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In recent years, increasing attention of researchers has been attracted to the study of multiple endocrine neoplasia (MEN) – neoplastic syndromes affecting two or more endocrine glands. The source of tumors are tissues with embryologically common neuroectodermal origin, related to the APUD system. MEN 2A (Sipple syndrome) includes medullary thyroid carcinoma (97%), hyperparathyroidism (50%) and pheochromocytoma (30%). Descriptions of observations of Sipple syndrome are found quite often in both domestic and foreign literature. However, when analyzing a large number of observations of MEN 2 A, it was found that pheochromocytoma is diagnosed primarily in only 10% of patients, in 50% during examination for medullary cancer, and in 40% in late stages of neoplasia. The presented clinical case of MEN 2A is recommended for study by doctors of various specialties, primarily endocrinologists, therapists and cardiologists.

Aggressiveness and age of manifestation of medullary thyroid cancer depend on the risk level of germline RET mutations. For high-risk mutations, preventive thyroidectomy is recommended at young age. In recent years, endoscopic operations for thyroid cancer were introduced in clinical practice. But such experience in pediatrics is very limited. We present a case report of a male patient, 6-year-old with the high-risk germline mutation С634R in RET gene. Close relatives (mother, cousin, and native sister) of the proband, were treated for medullary thyroid cancer. Also, his grandmother on the maternal line and her native brother died at the age of 38 and 37 years because of medullary thyroid cancer progression. Since 3 years old, our patient was under regular exams. At the age of six, calcitonin level was 8 ng/mL, and no evidence of pathology on ultrasound. According to recommendations of American Thyroid Association from 2015 (ATA 2015), preventive thyroidectomy was planned. This operation was performed by transoral vestibular approach. Oral nutrition started on the first day after the operation and the patient was discharged from the hospital. No major complications were observed. Transitory paresthesia and slight edema of the submental compartment were noticed. Consider this, endoscopic operation on the thyroid gland can be performed, as a preventive procedure, for RET gene germline mutation carriers in young age. This method helps avoid scars on the skin of the anterior neck.

The literature review presents the history on the deve­lopment of modern ideas about medullary thyroid cancer, which is a little more than fifty years. It demonstrates the impressive achievements of modern science, which made it possible to move from clinical and morphological descriptions of individual cases and variants of diseases to studying and elucidating the mechanisms of their development at the molecular genetic level within a short period of time. To a large extent, this became possible thanks to the discovery of a number of combined forms of endocrine pathology, in particular multiple endocrine neoplasia syndromes among which medullary thyroid cancer plays a leading role. Based on achievements in this field, a method of surgical correction of medullary cancer even before its occurrence was proposed, which marked the emergence of a new direction in surgery — a preventive surgery. The history of studying medullary thyroid cancer begins with the discovery of a separate population of cells present in a small amount of thyroid tissue. In his report made at the meeting of the Royal College of Physicians in London on January 27, 1876, called Contribution to the minute anatomy of the thyroid of the dog, E. Cresswell Barber first described the presence of clusters of unusual cells in the gland, which morphologically differed from the known follicular cells. Currently, a new direction of clinical surgery is being formed — a preventive surgery. The basic principle of prophylactic surgery is the removal of one or another organ, if the absolute risk of developing a specific pathological process in it is proven. In the situation under consideration, this is medullary thyroid cancer, which occurs in 100 % of individuals who are hereditary carriers of the mutant RET proto-oncogene. A similar risk exists for persons with some forms of colorectal cancer, malignant tumors of the mammary gland, ovaries in which their hereditary origin has been proven on the basis of detected mutations of certain genes. Intestinal resection, mastectomy, oophorectomy lead to the elimination of the potential threat of tumor development or its removal in situ, when it has not yet acquired the nature of a formed malignant neoplasm.

