Medullary thyroid carcinoma and pheochromocytoma accompanied with nodular hyperplasia in multiple endocrine neoplasia type 2

Three patients with familial multiple endocrine neoplasia type 2 underwent total adrenalectomy and subsequently near-total or total thyroidectomy. The overt pheochromocytomas were present bilaterally in two patients and unilaterally in another patient. In addition, multiple nodules measuring a few mm in diameter were demonstrated in all adrenal medullas examined. All patients exhibited bilateral medullary thyroid carcinomas which varied in size from a few minute nodules accompanied by the microscopic C-cell hyperplasia to distinct large tumors. The thyroid C-cell hyperplasia appeared to be confined to the upper and middle thirds of the lateral lobe, and micronodules of the C-cell hyperplasia enlarged to coalesce, forming one large carcinoma mass. On the other hand, nodular hyperplasia of the chromaffin cells was distributed diffusely throughout the adrenal medulla and each nodule appeared to develop individually into a large pheochromocytoma. These findings suggested that, at least in the family members at a high risk for multiple endocrine neoplasia type 2, the development of both medullary thyroid carcinoma and pheochromocytoma was always preceded by a multicentric nodular hyperplasia. On the basis of the pathogenesis of these tumors, the most rational surgical approach was presented. Presented at the 14th Annual Congress of the Japan Society for Cancer Therapy, Sendai, September 30, 1976.     

Dedifferentiation of neoplastic cells in medullary thyroid carcinoma: Report of a case

We report herein the unusual case of a man who was diagnosed as having sporadic medullary thyroid carcinoma (MTC) at the age of 29 years, and subsequently followed up for a period of 18 years. A total thyroidectomy with radical neck dissection was initially performed, followed by a stable interval of 16 years with regional metastases. He then developed widely disseminated metastases resulting in death within 2 years at the age of 47 years. While the neoplastic tissue from localized metastases in the soft tissue of the neck expressed strong immunohistochemical positivity to calcitonin (CT), calcitonin gene-related peptide, carcinoembryonic antigen, neuron-specific enolase, and chromogranin A during the stable interval, extremely weakened immunoreactivity to those markers was observed in samples from the disseminated metastases in the subcutaneous tissue after his clinical deterioration. Furthermore, only a few neoplastic cells in specimens obtained at postmortem sampling exhibited a weak response to CT. Ultrastructurally, the characteristic secretory granules in the neoplastic cells decreased remarkably in number, consistent with the immunohistochemical findings. These granules also diminished in diameter and intracytoplasmic small lumina and intercellular clefts with microvilli, interpreted as an attribute of anaplastic thyroid carcinomas, were frequently observed in tissues obtained after his clinical deterioration or at postmortem sampling. These cytological changes might represent dedifferentiation of the neoplastic cells or the anaplastic transformation of MTC. This work was supported in part by a Grant-in-Aid for Scientific Research (#01480322 and #07457268) from the Ministry of Education, Science, Sports and Culture of Japan.     

多发性内分泌腺瘤2A的诊治(附2例报告)

目的　提高对多发性内分泌腺瘤2A(MEN2A)的认识及诊治水平。方法　总结 2 例 MEN2A的诊治经验,并结合文献进行讨论。结果　B超、CT、MRI及131I 间 碘苄胍(MIBG)检查发现甲状腺肿块及嗜铬细胞瘤,血清降钙素及血、尿儿茶酚胺测定异常;例1 行嗜铬细胞瘤切除及甲状腺全切并淋巴结清扫术,随诊至今无复发;例 2 行双侧嗜铬细胞瘤切除及甲状腺穿刺活检术,术后随访9个月,效果良好。结论　行内分泌及影像学检查可诊断此病,肾上腺嗜铬细胞瘤切除及甲状腺全切并淋巴结清扫术是治疗的主要手段,高危家族的基因检测筛选及早期手术是治愈本病的关键。     

甲状腺髓样癌20例临床分析

目的 探讨甲状腺髓样癌临床特点、诊断要点及治疗原则.方法 回顾性分析2005年1月至2012年12月20例甲状腺髓样癌患者的临床资料,全组病例均经病理证实为甲状腺髓样癌,颈淋巴结转移9例,远处转移1例,总颈部淋巴结转移率达50％.20例均行手术治疗,至少行患侧腺叶及峡部切除16例,占80％ （16/20）,其中行甲状腺全切除9例.结果 术后常规监测血清降钙素,复发2例.术后随访17例,超过5年者9例,5年生存率达77.8％.结论 甲状腺髓样癌术前诊断困难,多数依赖组织病理学检查确诊,强调细针穿刺细胞学检查的重要性,治疗以根治性手术为主,术后监测降钙素能及早发现局部复发和转移.     

