[Pediatric Multiple Endocrine Neoplasia Type 2B with Pheochromocytoma Diagnosed after Perforation of a Colonic Diverticulum : A Case Report].

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.

Anterior segment optical coherence tomography, in vivo confocal microscopy, histopathologic, and immunohistochemical findings in a patient with multiple endocrine neoplasia type 2b.

PURPOSE: To describe clinical, anterior segment optical coherence tomography (AS-OCT), in vivo confocal microscopy (IVCM), histopathologic, and immunohistochemical findings in a patient with multiple endocrine neoplasia type 2b (MEN 2b) syndrome. MATERIALS AND METHODS: Retrospective case report of a patient with MEN 2b. RESULTS: A 31-year-old male diagnosed with MEN 2b presented with eye redness, burning, and visible conjunctival mass in both eyes. The patient's past medical history revealed that he underwent bilateral adrenalectomy and total thyroidectomy. Genetic testing revealed M918T heterozygous mutation in the RET proto-oncogene. Corrected visual acuity was 20/20 in both eyes. Anterior segment examination revealed bilateral thickened lid margins, ectropion, blepharitis, conjunctival injection, temporal and inferonasal subconjunctival lesions with corneal invasion, corneal neovascularization, and marked corneal nerves. AS-OCT showed a subepithelial mixed reflective lobular mass in both eyes. Hyperreflective and noticeable thickened stromal corneal nerves were observed on IVCM in the left eye. After incisional biopsy of the right perilimbal lesions, histopathological examination revealed that lesions consisted of spindle cells in hypocellular bundles with no atypia and mitosis. Immunohistochemical examination revealed diffuse staining with S100, focal staining with synaptophysin, and no staining with neurofilament protein. These findings were considered compatible with a benign nerve sheath tumor, probably schwannoma. CONCLUSIONS: We present clinical, AS-OCT, IVCM, histopathological, and immunohistochemical findings in a patient with MEN 2b. To our knowledge, this is the first case of a conjunctival schwannoma diagnosed histopathologically in MEN 2b.

Anesthesia Management for Pediatric Patient With Multiple Endocrine Neoplasia Type 2B: A Case Report.

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.

Pulmonary Function in Patients With Multiple Endocrine Neoplasia 2B.

CONTEXT: Multiple endocrine neoplasia type 2B (MEN2B) is a rare cancer predisposition syndrome resulting from an autosomal-dominant germline mutation of the RET proto-oncogene. No prior studies have investigated pulmonary function in patients with MEN2B. OBJECTIVE: This study characterized the pulmonary function of patients with MEN2B. DESIGN: This is a retrospective analysis of pulmonary function tests (PFTs) and chest imaging of patients enrolled in the Natural History Study of Children and Adults with MEN2A or MEN2B at the National Institutes of Health. RESULTS: Thirty-six patients with MEN2B (18 males, 18 females) were selected based on the availability of PFTs; 27 patients underwent at least 2 PFTs and imaging studies. Diffusion abnormalities were observed in 94% (33/35) of the patients, with 63% (22/35) having moderate to severe defects. A declining trend in diffusion capacity was seen over time, with an estimated slope of -2.9% per year (P = 0.0001). Restrictive and obstructive abnormalities were observed in 57% (20/35) and 39% (14/36), respectively. Computed tomography imaging revealed pulmonary thin-walled cavities (lung cysts) in 28% (9/32) of patients and metastatic lung disease in 34% (11/32) of patients; patients with metastatic lung lesions also tended to have thin-walled cavities (P = 0.035). CONCLUSIONS: This study characterized pulmonary function within a MEN2B cohort. Diffusion, restrictive, and obstructive abnormalities were evident, and lung cysts were present in 28% of patients. Further research is required to determine the mechanism of the atypical pulmonary features observed in this cohort.

Síndromes de neoplasia endocrina múltiple: revisión radiológica / Multiple Endocrine Neoplasia Syndromes: Radiological Review

Los 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.

Multiple endocrine neoplasia (MEN) encompasses a serial of familial genetically disorders in wich tumors simultaneusly occur in two or more endocrine organs. MEN síndromes are autosomal-dominant disorders categorized into three main patterns: MEN 1 (Wermer syndrome), MEN 2 (includes MEN 2A o Sipple syndrome and MEN 2B o Wagenmann-Froboese syndrome) and MEN 4. Parathyroid adenomas and medullary thyroid carcinoma are the most frecuent tumors in MEN 1 and MEN 2 respectively. These entities will be suspected in younger patients, bilateral, multiple or multifocal disease and, specially, in patients with family background. Cooperation between endocrinologist, surgeons, oncologists and radiologists is pivotal for optimizing patient treatment.

Multiple Endocrine Neoplasia Type 2B Unmasked by 18 F-FDG PET/CT and 131 I-MIBG SPECT/CT.