Aggressiveness and age of manifestation of medullary thyroid cancer depend on the risk level of germline RET mutations. For high-risk mutations, preventive thyroidectomy is recommended at young age. In recent years, endoscopic operations for thyroid cancer were introduced in clinical practice. But such experience in pediatrics is very limited. We present a case report of a male patient, 6-year-old with the high-risk germline mutation С634R in RET gene. Close relatives (mother, cousin, and native sister) of the proband, were treated for medullary thyroid cancer. Also, his grandmother on the maternal line and her native brother died at the age of 38 and 37 years because of medullary thyroid cancer progression. Since 3 years old, our patient was under regular exams. At the age of six, calcitonin level was 8 ng/mL, and no evidence of pathology on ultrasound. According to recommendations of American Thyroid Association from 2015 (ATA 2015), preventive thyroidectomy was planned. This operation was performed by transoral vestibular approach. Oral nutrition started on the first day after the operation and the patient was discharged from the hospital. No major complications were observed. Transitory paresthesia and slight edema of the submental compartment were noticed. Consider this, endoscopic operation on the thyroid gland can be performed, as a preventive procedure, for RET gene germline mutation carriers in young age. This method helps avoid scars on the skin of the anterior neck. [ABSTRACT FROM AUTHOR]

The literature review presents the history on the development of modern ideas about medullary thyroid cancer, which is a little more than fifty years. It demonstrates the impressive achievements of modern science, which made it possible to move from clinical and morphological descriptions of individual cases and variants of diseases to studying and elucidating the mechanisms of their development at the molecular genetic level within a short period of time. To a large extent, this became possible thanks to the discovery of a number of combined forms of endocrine pathology, in particular multiple endocrine neoplasia syndromes among which medullary thyroid cancer plays a leading role. Based on achievements in this field, a method of surgical correction of medullary cancer even before its occurrence was proposed, which marked the emergence of a new direction in surgery - a preventive surgery. The history of studying medullary thyroid cancer begins with the discovery of a separate population of cells present in a small amount of thyroid tissue. In his report made at the meeting of the Royal College of Physicians in London on January 27, 1876, called Contribution to the minute anatomy of the thyroid of the dog, E. Cresswell Barber first described the presence of clusters of unusual cells in the gland, which morphologically differed from the known follicular cells. Currently, a new direction of clinical surgery is being formed - a preventive surgery. The basic principle of prophylactic surgery is the removal of one or another organ, if the absolute risk of developing a specific pathological process in it is proven. In the situation under consideration, this is medullary thyroid cancer, which occurs in 100 % of individuals who are hereditary carriers of the mutant RET proto-oncogene. A similar risk exists for persons with some forms of colorectal cancer, malignant tumors of the mammary gland, ovaries in which their hereditary origin has been proven on the basis of detected mutations of certain genes. Intestinal resection, mastectomy, oophorectomy lead to the elimination of the potential threat of tumor development or its removal in situ, when it has not yet acquired the nature of a formed malignant neoplasm. [ABSTRACT FROM AUTHOR]

The simultaneous occurrence of more than two types of neoplasms is rare due to their significant phenotypic differences. Thyroid carcinoma is regularly associated with genetic alterations and endocrine syndromes. However, the etiology of the forms of papillary thyroid carcinoma (PTC)/medullary thyroid carcinoma (MTC) is still not fully understood. We present the case of a 60-year-old male with no significant history of thyroid disease who presented with dysphonia. Left vocal cord paralysis and a cervical tumor lesion were observed. A mixed medullary/papillary carcinoma was diagnosed. Surgical resection of the mediastinal tumor and hemithyroidectomy revealed a poorly differentiated blue cell MTC, with a tumor size of 6.5 x 6.4 x 4.4 cm and a Ki-67 proliferation index of 10%. The tumor was positive for cytokeratin AE1/AE3, carcinoembryonic antigen, synaptophysin, chromogranin, thyroid transcription factor 1 (TTF-1), S-100, and calcitonin. Metastasis was identified in a lymph node at the mediastinum, supporting a diagnosis of usual-type papillary thyroid carcinoma, with positivity for cytokeratin AE1/AE3, thyroglobulin, and TTF-1. Genetic tests related to hereditary cancer (Gencell Pharma, Bogotá, Columbia) were negative. The simultaneous presence of MTC and PTC in a patient is a rare event. The clinical characteristics and biological behavior of these cancer types can vary. The prognosis is directly related to the stage at presentation and the condition at the time of diagnosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sierra Castillo et al.)

