An Interesting Case of Familial Medullary Carcinoma Thyroid – Seldom Seen by Surgeons

Medullary thyroid carcinoma (MTC) constitutes around 5% of all thyroid cancers with a worse prognosis. It accounts for 13% ofthyroid cancer-related deaths. A 23-year-old male presented with a 4-year history of progressively increasing thyroid swellingwith similar family history. On examination, butterfly-shaped firm swelling of size 7 × 3 cm in the right and 7 × 4 cm in the leftseen on the anterior aspect of neck with regular margins and nodular surface moving with deglutition extending from the thyroidcartilage to clavicle head and laterally beyond the sternocleidomastoid into the posterior triangle muscle. Pemberton’s signwas negative. Computed tomography neck showed enlarged both thyroid lobes with areas of cystic degeneration and 15 mmretrosternal extension of the left lobe of thyroid with bilateral IB, II, and V lymphadenopathy. Serum calcitonin level was 4435 pg/ml.Fine-needle aspiration cytology favored features of MTC. Total thyroidectomy with central compartment neck dissection wasdone. Intraoperative frozen sections of bilateral level III were found to be tumor free, so proceeded with thyroid excision andcentral compartment neck dissection. Histopathology revealed MTC with bilateral multifocal capsular and lymphovascularinvasion and metastatic foci in the right central compartment lymph node. Hence, early diagnosis in family members offers ahigher likelihood of cure and long-term survival.

Medullary thyroid carcinoma: a 30-year experience at one institution in Korea

PURPOSE: The objective of this study was to review the clinical outcome and prognosis of patients with sporadic and hereditary medullary thyroid cancer (MTC) who were treated at a single tertiary hospital in Korea. METHODS: We retrospectively reviewed the case files of 85 patients treated from August 1982 to February 2012. RESULTS: In all, 65 patients (76.5%) had sporadic MTC and 20 patients (23.5%) had hereditary MTC. Patients in the sporadic group were older than in the hereditary group (P < 0.001). However, the hereditary group had more tumor multiplicity (P < 0.001) and bilaterality (P < 0.001). Neither survival rate was significantly different between the sporadic and hereditary groups (P = 0.775 and P = 0.866). By multivariate analysis, distant metastasis was a significant prognostic factor for overall and progression-free survival. CONCLUSION: In general, patients with MTC have favorable outcomes. Distant metastasis appears to be the strongest predictor of overall and progression-free survival.

The rare intracellular RET mutation p.S891A in a Chinese Han family with familial medullary thyroid carcinoma.

We report intracellular RET mutation in a Han Chinese pedigree with familial medullary thyroid carcinoma (FMTC). Direct sequencing of RET proto-oncogene identified a missense c.2671T>G (p.S891A) mutation in 6 of 14 family members. The single nucleotide polymorphisms c. 135A>G (p.A45A), IVS4+48A>G, c. 1296A>G (p.A432A), c. 2071G>A (p.G691S), c. 2307T>G (p.L769L) and a variant c. 833C>A (p.T278N) were also found in 6 carriers. Among 5 of the 6 carriers presented medullary thyroid carcinoma (MTC) as an isolated clinical phenotype, with elevated basal serum calcitonin (Ct). Two underwent non-normative thyroidectomy either two or four times without physician awareness or diagnosis of this disease at initial treatment, but with elevated Ct. One with elevated pre-Ct accepted total thyroidectomy (TT) with modified bilateral neck dissection (MBiND), and whose seventh posterior rib MTC metastases was confirmed 5 months after surgery. Moreover, results of two affected individuals with elevated Ct were reduced to normal after TT with MBiND or prophylactic VI compartmental dissection. However, only another carrier with the variant p.T278N had slightly elevated Ct rejected surgery and was strictly monitored. Given these case results, we suggest that screening of RET and pre-surgical Ct levels in the management of MTC patients is essential for earlier diagnosis and more normative initial treatment, that FMTC patients with cervical lymph nodes metastases may be cured by TT with MBiND, and that prophylactic VI compartmental dissection should be avoided when Ct levels are low.

Multiple Endocrine Neoplasia and Familial Medullary Thyroid Carcinoma / 대한갑상선학회지

Multiple endocrine neoplasia (MEN) is defined as a disorder with neoplasms in two or more different hormonal tissues in several members of a family. MEN1, or Wermer's syndrome, is inherited as an autosomal dominant trait. This syndrome is characterized by neoplasia of the parathyroid glands, enteropancreatic tumors, anterior pituitary adenomas, and other neuroendocrine tumors with variable penetrance. Inherited medullary thyroid carcinoma (MTC) consists of MEN2A, MEN2B, and familial medullary thyroid cancer (FMTC). The identification of hereditary MTC has been facilitated in recent years by direct analysis of germline RET proto-oncogene mutation.

A Korean Family of Familial Medullary Thyroid Cancer with Cys618Ser RET Germline Mutation

Familial medullary thyroid carcinoma (FMTC) is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. An identifiable RET mutation can be detected in about 85% of FMTC families. The majority of germline mutations in FMTC have been found in exons 10 and 11 of the RET proto-oncogene, specifically within the cysteine codons 609, 611, 618, 620, and 634. We screened members of a large Korean family that had a history of FMTC by genetic analyses, and propose a therapeutic approach for managing the disorder. We report a RET mutation in exon10, codon 618 that causes substitution of a cysteine by a serine in the cysteine-rich domain of the RET receptor in a three-generation FMTC family composed of 30 members with 11 carriers. Nine of the gene carriers were clinically affected. The FMTC with cysteine RET mutations found in the Korean population is consistent with the clinical pattern reported worldwide; to date there have been no ethnic differences identified for FMTC. Our results suggest that this genetic profile might be associated with usually aggressive clinical course with regional lymph node metastasis but late onset of MTC.

A Case of Familial Medullary Thyroid Carcinoma with a E768D Mutation in RET Proto-Oncogene / 대한내분비학회지

A medullary thyroid carcinoma, a neoplasm of parafollicular C cell origin, occurs as a sporadic or hereditary disease. A hereditary medullary thyroid carcinoma is an autosomal dominantly inherited disease, which is composed of multiple endocrine neoplasia 2A and 2B, with a familial medullary thyroid carcinoma. Germline mutations of the RET gene are the underlying cause of the majority of hereditary medullary carcinomas. Here, the case of a 42 years-old man with a familial medullary thyroid carcinoma, confirmed by the detection of a RET proto-oncogene mutation at exon 13 on codon 768 from a GAG(Glu) to a GAT(Asp), is described. The patient underwent a total thyroidectomy and modified radical neck dissection. His sister was found to have the same mutant gene.

A Case of Familial Medullary Thyroid Carcinoma / 대한이비인후과학회지

Medullary thyroid carcinoma(MTC) is a malignancy of the thyroid C-cells, and it compromises 5-10% of all thyroid cancers. MTC occurs in both sporadic and hereditary types, the latter making up 25% of all MTCs and being compromised of three distinct syndromesmultiple endocrine neoplasia type IIa(MEN IIa), multiple endocrine neoplasia type IIb(MEN IIb), and familial medullary thyroid carcinoma(FMTC). To date, screening for MTC subtype is important for proper diagnosis and treatment. Recently, the authors experienced a case of FMTC. So, we report this case with the review of the literatures.