RESUMO
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.
Assuntos
Ganglioneuroma , Neoplasia Endócrina Múltipla Tipo 2b , Humanos , Masculino , Adulto , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Neoplasia Endócrina Múltipla Tipo 2b/diagnóstico , Neoplasia Endócrina Múltipla Tipo 2b/genética , Neoplasia Endócrina Múltipla Tipo 2b/patologia , Ganglioneuroma/cirurgia , Ganglioneuroma/patologia , Ganglioneuroma/diagnósticoRESUMO
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.
Assuntos
Volvo Intestinal , Megacolo , Neoplasia Endócrina Múltipla Tipo 2b , Neoplasias da Glândula Tireoide , Humanos , Neoplasia Endócrina Múltipla Tipo 2b/complicações , Neoplasia Endócrina Múltipla Tipo 2b/diagnóstico , Neoplasia Endócrina Múltipla Tipo 2b/patologia , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Masculino , Volvo Intestinal/cirurgia , Volvo Intestinal/complicações , Adolescente , Megacolo/complicações , Megacolo/cirurgia , Megacolo/etiologia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Constipação Intestinal/etiologia , Proteínas Proto-Oncogênicas c-ret/genética , Carcinoma Neuroendócrino/complicações , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/patologia , Ganglioneuroma/complicações , Ganglioneuroma/cirurgia , Ganglioneuroma/patologia , Ganglioneuroma/diagnóstico , Intestino Delgado/patologiaRESUMO
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.
Assuntos
Neoplasia Endócrina Múltipla Tipo 2a , Neoplasia Endócrina Múltipla Tipo 2b , Feminino , Masculino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Neoplasia Endócrina Múltipla Tipo 2b/genética , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Tireoidectomia , Neoplasia Endócrina Múltipla Tipo 2a/genética , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Calcitonina , Mutação em Linhagem Germinativa , Proteínas Proto-Oncogênicas c-ret/genéticaRESUMO
Not required for Clinical Vignette.
Assuntos
Neoplasias das Glândulas Suprarrenais , Laparoscopia , Neoplasia Endócrina Múltipla Tipo 2a , Neoplasia Endócrina Múltipla Tipo 2b , Feocromocitoma , Neoplasias da Glândula Tireoide , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Humanos , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Feocromocitoma/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
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.
Assuntos
Neoplasias das Glândulas Suprarrenais , Divertículo do Colo , Neoplasia Endócrina Múltipla Tipo 2b , Feocromocitoma , Neoplasias da Glândula Tireoide , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Criança , Feminino , Humanos , Neoplasia Endócrina Múltipla Tipo 2b/diagnóstico por imagem , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
BACKGROUND: Intestinal Ganglioneuromatosis (IG) is a rare disorder of the enteric nervous system. In pediatric age it is often associated with genetic syndromes such as Neurofibromatosis 1 (NF1), multiple endocrine neoplasia type 2B (MEN2B) and Cowden syndrome (PTEN mutation), and ganglioneuromas (GNs) may be sometimes the first sign of the disease. Isolated GNs are rare and sporadic. Clinical symptom vary and depend on the size and on the location of the GNs. This disorder affects intestinal motility and it, consequently, causes changes in bowel habits, abdominal pain, occlusive symptoms and rarely lower gastrointestinal bleeding secondary to ulceration of the intestinal mucosa. On the other hand, patients can remain asymptomatic for many years. CASE PRESENTATION: We describe a 9-year-old boy referred to our emergency department for right lower quadrant abdominal pain. No familial history for gastrointestinal disorders. No history of fever or weight loss. At physical examination, he had diffused abdominal pain. Abdominal ultrasonography showed a hypoechoic formation measuring 41.8 mm by 35 mm in the right lower quadrant of the abdomen. Routine blood tests were normal, but fecal occult blood test was positive. Abdominal TC confirmed the hypodense formation, of about 5 cm in transverse diameter, in the right hypochondrium that apparently invaginated in the caecum-last ileal loop. Colonoscopy showed in the cecum an invaginated polypoid lesion of the terminal ileal loop. Laparoscopic resection of the polypoid lesion was performed. Histological diagnosis of the large neoplasm observed in the terminal ileum was diffuse ganglioneuromatosis. NF1, RET and PTEN gene tests resulted negative for specific mutations. At the 1 year follow-up, the patient presented good general condition and blood tests, fecal occult blood test, esophagogastroduodenoscopy, colonoscopy and MR-enterography were negative. CONCLUSIONS: Only few cases are reported in literature of IG in pediatric age. Although rare, the present case suggests that this disorder must be taken in consideration in every patient with GI symptoms such as abdominal pain, constipation, lower intestinal bleeding, in order to avoid a delayed diagnosis.