The natural history of multiple endocrine neoplasia type 2A—A clinical analysis

The records of 18 patients with multiple endocrine neoplasia (MEN) type 2A in a family consisting of 87 members in 5 generations, were reviewed with respect to age at onset and length of survival in a study of the natural history of this syndrome. Of these 18 patients, 8 were alive following surgical treatment, while 10 had died without treatment. The clinical onset of medullary thyroid carcinoma was noticed as a nodule in the neck at between 17 and 34 years of age (mean 24 years); the onset of pheochromocytoma was characterized by palpitation, hypertensive attacks or recurrent headache at between 17 and 42 years of age (mean 27 years); and death occurred in 10 patients at between 23 and 67 years of age (mean 40.6 years). This information on the age at onset of individual clinical manifestations, and on the length of survival of gene carriers, may be useful for clinicians who are asked to assess the risk of the development of this syndrome in a genetically predisposed asymptomatic individual, because screening tests are often refused by members of Japanese families with MEN type 2A.     

Medullary thyroid carcinoma: a 20-year experience from a centre in South India

BACKGROUND: Management of medullary thyroid carcinoma (MTC) remains controversial despite many advances over the past five decades. We attempt to review the presentation, management and prognosis of MTC at our institution over the last two decades. METHODS: We conducted a retrospective review of the records of 40 patients with MTC over a period of 20 years. RESULTS: Ten patients had hereditary MTC and 30 had sporadic MTC. The mean age of presentation was 41 years. Sixty-five per cent of the patients had a definite thyroid swelling and 43% had lymphadenopathy at the time of presentation. Total thyroidectomy with a central neck dissection was carried out in 82.5% of patients. Adjuvant therapy was given in 75% of patients because of extensive/residual disease. Postoperative hypercalcitoninaemia was seen 73% of patients. (131)I metaiodobenzylguanidine scanning was carried out in 16 patients with persistent hypercalcitoninaemia; the uptake was positive in 10 and negative in 6, indicating a positivity of 62%. CONCLUSION: Medullary thyroid carcinoma accounts for 2.5% of thyroid carcinomas. There is a small male preponderance. In our series (131)I metaiodobenzylguanidine scan had a better positivity than what has been reported in the published work. Persistent postoperative hypercalcitoninaemia was associated with a poorer prognosis that did not reach statistical significant.     

New era: prophylactic surgery for patients with multiple endocrine neoplasia-2a

BACKGROUND: The surgical management of patients with multiple endocrine neoplasia-2A (MEN-2A) continues to evolve with specific genotype-phenotype correlations allowing for a more tailored approach. In this study, we report the surgical management of one of the largest MEN-2A families with a rearranged during transfection (RET) codon 804 mutation. METHOD: This is a cohort study comprising all at-risk kindred within a single known MEN-2A family. Prophylactic total thyroidectomy with lymph node dissection was recommended to all mutation carriers aged 5 years and older. RESULTS: There were a total of 48 at-risk individuals in the MEN-2A kindred, with 22 patients undergoing thyroidectomy after appropriate preoperative evaluation. A total of 9 patients had medullary thyroid cancer including 5 with a normal preoperative calcitonin level. A total of 11 patients had C-cell hyperplasia and 7 showed histological evidence of parathyroid disease. Only the index case had a phaeochromocytoma. CONCLUSIONS: Genetic testing for germline mutations in the RET proto-oncogene has allowed precise identification of affected RET carriers and provided the opportunity for prophylactic or 'preclinical' surgery to treat and in fact to prevent medullary thyroid cancer. This concept of prophylactic surgery based on a genetic test is likely to be applied more widely as the tools of molecular biology advance.     

