RESUMEN
Multiple endocrine neoplasia type 1 is a rare genetic neuroendocrine syndrome caused by over 1500 different germline mutations. It can cause 20 different endocrine tumors affecting primarily the parathyroid glands, gastroenteropancreatic tract, and the anterior pituitary gland. Multiple endocrine neoplasia type 2A (MEN2A) and Multiple endocrine neoplasia type 2B (MEN2B) are autosomal dominant genetic syndromes because of a germline variant in the 'rearranged during transfection' (RET) proto-oncogene. There are common RET mutations causing receptor hyperactivation and induction of downstream signals that cause oncogenesis. Common conditions with MEN2A are medullary thyroid cancer (MTC), pheochromocytoma, and primary hyperparathyroidism. Common conditions with MEN2B include MTC, pheochromocytomas, and benign ganglioneuromas.
Asunto(s)
Neoplasia Endocrina Múltiple Tipo 2a , Neoplasia Endocrina Múltiple Tipo 2b , Feocromocitoma , Proto-Oncogenes Mas , Neoplasias de la Tiroides , Humanos , Neoplasia Endocrina Múltiple Tipo 2a/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2a/genética , Neoplasia Endocrina Múltiple Tipo 2a/terapia , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2b/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/terapia , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/terapia , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/terapia , Neoplasia Endocrina Múltiple Tipo 1/genética , Proteínas Proto-Oncogénicas c-ret/genética , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/terapia , Hiperparatiroidismo Primario/diagnóstico , Hiperparatiroidismo Primario/terapia , Atención Primaria de Salud , Mutación de Línea Germinal , Carcinoma NeuroendocrinoRESUMEN
Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant hereditary cancer syndrome which is characterized by the appearance of medullary thyroid carcinoma (MTC), pheochromocytoma, parathyroid adenomas, ganglioneuromas of the digestive tract, and musculoskeletal abnormalities. The case is presented of a 31-year-old male patient with numerous polyps in the colon described as ganglioneuromas which are ectodermal neoplasms emerging from a proliferation of ganglionic cells of the sympathetic nervous system. The results show elevated levels of normetanephrine, which is an endogenous catecholamine metabolite, and has high diagnostic sensitivity as well as specificity in pheochromocytoma detection. The patient underwent partial thyreoidectomy due to a nodular goiter. He was admitted to the Department of Gastroenterology to lead a diagnostic pathway towards MEN 2B.
Asunto(s)
Ganglioneuroma , Neoplasia Endocrina Múltiple Tipo 2b , Humanos , Masculino , Adulto , Neoplasia Endocrina Múltiple Tipo 2b/cirugía , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2b/genética , Neoplasia Endocrina Múltiple Tipo 2b/patología , Ganglioneuroma/cirugía , Ganglioneuroma/patología , Ganglioneuroma/diagnósticoRESUMEN
The age-specific development of the three constituent components of multiple endocrine neoplasia type 2 (MEN 2) is incompletely characterized for many of the >30 causative rearranged during transfection (RET) mutations, which this genetic association study aimed to specify. Included in the study were 683 carriers of heterogeneous RET germline mutations: 53 carriers with 1 highest-risk mutation (codon 918); 240 carriers with 8 different high-risk mutations (codon 634); 176 carriers with 16 different intermediate-risk mutations (codon 609, 611, 618, 620, or 630); and 214 carriers with 6 different low-risk mutations (codon 768, 790, 804, or 891).There was a strong genotype-specific development of MEN 2 constituent components, with distinct age gradients from C cell disease to node negative medullary thyroid cancer (MTC), from node negative to node positive MTC, from node positive MTC to pheochromocytoma, and from pheochromocytoma to primary hyperparathyroidism. Primary hyperparathyroidism was not observed among the 53 MEN 2B patients who carried highest-risk mutations (age range: 0.5-50 years), of whom no more than 12 (23%) and 3 (6%) carriers were older than age 30 years and 35 years, respectively. The age-specific development of MTC differed significantly between the four RET risk categories, whereas the age-specific development of pheochromocytoma differed significantly only between the two strongest RET risk categories. No significant differences were noted in the development of primary hyperparathyroidism. These findings delineate age-specific disease manifestation corridors for the three constituent components of MEN 2 by RET genotype. These corridors are useful for initial risk assessment and organ-specific surveillance of newly identified RET carriers going forward.