Medullary thyroid carcinoma: Prognostic factors and treatment

Seventy-five patients with medullary thyroid carcinoma (MTC) have been treated at Institut Gustave-Roussy from 1932 to 1979. Of these, 13 patients had distant metastases and received palliative treatment, their median survival was 3 years. Sixty-two patients with WC limited to the neck received curative treatment: 6 had exclusive external radiotherapy for inoperable disease and 56 were surgically treated: 23 by total thyroidectomy and 33 by partial thyroidectomy. After surgery 29 patients received external radiotherapy for cervical lymph node involvement ($\text{25}\text{29}$) and/or incomplete surgical resection ($\text{12}\text{27}$). The survival rate was 69% at 5 years and 48% at 10 years. It was lower in patients with distant metastases at presentation (p < 10^?5), with tumoral infiltration of the posterior tissue planes (p < 0.025) and in patients in whom surgical excision bad not been satisfactory (p < 0.01). It was not correlated with cervical lymph node involvement probably because those patients with lymph node involvement had been irradiated. The 29 patients who received post-operative cervical radiotherapy had initially more extensive local disease (p < 0.05) than the 27 patients treated by surgery alone, nevertheless their survival was slightly higher. No difference in survival rate was observed between patients treated by total thyroidectomy or partial thyroidectomy, among whom only 4 local recurrences occurred. Three of the 6 patients treated with external radiotherapy alone experienced long survival (4, 7 and 10 years) and a fourth is still in clinical remission 4 years after treatment. The effectiveness of chemotherapy in patients with metastases was poor, only one patient out of 6 had a partial remission following a treatment by adriamycin. In the familial form and multiple endocrine neoplasia type II, total thyroidectomy appears to be indicated. In the sporadic cases, partial thyroidectomy is usually sufficient. External radiotherapy is effective in MTC and seem to be able to eradicate small foci of residual tumor; it is indicated when surgical excision is impossible or Incomplete.     

Medullary thyroid carcinoma

Opinion statement Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy that occurs in hereditary (25%) and sporadic (75%) clinical settings. MTC is present in all patients with the multiple endocrine neoplasia type 2 syndromes. MTCs produce calcitonin, the measurement of which can indicate the presence of tumors in people who are at risk and the effectiveness of therapy in treated patients. Surgical cure is possible in young patients with multiple endocrine neoplasia type 2 who undergo preventative thyroidectomy (approximately 50% of patients who are diagnosed with a palpable thyroid mass) and in some patients with recurrent nodal metastatic disease in the neck. Mortality from MTC is caused by tumor invasion of the trachea, great vessels in the neck, or mediastinum or by the effects of distant metastatic disease. Surgery for cervical recurrence can prevent death from tracheal invasion. The role of radiation therapy is not well defined. There is no effective systemic therapy for MTC. Activating mutations in a tyrosine kinase receptor gene (RET) are present in most MTCs, and experience with tyrosine kinase inhibitors and other agents in clinical trials is critical for the identification of effective systemic treatment.     

Medullary thyroid carcinoma

Medullary thyroid carcinoma is a neuroendocrine tumor derived from the C cells of the thyroid gland and accounts for approximately 5% of all thyroid carcinomas. Approximately 30% of the cases are associated with an autosomal dominant syndrome called multiple endocrine neoplasia type 2, and the identification of these individuals is important because affected family members may benefit from an early diagnosis. The treatment of this disease is predominantly surgical, and the impact of radiotherapy and chemotherapy is limited. The identification of the associated molecular events has lead to the development of specific molecular targeted agents that may change the way this disease is treated in the near future.     

Medullary thyroid carcinoma: surgical management of primary tumor and locoregional recurrence

Medullary thyroid carcinoma is a rare neoplasm (3-9% of all thyroid tumors). Surgery represents the only strategy for potential cure of the disease in whichi. Medullary thyroid carcinoma in which locoregional lymph node metastases are an early occurrence cannot be treated with radioiodine therapy and it is minimally sensitive to chemotherapy and external beam radiation therapy. Therefore total thyroidectomy with lymphadenectomy is the treatment of choice. Ipsilateral laterocervical lymphadenectomy is essential for neoplasms > 10 mm in size in case of central and ipsilateral laterocervical lymph node involvement; bilateral laterocervical lymphadenectomy should be performed in all patients with bilateral lymphadenopathy and in some cases of MEN 2B. In recurrence, reoperation is the single possible treatment with satisfactory results in terms of prognosis.     

