RET基因C634Y突变致多发性内分泌腺瘤病2A型一例报道并文献复习

doi:10.12114/j.issn.1007-9572.2022.0464

中国全科医学 ›› 2023, Vol. 26 ›› Issue (14): 1794-1798.DOI: 10.12114/j.issn.1007-9572.2022.0464

• 典型病例 • 上一篇

RET基因C634Y突变致多发性内分泌腺瘤病2A型一例报道并文献复习

邓煜璇¹, 何立², 宋志旺³, 江妍霞¹^,^*()

1．330006　江西省南昌市，南昌大学第一附属医院内分泌科
2．333000　江西省景德镇市第一人民医院病理科
3．330006　江西省南昌市，南昌大学第一附属医院肿瘤科

收稿日期:2022-06-20 修回日期:2022-07-22 出版日期:2023-05-15 发布日期:2022-08-11
通讯作者: 江妍霞
作者贡献：邓煜璇负责资料收集与整理、论文构思和撰写；何立负责病例采集和论文修订；宋志旺负责肿瘤诊断和免疫组化；江妍霞负责论文指导和审校，对论文整体负责。
基金资助:
国家自然科学基金资助项目(82060043); 江西省青年科学基金资助项目(20192BAB215017); 江西省卫生健康委科技计划(20203118)

RET Proto-oncogene C634Y Mutation-associated Multiple Endocrine Adenomatosis Type 2A: a Case Report and Literature Review

DENG Yuxuan¹, HE Li², SONG Zhiwang³, JIANG Yanxia¹^,^*()

1. Department of Endocrinology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China
2. Department of Pathology, Jingdezhen First People's Hospitial, Jingdezhen 333000, China
3. Department of Oncology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China

Received:2022-06-20 Revised:2022-07-22 Published:2023-05-15 Online:2022-08-11
Contact: JIANG Yanxia

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摘要/Abstract

摘要： 多发性内分泌腺瘤病2A型（MEN2A）是多发性内分泌腺瘤病2型（MEN2）的一种，临床通常表现为甲状腺髓样癌（MTC）、嗜铬细胞瘤（PHEO）及甲状旁腺功能亢进。研究表明MEN2A由10号染色体RET基因突变导致。本文报道了一例由RET基因C634Y突变导致的MEN2A患者，并对其家族成员进行了基因检测，绘制系谱图。基因检测结果显示患者同胞及同胞的子女存在C634Y突变。通过本病例诊疗结合文献复习，提示临床当患者出现内分泌腺体肿瘤时，需引起警惕，应对患者其他内分泌腺体进行进一步检查，并进行RET基因检测，以防出现误诊、漏诊，实现早期治疗，提高治疗效果，改善患者预后。MEN2A患者亲属也应进行RET基因检测。

关键词: 多发性内分泌腺瘤病2A型, RET基因, 嗜铬细胞瘤, 甲状腺髓样癌

Abstract:

Multiple endocrine adenomatosis type 2A (MEN2A) is a subtype of multiple endocrine adenomatosis type 2, which is clinically characterized by medulloid thyroid carcinoma (MTC) , pheochromocytoma (PHEO) , and hyperparathyroidism, and has been reported to be caused by mutations in the RET proto-oncogene on chromosome 10. We reported a case of MEN2A caused by RET proto-oncogene C634Y mutation, and conducted a pedigree analysis of the patient. Genetic test results showed C634Y mutation in the patient's siblings and their offspring. The diagnosis and treatment of this case in combination with a review of the relevant literature suggest that endocrine gland tests and RET proto-oncogene test should be performed for a patient diagnosed with endocrine adenomatosis to reduce the possibility of misdiagnosis and missed diagnosis, and to achieve early treatment, improve the effect of treatment and the prognosis of patients. In addition, the first- and second-degree relatives of the patient should also be tested for the mutation of the RET proto-oncogene.

Key words: Multiple endocrine neoplasia type 2A, RET gene, Pheochromocytoma, Medullothyoid carcinoma

邓煜璇,何立,宋志旺,等. RET基因C634Y突变致多发性内分泌腺瘤病2A型一例报道并文献复习[J]. 中国全科医学, 2023, 26(14): 1794-1798. DOI: 10.12114/j.issn.1007-9572.2022.0464.
DENG Yuxuan,HE Li,SONG Zhiwang, et al. RET Proto-oncogene C634Y Mutation-associated Multiple Endocrine Adenomatosis Type 2A: a Case Report and Literature Review[J]. Chinese General Practice, 2023, 26(14): 1794-1798. DOI: 10.12114/j.issn.1007-9572.2022.0464.