Assuntos
Neoplasias do Sistema Digestório/diagnóstico , Ganglioneuroma/diagnóstico , Neoplasia Endócrina Múltipla Tipo 2b/diagnóstico , Dor Abdominal/etiologia , Criança , Colo/diagnóstico por imagem , Colonoscopia , Neoplasias do Sistema Digestório/cirurgia , Ganglioneuroma/cirurgia , Humanos , Masculino , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
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. METHODS: 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; >2000pg/mL), carcinoembryonic antigen (CEA; 719.27ng/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.
Assuntos
Adenocarcinoma Folicular/genética , Biomarcadores Tumorais/genética , Carcinoma Neuroendócrino/genética , Mutação em Linhagem Germinativa , Neoplasia Endócrina Múltipla Tipo 2b/genética , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/sangue , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/cirurgia , Adulto , Biomarcadores Tumorais/sangue , Calcitonina/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Predisposição Genética para Doença , Humanos , Masculino , Neoplasia Endócrina Múltipla Tipo 2b/sangue , Neoplasia Endócrina Múltipla Tipo 2b/patologia , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Fenótipo , Proto-Oncogene Mas , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Resultado do TratamentoRESUMO
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. METHODS: This study reports 5 Chinese pedigrees with 5 individuals harboring germline RETM918T, and systematically reviewed previous Chinese literature reported. 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, a total of 32 MEN 2B patients from literature 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 the 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.
Assuntos
Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Excisão de Linfonodo , Neoplasia Endócrina Múltipla Tipo 2b/genética , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Mutação , Proteínas Proto-Oncogênicas c-ret/genética , Tireoidectomia , Adolescente , Adulto , Povo Asiático/genética , Calcitonina/sangue , Criança , China/epidemiologia , Detecção Precoce de Câncer , Feminino , Predisposição Genética para Doença , Hereditariedade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2b/etnologia , Neoplasia Endócrina Múltipla Tipo 2b/patologia , Linhagem , Valor Preditivo dos Testes , Proto-Oncogene Mas , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
There is no evidence-based guidance on the extent of prophylactic neck surgery for second-generation multiple endocrine neoplasia type 2B (MEN 2B), a newly emerging entity in the molecular era. In this investigation of MEN 2B children who inherited the M918T RET germline mutation from a phenotypically affected MEN 2B parent, 6 MEN 2B children (4 girls and 2 boys) from 5 MEN 2B parents (4 mothers and 1 father) were identified. None of the 6 second-generation MEN 2B children who had preoperative calcitonin serum levels between 2 and 105 pg/mL and underwent prophylactic total thyroidectomy before the age of 4 years after receiving a positive RET gene test harbored node metastases. There was no recurrent laryngeal nerve palsy or postoperative hypoparathyroidism. Within the limitations of this study, total thyroidectomy alone is adequate therapy for second-generation MEN 2B children aged 1-4 years old with preoperative calcitonin serum levels ≤100 pg/mL.
Assuntos
Linfonodos/cirurgia , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/prevenção & controle , Tireoidectomia , Biomarcadores Tumorais/sangue , Calcitonina/sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Linfonodos/patologia , Metástase Linfática/prevenção & controle , Masculino , Neoplasia Endócrina Múltipla Tipo 2b/sangue , Pescoço , Esvaziamento Cervical/efeitos adversos , Linhagem , Neoplasias da Glândula Tireoide/sangue , Tireoidectomia/efeitos adversosRESUMO
Administering anesthesia to patients with pheochromocytoma may cause an exacerbation of catecholamine secretion from the pheochromocytoma secondary to drug administration, stress, or manipulation of the tumor. We present a pediatric patient with undiagnosed multiple endocrine neoplasia type 2B (pheochromocytoma, thyroid carcinoma, and mucosal neuromas), initially diagnosed and treated for postviral myocarditis and cardiomyopathy, who presented for abdominal magnetic resonance imaging (MRI) under general anesthesia. Untreated cardiomyopathy poses an extra anesthesia mortality risk for patients with pheochromocytoma usually due to myocardial failure, myocardial infarction, or hypertensive hemorrhage into the myocardium or brain.