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Genotipo , Neoplasia Endocrina Múltiple Tipo 2a , Feocromocitoma , Proteínas Proto-Oncogénicas c-ret , Neoplasias de la Tiroides , Humanos , Proteínas Proto-Oncogénicas c-ret/genética , Persona de Mediana Edad , Adulto , Neoplasia Endocrina Múltiple Tipo 2a/genética , Adolescente , Masculino , Femenino , Neoplasias de la Tiroides/genética , Adulto Joven , Feocromocitoma/genética , Niño , Anciano , Preescolar , Neoplasias de las Glándulas Suprarrenales/genética , Lactante , Mutación de Línea Germinal , Carcinoma Neuroendocrino/genética , Heterocigoto , Hiperparatiroidismo Primario/genética , Neoplasia Endocrina Múltiple Tipo 2b/genética , Anciano de 80 o más AñosRESUMEN
PURPOSE: Medullary thyroid carcinoma (MTC) in MEN2B syndrome is associated with germline RET mutation. Patients harboring de novo mutations are usually diagnosed at more advanced disease stages. We present a young woman with Met918Th mutation diagnosed with stage IV MTC at age 10 years. METHODS: The disease progressed despite total thyroidectomy and multiple surgical interventions for cervical lymph node recurrences, leading to distant metastases in the fifth year after the initial diagnosis. Subsequently, she underwent five different types of tyrosine kinase inhibitor (TKI) treatments. The 17-year disease course was divided into periods defined by four surgical interventions and sequential treatment intervals with four multikinase (sunitinib, vandetanib, cabozantinib, and lenvatinib) and one RET-selective TKI (selpercatinib). Tumor growth for different phases of spontaneous development and drug treatment intervals was characterized by changes in serial log-transformed calcitonin measurements (n = 114). RESULTS: Three operations (one for calcitonin-producing adrenal pheochromocytoma) were associated with drops in calcitonin levels. All of the nonselective TKIs were stopped due to adverse effects. As reflected by the negative calcitonin doubling rate, the best treatment response was observed with selpercatinib, which was associated with an initial large drop followed by a decreasing calcitonin trajectory over 514 days without any major side effects. CONCLUSION: This case of MEN2B medullary thyroid cancer with long-term survival presents how the effectiveness of different treatment modalities can be estimated using log-transformed calcitonin levels. Furthermore, our experience supports the view that serial calcitonin measurements may be more sensitive than radiological follow-up in advanced MTC. Our patient also represents a new case of rarely reported calcitonin-producing pheochromocytomas.
Asunto(s)
Calcitonina , Carcinoma Neuroendocrino , Neoplasia Endocrina Múltiple Tipo 2b , Neoplasias de la Tiroides , Humanos , Calcitonina/sangre , Calcitonina/uso terapéutico , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Femenino , Neoplasia Endocrina Múltiple Tipo 2b/genética , Neoplasia Endocrina Múltiple Tipo 2b/sangre , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/sangre , Carcinoma Neuroendocrino/genética , Proteínas Proto-Oncogénicas c-ret/genética , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
Multiple endocrine neoplasia type 2B is a rare autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, pheochromocytoma, Marfan-like fatigue, a peculiar face with thickening of the lips, mucosal neuromas on the lips and tongue, and gastrointestinal phenomena. Most patients harbor pathological variants of the RET gene. Herein, we present the first case of a 14 year-old boy who experienced small intestinal volvulus along with a megacolon, and he was diagnosed with multiple endocrine neoplasia type 2B. The patient complained of constipation since he was 2 years old and slowly progressive abdominal distension at school age. At 14 years of age, he presented with remarkable megacolon mimicking Hirschsprung's disease and complicated with small intestinal volvulus. The volvulus was successfully repaired, and the particularly dilated transverse colon was resected following a rectal biopsy. Histopathological evaluation of the resected transverse colon revealed to be compatible with ganglioneuromatosis. After emergency surgery, the patient was diagnosed with multiple endocrine neoplasia type 2B with medullary thyroid carcinoma, and a de novo variant of RET was confirmed. Gastroenterologists should consider it when treating patients with constipation, especially those with megacolon. Therefore, timely diagnosis may lead to appropriate treatment of medullary thyroid carcinoma and improve mortality.
