Molecular diagnosis and treatment of multiple endocrine neoplasia type 2B in Ethnic Han Chinese

2020 ◽  
Vol 20 ◽  
Author(s):  
Zhe-Wei Zhang ◽  
Xiao Guo ◽  
Xiao-Ping Qi
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Histopathological Examination ◽  
Diagnosis And Treatment ◽  
De Novo Mutation ◽  
Neck Lymph Node ◽  
Serum Calcitonin ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2B

Background: Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and non-endocrine features. However, the diagnosis and treatment are usually delayed. Materials & Methods: This study reports 5 Chinese pedigrees with 5 individuals harboring germline RET-M918T, and systematically reviewed previous Chinese literatures. Results: All 5 patients initially presented MTC, but none had biochemically cured postoperatively. 2 also presented bilateral PHEO after adrenal-sparing surgery, 1 needed steroid replacement. Further, totally 32 MEN 2B patients from literatures were clustered with 28 available for analysis. 26 (92.8%) were diagnosed by endocrine-related symptoms; the remaining 2 (7.2%) due to RET testing and oral symptoms respectively. 25 patients underwent thyroidectomy with/without neck lymph node dissection at mean age of (23.3 ± 10.4) years. Histopathological examination revealed MTC (100%). Of them, 17 had definite TNM stage, with 1 in stage Ⅲ and others in Ⅳ. Other information of MEN 2B-related symptoms included penetrance of PHEO (60.7%), constipation (32.1%), Hirschsprung disease (25%), alacrima (17.8%), mucosal ganglioneuroma (96.4%) and marfanoid habitus (71.4%). 19 patients were verified harboring RET-M918T (c.2753T>C), of whom 15 (78.9%) were de novo mutation. The other 9 were clinically diagnosed as MEN 2B. Discussion & Conclusion : The initial diagnosis of MEN 2B is relatively later, and diagnosed by non-endocrine components is extremely lower. Recognition of MEN 2B and its non-endocrine-related components is still the utmost requirement for a Chinese physician. Combined RET screening and serum calcitonin detection can facilitate early diagnosis.

scholarly journals Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634)

2014 ◽  
Vol 142 (1-2) ◽  
pp. 72-74 ◽  
Author(s):  
Maja Jesic ◽  
Milina Tancic-Gajic ◽  
Milos Jesic ◽  
Vladan Zivaljevic ◽  
Silvija Sajic ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Prophylactic Thyroidectomy ◽  
Urinary Catecholamines ◽  
Serum Calcitonin ◽  
Long Term Outcome ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2A

Introduction. The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. Case Outline. This is a case report of 3-year-old boy from the MEN 2A family (the boy?s father and grandmother and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is <2 pg/ml (normal <13 pg/ml), has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Conclusion. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

scholarly journals Isolated intestinal ganglioneuromatosis - A rare entity

2017 ◽  
Vol 5 (4) ◽  
pp. 131-135 ◽  
Author(s):  
Uttam Laudari ◽  
Shail Rupakheti ◽  
Tanka Prasad Bohara ◽  
Mukunda Raj Joshi ◽  
Mamta Lakhey
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Histopathological Examination ◽  
Neurofibromatosis Type ◽  
Type I ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Benign Tumours ◽  
Rare Benign Tumour ◽  
Intestinal Ganglioneuromatosis

Intestinal ganglioneuromatosis are rare benign tumour of ganglionic cell origin, most of them associated with neurofi bromatosis type I and multiple endocrine neoplasia type IIB. They are benign tumours with rare malignant transformation, have a varied clinical presentation and long indolent course. Surgical resection is the only modality of treatment and diagnosis is based on histopathological examination and immunohistochemistry. We report a case, 55 year old male who was diagnosed as a case of isolated intestinal ganglioneuromatosis, i.e no association with neurofibromatosis type I and multiple endocrine neoplasia type IIB. He is on regular follow up with normal daily activities and no evidence of recurrence.Journal of Kathmandu Medical College, Vol. 5, No. 4, Issue 18, Oct.-Dec., 2016, Page: 131-135