Assuntos
Neoplasias das Glândulas Suprarrenais , Anestesia Geral , Neoplasia Endócrina Múltipla Tipo 2b , Neuroma , Feocromocitoma , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Criança , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasia Endócrina Múltipla Tipo 2b/diagnóstico por imagem , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Neuroma/diagnóstico por imagem , Neuroma/cirurgia , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagemRESUMO
BACKGROUND: Multiple endocrine neoplasia (MEN) 2B is characterized by early development of aggressive medullary thyroid carcinoma (MTC), visible physical stigmata, and associated symptoms. In most cases, de novo mutations are revealed. There are premonitory symptoms and stigmata that enable early diagnosis, before an inoperable MTC develops. The German Society for Paediatric Oncology and Haematology (GPOH)-Malignant Endocrine Tumours (MET) registry maintains records of children with MTC in Germany since 1997. METHODS: Children with a diagnosis of MTC in MEN 2B recorded in the GPOH-MET study were analyzed retrospectively. Stigmata and symptoms associated with MEN 2B were examined. RESULTS: From inception through 2017, 24 patients aged 0.2-17.3 years were included. Symptoms affecting the oral/dental (88.0%), musculoskeletal (79.2%), and gastrointestinal (70.8%) systems were recognized most frequently. Gastrointestinal and musculoskeletal symptoms preceded symptoms of MTC. Twelve patients had short stature. Regarding the prevalence of single symptoms, neuromas of the lips and the oral cavity were mentioned most frequently. Five patients died from MTC. Patients diagnosed by tumor symptoms showed more advanced disease than those with disease detected by other means. Children diagnosed via associated stigmata and symptoms or positive family history had significantly improved overall survival (OS) compared to children diagnosed via symptoms of MTC (OS 100% vs 53.3%). CONCLUSIONS: In children with MEN 2B, oral/dental, musculoskeletal, and gastrointestinal symptoms are most common. If children are diagnosed via associated symptoms and stigmata, OS is improved. Most of the children were diagnosed with growth disturbances; this finding requires verification and ranging in other patient cohorts.
Assuntos
Carcinoma Neuroendócrino/complicações , Neoplasia Endócrina Múltipla Tipo 2b/patologia , Sistema de Registros/estatística & dados numéricos , Índice de Gravidade de Doença , Neoplasias da Glândula Tireoide/complicações , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasia Endócrina Múltipla Tipo 2b/etiologia , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. METHODS: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. FINDINGS: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. INTERPRETATION: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year. FUNDING: None.
Assuntos
Neoplasias das Glândulas Suprarrenais/mortalidade , Carcinoma Neuroendócrino/mortalidade , Neoplasia Endócrina Múltipla Tipo 2b/mortalidade , Feocromocitoma/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Tireoidectomia/mortalidade , Adolescente , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2b/patologia , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Adulto JovemAssuntos
Neoplasias do Sistema Digestório/complicações , Ganglioneuroma/complicações , Hemorragia Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Neoplasia Endócrina Múltipla Tipo 2b/complicações , Neurofibromatose 1/complicações , Doença Aguda , Idoso , Anastomose Cirúrgica , Calbindina 2/metabolismo , Neoplasias do Sistema Digestório/patologia , Neoplasias do Sistema Digestório/cirurgia , Ganglioneuroma/patologia , Ganglioneuroma/cirurgia , Hemorragia Gastrointestinal/etiologia , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Masculino , Neoplasia Endócrina Múltipla Tipo 2b/patologia , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Neurofibromatose 1/metabolismo , Neurofibromatose 1/patologia , Neurofibromatose 1/cirurgia , Proteínas S100/metabolismo , Tomógrafos Computadorizados , Resultado do TratamentoAssuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Megacolo/diagnóstico , Neoplasia Endócrina Múltipla Tipo 2b/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Dor Abdominal/etiologia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Colectomia , Diagnóstico Diferencial , Humanos , Masculino , Megacolo/complicações , Megacolo/diagnóstico por imagem , Megacolo/cirurgia , Neoplasia Endócrina Múltipla Tipo 2b/diagnóstico por imagem , Neoplasia Endócrina Múltipla Tipo 2b/secundário , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Sigmoidoscopia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/secundário , Neoplasias da Glândula Tireoide/cirurgia , Tomografia Computadorizada por Raios XAssuntos
Lábio/fisiopatologia , Neoplasia Endócrina Múltipla Tipo 2b/diagnóstico , Puberdade Tardia/diagnóstico , Adolescente , Éxons , Feminino , Genes Dominantes , Humanos , Neoplasia Endócrina Múltipla Tipo 2b/complicações , Neoplasia Endócrina Múltipla Tipo 2b/genética , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Metástase Neoplásica , Puberdade Tardia/complicações , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Língua/fisiopatologiaRESUMO
Multiple endocrine neoplasia (MEN) is an uncommon genetic syndrome transmitted as an autosomal dominant condition characterized by multiple tumors or hyperplasia of neuroendocrine tissues. MEN type 2b (MEN2B) often has clinical signs of marfanoid facial appearance and mucosal neuromas of the head. This report describes the diagnosis of MEN2B in a previously undiagnosed 9 year old who presented for biopsy of an oral lesion.
Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasia Endócrina Múltipla Tipo 2b/diagnóstico , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Biomarcadores Tumorais/sangue , Biópsia , Criança , Diagnóstico Diferencial , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasia Endócrina Múltipla Tipo 2b/patologia , Esvaziamento Cervical , Estadiamento de Neoplasias , TireoidectomiaRESUMO
BACKGROUND: In patients with multiple endocrine neoplasia type 2 (MEN2) syndrome, genetic testing offers early diagnosis, stratifies the risk of developing medullary thyroid cancer (MTC) and informs the timing of thyroidectomy. The efficacy of treatment, which depends on timely and safe surgery, is not well established. METHODS: This was a retrospective review of diagnostic and clinicopathological outcomes of prophylactic thyroidectomy in children with MEN2 between 1995 and 2013 in the UK. American Thyroid Association (ATA) 2009 guidelines were used as a benchmark for adequate treatment. RESULTS: Seventy-nine children from 16 centres underwent total thyroidectomy. Thirty-eight patients (48 per cent) underwent genetic testing and 36 (46 per cent) had an operation performed above the age recommended by the ATA 2009 guidelines; pathology showed MTC in 30 patients (38 per cent). Late surgery, above-normal preoperative calcitonin level and MTC on pathology correlated with late genetic testing. Twenty-five children had lymphadenectomy; these patients had more parathyroid glands excised (mean difference 0·61, 95 per cent c.i. 0·24 to 0·98; P = 0·001), and were more likely to have hypocalcaemia requiring medication (relative risk (RR) 3·12, 95 per cent c.i. 1·54 to 6·32; P = 0·002) and permanent hypoparathyroidism (RR 3·24, 1·29 to 8·11; P = 0·010) compared with those who underwent total thyroidectomy alone. Age did not influence the development of complications. CONCLUSION: Late genetic testing may preclude age-appropriate surgery, increasing the risk of operating when MTC has already developed. Early genetic testing and age-appropriate surgery may help avoid unnecessary lymphadenectomy and improve outcomes.
Assuntos
Carcinoma Neuroendócrino/prevenção & controle , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Procedimentos Cirúrgicos Profiláticos , Neoplasias da Glândula Tireoide/prevenção & controle , Tireoidectomia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Modelos Logísticos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Context: Recent long-term outcomes and survival data are lacking for patients with multiple endocrine neoplasia type 2B (MEN2B). Objectives: To analyze long-term MEN2B outcomes and define prognostic factors. Design, Setting, and Participants: Retrospective comparative study of 75 patients with MEN2B from two German tertiary referral centers. Patients diagnosed and treated before and after 2000 were compared for demographic, biochemical, surgical, and outcome parameters. Intervention: Surgery. Main Outcome measure: Long-term survival. Results: We identified seven familial and 68 de novo cases of MEN2B; 61 exhibited the RET M918T genotype (2 others exhibited A883F and E768D/L790T mutations). Surgery was performed at a mean age of 16.4 ± 11.2 years. The tumor stages at diagnosis for 71 patients were stage I, 15%; stage II, 6%; stage III, 35%; and stage IV, 44%. The mean follow-up was 9.6 ± 9.0 years. The outcomes were 15 (20%) cured, 9 (12%) with minimal residual disease, 19 (25%) with metastatic disease, and 10 (13%) unknown. Medullary thyroid cancer (MTC) caused 22 deaths (29%) 7.3 ± 6.2 years after diagnosis (mean age, 22.9 ± 10.7 years). The overall survival rates at 5, 10, and 20 years were 85%, 74%, and 58%, respectively. After 2000 (vs before 2000), significantly more patients had stage I and II (32% vs 11%) and more were cured (43% vs 20%), with a higher survival trend (P = 0.058). The only prognostic factor was tumor stage at diagnosis. Conclusions: Patients with MEN2B developed MTC at an early age with wide ranging aggressiveness, but the outcome was generally better after 2000 than before 2000.
Assuntos
Biomarcadores/análise , Carcinoma Medular/mortalidade , Neoplasia Endócrina Múltipla Tipo 2b/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Tireoidectomia/mortalidade , Adolescente , Adulto , Carcinoma Medular/genética , Carcinoma Medular/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2b/genética , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Mutação , Prognóstico , Proteínas Proto-Oncogênicas c-ret/genética , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Fatores de Tempo , Adulto JovemRESUMO
Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome with major components of medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. MEN2B is the most aggressive and rarest of the MEN2 variants. Pheochromocytoma in MEN2 is virtually always located in the adrenal medulla, but MEN2-associated extra-adrenal pheochromocytomas (paraganglioma) are rare. A 59-year-old man who has been diagnosed with MEN2B consulted our hospital for surgical treatment of a 10-mm left adrenal mass and a 30-mm retroperitoneal mass. He had paroxysmal elevations in blood pressure and in urinary metanephrine and vanillylmandelic acid values. Laparoscopic excision of the left adrenal gland and retroperitoneal mass was performed. We experienced an extremely rare case of composite paraganglioma-ganglioneuroma concomitant with adrenal metastasis of medullary thyroid carcinoma in a patient with MEN2B.