Asunto(s)
Vólvulo Intestinal , Megacolon , Neoplasia Endocrina Múltiple Tipo 2b , Neoplasias de la Tiroides , Humanos , Neoplasia Endocrina Múltiple Tipo 2b/complicaciones , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2b/patología , Neoplasia Endocrina Múltiple Tipo 2b/cirugía , Masculino , Vólvulo Intestinal/cirugía , Vólvulo Intestinal/complicaciones , Adolescente , Megacolon/complicaciones , Megacolon/cirugía , Megacolon/etiología , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Estreñimiento/etiología , Proteínas Proto-Oncogénicas c-ret/genética , Carcinoma Neuroendocrino/complicaciones , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/patología , Ganglioneuroma/complicaciones , Ganglioneuroma/cirugía , Ganglioneuroma/patología , Ganglioneuroma/diagnóstico , Intestino Delgado/patologíaRESUMEN
PURPOSE: Multiple endocrine neoplasia types 1 (MEN1) and 2 (MEN2) are inherited endocrine tumor syndromes caused by mutations in the MEN1 or RET genes. This study aimed to investigate clinical outcomes and molecular characteristics among children with MEN. METHODS: This study included eight patients from seven unrelated families. Data on clinical course, biochemical findings, and radiologic studies were collected by retrospective chart review. All diagnoses were genetically confirmed by Sanger sequencing of MEN1 in three MEN1 patients and RET in four patients with MEN2A and one patient with MEN2B. RESULTS: Three patients with MEN1 from two families presented with hypoglycemia at a mean age of 11±2.6 years. Four patients with MEN2A were genetically diagnosed at a mean of 3.0±2.2 years of age by family screening; one of them was prenatally diagnosed by chorionic villus sampling. Three patients with MEN2A underwent prophylactic thyroidectomy from 5 to 6 years of age, whereas one patient refused surgery. The patient with MEN2B presented with a tongue neuroma and medullary thyroid carcinoma at 6 years of age. Subsequently, he underwent a subtotal colectomy because of bowel perforation and submucosal ganglioneuromatosis at 18 years of age. CONCLUSION: This study described the relatively long clinical course of pediatric MEN with a mean follow-up duration of 7.5±3.8 years. Insulinoma was the first manifestation in children with MEN1. Early diagnosis by family screening during the asymptomatic period enabled early intervention. The patient with MEN2B exhibited the most aggressive clinical course.
Asunto(s)
Neoplasia Endocrina Múltiple Tipo 1 , Neoplasia Endocrina Múltiple Tipo 2a , Neoplasia Endocrina Múltiple Tipo 2b , Neoplasias de la Tiroides , Masculino , Humanos , Adolescente , Niño , Neoplasia Endocrina Múltiple Tipo 2a/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2a/genética , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2b/genética , Estudios Retrospectivos , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/genética , Neoplasia Endocrina Múltiple Tipo 1/terapia , Progresión de la EnfermedadRESUMEN
INTRODUCTION: Multiple endocrine neoplasia (MEN) syndromes are a group of hereditary cancer syndromes that can predispose children to endocrine neoplasms developing within the head and neck. OBJECTIVE: To examine the neoplastic manifestations of MEN type 1 (MEN1) and MEN type 2 (MEN2) in the pediatric head and neck. METHODS: Single-institution, retrospective review of pediatric MEN between 2005 and 2022. RESULTS: Fifty-three children were genetically confirmed with MEN (15 MEN1, 34 MEN2A, and 4 MEN2B), while three patients received clinical diagnoses of MEN1. The male to female ratio was essentially equal (1.15:1), and a documented family history of cancer was present in 89% (50/56). After multidisciplinary evaluation, a familial MEN diagnosis was confirmed in 91% (51/56). The mean ages of initial presentation and surgical intervention were 8.9 years (SD 5) and 9.8 years (SD 4.8), respectively. Although patients with MEN2 received surgery