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Background: Medullary thyroid carcinoma (MTC) is a rare neuro-endocrine tumor that arises from the C-cells of the thyroid. About 20- 25 % of MTC cases may be associated with hereditary syndromes like MEN 2A, MEN 2B and Familial MTC. The survival rate is related mainly to the age of the patient, stage of the disease and completion of the surgical resection. Methods: Retrospective review of 11 patients who were diagnosed with medullary thyroid cancer in our general surgery department during the period from 2011 to 2021. All patients had preoperative assessment including history taking, clinical examination, tumor marker (calcitonin and CEA), thyroid function testing, ultrasonography and FNAC. All patients underwent genetic assessment to exclude any underlying genetic mutation. Results: The mean age of diagnosis was 57.73 ± 16.45 years of age. Three patients were males and eight were females. All patients had total thyroidectomy, central and lateral neck dissection except one patient who had prophylactic thyroidectomy due to familial inherited RET mutation. Two patients had recurrence; both of them had high-stage tumor (T3 and T4) with multiple cervical lymph nodes metastasis. The sensitivity of serum calcitonin for the detection of MTC was about 98%. Patients, who had localized disease and underwent complete surgical resection, had good overall survival rates compared with patients with advanced disease. Conclusion: MTC represent a heterogeneous group of thyroid cancers. The overall survival is better than that of undifferentiated thyroid cancers. Complete resection of the thyroid tumor and any local or regional metastases provides the only cure for patients with MTC. Further researches are still needed to improve our understanding and management of MTC.

The metastatic risk profile of microscopic lymphatic and venous invasion in medullary thyroid cancer is ill-defined. This evidence gap calls for evaluation of the suitability of microscopic lymphatic and venous invasion at thyroidectomy for prediction of lymph node and distant metastases in medullary thyroid cancer. In this study of 484 patients with medullary thyroid cancer who had≥5 lymph nodes removed at initial thyroidectomy, microscopic lymphatic and venous invasion were significantly associated with greater primary tumor size (27.6 vs. 14.5 mm, and 30.8 vs. 16.2 mm) and more frequent lymph node metastasis (97.0 vs. 25.9%, and 85.2 vs. 39.5%) and distant metastasis (25.0 vs. 5.1%, and 32.8 vs. 7.3%). Prediction of lymph node metastases by microscopic lymphatic invasion was better than prediction of distant metastases by microscopic venous invasion regarding sensitivity (97.0 vs. 32.8%) and positive predictive value (58.4 vs. 39.2%); comparable regarding negative predictive value (98.5 vs. 90.5%) and accuracy (80.4 vs. 85.1%); and worse regarding specificity (74.1 vs. 92.7%). On multivariable logistic regression, microscopic lymphatic invasion predicted lymph node metastasis better (odds ratio [OR] 65.6) than primary tumor size (OR 4.6 for tumors>40 mm and OR 2.7 for tumors 21–40 mm, relative to tumors≤20 mm), whereas primary tumor size was better in predicting distant metastasis (OR 8.3 for tumors>40 mm and OR 3.9 for tumors 21–40 mm, relative to tumors≤20 mm) than microscopic venous invasion (OR 3.2). These data show that lymphatic invasion predicts lymph node metastases better in medullary thyroid cancer than venous invasion heralds distant metastases.

Multiple endocrine neoplasia (MEN) describes the occurrence of tumours affecting two or more endocrine glands in one patient. Two main forms are recognized: MEN type 1 (MEN1) and type 2 (MEN2). MEN1 is characterized by the combined occurrence of parathyroid, pituitary and pancreatic neuroendocrine tumours, whereas MEN2 features medullary thyroid cancer in association with phaeochromocytoma and parathyroid tumours. Although both MEN1 and MEN2 are autosomal dominant disorders, they have contrasting molecular aetiologies: MEN1 results from inactivating germline mutations of the MEN1 tumour suppressor gene, whereas MEN2 results from activating mutations in the RET proto-oncogene. The clinical features arising in each condition relate to the location of tumour development and/or hormonal hypersecretion, while treatment approaches aim to minimize morbidity and mortality, and preserve quality of life. Genetic testing is a key component of management, not only to confirm the diagnosis in affected patients, but also to identify family members who are at risk of disease but may be asymptomatic. It is recommended that patients ‘at risk' of developing MEN1 and MEN2 (i.e. mutation carriers) undergo periodic clinical, biochemical and radiological surveillance to enable the early identification and/or treatment of tumours. Here, a brief overview of MEN1 and MEN2 is provided.