甲状腺髓样癌与RET基因

甲状腺髓样癌(MTC)源于甲状腺滤泡旁细胞,预后较分化型甲状腺癌为差,早期手术是最为有效的治疗方法.近年发现RET基因突变是MTC的主要分子病因学基础,对RET基因突变的研究成果已经用于临床早期诊断、指导预防性外科干预以及生物靶向治疗等方面.     

Medullary thyroid carcinoma: The third most common thyroid cancer reviewed

Medullary thyroid cancer is a type of thyroid cancer of neuroendocrine origin. It occurs in hereditary and sporadic forms, and its aggressive behavior is associated with the clinical presentation and type of RET mutation. Total thyroidectomy remains the ideal choice of treatment. Early diagnosis and treatment are the fundamental for a 100% cure rate. In this study, we present our experience of 3 cases, along with a complete review of the literature derived from a Pubmed Database search.     

Medullary thyroid carcinoma: Management of lymph node metastases

Opinion statement Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells. Spread of MTC commonly occurs to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine, and are not sensitive to hormonal manipulation. Because of these features, the treatment of metastatic or recurrent MTC is different from the treatment of differentiated thyroid cancer. Surgery is the only effective therapy at present that can result in cure, or reduction in tumor burden, or effective palliation. Systematic surgical removal of at-risk or involved lymph node basins should be done in patients with palpable primary tumors and recurrence. A “berry-picking” approach is discouraged. Although data are limited, standard chemotherapy and radiation therapy have not been effective in the treatment of MTC. Newer targeted drug therapies are being examined in therapeutic clinical trials.     

Medullary carcinoma of the thyroid: current diagnosis and management

Medullary thyroid carcinoma (MTC) accounts for 5-10% of thyroid malignancies and occurs in either a sporadic or a familial form. The familial form is inherited in an autosomal dominant pattern, and expressed clinically as multiple endocrine neoplasia (MEN), types IIa and IIb, or as familial MTC alone. This neoplasm is derived from the parafollicular or C-cells, and has the ability to secrete a variety of polypeptide hormones including calcitonin, which serves as a tumor marker for the presence of MTC. The development of a calcitonin radioimmunoassay and the screening of patients at risk for the familial forms of MTC allows the diagnosis of the neoplasm in an occult stage when total thyroidectomy results in virtually 100% cure. We will present our experience with the diagnosis, treatment, and postoperative follow-up of our patients with this interesting neoplasm.     

甲状腺乳头状癌外科治疗分析

目的 分析甲状腺乳头状癌患者外科治疗后的复发和生存情况,以探讨规范化治疗方案.方法 收集和分析1994-1999年中国医学科学院肿瘤医院头颈外科收治的600例甲状腺乳头状癌患者的临床资料和随访资料.600例患者中,原发灶位于甲状腺左叶188例,右叶290例,峡部8例,双侧同时发生109例,单侧同时多发病灶5例.TNM分期为Ⅰ期385例,Ⅱ期37例,Ⅲ期17例,Ⅳ期161例.患者均接受手术治疗,其中术后放疗19例,131Ⅰ治疗71例,同时行放疗和131Ⅰ治疗1例.结果 术后复发94例.随访期内死亡27例,以复发和转移为主要死因.600例患者的中位生存时间为96个月,10年生存率为93.2％.Ⅰ期患者10年生存率为99.1％,Ⅱ期为94.7％,Ⅲ期为93.8％,Ⅳ期为78.5％,差异有统计学意义(P＜0.01).年龄＜45岁组10年生存率为99.4％,≥45岁组为82.1％,差异有统计学意义(P＜0.01).气管受侵者10年生存率为66.5％,气管未受侵者为95.1％,差异有统计学意义(P＜0.01).高分化乳头状癌患者10年生存率为94.9％,低分化乳头状癌为38.9％,差异有统计学意义(P＜0.01).多因素Cox回归分析显示,TNM分期、病理分级和手术切除彻底性是甲状腺乳头状癌患者预后的独立影响因素,相对危险度分别为2.380、7.057和2.751.结论 甲状腺乳头状癌患者生存率较高,TNM分期、病理分级和手术切除彻底性是患者预后的独立影响因素.     