earlier than patients with MEN1 (8.7 vs 12.7 years), surgical patients with MEN2 in this cohort were older relative to current American Thyroid Association (ATA) guidelines primarily due to late presentation. Thyroid malignancies were identified in 36% (9/25) of thyroidectomy specimens (21 MEN2A, 4 MEN2B), with medullary thyroid carcinoma (MTC) present in five MEN2A patients and three MEN2B patients (89%), and papillary thyroid carcinoma (PTC) present in one MEN2A patient (11%). Nearly 90% (8/9) of thyroid malignancies were occult, with some occurring earlier than predicted by current guidelines (ATA-MOD and ATA-H). Central neck dissections were performed in 24% (2 MEN1, 2 MEN2A, and 4 MEN2B), with two MEN2B (50%) demonstrating cervical lymph node (LN) metastases. Additional histopathologic findings included C-cell hyperplasia in 57% (12/21) of MEN2A thyroidectomy patients. Of the eight MEN1 parathyroidectomy patients, four demonstrated parathyroid hyperplasia and four presented with parathyroid adenoma. CONCLUSION: Nearly 60% required head and neck procedures. While MEN1 guidelines were appropriate for our cohort, we identified patients with MEN2 that developed MTC earlier than expected based on current ATA guidelines, including children in categories considered lower risk. In conjunction with a multidisciplinary approach, pediatric head and neck surgeons should be aware of the potential need for earlier surgical intervention in the pediatric MEN2 population.
Asunto(s)
Neoplasia Endocrina Múltiple Tipo 2a , Neoplasia Endocrina Múltiple Tipo 2b , Neoplasia Endocrina Múltiple , Neoplasias de la Tiroides , Humanos , Niño , Femenino , Masculino , Neoplasia Endocrina Múltiple Tipo 2a/complicaciones , Neoplasia Endocrina Múltiple Tipo 2b/complicaciones , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Hiperplasia , Neoplasia Endocrina Múltiple/complicaciones , Neoplasia Endocrina Múltiple/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/cirugíaRESUMEN
Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize to other tumors. Herein, we report an extremely rare case of tumor-to-tumor metastasis of medullary thyroid carcinoma to a paraganglioma in a patient with multiple endocrine neoplasia type 2B. Based on genetic examination, a 36-year-old woman was diagnosed with multiple endocrine neoplasia type 2B when she was 24 years old. She had a history of total thyroidectomy for medullary thyroid carcinoma and bilateral adrenalectomy for pheochromocytomas, which were performed when she was 15 years and 29 years old, respectively. Follow-up computed tomography demonstrated a retroperitoneal tumor of 30 mm in diameter beside the left kidney and a liver tumor of 16 mm in diameter located in segment 6. The retroperitoneal and liver tumors were surgically resected and examined by a pathologist. Histological examination revealed the classic Zellballen pattern in the retroperitoneal tumor, rendering the diagnosis of a paraganglioma recurrence. Inside the tumor, a white nodule positive for carcinoembryonic antigen, weakly positive for calcitonin, and negative for tyrosine hydroxylase, was identified and diagnosed as a metastatic medullary thyroid carcinoma with high malignant potential. The liver lesion was diagnosed as a metastasis of the medullary thyroid carcinoma. This is the first report of tumor-to-tumor metastasis of medullary thyroid carcinoma to paraganglioma in a patient with multiple endocrine neoplasia type 2B twenty years after total thyroidectomy.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Carcinoma Medular , Neoplasia Endocrina Múltiple Tipo 2b , Paraganglioma , Neoplasias Retroperitoneales , Neoplasias de la Tiroides , Femenino , Humanos , Adulto , Adulto Joven , Adolescente , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2b/genética , Neoplasia Endocrina Múltiple Tipo 2b/patología , Carcinoma Medular/diagnóstico por imagen , Carcinoma Medular/cirugía , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/cirugía , Paraganglioma/diagnóstico por imagen , Paraganglioma/cirugíaRESUMEN