Introduction/Objective. Alcohol abuse influence on developing thyroid cancer is controversial. While some studies consider it a protective factor, others deny any impact on thyroid cancer. The objective of the paper was to establish a possible link between alcohol abuse and certain types of thyroid cancers. Methods. The retrospective study included 502 patients with thyroid cancer and a control group of 600 patients with benign forms of thyroid diseases (e.g. nodular, multinodular, and toxic nodular goiter). Thyroid cancer patients were divided into four groups: I – papillary, II – medullary, III – anaplastic, and IV – follicular carcinoma, and grouped by sex, age (< 30 years; > 30 years) and alcohol abuse, as defined by the World Health Organization. Results. Thyroid cancer patients were predominantly male of younger age. This distribution difference was statistically significant in groups I and II (p < 0.001). Of total 10 (0.9%) patients with chronic alcohol abuse, eight (1.6%) had thyroid cancer, while two (0.3%) belonged to the control group (p < 0.001). In thyroid cancer patients, chronic alcohol abuse was absent from groups III and IV. Distribution in groups I and II was six (1.6%) and two (2%), respectively (p < 0.001). Conclusion. Alcohol abuse deserves to be considered as a risk factor for papillary and medullary forms of thyroid cancer, while it does not stay the same for anaplastic and follicular thyroid cancers.

The paper presents many years’ international experience in treating medullary thyroid cancer (TC). Two hundred and forty-two patients with different stages of the disease were followed up. The morphological and genetic features of this tumor are given. The results of used treatment options for medullary cancer, such as surgical, radiation, multimodality, and drug therapies, are analyzed. Surgery is a leading treatment option for this disease. The volume of surgery on a primary tumor focus depends on both the shape of a (sporadic or hereditary) tumor and its sizes. Removal of pre- and paratracheal fat is indicated for any volume of surgery for TC due to the high risk of its metastases to lymph nodes at this site. For radiotherapy there are three main indications: 1) the dubious, macroscopically and microscopically evaluated efficiency of an operation; 2) inoperable cancer; 3) distant bone metastases for palliative and symptomatic care. The now chemicals available at an oncologist’s disposal exert no significant effect on increased survival in a patient with medullary TC.

The paper deals with current trends in the diagnosis and treatment of locally advanced, recurrent and metastatic medullary and low-grade thyroid cancer. It highlights problems in the diagnosis and surgical treatment of this pathology on the basis of our clinic’s experience. Data on global trends in medical treatment for low-grade radioactive iodine therapy-refractory thyroid tumors, as well as disseminated and metastatic medullary cancer are given.

Background: Medullary thyroid cancer (MTC) is an infrequent form of thyroid cancer. We aimed to examine how gender and histological characteristics influence the rate of recurrence/persistent disease, distant metastases and survival and also to define specific characteristics of MTC microcarcinomas. Methods: The medical records of 85 patients with MTC were reviewed. The following characteristics were recorded: year of diagnosis, age at diagnosis, sex, tumor size, number of tumor foci, lymph node metastases, thyroid capsule and vascular invasion, infiltration of thyroid parenchyma and extrathyroid extension, and distant metastases. Results: During follow-up (mean 78.8 months), persistent disease occurred in 40 patients, local recurrences in 5 and distant metastases in 32 patients. Local and distant disease appeared more frequently in patients with larger tumors ( p < 0.005) and lymph node metastases ( p < 0.01). In addition, patients with invasive tumors had local and distant disease more frequently. The percentage of males who had persistent disease and/or local recurrence was significantly higher than the percentage of males who did not ( p < 0.05). Similar results were observed for distant disease ( p < 0.01). Independent predictors of recurrence and persistent disease was the presence of lymph node metastases at diagnosis (risk ratio 11.66) and of distant metastases were the presence of lymph node metastases at diagnosis (risk ratio 17.42) and the presence of vascular invasion (risk ratio 2.41). Fifteen patients died due to MTC during follow-up (17.6 %). Patients who died were more frequently males, and had thyroid capsule invasion, extrathyroidal extension, vascular invasion and metastatic disease. Conclusions: Male sex, tumor size and invasive characteristics of the tumor are negative predictive factors for evolution of MTC. [ABSTRACT FROM AUTHOR]