图/表 4

图1 患者腹部CT检查结果注：A为全腹部CT冠状位，B为全腹部CT横断位，CT结果示右肾上腺区可见软组织密度影，大小5.8 cm×5.2 cm，左侧肾上腺见两个结节影，较大者1.4 cm×12 cm

Figure 1 Abdominal CT findings in the patient

图2 MEN2A甲状腺髓样癌病理表现及免疫组化注：A、B为HE染色（100×），甲状腺穿刺病理（左颈侧区淋巴结及甲状腺左叶穿刺活检）示间质中见小细胞呈巢状或弥漫增生，细胞体积小，胞质中等，嗜碱性，核小深染，核仁不明显，核分裂少见，意义不明的非典型增生；C为Syn（100×），D为CgA（100×），甲状腺免疫组化示增生细胞Calcitonin（+）、Syn（3+）、CD56（+）、CgA（3+）、CEA（3+）、CK（-）、TG（-）、PTH（-）、Ki67（1%+）、NSE（2+）、CT（-）、MC（-）、Vimentin（-），结合术后病理，符合甲状腺髓样癌

Figure 2 Pathological features and immunohistochemical staining of medullary thyroid carcinoma in this case of MEN2A

图3 肾脏嗜铬细胞瘤病理结果注：右侧肾上腺肿瘤术后病理：病变呈结节状，被覆纤维包膜，结节内见肿瘤细胞呈不规则腺样或器官样排列，细胞中等大小，胞浆丰富，嗜酸性，核圆形，核仁可见。诊断为（右侧肾上腺）嗜铬细胞瘤，目前无包膜侵犯

Figure 3 Pathological results of a pheochromocytoma in the right adrenal gland in this case of MEN2A