BACKGROUND: Pure mucosal neuroma syndrome (MNS), an autosomal dominant neurocutaneous disorder, is a rare discrete subgroup in multiple endocrine neoplasia (MEN) type 2B, which present without associated endocrinopathies of MEN2B but with typical physical features such as prominent corneal nerves. Case presentation This report describes a 41-year-old patient with complaint of itchy eyes and irritation, presenting with blocked gland orifices in the upper and lower eyelids, light conjunctival hyperemia, a semitransparent neoplasm measuring 2 mm*2 mm on the nasal limbus suggestive of neuromas, and prominent corneal nerves. In vivo confocal microscopy (IVCM) revealed structural alterations-namely a prominent hyperreflective, thickened nerve plexus and a normal endothelium-in both eyes. Testing for SOS1 mutation was positive. This patient may represent a discrete subgroup termed pure mucosal neuroma syndrome (MNS), which presents with the characteristic appearance of MEN2B but without RET gene mutations. CONCLUSION: Prominent corneal nerves have been described in some diseases, such as multiple endocrine neoplasia (MEN) type 1 and type 2A and 2B, congenital ichthyosis, Refsum's disease, leprosy, etc. Ophthalmic assessment including prominent corneal nerves has proven valuable in asymptomatic individuals of MEN2B. Our case illustrates the importance of recognizing the ocular features of MNS, a rare presentation of MEN2B, in order to prevent prophylactic thyroidectomy in these patients for prophylactic thyroidectomy is not mandatory in MNS. However, regular monitoring and genetic counseling are still necessary.
Asunto(s)
Neoplasia Endocrina Múltiple Tipo 2b , Humanos , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2b/genética , Párpados , Cara , Mutación , FenotipoRESUMEN
Objective: To explore the reasonable time of prophylactic thyroidectomy for RET gene carriers in multiple endocrine neoplasia(MEN) 2A/2B families. Methods: From May 2015 to August 2021, RET gene carriers in MEN2A/MEN2B families were dynamically followed up at the Department of Thyroid Head and Neck Surgery, Beijing Tongren Hospital of Capital Medical University. The high-risk patients were encouraged to undergo prophylacitc total thyroidectomy according to the principle of "graded early warning system", namely the evaluation of gene detection, calcitonin value and ultrasound examination successively. Seven cases underwent the surgery, including 3 males and 4 females, aged from 7 to 29 years. According to the risk stratification listed in the guidelines of the American Thyroid Association in 2015, there were 2 cases of the highest risk, 2 cases of the high risk and 3 cases of the modest risk. Calcitonin index remained within the normal range in 3 cases and elevated in 4 cases before operation. All 7 patients underwent thyroidectomy with lymph node dissection of the level â ¥ performed in 4 patients. Results: The time from suggestion to operation was 2 to 37 months, with an average of 15.1 months. The 6 patients were medullary thyroid carcinoma and 1 case with C-cell hyperplasia. The follow-up time was 2 to 82 months, with an average of 38.4 months. Postoperative serum calcitonin levels of all cases decreased to normal level, with biochemical cure. There was no sign of recurrence on ultrasound examination. All 7 patients had no serious complications, no obvious thyroid dysfunction. Their height, weight and other indicators of pediatric patients were similar to those of their peers, with normal growth and development. Conclusion: For healthy people with MEN2A/MEN2B family history, prophylactic thyroidectomy can be carried out selectively based on the comprehensive evaluation of "graded early warning system" with strict screening and close monitoring.
