Chirurgische Aspekte der Multiplen Endokrinen Neoplasie Typ 2

Zusammenfassung. Die multiple Endokrine Neoplasie Typ 2 (MEN 2) ist ein autosomal-dominant vererbbares Tumorsyndrom. In den Subtypen sind verschiedene Erkrankungsmanifestationen spezifisch. Bei der MEN 2a treten medulläres Schilddrüsenkarzinom, Phäochromozytom und primärer Hyperparathyreoidismus, beim familiären medullären Schilddrüsenkarzinom-Syndrom (FMTC) nur das medulläre Schilddrüsenkarzinom und bei der MEN 2b das medulläre Schilddrüsenkarzinom und Phäochromozytom klinisch in den Vordergrund. Alle relevanten Erkrankungen der MEN 2 werden primär chirurgisch therapiert. Da die zeitgerechte chirurgische Therapie die Chance bietet, einer malignen Entartung zuvorzukommen (prophylaktische Operation) oder eine Heilung zu ermöglichen ist es bedeutsam, die MEN 2 im Einzelfall zu diagnostizieren und damit blutsverwandte Betroffene MEN-2-Genträger identifizieren zu können. Typische MEN-2-Manifestationen und klinische Zeichen, die chirurgisch relevant sind, werden aufgezeigt. Bei V.a. auf eine zugrundeliegende MEN 2 ist es obligat, ein zugrundeliegendes Phäochromozytom auszuschliessen, um nicht unvorbereitet eine hyperadrenerge Krise bei diagnostischen oder therapeutischen Massnahmen auszulösen, die lebensbedrohlich sein kann.

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

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.

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

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.

SUN-921 Indolent Presentation of Medullary Thyroid Cancer in a Patient with MEN Type 2B Due to a Germline RET M918T Mutationo

Background: MEN type 2B is rare and most commonly due to a germline methionine-to-threonine substitution at codon 918 (M918T) of the RET proto-oncogene. Medullary thyroid cancer (MTC) occurs in 100% of the patients affected with the mutation. This mutation is considered the highest risk and is typically associated with aggressive disease and worse overall survival. We describe a case of a late diagnosis of MEN 2B in a patient and his son, both with a relatively indolent presentation of MTC. Clinical Case: A 39-year-old man presented to an outside institution with difficult to control hypertension, headaches and anxiety and was found to have bilateral pheochromocytomas (left, 5.8 x 5.5 x 3.8 cm and right, 9 x 5.2 x 7.3 cm). Upon presentation to our institution, he was noted to have classic phenotypic features of MEN 2B with a marfanoid habitus and multiple mucosal neuromas. Genetic testing confirmed RET M918T mutation. His family history was negative for similar features in his parents and siblings. However, one of his three children, age 12, had similar phenotypic features and was found to have the same mutation. The patient subsequently underwent a successful bilateral adrenalectomy and pathology confirmed pheochromocytomas. Thyroid ultrasound showed multiple nodules with calcifications but no lateral nodal metastases. Calcitonin and carcinoembryonic antigen (CEA) levels were elevated (170 pg/mL, normal ≤10, and 180.4 ug/L, normal <3.8, respectively). He underwent a total thyroidectomy and bilateral central node dissection, with pathology confirming bilateral MTC (2.7 cm and 1.0 cm), metastatic in 4 of 10 positive lymph nodes (largest focus 2 mm). Whole body PET/CT post-operatively did not show metastatic disease. The patient’s son also had multiple thyroid nodules on ultrasound without lateral nodal metastases and elevated calcitonin and CEA levels (3015 pg/ml, normal ≤10, and 433 ng/mL, normal <2.5, respectively). MRI of the abdomen and pelvis was negative for pheochromocytomas. He underwent total thyroidectomy and bilateral central neck dissection, with pathology showing bilateral MTC (2.7 cm and 1.0 cm) with 0 of 14 positive lymph nodes. For both the patient and his son, calcitonin and CEA levels normalized following thyroidectomy and surveillance over a year later reveals no evidence of disease. Conclusion: Early diagnosis of MEN type 2B is important as MTC develops early in life and is the leading cause of death in these patients. When diagnosed early, prophylactic thyroidectomy in childhood is indicated and can improve long-term survival. There are salient phenotypic features associated with this disease which were unfortunately not recognized early in this patient and his son. Fortunately, their MTC presentations appear to be relatively indolent despite their late diagnoses, and they will continue to be closely monitored for recurrent disease.

Síndromes de neoplasia endocrina múltiple: revisión radiológica

ResumenLos síndromes de neoplasia endocrina múltiple (MEN), incluyen una serie de enfermedades con alteraciones genéticas que se caracterizan por la presencia de tumores que afectan a dos o más glándulas endocrinas. Son síndromes con una herencia autosómica dominante e incluyen tres patrones: MEN 1 (síndrome de Wermer), MEN 2 (que incluye MEN 2A o síndrome de Sipple y MEN 2B o síndrome de Wagenmann-Froboese) y MEN 4. Los adenomas paratiroideos y el carcinoma medular tiroideo, son los tumores más frecuentes del MEN tipo 1 y 2 respectivamente. Esos síndromes son más comunes en pacientes jóvenes, con patología de afectación bilateral, múltiple o multifocal y, sobre todo, en pacientes con antecedentes familiares. Es necesario el trabajo en equipo de endocrinólogos, cirujanos, oncólogos y radiólogos para optimizar el tratamiento de esos pacientes.