甲状腺髓样癌病人围手术期降钙素及癌胚抗原水平变化研究

目的 研究术前血清降钙素（Ctn）及癌胚抗原（CEA）水平与甲状腺髓样癌（MTC）病人临床病理特征的相关性,探讨术后血清Ctn及CEA水平的变化以及其对MTC预后的预测价值。方法 收集2008年6月至2020年6月于吉林大学中日联谊医院甲状腺外科手术治疗的92例甲状腺髓样癌病人的血清Ctn、CEA水平及临床病理特征信息和随访资料,回顾性分析围手术期及术后血清Ctn和CEA水平的变化及其与疾病进展的相关性。结果 术前血清Ctn水平与临床病理特征的单因素分析结果显示,多癌灶、N分期较高、肿瘤直径较大病人的术前Ctn水平更高（P＜0.01）。多因素分析结果显示,肿瘤大小、N分期与术前Ctn水平呈正相关。应用ROC曲线分析预测N1b转移的最佳血清Ctn水平切点值为167 ng/L,曲线下面积为0.842,灵敏度85.3%,特异度77.6%。术前血清CEA的分析结果显示,肿瘤直径≥4 cm时,术前CEA水平值更高。根据血清Ctn变化情况,将术后随访病人分为缓解组、稳定组和进展组。绘制3组病人的无病生存情况（DFS）的K-M曲线,结果显示不同Ctn水平变化情况与DFS显著相关,进展组病人的DFS较差。Ctn水平进展组病人的原发灶肿瘤直径更大（P=0.012）或N分期更高（P＜0.01）。大部分进展组病人在术后12~36个月出现明显的血清Ctn水平倍增,但CEA水平并无明显变化。结论 术前血清Ctn水平对MTC病人的瘤负荷和淋巴结转移具有较好的预测能力,术后血清Ctn水平变化可较好地反映MTC病人的病情进展情况,而围手术期CEA水平的变化没有Ctn水平敏感。     

甲状腺髓样癌诊治的若干问题

甲状腺髓样癌来源于甲状腺滤泡旁细胞,约占甲状腺癌的4%,其中25%为多发性内分泌肿瘤2型相关的遗传性病变,主要包括2a型、2b型和家族性甲状腺髓样癌。降钙素是甲状腺髓样癌特异的肿瘤指标,提示肿瘤发生、残留或复发,而其翻倍时间与预后相关。全甲状腺切除及颈部淋巴结清扫是根治甲状腺髓样癌的唯一希望。基因测序技术的应用使多发性内分泌肿瘤2型相关的甲状腺髓样癌家系病人通过预防性手术而获益。     

甲状腺髓样癌诊治中值得关注的几个问题

甲状腺髓样癌（medullary thyroid carcinoma,MTC）是甲状腺滤泡旁（C细胞）恶性增殖异常分化导致的恶性肿瘤。多数MTC会出现RET基因突变,该疾病缺乏特定的临床特点,病程进展迅速,易发生转移,预后相对较差。目前对于MTC的诊断标准、辅助检查及治疗方案等方面仍然存在争议与分歧,在治疗方面主要采取以外科手术为基础的综合治疗模式。     

The significance of immunochemically staining calcitonin and CEA in fine-needle aspiration biopsy materials from medullary carcinoma of the thyroid

A review of ten surgical cases of medullary carcinoma of the thyroid (MCT) demonstrates the usefulness of establishing a preoperative cytological diagnosis through the immunochemical staining of calcitonin (CT) and CEA in fine-needle aspiration (FNA) biopsy smears. If MCT is suspected after routinely performing May-Grünwald-Giemsa stained cytology of an FNA biopsy in the outpatient clinic, then CT and CEA staining is recommended for confirmation of MCT. The advantages of this immunochemical staining include that it can be carried out in the outpatient clinic within one day and also that it is much less costly than measuring serum CT and CEA.     

Multiple endocrine neoplasia type 2B

We report a case of multiple endocrine neoplasia type 2B (MEN 2B) in a 30-year-old woman. There was no family history of MEN 2B in her family. DNA testing was carried out and a point mutation was found in exon 16, codon 918 (ATG to ACG) in the RET proto-oncogene. The woman died of medullary thyroid carcinoma, 13 years after a total thyroidectomy.     