F-FDG PET/CT was performed to detect an occult malignancy in a 26-year-old woman with complicated medical history which included paroxysmal hypertension and significantly elevated tumor marker. The images revealed lesions in the thyroid, lymph nodes, and bilateral adrenal glands. Further I-MIBG SPECT/CT revealed intense activity in the lesion in the left adrenal gland, which was consistent with pheochromocytoma. The pathology examination after subsequent neck biopsy demonstrated medullary thyroid carcinoma. A diagnosis of multiple endocrine neoplasia type 2B was eventually made.

In Vivo Confocal Microscopic Architecture of Corneal Nerves in a Case of Multiple Endocrine Neoplasia Type 2b.

A detailed ocular examination and in vivo confocal microscopy (IVCM) using the Heidelberg retinal tomograph 3 with Rostock cornea module were performed in a patient with multiple endocrine neoplasia (MEN) 2b syndrome. Ocular findings included ptosis secondary to thickening of the lid margins, subconjunctival and perilimbal neuromas, and prominent corneal nerves extending up to the pupillary area. IVCM demonstrated structural alterations of both the main nerve trunks and the smaller branches. The main nerve trunks were grossly thickened while the smaller fibers were present in an intertwining manner in the anterior stroma. Some fibers showed prominent looping and nodular dilatations at irregular intervals along the length of the nerves. These nodular dilatations were in all probability ganglioneuromas of corneal nerves demonstrated by histopathology in earlier reports of MEN 2b. IVCM may be potentially useful in detecting the nerve alterations in MEN 2b even before other ocular or systemic features become apparent clinically.

Isolated ileal ganglioneuromatosis in an 11-year-old boy: Case report and review of literature.

Ganglioneuromatous proliferation in the gastrointestinal tract is a rare occurrence and is usually associated with specific syndrome complexes such as multiple endocrine neoplasia Type 2B or von Recklinghausen's disease. We report here a case of diffuse intestinal ganglioneuromatosis, presenting as intestinal obstruction and chronic constipation in an 11-year-old boy. Sporadic cases of intestinal ganglioneuromatosis in the absence of any systemic manifestations are a very rare cause of enteric motility disorders in childhood, and we discuss the pathological and clinical significance of this finding. Histopathological identification of this uncommon cause of a common pediatric problem is important since the condition is amenable to surgical treatment.

MEN2B syndrome presenting as an acute respiratory emergency.

An 18-year-old girl presented to the emergency department with a history of noisy breathing and breathlessness progressively increasing for few days. The patient had stridor and tachypnoea. She was tall with a long thin face, wrist sign and high-arched palate suggestive of marfanoid features. X-ray of the neck revealed critical tracheal narrowing. Emergency tracheostomy was performed as a lifesaving procedure. Non-contrast CT neck revealed extratracheal compression by a mass surrounding it. Contrast-enhanced CT scan of the neck revealed heterogeneous mass arising from the right lobe of the thyroid and tracheal deviation with narrowing. Fine-needle aspiration cytology of the mass revealed medullary carcinoma of the thyroid, positive for calcitonin. Calcitonin levels were raised. Apart from the marfanoid features she had localised swellings over the lips, lower eyelid and the lateral aspects of the tongue, clinically suggestive of neuromas. A clinical diagnosis of multiple endocrine neoplasia type 2B syndrome was made. The patient underwent total thyroidectomy with central lymphnode dissection. This case highlights an unusual presentation of a rare disease.

Small intestinal ganglioneuromatosis in a dog.

A 9-year-old female neutered collie-cross dog was presented with a 2-month history of persistent diarrhoea, weight loss and intermittent vomiting. Abdominal ultrasonography revealed one loop of jejunum with a markedly thickened and multifocally hyperechoic wall, without loss of wall layering. Laparotomies were performed for biopsy and resection of affected intestine. Histopathological examination revealed small intestinal ganglioneuromatosis (GN). The dog recovered well from surgery and the diarrhoea resolved. Eleven months later the dog has gained weight and remains asymptomatic. This is the first report of small intestinal GN affecting a mature dog, in which pathology was localized to the mucosal lamina propria and surgical treatment resulted in a successful outcome.

[Evaluation of efficacy and clinical impact of 18F-FDG-PET in the diagnosis of recurrent medullary thyroid cancer with increased calcitonin and negative imaging test]. / Evaluación de la eficacia y del impacto clínico de la PET-18F-FDG en el diagnóstico de recurrencia del carcinoma medular de tiroides con calcitonina elevada y pruebas de imagen negativas.

