Thyroid tumors and thyroid cancer

Primary thyroid tumors are formations that arise from autonomous growth from a single thyroid cell and depending on their biological potential, they can be benign or malignant. Malignant tumors are also called thyroid cancer. Unlike benign tumors, malignant thyroid tumors represent a diagnostic and therapeutic challenge. They most often occur in the younger population (between the ages of 20 and 60) and in a large number of cases are associated with genetic changes and show a hereditary component.

Thyroid cancer is the most common malignant tumor of the endocrine system! The number of cases is constantly increasing, which is not accompanied by an increase in mortality and it occurs 3-4 times more often in women than in men. According to data from the cancer registry, 831 cases of thyroid cancer were detected in Croatia in year 2019 (of which as many as 650 cases were in women). Genetic inheritance, exposure to ionizing radiation in the head and neck area and immune disorders are the most common causes. Genotypically, various changes are found in proto-oncogenes and tumor-suppressor genes, such as RAS, RET, MET, p53, BRAF, AXIN1, C-myc, H-ras and Nm23.

Types of malignant tumors

The most common types of malignant tumors are papillary and follicular carcinomas, followed by medullary and anaplastic carcinomas. Primary lymphoma and primary thyroid sarcoma and Hürtl's carcinoma occur extremely rarely.

• Papillary carcinoma accounts for about 80% of all thyroid cancers and has the best prognosis. It most often occurs between the ages of 30 and 40, develops slowly and sometimes occurs in families. In 5% - 10% of patients, in addition to metastases in the lymph nodes of the neck, we also find distant metastases.

• Follicular carcinoma and its subtype, Hürtl cell carcinoma, account for about 10% of thyroid cancer cases. It usually occurs after the age of 40 and is characterized by a slightly higher frequency of metastatic spread compared to papillary carcinoma.

• Medullary carcinoma accounts for about 5% of malignant thyroid tumors. It is characterized by excessive production of the hormone calcitonin. It occurs sporadically (isolated) and hereditary as a component of multiple endocrine neoplasia-2 syndrome (MEN2).

• Anaplastic carcinoma comprises 1% - 2% of all malignant thyroid tumors, occurs almost exclusively in the elderly and is characterized by an aggressive clinical course, rapid growth with locoregional and distant spread.

Clinical picture

The clinical picture largely depends on the type of tumor.

In addition to anaplastic carcinoma, other forms of thyroid cancer can be asymptomatic for a long time, be discovered as an incidental finding during an ultrasound examination of the thyroid gland or present as a slow-growing, painless, stationary nodule inside the thyroid gland. Rarely, the tumor is of such a size that it causes pressure on the surrounding structures. Sometimes tumorous enlargement of the lymph nodes of the neck is also found.

Medullary thyroid cancer, due to the increased production of calcitonin causes a decrease in the level of calcium in the blood (increased urination, muscle weakness, indigestion, confusion, memory loss, depression, heart rhythm disorders, nausea, vomiting).

Anaplastic cancer grows extremely fast, destroys the local anatomical structures of the neck, causes compressive and obstructive symptoms and already at the time of diagnosis of the primary tumor, in most cases there are distant metastases (most often in the lungs and bones).

Diagnosis and treatment

The diagnostic algorithm is complex. It includes a specialist and ultrasound examination of the thyroid, cytological puncture of a suspicious formation and possibly enlarged lymph nodes, thyroid scintigraphy and laboratory tests (determination of thyroid hormone and tumor markers: thyroglobulin - Tg and carcinoembryonic antigen - CEA. Radiological (CT, MR) and nuclear medical (scintigraphy, PET) diagnostic methods are extremely useful for assessing the spread of a malignant disease. Molecular diagnostic methods, i.e. genetic testing can also prove specific mutations within the most common genes involved in the development of thyroid cancer (e.g. RET, BRAF). A definitive diagnosis is made by pathohistological analysis of the tumor after surgery.

Primary treatment is based on surgical removal of the thyroid gland (total thyroidectomy). In case of locoregional expansion of the tumor and/or involvement of the lymph nodes a partial or radical dissection of the neck is performed in which the lymph nodes are removed. Surgical treatment removes the tumor, but it also causes a lack of thyroid function in the patient (postoperative hypothyroidism). After about a month, there is an increase in TSH, which stimulates the growth of possibly remaining cancer microtissue. Then a diagnostic scintigraphy is performed (it should be repeated for control approximately once a year). In the case of a positive scintigraphic finding, radioiodine treatment is applied, which destroys the rest of the tumor tissue. If tumor resistance to radioiodine treatment occurs, specific oncological treatment is applied, the so-called tyrosine kinase inhibitors. In all patients, it is safest to carry out lifelong suppression of TSH with thyroid hormones, which reduces the possibility of recurrence of the malignant disease and at the same time treats postoperative hypothyroidism.

Generally speaking, the prognosis of papillary and follicular thyroid cancer is mostly good. Unfortunately, unlike other forms, anaplastic carcinoma has an extremely poor prognosis and treatment is mostly palliative (patients with the V600E mutation in the BRAF gene are treated with targeted drugs, the so-called tyrosine kinase inhibitors dabrafenib and trametinib).