Asunto(s)
Neoplasia Endocrina Múltiple Tipo 2a , Neoplasia Endocrina Múltiple Tipo 2b , Femenino , Masculino , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Neoplasia Endocrina Múltiple Tipo 2b/genética , Neoplasia Endocrina Múltiple Tipo 2b/cirugía , Tiroidectomía , Neoplasia Endocrina Múltiple Tipo 2a/genética , Neoplasia Endocrina Múltiple Tipo 2a/cirugía , Calcitonina , Mutación de Línea Germinal , Proteínas Proto-Oncogénicas c-ret/genéticaRESUMEN
OBJECTIVE: To investigate the impact of musculoskeletal (MSK)-related symptoms on the quality of life of patients with multiple endocrine neoplasia Type 2b (MEN2B). DESIGN: An online survey was distributed by the Association for Multiple Endocrine Neoplasia Disorders (AMEND) to their members and worldwide via a social media group for MEN2B patients. METHODS: The survey consisted of a detailed questionnaire analysing the MSK-related symptoms and structural deformities of MEN2B patients and their impact on patient's lives. PARTICIPANTS: Forty-eight participants completed the survey. RESULTS: Participants reported several musculoskeletal complaints; the most prevalent being musculoskeletal weakness at 73% (n = 35) and pain 58% (n = 28). The median pain score was 7 (interquartile range [IQR]: 5-8) and the frequency of pain was daily in 44% (n = 15) and constant in 21% (n = 7). Structural complaints were common with 63% (n = 30) stating their physique was 'different' and 40% (n = 19) describing marfanoid body features. Spinal curvature and foot deformities were the commonest structural abnormalities with scoliosis 70% (n = 16) and pes cavus 63% (n = 22) prevailing. Dental problems were mentioned by 69% (n = 33) with interdental spacing being the most common complaint at 61% (n = 20). The musculoskeletal symptoms of MEN2B had a median impact of 6 (IQR: 3-9) on quality of life (QOL) with structural deformities 53% (n = 18) and pain 26% (n = 9) listed as having the highest impact. Poor MSK health affected exercise, work and mobility. CONCLUSIONS: We report a high prevalence of musculoskeletal-related complaints in MEN2B which significantly affects QOL. This suggests a need to provide better holistic care including a multidisciplinary team with physiotherapist, orthopaedic and dental specialist input.
Asunto(s)
Neoplasia Endocrina Múltiple Tipo 2b , Humanos , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Calidad de Vida , Dolor , Proteínas Proto-Oncogénicas c-retRESUMEN
Multiple endocrine neoplasia type 2B (MEN 2B) is a rare variant of hereditary tumor syndromes caused by germinal mutations in the proto-oncogene RET. One of the components of the syndrome is multiple neurinomas, the early detection of which is not always given due attention. We present a description of the case of MEN 2B, manifested in the first months of life by intestinal ganglioneuromatosis. The disease presented with chronic constipation, including episodes of intestinal obstruction that required repeated surgical interventions. MEN 2B was suspected at the age of 15. At the time of diagnosis, an increase in serum calcitonin levels was noted (1041 pg/ml, norm <9.5 pg/ml), and a node in the thyroid gland was also determined (1,3*1,0*1,2 see, TIRADS 5), subsequently verified as a neoplasm of C-cells. By DNA analysis, a pathogenic variant p.Met918Thr, typical for MEN2 B, was detected in the RET gene. No signs of pheochromocytoma were found at the time of investigation. The patient underwent a thyroidectomy with lymphadenectomy. The difficulties of early diagnosis of sporadic cases of MEN 2B due to the nonspecificity of gastrointestinal manifestations of the disease are discussed.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Ganglioneuroma , Neoplasia Endocrina Múltiple Tipo 2b , Feocromocitoma , Neoplasias de la Tiroides , Humanos , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2b/genética , Neoplasia Endocrina Múltiple Tipo 2b/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Ganglioneuroma/diagnóstico , Ganglioneuroma/cirugía , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/cirugía , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/cirugíaRESUMEN
CONTEXT: The skeletal phenotype of patients with MEN2B has been described but fracture risk in these patients has not yet been evaluated. OBJECTIVE: This work aims to better delineate fracture risk in patients with multiple endocrine neoplasia type 2B (MEN2B). METHODS: This case series with chart review was conducted at the National Institutes of Health, Pediatric Oncology Branch. A total of 48 patients with MEN2B were identified, with an age range of 5 to 36 years, median of 19; 24 of 48 (50%) patients were female. Medical records, demographic information, available imaging, and laboratory results were reviewed. History up to age 19 was included in the statistical analyses. RESULTS: Of the 48 patients with MEN2B, 20 patients experienced at least one fracture. The majority (n = 18) experienced their first fracture at or before age 19. The observed frequency of fracture occurrence throughout childhood (0-19 years) was 38%, with very little difference between males and females. This frequency is higher than the 9.47 to 36.1 fractures per 1000 persons per year that has been reported in healthy pediatric cohorts in the United States. Less common sites of fracture including vertebral compression fracture and pelvic fractures were observed in patients with MEN2B. CONCLUSION: In this group of patients with MEN2B, there was an increased overall risk of fracture compared to general pediatric cohorts in the United States. Less common sites of fracture were also observed. This suggests a possible effect of an activating RET mutation on bone physiology and warrants further investigation.