Multiple Endocrine Neoplasia Type 2b Associated Mixed Medullary and Follicular Thyroid Carcinoma in A Chinese Patient with RET M918T Germline Mutation

2020 ◽  
Vol 20 ◽  
Author(s):  
Xiao-Ping Qi ◽  
Guo-Bing Lin ◽  
Bo Chen ◽  
Feng Li ◽  
Zhi-Lie Cao ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Follicular Thyroid Carcinoma ◽  
Histopathological Examination ◽  
Follicular Carcinoma ◽  
Chinese Patient ◽  
Biological Behavior ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

Background: Mixed medullary and follicular thyroid carcinoma (MMFC) displays heterogeneous morphological components and immunophenotypical features intermingled within the same lesion, which is rare and most described in the sporadic form. We report herein a Chinese patient with multiple endocrine neoplasia type 2B (MEN2B) harboring germline RET M918T and associated MMFC. Method: A case of a 39-year-old male patient with MEN2B presented palpable neck masses in both thyroid lobes (maximum sizes: left, 3.9 cm; right, 5.4 cm) and a definitive phenotype. Serum levels of calcitonin (Ctn; 719.27ng/mL), carcinoembryonic antigen (CEA; > 2000pg/ml), and thyroglobulin (Tg; 98.54ng/mL) were high. Fine-needle aspiration cytology showed features positive for malignancy, suggesting the possibility of medullary thyroid carcinoma (MTC). Total thyroidectomy along with extending bilateral neck lymph nodes dissection, and subsequently, genetics family screening were performed. Results: The histopathological examination yielded a diagnosis of MMFC that showed immunohistochemical characteristic patterns of the component of MTC positive for Ctn and CEA, chromogranin A, and the follicular carcinoma components were positive for Tg. Lymph node metastasis was observed showing medullary tumoral cells positive for Ctn and follicular-like structures lacking tumor cells positive for Tg staining (T4bN1bM0). Genetics screening confirmed RET M918T (c.2753T>C) mutation manifested in the patient, but was not detected in other family members. Follow up showed that the serum Ctn, CEA and Tg levels respectively dropped to 54.38pg/ml, 4.16ng/mL and 0.04ng/mL 16 months after the surgery. Conclusion: Particular and diverse patterns of MMFC should be recognized with immunostaining features. MMFC occurring in a patient with MEN2B harboring RET M918T may be unique biological behavior and the treatment is mostly radical surgery.

scholarly journals Surgical treatment of a patient with multiple endocrine neoplasia type 2A

2020 ◽  
Vol 179 (4) ◽  
pp. 79-86
Author(s):  
T. A. Britvin ◽  
E. V. Bondarenko ◽  
A. V. Krivosheev ◽  
O. A. Nechaeva ◽  
T. S. Tamazyan ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Clinical Laboratory ◽  
Histopathological Examination ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Comprehensive Examination ◽  
Abdominal Ct Scan ◽  
High Level

The diagnosis and treatment of multiple endocrine neoplasia type 2A syndrome or Sipple’s syndrome, as well as other endocrine hereditary syndromes, presents certain difficulties for several reasons. One of them is the rarity of this pathology and, as a result, the lack of awareness of physicians. In addition, the diagnosis requires a comprehensive examination and a high level of clinical, laboratory, radiation and morphological diagnostics. And finally, surgical treatment, which is essentially the only method, involves an individual approach to each patient. We present the clinical case of Sipple's syndrome in a 39-year-old man. The diagnosis was carried out of medical history, clinical examination, laboratory tests (24-hour urine excretion of metanephrines and normetanephrines; serum calcium, calcitonin and parathyroid hormone levels), neck ultrasound and abdominal CT scan and was confirmed by histopathological examination and genetic testing for RET mutation. The achievement of the endpoint in the form of normalization of blood pressure and the absence of adrenal insufficiency was due to radical surgical treatment.

scholarly journals Solitary mucosal neuroma in the maxillary incisor gingival papilla without multiple endocrine neoplasia type 2B (MEN 2B): a case report and literature review