Objective: Medullary thyroid cancer (MTC) is a rare and particularly aggressive type of thyroid cancer of neuroendocrine origin. It occurs in hereditary and sporadic forms and its aggressiveness is related to the clinical presentation and the type of RET mutation. Methods: In this article, we present the criteria, as reviewed in contemporary literature, regarding lymph node dissection and radical neck dissection in patients with either sporadic or hereditary MTC. Results: Early diagnosis and treatment remains the key to a 100% cure rate. Conclusions: Routine central lymph node dissection is the minimum procedure recommended for all sporadic and hereditary MTCs. Routine lateral lymph node dissection on either side is necessary when lymph node metastases are found in the central neck compartment. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Hyalinizing trabecular adenoma (HTA) is an uncommon benign thyroid tumor that can present as a solitary thyroid nodule, a prominent nodule in a multinodular goiter, or as an incidental finding in a thyroidectomy specimen. The clinical significance of the lesion is that it is frequently misdiagnosed as papillary carcinoma on fine-needle aspiration cytology or as papillary or medullary carcinoma on histopathological section. We reviewed our recent experience with 7 patients diagnosed with HTA. Methods: Fine-needle aspiration biopsy was performed in 7 patients presenting with a solitary thyroid nodule (n = 4) or a multinodular goiter (n = 3). The patients underwent total thyroidectomy (n = 6) or hemithyroidectomy (n = 1). Results: In 4 patients, the preoperative cytology was suggestive of papillary carcinoma, in 2 patients suspicious, and in 1 patient positive for papillary carcinoma. On histopathological section, 2 patients had a microscopic HTA, 2 patients had HTA in 1 or 2 nodules of a multinodular goiter, and 3 patients had HTA in a solitary nodule. Except in 1 patient, who had a microscopic focus (3.2 mm) of papillary carcinoma, there was no evidence of malignancy in the surgical specimens on permanent histopathological section. Conclusions: Although HTA is a rare condition of the thyroid, the surgeon needs to be aware of this entity to be able to better discuss the pathological findings with the patient, particularly since some pathologists and endocrinologists believe that HTA may represent a malignant neoplasm of low metastatic potential. [Copyright &y& Elsevier]

Lü B-J, Lai M, Cheng L, Xu J-Y&Huang Q(2004)Histopathology45,485–492Gastric medullary carcinoma, a distinct entity associated with microsatellite instability-H, prominent intraepithelial lymphocytes and improved prognosisTo determine the clinicopathological and molecular features of gastric medullary cancer.Clinicopathological review and microsatellite instability (MSI) analysis were carried out on 17 gastric medullary and 64 non-medullary cancers. In addition to characteristic histopathology, gastric medullary cancers had certain prominent features: (i) the average survival time was longer in medullary and low-grade non-medullary cancers than in high-grade (P = 0.004); (ii) serosal involvement was less common in medullary cancers (29.4%, 5/17) than in non-medullary cancers (9.4%, 6/64) (P <0.05) while pushing borders were more common in medullary cancers (70.6%, 12/17 versus 17.2%, 11/64,P = 0); (iii) the presence of intraepithelial lymphocytes (IELs) in medullary and non-medullary cancers was 2380/10 high-power field (HPF) and 147/10 HPF (P = 0), respectively. Both peritumoural infiltrating lymphocytes (pTIL) and a Crohn's-like reaction were more common in medullary cancers than in non-medullary (pTIL 35.3%, 6/17 versus 3.1%, 2/64; a Crohn's-like reaction 70.6%, 12/17 versus 32.8%, 21/64;P < 0.05); (iv) medullary and high-grade non-medullary cancers were more associated with reducedECDexpression in comparison with low-grade cancers (P < 0.05); (v) higher MSI-H (Bat26+) rate was observed in medullary cancers (41.2%, 7/17) than in non-medullary (1.6%, 1/64) (P = 0).Gastric medullary cancer has distinct clinicopathological features and genetic alterations. Two subtypes of gastric medullary cancers, Bat26+ and Bat26–, might have prognostic implications, thus analysis of Bat26 may be of clinical value. [ABSTRACT FROM AUTHOR]