Asunto(s)
Fracturas por Compresión , Neoplasia Endocrina Múltiple Tipo 2b , Fracturas de la Columna Vertebral , Masculino , Femenino , Humanos , Neoplasia Endocrina Múltiple Tipo 2b/genética , Proteínas Proto-Oncogénicas c-ret/genética , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/etiología , FenotipoRESUMEN
Amphicrine phenotype in medullary thyroid carcinoma (MTC) is a rare phenomenon characterized by tumor cells that show both endocrine differentiation (calcitonin secretion) and exocrine differentiation (mucin production and secretion). Not much is known about the pathobiology of amphicrine MTCs. This report undertook a case-based review approach by discussing the cytological, histopathological, and ultrastructural features of this rare enigmatic entity, expanding on the radiological and novel MUC immunohistochemistry findings from a 28-year-old MEN2B syndrome patient with C cell hyperplasia and multifocal MTC with amphicrine features. The patient had widespread hematogenous metastases at presentation. MUC immunoexpression analysis revealed evidence of micro-lumina formation, and unique to-date unreported expression patterns of MUC1, MUC5AC, and MUC6 in an amphicrine subtype of MTC. Review of the literature identified five other MTC cases with well-documented amphicrine features. Of these six cases, two were associated with MEN2B syndrome, and four had metastatic disease. Follow-up was available in three patients, and two died of disease. Recognition of this rare subtype of MTC may be of clinical interest given their frequent link to MEN2B syndrome and biological aggressiveness.
Asunto(s)
Carcinoma Neuroendocrino , Neoplasia Endocrina Múltiple Tipo 2b , Neoplasias de la Tiroides , Humanos , InmunohistoquímicaRESUMEN
Not required for Clinical Vignette.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Laparoscopía , Neoplasia Endocrina Múltiple Tipo 2a , Neoplasia Endocrina Múltiple Tipo 2b , Feocromocitoma , Neoplasias de la Tiroides , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía , Humanos , Neoplasia Endocrina Múltiple Tipo 2a/cirugía , Neoplasia Endocrina Múltiple Tipo 2b/cirugía , Feocromocitoma/cirugía , Neoplasias de la Tiroides/cirugía , TiroidectomíaRESUMEN
Multiple endocrine neoplasias are rare hereditary syndromes some of them with malignant potential. Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome due to germline variants in the REarranged during Transfection (RET) proto-oncogene. There are two distinct clinical entities: MEN 2A and MEN 2B. MEN 2A is associated with medullary thyroid carcinoma (MTC), phaeochromocytoma, primary hyperparathyroidism, cutaneous lichen amyloidosis and Hirschprung's disease and MEN 2B with MTC, phaeochromocytoma, ganglioneuromatosis of the aerodigestive tract, musculoskeletal and ophthalmologic abnormalities. Germline RET variants causing MEN 2 result in gain-of-function; since the discovery of the genetic variants a thorough search for genotype-phenotype associations began in order to understand the high variability both between families and within family members. These studies have successfully led to improved risk classification of prognosis in relation to the genotype, thus improving the management of the patients by thorough genetic counseling. The present review summarizes the recent developments in the knowledge of these hereditary syndromes as well as the impact on clinical management, including genetic counseling, of both individual patients and families. It furthermore points to future directions of research for better clarification of timing of treatments of the various manifestations of the syndromes in order to improve survival and morbidity in these patients.