AIM: To evaluate the efficacy and clinical impact of the FDG-PET in the diagnosis of suspicion of recurrence of medullary thyroid cancer (MTC) in patients with elevated serum calcitonin and negative imaging test. MATERIAL AND METHODS: We performed a retrospective study of 31 consecutive cases from february 2001 to october 2007 of 17 women and 14 men, mean age 56.2 years (range: 26-88), with anatomical-pathology diagnosis of medullary thyroid cancer and suspicion of recurrence due to abnormal elevation of calcitonin and negative imaging tests. All of the patients underwent whole body FDG-PET scan with a dedicated PET or PET-CT 60 minutes after intravenous injection of 333-434 MBq of (18)F-FDG. Results were confirmed by pathology study in 45.2% of the patients and by clinical follow-up with a mean of 4 years (range: 16 m-8 years) RESULTS: Sensitivity was 88%, specificity 84.6%, positive predictive value 88%, negative predictive value 84.6% and diagnostic accuracy 87%. The results of the FDG PET modified the therapeutic strategy in 14 cases (45.2%). A comparison was made of the mean values of calcitonin using the Student's "t" test between positive PET studies for the disease and negative ones. No significant differences were found (P=.3). CONCLUSIONS: In patients with MTC and suspected recurrence with elevated calcitonin and negative imaging test, the FDG is the best test for the diagnosis of occult recurrence in MTC with elevated calcitonin and negative imaging techniques with elevated clinical impact. It facilitates the therapeutic management of the patients with MTC recurrence, and should be included in the diagnosis algorithm in these patients.

[Detection by SPECT-CT scan with (99m)Tc-(V) DMSA of bone metastases in patient with medullary thyroid cancer]. / Detección mediante SPECT-TAC con (99m)Tc-(V) DMSA de metástasis óseas en paciente con cáncer medular de tiroides.

Multiple endocrine neoplasia syndrome, type 2B (MEN 2B), is a rare entity characterized by the presence of medullary thyroid cancer in 100% of the cases. The phenotype of this syndrome consists in the presence of marfanoid features and mucocutaneous neuromas. We describe the case of a male patient with MEN 2B syndrome who was diagnosed with medullary thyroid cancer after lung metastases was found. We analyze the role of DMSA-V and the new hybrid SPECT-CT scan systems in the extension study and monitoring of medullary thyroid cancer.

Iodine 123 metaiodobenzylguanidine radio-guided navigation surgery for recurrent medullary thyroid carcinoma in a girl with multiple endocrine neoplasia type 2B.

Multiple endocrine neoplasia type 2B (MEN 2B) is an inherited cancerous syndrome characterized by medullary thyroid carcinoma (MTC), adrenal pheochromocytoma, marfanoid habitus, and enteric ganglioneuromatosis. In this syndrome, a high frequency of persistent elevation of the serum calcitonin level, a sensitive marker for MTC, after total thyroidectomy has been reported, and the prognosis of such patients depends upon complete resection of recurrent MTC by repeated surgery. The authors performed iodine 123 metaiodobenzylguanidine ((123)I-MIBG) radio-guided navigation surgery for recurrent MTC in a 14-year-old girl with MEN 2B. She had undergone 4 neck operations, including total thyroidectomy at the age of 7 years. An intravenous injection of 100 MBq (123)I-MIBG was followed by the fifth surgery. At surgery, the cervical and upper mediastinal areas were filled with adhesional scar tissue, in which a gamma-scintillation probe conducted hot spots of isotope uptake by cancerous cells. Histopathology of resected specimens showed scattered nests of MTC cells corresponding to gamma-scintillation counts. Intraoperative (123)I-MIBG scanning is of substantial benefit for children with MEN 2B undergoing surgery for recurrent MTC.

[(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in begnign and malignant pheochromocytomas.

