathyroidal invasion, extensive neck lymph node metastasis, more frequent distant metastasis, higher serum Ctn levels, frequent postoperative recurrences, and higher mortality. For female patients, who suffer from MTC more often than men, and for whom the peak incidence occurs 10 years later than in men, a negative factor in the course of the disease may be age over 60 years.