Medullary thyroid carcinoma experienced at Kanazawa University Hospital

Eleven cases of medullary thyroid carcinoma (MTC), which were experienced at Kanazawa University Hospital between 1975 and 1993, were examined to correlate the clinical, histologic, and immunohistochemical findings. Seven patients were women and four men, and the mean age was 46.6 years. The mean follow-up was 88.3 months. Three patients had familial non-multiple endocrine neoplasia (MEN) MTC (familial MTC unassociated with other endocrinopathies) and the remaining eight had sporadic disease. At the end of the observation period, six patients were alive without disease and four were alive with metastatic disease. One patient died of MTC 8.3 years after surgery. Thus, the 10-year survival and disease-free survival rates were 67% and 53%, respectively. Histologically MTCs from the 10 surviving patients showed a classic type, while the one patient who died had a tubular variant MTC. Immunohistochemically, there were no significant correlations between the outcome of the patients and the expression of calcitonin (CT), carcinoembryonic antigen (CEA), calcitonin gene-related peptide (CGRP), or chromogranin A (CgA) in the primary tumors, and there were no differences in expression of these antigens between the primary and the recurrent tumors. Although only a small number of patients with MTC were studied here, it was suggested that the prognosis of MTC is worse than that of papillary and follicular thyroid carcinoma. The patients with lymph node involvement at the time of primary surgery showed a high risk of persistent or recurrent disease. The expressional level for the antigens did not influence the prognosis of MTC. © 1996 Wiley-Liss, Inc.     

Medullary thyroid carcinoma: importance of serial serum calcitonin measurement.

Thirty-two patients with medullary carcinoma of the thyroid (MCT) were studied before and after therapy. Sixteen patients had familial and 16 had the sporadic type of disease. The groups differed in several features: Patients with sporadic disease were older at diagnosis and presented with enlargements in the thyroid or lymph nodes, and one patient had neuromata; in the familial group the disease was more often bilateral and was associated at times with the MEA syndrome (parathyroid adenoma or pheochromocytomas, or both). The immunoreactive serum calcitonin (CT) level was measured before and after some form of therapy in all 32 patients. Our investigations showed: 1) Delaying treatment was clearly detrimental in this progressive disease; 2) The most effective therapy was surgery, while radiotherapy and chemotherapy were less effective; 3) Postoperatively, the CT level usually fell sharply, when the disease was thought extirpated, but the lowest nadir might be reached at from 1 month to 6 years; 4) In all such patients the CT level eventually rose from the postoperative nadir; 5) Patients with no clinical or radiological evidence of disease, had high CT levels for a mean of 3 years of observation; 6) A marked rise of CT levels in three patients preceded metastases and death; 7) Patients with abdominal, particularly liver disease had the highest CT levels; and 8) Patients who died had relatively high CT levels, corresponding in general with the extent of disease.     

Medullary thyroid carcinoma: multivariate analysis of prognostic factors influencing survival

Background Medullary thyroid carcinoma (MTC) is a rare development of thyroid cancer with a no negligible mortality rate. Our aim was to determine factors that predict outcome in patients with MTC. Methods We reviewed the records of all patients with MTC (n=56) who underwent treatment at our institution between January 1990 and December 2000. Univariate and multivariate analysis of clinicopathologic predictors of MTC outcome were performed to identify subsets of patients with different probabilities in terms of overall survival, local recurrence, and distant metastases. Results Multivariate analysis demonstrated that a statistically significant decrease in overall survival is associated with T4b tumours (p=0.06), the presence of distant metastases at the time of presentation (p=0.033), lymphatic invasion (p=0.099), and postoperative treatment (p=0.045). Conclusions The analysis of survival curves of patients with MTC shows that the occurrence of locoregional and distant metastases occurs preferentially within the first 5 years, which identifies this as a crucial period for follow-up. In this series of patients with MTC, the tumours classified as T4b, metastases at presentation, the presence of lymphovascular invasion, and postoperative treatment were the most important prognostic features. At present, there is no available beneficial adjuvant therapy. However, as the development of molecular therapy progresses, it should be tested in clinical trials with the purpose of achievement of novel targeted therapies for selected MTC patients with risk factors.     