Selecting the appropriate approach for resection and follow-up of pheochromocytomas (PCCs) is highly dependent upon reliable localization and exclusion of multifocal, bilateral, or metastatic disease. Metaiodobenzylguanidine (MIBG) scintigraphy was developed for functional localization of catecholamine-secreting tissues. Somatostatin receptor imaging (SRI) has a high sensitivity for localizing head and neck paragangliomas, but studies of intraabdominal PCCs are rare. In this study we review our experience of [(123)I]MIBG and SRI, performed since 1983 and 1989, respectively, in the work-up of primary and recurrent PCCs. Scintigraphic results were correlated with catecholamine secretion, size and site, malignancy, associated tumor syndromes, and morphological features. [(123)I]MIBG scans were performed in a total of 75 patients, in 70 cases before resection of primary PCCs and in 5 cases because of recurrent disease. Ninety-one PCCs were resected. The overall detection rates were 83.3% and 89.8% for PCCs larger than 1.0 cm. Multifocal disease was detected in 4 patients with [(123)I]MIBG. [(123)I]MIBG uptake correlated with greater size of PCC (r = 0.33; P = 0.008) and greater concentration of plasma epinephrine (r = 0.32; P = 0.006). [(123)I]MIBG-negative PCCs (n = 14) had significantly (P = 0.01) smaller diameters than [(123I)]MIBG-positive tumors. Furthermore, [(123)I]MIBG uptake was significantly higher in unilateral (P = 0.02), benign (P = 0.02), sporadic (P = 0.02), intraadrenal (P = 0.02), and capsular invasive (P = 0.03) PCCs than in bilateral, malignant, MEN2A/2B-related, extraadrenal, and noninvasive PCCs, respectively. The detection rate of SRI was only 25% (8 of 32) for primary benign PCCs. In 14 patients metastases occurred, which were effectively visualized with [(123)I]MIBG in 8 of 14 cases. SRI was able to detect metastases in 7 of 8 cases, including 3 [(123)I]MIBG-negative metastatic cases. In addition, [(123)I]MIBG and SRI detected 2 recurrences. In conclusion, [(123)I]MIBG uptake is correlated with the size, epinephrine production, and site of PCCs. Its role in bilateral and MEN2A/2B-related PCCs seems limited. In cases of recurrent elevation of catecholamines, localization of metastases and/or recurrence should be attempted with [(123)I]MIBG scintigraphy. In suspicious metastatic PCCs, SRI might be considered to supplement [(123)I]MIBG scintigraphy.

Limited role of meta-iodobenzylguanidine scintigraphy in imaging phaeochromocytoma in patients with multiple endocrine neoplasia type II.

OBJECTIVE: To compare diagnostic applicability of combined computed tomography (CT) and magnetic resonance imaging (MRI), with that of meta-iodobenzylguanidine (MIBG) scintigraphy in the preoperative localisation of MEN II related phaeochromocytoma. DESIGN: Retrospective study SETTING: University hospital, The Netherlands. MATERIALS: 17 patients with MEN II patients (33 adrenal glands) who were operated on for phaeochromocytoma. MIBG scintigraphy, CT and MRI were used to localize phaeochromocytoma. Histopathologically, an adrenomedullary lesion more than 1 cm in size was classified as a phaeochromocytoma. MAIN OUTCOME MEASURES: Sensitivity, specificity, and diagnostic accuracy of combined CT and MRI and MIBG scintigraphy, compared with histopathological findings. RESULTS: Sensitivity of combined CT and MRI (27 adrenal glands) was 87%, with a specificity of 100% and a diagnostic accuracy of 89%. MIBG scintigraphy (31 adrenal glands) had a sensitivity of 92%, a specificity of only 17%, and a diagnostic accuracy of 77%. CONCLUSION: If unilateral adrenalectomy is done when only one adrenal gland contains a phaeochromocytoma, then MRI should be the method of choice for localising MEN type II related phaeochromocytoma. MIBG scintigraphy can be restricted to those patients in whom MRI does not show a tumour.

Iodine-131 MIBG imaging in multiple endocrine neoplasia type 2B.

A 16-year-old boy had a swollen neck that was a result of multiple endocrine neoplasia Type 2B (MEN 2B). CT revealed bilateral thyroid tumors, swelling of right cervical lymph nodes, and slight enlargement of the right adrenal gland. I-131 metaiodobenzylguanidine (MIBG) scintigraphy demonstrated increased uptake in the right adrenal gland and the left thyroid tumor, but no abnormal uptake in the right thyroid tumor and the right cervical lymph nodes. Postoperative pathologic findings were consistent with the diagnosis of right adrenal medullary hyperplasia, which is a precursor of pheochromocytoma. In patients with MEN 2B, I-131 MIBG scintigraphy in conjunction with CT of the adrenal glands should be performed to determine the disease stage of the adrenal medullae. In the cervical region, the diagnosis was medullary thyroid carcinoma (MTC) in both thyroid tumors and metastases in the right cervical lymph nodes. The right MTC was more aggressive than the left MTC. It is interesting that not all sites of known MTC take up I-131 MIBG to the same degree.

[Multiple endocrine adenomatosis IIB]. / Multiplex endokrin adenomatosis IIB.

The first Hungarian MEN IIB (multiplex endocrine neoplasia) syndrome is reported with the short summary of the literature about the pathogenesis and diagnosis of medullary thyroid carcinoma, presenting 80% in sporadic, 20% in hereditary form. The appearance of the patients alone (marfanoid stature, bulky lips, and ganglioneuromatosis of the tongue) may be almost enough for the presumption for the diagnosis of MEN IIB: For screening and preventing the clinical manifestation of the very aggressive medullary carcinoma in the relatives of the patient, the genetic screening is indispensable. The costs of the genetic screening and early treatment of the patients are much lower than the expenses of the traditional annual biochemical screening and the--delayed, often only supportive--treatment of the clinically manifested illness.