Asunto(s)
Neoplasia Endocrina Múltiple Tipo 2a , Neoplasia Endocrina Múltiple Tipo 2b , Proteínas Proto-Oncogénicas c-ret/genética , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/patología , Neoplasias del Sistema Digestivo/genética , Neoplasias del Sistema Digestivo/patología , Ganglioneuroma/genética , Ganglioneuroma/patología , Asesoramiento Genético , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas , Genotipo , Mutación de Línea Germinal/genética , Humanos , Hiperparatiroidismo/genética , Hiperparatiroidismo/patología , Neoplasia Endocrina Múltiple Tipo 2a/genética , Neoplasia Endocrina Múltiple Tipo 2a/patología , Neoplasia Endocrina Múltiple Tipo 2a/terapia , Neoplasia Endocrina Múltiple Tipo 2b/genética , Neoplasia Endocrina Múltiple Tipo 2b/patología , Neoplasia Endocrina Múltiple Tipo 2b/terapia , Pronóstico , Factores de Riesgo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , TiroidectomíaAsunto(s)
Pólipos del Colon/diagnóstico por imagen , Pólipos del Colon/patología , Neoplasias del Sistema Digestivo/diagnóstico por imagen , Neoplasias del Sistema Digestivo/patología , Ganglioneuroma/diagnóstico por imagen , Ganglioneuroma/patología , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico por imagen , Neoplasia Endocrina Múltiple Tipo 2b/patología , Dolor Abdominal/etiología , Pólipos del Colon/complicaciones , Colonoscopía , Neoplasias del Sistema Digestivo/complicaciones , Femenino , Ganglioneuroma/complicaciones , Humanos , Neoplasia Endocrina Múltiple Tipo 2b/complicaciones , Adulto JovenRESUMEN
BACKGROUND: We describe early and typical nonendocrine symptoms of Multiple Endocrine Neoplasia type 2B (MEN2B) presented in our patients with de novo M918T mutation in the RET proto-oncogene in early childhood, however, the diagnosis of MEN2B and medullary thyroid carcinoma (MTC) was confirmed late, in the second decade of life. In this paper, we emphasize the possibility of growth retardation, growth hormone (GH) deficiency and ovarian teratoma as a new symptom of MEN2B. CASE REPORTS: Advanced MTC with palpable mass on the neck and nonendocrine symptoms such as marfanoid habitus, thickened lips, mucosal neuromas led to the diagnosis in case 1 at the age of 13 years and GH deficiency and nonendocrine symptoms in case 2 at the age of 11 years. The earliest feature of MEN2B was alacrima and constipation. Patient 1 was operated on for a slipped femoral capital epiphysis and for a cystic ovarian teratoma. CONCLUSIONS: Improved awareness of nonendocrine signs of MEN2B could lead to earlier diagnosis, when surgical cure of MTC is possible. Alacrima is the first sign of MEN2B. We confirmed the possibility of growth retardation and GH deficiency in MEN2B, which had been previously rarely described. We suggest that patients with MEN2B may develop cystic ovarian teratoma, to the best of our knowledge, which has never been described so far in the literature. The results of this study could be used to guide further diagnosing of MENB2 at the early stage for better clinical outcome. We emphasize that MEN2B carries a risk for development of cystic ovarian teratoma as a novel tumor in this disease.
Asunto(s)
Neoplasia Endocrina Múltiple Tipo 2b , Teratoma , Neoplasias de la Tiroides , Adolescente , Niño , Hormona del Crecimiento , Humanos , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2b/genética , Neoplasia Endocrina Múltiple Tipo 2b/patología , Proteínas Proto-Oncogénicas c-ret/genética , Teratoma/complicaciones , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/cirugíaRESUMEN
A 12-year-old girl was found to have decending colon diverticulum perforation and retroperitoneal abscess on computed tomography (CT) carried out to determine the cause of fever and stomachache. CT-guided drainage tube placement was performed. She was suspected of having MEN2B from her specific facial appearance, Marfan-like body shape and lingual mucosa neuroma. Cervical ultrasonography and serum tumor marker revealed medullary thyroid carcinoma and metastasis to cervical lymph node. Genetic examination revealed a mutation of RET gene codon 918. Therefore, she was diagnosed as having MEN2B. Laboratory data showed elevated urinary catecholamines. Metaiodobenzylguanidine (MIBG) adrenal scintigraphy showed bilateral adrenal uptake and a definitive diagnosis of bilateral adrenal pheochromocytomas was made. Discharge from the drainage tube persisted and it was difficult to continue conservative treatment. Therefore, laparoscopic bilateral adrenalectomy and transverse colon colostomy were performed. Subsequently, total thyroidectomy and cervical lymph node dissection were performed. At five years of follow up, bilateral lung metastases were observed, but the serum calcitonin level was normal and the patient is under observation.