有完整包膜的甲状腺髓样癌临床病理特征

目的:探讨有完整包膜的甲状腺髓样癌(MTC)的临床病理学特征.方法:对有完整包膜的1例MTC进行大体、组织病理学和免疫组化染色观察,并复习相关文献.结果:肿瘤有完整包膜,癌组织免疫组化:NSE、CgA、SyN、CT、CEA阳性;CK19、TG阴性.淀粉样物质染色阳性.结论:有完整包膜的甲状腺髓样癌极其少见,其诊断依赖于组织病理学、免疫组化和组织化学.     

Medullary thyroid carcinoma relapse reversed with dichloroacetate: A case report

A 51-year-old male patient diagnosed with medullary thyroid carcinoma (MTC) in 2001, with progression to lung metastases following adriamycin therapy, was then successfully treated with dimethyltriazenoimidazole carboximide. He remained in partial remission for 7 years following numerous chemotherapy attempts to induce partial remission. In October 2008, the patient, then 58 years old, relapsed with numerous tumors throughout his central body. On December 1, 2008, the tumor marker for MTC, calcitonin, was at 38,611 pg/ml, i.e., much higher than the norm of <20 pg/ml. Since all other chemotherapy attempts had failed, he was ineligible for any new studies. Subsequently, the patient was immediately started on 10 mg/kg of dichloroacetate (DCA). By April 2009, the calcitonin level was reduced to 2,000 pg/ml. In May 2009, a new positron emission tomography showed a dramatic reduction in all tumor locations. The patient presently remains in remission and continues receiving the same dosage of DCA, with his tumor marker remaining stable in laboratory data since November 2009.     

Medullary carcinoma of the thyroid with atypical patterns.

A case of a highly invasive thyroid carcinoma, which occurred in a 68-year-old woman, was studied by light and electron microscopy, and histochemical and biochemical analysis. Light microscopical, histochemical, and biochemical features were consistent with a diagnosis of a calcitonin-producing, amyloid-rich medullary carcinoma; electron microscopical patterns, mainly the presence of lumina, microvilli, and extensively dilated cytoplasmic E.R., were reminiscent of the ultrastructural features of the follicular carcinoma. Electron-dense bodies interpreted as "secretory granules" were very scarce. This case appears very similar to the case recently presented by Valenta et al. and interpreted as a microfollicular carcinoma. The atypical features of our case of MCT seem to indicate that this tumor should be included in a group of atypical MCT; these should be kept separate from the typical (differentiated) ones on morphological, functional, and prognostic grounds.     

Medullary thyroid cancer

Opinion statement Patients with clinically evident medullary thyroid cancer should have a total extracapsular thyroidectomy with bilateral central neck dissection and an ipsilateral prophylactic or therapeutic modified (functional) radical neck dissection when the primary tumor is greater than 1 cm and when the central neck nodes are positive. A prophylactic contralateral neck dissection should be done when the primary tumor is bilateral and when there is extensive lymphadenopathy on the side of the primary tumor. Patients who have gross, unresectable residual medullary thyroid cancer should receive postoperative external radiotherapy. Patients who are carriers of germ-line RET proto-oncogene point mutations or have an elevated (basal or stimulated) calcitonin levels on screening should have a prophylactic total thyroidectomy before age 6 years. In patients with an elevated basal or stimulated plasma calcitonin level and an intrathyroidal nodule on ultrasound, a total thyroidectomy and central neck lymph node dissection should be done. Patients with persistent or recurrent medullary thyroid cancer should have a complete thyroidectomy (if not done initially) and bilateral central and modified radical neck dissection, including upper mediastinal lymphadenectomy. Patients who are symptomatic from distant medullary thyroid cancer metastases (diarrhea, flushing, weight loss, or bone pain) should be treated with somatostatin analogs. Bone metastases should be resected if possible, and symptomatic lesions that are unresectable should be treated with external radiotherapy. Cytoreductive procedures such as radiofrequency ablation or cryoablation for liver metastases should be considered in symptomatic patients to reduce tumor burden. Localized pulmonary metastases should be resected. Chemotherapy or radioactive immunotherapy (iodine 131 labeled carcinoembryonic antigen monoclonal antibody) protocols should be considered in patients with nonoperative widely metastatic progressing medullary thyroid cancer.