Objectives: During this ongoing pandemic of coronavirus disease 2019 (COVID-19), procalcitonin (PCT) assay has proven to be a useful tool in assisting clinicians to diagnose bacterial superinfection. However, in the absence of signs of infection or at resolution thereof, inappropriately and persistently high PCT may suggest and reveal the presence of other pathologies. We report a patient with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia in whom persistence of initially elevated PCT during recovery prompted the diagnosis of medullary thyroid cancer (MTC). Case report: A 43- year-old man presented with a two-day history of fever, sneezing, sore throat and dry cough. Physical exam revealed decreased sounds and coarse crackles in both lung bases at auscultation. Medical history was positive for cognitive impairment since birth, arterial hypertension, systemic lupus erythematosus with nephritis. Initial studies included mild lymphocytopenia 650/µl (760 - 5000), D-Dimer 0.73 µg/ml (< 0.5), C reactive protein (CRP) of 62 mg/l (< 5) and PCT of 94 ng/ml (0.00 - 0.10). Positivity for SARS-Cov-2 RNA was detected and chest computerized tomography showed bilateral ground-glass opacities in the basilar lung zones and hyperdense and irregular foci in the thoracic vertebral bodies. Empirical antibiotic therapy was started and was maintained for seven days but, despite clinical improvement and the normalization of CRP, serum PCT was persistently high (84 ng/ml). Serum calcitonin (CTN) was 2120 pg/ml (normal up to 12 pg/ml). Neck ultrasound revealed inhomogeneously echogenic lymph nodes with small punctate calcifications and a non-homogeneous thyroid with multiple nodules. Cytological examination by fine needle aspiration and CTN measurement on washing liquid confirmed the suspicion of MTC. The patient underwent total thyroidectomy with bilateral cervical lymph node dissection. Histological analysis confirmed MTC of right thyroid lobe and metastasis at lymph nodes of the central right midneck area. Blood tests performed 48 hours after surgery showed a lowering of CTN (986 pg/mL) and PCT (16 ng/mL). A 6-months follow up showed persistent increased CTN and PCT levels (921 pg/ml and 16 ng/ml, respectively) while a (18)F-fluorodihydro-xyphenylalanine ((18)F-DOPA) PET did not reveal any suspicious fixations at thyroid lodge and cervical lymph node stations while multiple osteoblastic foci in the skeletal area were described. A close follow-up was planned with establishment of the results of RET gene analysis. Discussion: Although CTN is the gold standard biochemical parameter for the diagnosis and follow-up of MTC, PCT can be useful as a biochemical marker of MTC suspicion in patients with inflammatory conditions and persistently elevated PCT even after resolution. In the present CASE, high levels of PCT in a patient with Covid-19 pneumonia without signs of bacterial infection, allowed to diagnose MCT. Conclusion: In the absence of any other signs of infection, a complete clinical assessment, including neck palpation, CTN measurement and thyroid ultrasound should be performed in the presence of persistently elevated PCT.

The discovery of a pivotal role of tyrosine kinases in the pathogenesis of medullary thyroid carcinoma (MTC) opened up new options in the systemic treatment of advanced disease. During the last dec...

Abstract The role of radiotherapy in advanced medullary thyroid carcinoma (MTC) is confined to patients in whom surgical treatment or the administration of tyrosine kinase inhibitors are not possible or contraindicated. High fractionated radiation doses during radiosurgery or fractionated stereotactic radiotherapy are applied to reduce cancer-related symptoms and stabilize irradiated lesions. This study aimed to retrospectively evaluate the therapeutic effect of stereotactic radiotherapy in MTC patients. Material and methods The study group involved 11 MTC patients, treated due to 16 cancer lesions, mainly bone metastases (10 lesions), lymph node (2 lesions) metastases, or liver metastases (2 lesions), one primary thyroid tumor, and one MTC recurrence in the thyroid bed. The fractionated and total radiation doses ranged between 5 and 12 Gy and 8–44 Gy, respectively. Six lesions were treated with a single radiation fraction, three lesions with 2 fractions, another 6 lesions with 3 fractions, whereas the remaining one metastatic lesion with 9 fractions of stereotactic radiosurgery. Results The beneficial effect of stereotactic radiosurgery was obtained in all treated lesions. None of treated lesions progressed in the further disease course. Fourteen lesions were stable (87.5 %), including eight lesions showing progression before radiosurgery (good response). Disease control was obtained in all soft-tissue metastases. Regarding bone metastases, partial regression was achieved in 20 % lesions, whereas in 30 % lesions progressive before radiotherapy, the treatment led to disease stabilization. Conclusions Our data pointed to the effectiveness of high-dose fractionated radiotherapy in MTC. However, an observation of a larger group of patients is required to confirm it.

Aim. The research aims at analyzing the main changes in classification of medullary thyroid cancer and outlining the principles of staging according to modern studies. Material and Methods. Specific scientific articles for the period of 2009-2019 referring to the principles and rules of the TNM classification process, as well as recommendations of the TNM committees of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (IUAC) were selected for the analysis. The basic principles of classification and staging for 8th edition of TNM, as well as changes that have taken place in comparison with 7th edition of TNM It were defined. Results and Discussion. Medullary thyroid cancer accounts for 1-2 percent in the structure of cancers of the thyroid gland, however it is associated with a high mortality rate compared to highly differentiated forms of thyroid cancer. The main radical method of treatment is an adequate volume of surgical intervention, which is determined on the basis of proper staging, the use of visualization methods and the practical experience of doctors. The 7th edition of the TNM was introduced to the scientific society in 2009. It has been 10 years since a new version of the 8th edition based on the new data in evidence-based medicine appeared. It included numerous changes and additions, namely for medullary thyroid cancer. The following research suggests a detailed review and analysis of the basic principles of the staging and classification of medullary thyroid cancer for AJCC TNM-8 in order to improve the diagnosis and treatment of patients with the mentioned above disease. Conclusions. The use of modern principles of classification and staging of medullary thyroid cancer in clinical practice promotes choosing the adequate treatment method and estimating the patient's prognosis. In addition, further improvement of the staging system by TNM-committee and cancer registers depends on the presence of detailed information on additional "parameters for collection and further evaluation" in medical documentation.