图4 MEN2A患者家系图

Figure 4 Family pedigree chart of this case of MEN2A

参考文献 27

[1]	REDAELLI S，PLAZA-MENACHO I，MOLOGNI L. Novel targeted therapeutics for MEN2[J]. Endocr Relat Cancer，2018，25（2）：T53-68. DOI：10.1530/ERC-17-0297.
[2]	GUERIN C，ROMANET P，TAIEB D，et al. Looking beyond the thyroid：advances in the understanding of pheochromocytoma and hyperparathyroidism phenotypes in MEN2 and of non-MEN2 familial forms[J]. Endocr Relat Cancer，2018，25（2）：T15-28. DOI：10.1530/ERC-17-0266.
[3]	MCDONNELL J E，GILD M L，CLIFTON-BLIGH R J，et al. Multiple endocrine neoplasia：an update[J]. Intern Med J，2019，49（8）：954-961. DOI：10.1111/imj.14394.
[4]	刘桂，张祖杰，魏世超，等. 一MEN2A家系的遗传学分析及ATA 2015年MTC管理指南基因检测解读[J]. 中华临床医师杂志：电子版，2016，10（21）：3155-3159. DOI：10.3877/cma.j.issn.1674-0785.2016.21.003.
[5]	WELLS S A Jr，ASA S L，DRALLE H，et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma[J]. Thyroid，2015，25（6）：567-610. DOI：10.1089/thy.2014.0335.
[6]	WANG Y P，LI F P，WANG H H，et al. Impact of RET screening on the management of multiple endocrine neoplasia type 2A：10 years experience and follow-up in three families[J]. Endocr Metab Immune Disord Drug Targets，2022，22（3）：339-347. DOI：10.2174/2214083203666210826094602.
[7]	BREZA J Jr，SR J B. Multiple endocrine neoplasia 2A（MEN 2A） syndrome[J]. Bratisl Lek Listy，2018，119（2）：120-125. DOI：10.4149/BLL_2018_034.
[8]	SARAVANA-BAWAN B，PASTERNAK J D. Multiple endocrine neoplasia 2：an overview[J]. Ther Adv Chronic Dis，2022. DOI：10.1177/20406223221079246.
[9]	KIERNAN C M，GRUBBS E G. Surgical management of multiple endocrine neoplasia 1 and multiple endocrine neoplasia 2[J]. Surg Clin North Am，2019，99（4）：693-709. DOI：10.1016/j.suc.2019.04.015.
[10]	郭敏，薛铮，药红梅，等. 误诊为心肌炎的多发性内分泌腺瘤2型一例[J]. 中华心血管病杂志，2021（2）：182-184.
[11]	METE O，ESSA A，BRAMDEV A，et al. MEN2 syndrome-related medullary thyroid carcinoma with focal tyrosine hydroxylase expression：does it represent a hybrid cellular phenotype or functional state of tumor cells? [J]. Endocr Pathol，2017，28（4）：362-366. DOI：10.1007/s12022-017-9485-4.
[12]	QI X P，ZHAO J Q，FANG X D，et al. Spectrum of germline RET variants identified by targeted sequencing and associated multiple endocrine neoplasia type 2 susceptibility in China[J]. BMC Cancer，2021，21（1）：369. DOI：10.1186/s12885-021-08116-9.
[13]	LEE J Y，KIM S Y，JO K H，et al. Clinical features and signaling effects of RET D631Y variant multiple endocrine neoplasia type 2（MEN2）[J]. Korean J Intern Med，2022，37（2）：398-410. DOI：10.3904/kjim.2021.311.
[14]	FEBRERO B，RODRÍGUEZ J M，RÍOS A，et al. Prophylactic thyroidectomy in multiple endocrine neoplasia 2（MEN2） patients with the C634Y mutation：a long-term follow-up in a large single-center cohort[J]. Eur J Surg Oncol，2019，45（4）：625-630. DOI：10.1016/j.ejso.2018.09.002.
[15]	OSPINA N S，MARAKA S，DONEGAN D，et al. Clinical features of a family with multiple endocrine neoplasia type 2A caused by the D631Y RET mutation[J]. Thyroid，2017，27（10）：1332-1334. DOI：10.1089/thy.2016.0536.
[16]	SIQUEIRA D R，CEOLIN L，FERREIRA C V，et al. Role of RET genetic variants in MEN2-associated pheochromocytoma[J]. Eur J Endocrinol，2014，170（6）：821-828. DOI：10.1530/EJE-14-0084.
[17]	WEBER T，POPLAWSKI A，VORLÄNDER C，et al. Preoperative calcitonin testing improves the diagnosis of medullary thyroid carcinoma in female and male patients[J]. Eur J Endocrinol，2022，186（2）：223-231. DOI：10.1530/EJE-21-1015.
[18]	LI Y，TAN Y Q，TANG Z X，et al. Multiple endocrine neoplasia 2A with RET mutation p.Cys611Tyr：a case report[J]. Medicine（Baltimore），2021，100（22）：e26230. DOI：10.1097/MD.0000000000026230.
[19]	ILANCHEZHIAN M，KHAN S，OKAFOR C，et al. Update on the treatment of medullary thyroid carcinoma in patients with multiple endocrine neoplasia type 2[J]. Horm Metab，2020，52（8）：588-597. DOI：10.1055/a-1145-8479.
[20]	MUCHA L，LEIDIG-BRUCKNER G，FRANK-RAUE K，et al. Phaeochromocytoma in multiple endocrine neoplasia type 2：RET Codon-specific penetrance and changes in management during the last four decades[J]. Clin Endocrinol（Oxf），2017，87（4）：320-326. DOI：10.1111/cen.13386.
[21]	OHSUGI H，TAKIZAWA N，KINOSHITA H，et al. Pheochromocytoma arising from an ectopic adrenal tissue in multiple endocrine neoplasia type 2A[J]. Endocrinol Diabetes Metab Case Rep，2019，2019：EDM190073. DOI：10.1530/EDM-19-0073.
[22]	PAL R，RASTOGI A，KUMAR S，et al. Metastatic pheochromocytoma in MEN 2A：a rare association[J]. BMJ Case Rep，2018，2018：bcr-2017-222758. DOI：10.1136/bcr-2017-222758.
[23]	IGLESIAS P，SANTACRUZ E，GARCÍA-SANCHO P，et al. Pheochromocytoma：a three-decade clinical experience in a multicenter study[J]. Rev Clin Esp（Barc），2021，221（1）：18-25. DOI：10.1016/j.rceng.2019.12.011.
[24]	MIYATA Y，HATANO K，OKUNO Y，et al. Laparoscopic resection of aortocaval paraganglioma diagnosed by serial increase in urinary metanephrines after bilateral adrenalectomy in a patient with multiple endocrine neoplasia type 2A[J]. IJU Case Rep，2021，4（6）：347-350. DOI：10.1002/iju5.12345.
[25]	KUMAR S，LILA A R，MEMON S S，et al. Metastatic cluster 2-related pheochromocytoma/paraganglioma：a single-center experience and systematic review[J]. Endocr Connect，2021，10（11）：1463-1476. DOI：10.1530/EC-21-0455.
[26]	HU X F，GUAN J，WANG Y D，et al. A narrative review of multiple endocrine neoplasia syndromes：genetics，clinical features，imaging findings，and diagnosis[J]. Ann Transl Med，2021，9（11）：944. DOI：10.21037/atm-21-1165.
[27]	ROMEI C，CIAMPI R，ELISEI R. A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma[J]. Nat Rev Endocrinol，2016，12（4）：192-202. DOI：10.1038/nrendo.2016.11.

RET基因C634Y突变致多发性内分泌腺瘤病2A型一例报道并文献复习

RET Proto-oncogene C634Y Mutation-associated Multiple Endocrine Adenomatosis Type 2A: a Case Report and Literature Review

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