2020 ◽  
Author(s):  
Che Qiu ◽  
Lizhen Wang ◽  
Huiwen Chen ◽  
Zhongchen Song
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Maxillary Incisor ◽  
Positive Staining ◽  
Anterior Teeth ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Complete Surgical Excision ◽  
Men 2B

Abstract Background Mucosal neuroma (MN) is a benign neural tumor of peripheral nerves histologically characterized by irregular tortuous bundles of nerve cells with prominent perineurium that lie scattered throughout the submucosa. The tumor is usually associated with the multiple endocrine neoplasia type 2B (MEN 2B) but rarely occurs without the other components of MEN 2B. We present a case of solitary MN without MEN 2B that occurs in the maxillary incisor gingival papilla that has not been reported yet and review the literature. Case presentation: A 29-year-old woman presented to our outpatient department with an upper anterior teeth gingiva painless mass for 2-year. Intraoral examination revealed a small, tough, basal wide, well-defined mass in the labial gingival papilla between maxillary central incisor. Excisional biopsy showed that it was characterized by nerve bundles in various sizes surrounded by normal connective tissue in the submucosa under HE staining; Immunohistochemically, the mass showed strongly positive staining of S-100 protein, NSE,NF and weakly positive of EMA. The Laboratory examination and ultrasonography showed no signs of MEN 2B. In the first 6 months of follow-up, there was no evidence of recurrence and other components of MEN 2B. The patient was asymptomatic and she is still being followed up every 6 months. Based on these features, the lesion was finally diagnosed as a solitary gingival MN. Conclusions This study showed a rare solitary MN in the gingiva papilla without MEN 2B that has not been reported yet. The histopathological evaluation can be helpful in the differential diagnosis of MN. It is hoped that a greater understanding of solitary MN without MEN 2B in the oral cavity will avoid potential misdiagnosis, and contribute to determining the correct management, which appears to be complete surgical excision with close follow-up for recurrence and other components of MEN 2B surveillance.

Impact of RET Screening on the Management of Multiple Endocrine Neoplasia Type 2A: 10 Years Experience and Follow-up in Three Families

2021 ◽  
Vol 21 ◽  
Author(s):  
Yue-Ping Wang ◽  
Fei-Ping Li ◽  
Hui-Hong Wang ◽  
Xu-Dong Fang ◽  
Zai-Sheng Zhu ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Term Outcome ◽  
Serum Calcitonin ◽  
Long Term Outcome ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Younger Age

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is mainly caused by germline RET codon C634 mutation and is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), and hyperparathyroidism (HPTH). The early diagnosis and initial normative treatment are helpful for the long-term outcome of MEN2A. Methods: Three index cases and their 29 relatives from three families with MEN2A were included in this study. Genetic screening was performed on all participants. Demographic, clinical profiles, tumor histopathologic features, and follow-up records were systematically analyzed. Results: In total, RET C634Y mutation was identified in 10 individuals (10/32, 31.3%). Among them, 5 presented with MTC symptoms, whereas the other 5 did not show apparent clinical manifestation, and all were subjected to thyroidectomy with varying neck dissection. Compared to individuals in the former, the latter benefited greatly from RET screening with significantly younger age at diagnosis of MTC and surgery (18.1 ± 13.8 years vs. 39.0 ± 14.1 years, P =0.045), and less-aggressive MTC behavior (size: 0.74 vs. 2.82 cm, P =0.026; LN+/resected: 20.0% vs. 100.0%, P =0.048) and also lower recurrence rate of MTC (20.0% vs. 100.0%, P =0.048). The PHEO was identified in 6 of the 10 carriers (60.0%), and all had undergone adrenal-sparing surgery. During the 10 years of follow-up, one (16.7%) developed recurrence of PHEO. Conclusion: Integrated RET screening, serum calcitonin, and plasma metanephrine/normetanephrine levels can facilitate the early diagnosis and standardized MTC/PHEO surgery to improve the prognosis of MEN2A. Laparoscopic adrenal-sparing surgery prior to the bilateral total thyroidectomy is a preferred surgical approach for PHEO.

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