The article reviews domestic and foreign literature on the use of radiation therapy in the treatment of medullary thyroid cancer. The possibilities of various radiation methods in the treatment of patients with distant metastases are shown. In addition to classical types of remote irradiation, data are presented on the possibilities of radionuclide therapy (peptide-receptor therapy with somatostatin analogs and radionuclide therapy with osteotropic drugs for bone metastases). Methods of combined therapy with the use of osteomodifying agents, targeted drugs and other methods are described, which make it possible to increase the effectiveness of treatment of patients with medullary thyroid cancer with bone metastases.

Medullary thyroid carcinomas make up 9,4% of all cancers of the thyroid gland [1]. We can divide them into sporadic and familial form. Sporadic forms are most common. The rest of medullary thyroid carcinomas are familial forms which in most cases are associated with MEN2a and MEN2b syndromes. If neoplasm is associated with MEN2a or MEN2b syndromes, other tumors can occur: pheochromocytoma or adenomas of parathyroids glands. Medullary thyroid carcinoma typically occurs as a solid tumor in the thyroid region of the neck. It can produce also: pain in thyroid region, dysphagia, hoarseness, cervical lymphadenopathy. These symptoms are caused by infiltration of adjacent tissues by neoplasm and by metastases to cervical lymph nodes. It is very rare that there is no tumor in the thyroid region, when a patient complains about signs associated with infiltration of the tumor, but in some cases lymphadenopathy can be the first sign of medullary thyroid carcinoma [2]. Rarer than that there is no tumor in thyroid gland visualized in CT scans when there are signs of cervical lymphadenopathy. In this case report we present the patient with metastases of the medullary thyroid carcinoma to the neck and no other findings in physical examination and additional testing.

PET imaging with F-18 DOPA (FDOPA) and Ga-68 DOTATATE (TATE) shows the most promising results to detect medullary thyroid cancer (MTC) recurrence. We performed this comparative study to detect the site of recurrent or metastatic disease in MTC patients with elevated serum calcitonin (Ctn) and/or carcinoembryonic antigen (CEA) levels. We studied 46 MTC patients (25 women, 21 men) with elevated Ctn and/or CEA levels during follow-up who had both FDOPA and TATE PET/CT scans for re-staging purposes. FDOPA PET imaging yielded an overall sensitivity of 86.8%, specificity of 100%, PPV of 100%, NPV of 61.5%, and accuracy of 89.1%, while TATE PET scan had the same values as 84.2%, 87.5%, 96.9%, 53.8%, and 84.6%, respectively, and there was no statistically significant difference between the two modalities with the exception of the specificity value that was higher for FDOPA imaging. In a subgroup of patients with overt Ctn or CEA elevation, sensitivity of FDOPA increased significantly, whereas TATE sensitivity did not change. FDOPA PET imaging was significantly superior in detecting liver and regional lymph node (LN) metastases, while TATE PET scan was significantly better in the skeletal metastases. Early FDOPA demonstrated 11 invisible lesions on late FDOPA. Both FDOPA and TATE PET/CT imaging are useful to localize recurrences in MTC patients. While TATE imaging is superior to reveal skeletal disease, FDOPA seems better in liver and regional LN metastases; therefore, the two modalities appear complementary in monitoring MTC patients with elevated serum Ctn and/or CEA levels.

Objectives We initiate this comprehensive review to update the advances in this field by objectively elucidating the efficacies of promising radiopharmaceuticals. Methods We performed a comprehensive PUBMED search using the combined terms of “thyroid cancer” and “radiopharmaceuticals” or “nuclear medicine”, yielding 3273 and 11026 articles prior to December 31, 2020, respectively. Results Based on the mechanism of molecular metabolism, the evaluation of differentiated thyroid cancer and dedifferentiated thyroid cancer is largely centered around radioiodine and fluorine 18 (18F)-fludeoxyglucose, respectively. Further, 18F-L-dihydroxyphenylalanine and gallium 68 DOTATATE are the preferred tracers for medullary thyroid cancer. In dedifferentiated medullary thyroid cancer and anaplastic thyroid cancer, 18F-fludeoxyglucose is superior. Conclusions The future lies in advances in molecular biology, novel radiopharmaceuticals and imaging devices, paving ways to the development of personalized medication for thyroid cancer patients.