Familial non-multiple endocrine neoplasia medullary thyroid carcinoma: Report of a case confirming a new clinical entity in Japan

Most hereditary medullary thyroid carcinomas (MTC) occur in association with multiple endocrine neoplasia (MEN) type 2 syndromes. Since Farndon et al. reported two kindreds, that is collections of relatives, with familial non-MEN MTC in 1986, only five kindreds with this disorder have been reported in the English literature. In this paper, we describe a rare Japanese kindred with familial non-MEN MTC, confirming the existence of this distinct clinical entity in Japan. A 42-year-old woman underwent a left hemithyroidectomy with modified neck dissection (MND) under a diagnosis of sporadic MTC at 28 years of age. She developed lymph node metastasis in the right neck region 7 years after the initial surgery, and underwent MND and right hemithyroidectomy. Although no findings of MTC were histologically confirmed in the resected right thyroid lobe, C-cell hyperplasia was observed. Hereditary MTC was strongly suspected, but we could not confirm specific manifestations associated with MEN type 2 in any family members. However, 7 years later, a paternal aunt and cousin were diagnosed with MTC. Other family members were evaluated by ultrasonography and calcium-pentagastrin provocation testing, and three additional patients with MTC across two generations were found. None of these patients had any extrathyroidal manifestations associated with MEN type 2, and the entity of familial non-MEN MTC was confirmed.     

Retrocecal hernia preoperatively diagnosed by computed tomography: A case report

IntroductionRetrocecal hernia is a rare type of pericecal hernia. Because it is difficult to diagnose preoperatively, it is often treated with emergency operation.Case presentationAn 83-year-old male patient experienced sudden abdominal pain. Marked small bowel dilatation and intestinal obstruction were detected by abdominal computed tomography (CT). An enhanced CT scan also revealed a trapped cluster of small bowel loops behind the cecum and ascending colon. We preoperatively diagnosed small bowel ileus as a result of retrocecal hernia. After conservative therapy with a long intestinal tube, an emergency operation was performed. During the surgery, a portion of the ileum was found to be incarcerated in the retrocecal fossa. Intestinal resection was not necessary because the incarcerated ileum appeared viable, and the orifice to the hernia was opened. The patient was discharged without postoperative complications.DiscussionThe diagnosis of retrocecal hernia can often be confirmed intraoperatively. This disease is identified based on a minimal error in rotation with incarceration behind the cecum during the final phase of descent and fixation of the right colon or failure of cecal and retroperitoneal fixation. Early preoperative diagnosis is important to prevent intestinal ischemia, necrosis, and perforation and to reduce resection rates.ConclusionEarly preoperative diagnosis is important to avoid resection of the small intestine. CT scans are useful for preoperative diagnosis in case of retrocecal hernia.     

Multiple endocrine neoplasia

Summary The MEN syndromes continue to be the focus of considerable interest and research. Since successful treatment requires early diagnosis, proper screening and follow-up of patients at risk is important. In the individual at risk for developing MEN IIa, annual screening should include measurement of the basal and stimulated plasma CT levels, and determination of plasma levels of calcium, PTH, and CEA. Twenty-four hour urine excretion rates of norepinephrine, epinephrine, metanephrine, dopamine, and VMA should also be obtained. It is our recommendation that this screening be continued through the third decade of life. Patients having thyroidectomy for MTC need to be tested annually for recurrent MTC and the development of adrenal medullary disease. All patients at risk for developing MEN IIb should be evaluated in a similar fashion. Recently, several groups using DNA linkage analysis have mapped the gene for MEN IIa to chromosome 10, althought the exact location of the gene is yet to be determined.^50,51 Preliminary linkage studies have mapped the gene for MEN I to chromosome 11.⁵² The identification of the genes for MEN I and MEN II will greatly simplify the diagnosis of the disease and perhaps also the therapy of affected patients. This report is the gist of a paper read by S.A. Wells, Jr. at the 87th Annual Meeting of the Japan Surgical Society, Tokyo, Japan, 1989