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Clinical Cancer Research : An Official... Jul 2017Children and adolescents who present with neuroendocrine tumors are at extremely high likelihood of having an underlying germline predisposition for the multiple... (Review)
Review
Children and adolescents who present with neuroendocrine tumors are at extremely high likelihood of having an underlying germline predisposition for the multiple endocrine neoplasia (MEN) syndromes, including MEN1, MEN2A and MEN2B, MEN4, and hyperparathyroid-jaw tumor (HPT-JT) syndromes. Each of these autosomal dominant syndromes results from a specific germline mutation in unique genes: MEN1 is due to pathogenic variants (11q13), MEN2A and MEN2B are due to pathogenic variants (10q11.21), MEN4 is due to pathogenic variants (12p13.1), and the HPT-JT syndrome is due to pathogenic variants (1q25). Although each of these genetic syndromes share the presence of neuroendocrine tumors, each syndrome has a slightly different tumor spectrum with specific surveillance recommendations based upon tumor penetrance, including the age and location for which specific tumor types most commonly present. Although the recommended surveillance strategies for each syndrome contain similar approaches, important differences do exist among them. Therefore, it is important for caregivers of children and adolescents with these syndromes to become familiar with the unique diagnostic criteria for each syndrome, and also to be aware of the specific tumor screening and prophylactic surgery recommendations for each syndrome. .
Topics: Adenoma; Adolescent; Child; Fibroma; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Hyperparathyroidism; Jaw Neoplasms; Multiple Endocrine Neoplasia; Multiple Endocrine Neoplasia Type 2b; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ret; Risk Factors; Tumor Suppressor Proteins
PubMed: 28674121
DOI: 10.1158/1078-0432.CCR-17-0548 -
Aging Jun 2019
Topics: Age Factors; Age of Onset; Humans; Multiple Endocrine Neoplasia Type 2a; Mutation; Prognosis; Proto-Oncogene Proteins c-ret
PubMed: 31188782
DOI: 10.18632/aging.102030 -
Journal of Veterinary Diagnostic... Jul 2023An ~10-y-old male sheep had anorexia and progressive weight loss for ~1 mo. The sheep was emaciated, and 20 d later, became recumbent and lethargic, and was...
An ~10-y-old male sheep had anorexia and progressive weight loss for ~1 mo. The sheep was emaciated, and 20 d later, became recumbent and lethargic, and was hypoglycemic (0.33 mmol/L; RI: 2.6-4.4 mmol/L). The sheep was euthanized because of poor prognosis, and submitted for autopsy. We found no gross lesions in the pancreas; however, histologically, focal proliferations of round-to-polygonal cells were separated by connective tissue into small nests. These proliferating cells, which had abundant eosinophilic-to-amphophilic cytoplasm and hyperchromatic nuclei, were immunopositive for insulin and negative for glucagon and somatostatin; the lesion was diagnosed as an insulinoma. Insulinoma has not been reported previously in sheep, to our knowledge. In addition, autopsy and histologic examination revealed the presence of an adrenocortical carcinoma with myxoid differentiation and a thyroid C-cell carcinoma. Our case indicates that multiple endocrine neoplasms can occur in sheep, as in other animal species.
Topics: Male; Animals; Sheep; Adrenocortical Carcinoma; Insulinoma; Thyroid Gland; Multiple Endocrine Neoplasia; Adrenal Cortex Neoplasms; Pancreatic Neoplasms; Cell Differentiation; Sheep Diseases
PubMed: 37148257
DOI: 10.1177/10406387231168096 -
World Journal of Surgical Oncology May 2022Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant tumor syndrome with a high degree of heterogeneity in clinical phenotypes, generally involving...
BACKGROUND
Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant tumor syndrome with a high degree of heterogeneity in clinical phenotypes, generally involving the parathyroid, anterior pituitary, and enteropancreas. In recent years, several new insights into the clinical features of MEN1 have been reported in the literature. However, it is not clear whether MEN1-associated primary tumors can occur in the liver.
CASE PRESENTATION
We report the case of a 52-year-old man with multiple endocrine neoplasia type 1 diagnosed by genetic sequencing. After uniportal thoracoscopic right middle lobectomy, laparoscopic radical resection of the liver tumors, and radiofrequency ablation of the parathyroid space, the parathyroid hormone level decreased from 177 pg/ml to a normal level (20 pg/ml). No local tumor recurrence was observed during a follow-up of 5 months.
CONCLUSION
We report the first case of MEN1 with simultaneous liver and lung involvement in which the patient underwent radical resection of the tumors, and we propose the possibility that the liver and other nonendocrine organs may also develop diseases associated with MEN1; although, this view needs further verification. Gene detection has crucial clinical significance for guiding diagnosis and treatment.
Topics: Abdomen; Humans; Liver; Lung; Multiple Endocrine Neoplasia Type 1; Neoplasm Recurrence, Local
PubMed: 35538538
DOI: 10.1186/s12957-022-02622-1 -
Clinical Endocrinology Sep 2021Multiple endocrine neoplasia 2B (MEN2B) is characterised by early-onset medullary thyroid carcinoma (MTC), pheochromocytoma and several nonendocrine manifestations....
OBJECTIVE
Multiple endocrine neoplasia 2B (MEN2B) is characterised by early-onset medullary thyroid carcinoma (MTC), pheochromocytoma and several nonendocrine manifestations. Unfortunately, MEN2B is often diagnosed late, after the development of clinically significant MTC. Marfanoid habitus is considered an important related feature, which may lead to the assumption that patients with MEN2B have tall stature. Here, we describe the longitudinal growth and body proportions of eight MEN2B patients during childhood.
DESIGN
It is a retrospective case series.
METHODS
Patients were under the care of a Dutch MEN expertise centre. Growth patterns were assessed and interpreted in relation to body mass index (BMI), age at diagnosis and at thyroidectomy, extensiveness of disease manifestations and parental height.
RESULTS
Seven patients were short during childhood, of whom four showed growth below target height range (THR) and three at the lowest margin of THR. Only one patient grew well within THR. All patients who attained final height (n = 4) ended within THR, despite short stature during childhood. Arm span/height ratio was not increased and upper segment/lower segment ratio was not reduced in any patient. Short stature in childhood in this study did not seem to be associated with age at diagnosis, age at thyroidectomy, extensiveness of MTC, endocrine deficiencies or BMI.
CONCLUSIONS
This study shows that children with MEN2B may well present with short rather than tall stature. Thereafter, final height within THR was attained in those who already reached adulthood, but none had tall stature. Finally, body proportions were normal in all children and adults in this case series, not underlining a 'marfanoid' body habitus.
Topics: Adrenal Gland Neoplasms; Adult; Carcinoma, Neuroendocrine; Child; Humans; Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b; Retrospective Studies; Thyroid Neoplasms
PubMed: 34160841
DOI: 10.1111/cen.14536 -
International Journal of Molecular... Apr 2021Pancreatic neuroendocrine tumors (pNETs) are a rare group of cancers accounting for about 1-2% of all pancreatic neoplasms. About 10% of pNETs arise within endocrine... (Review)
Review
Pancreatic neuroendocrine tumors (pNETs) are a rare group of cancers accounting for about 1-2% of all pancreatic neoplasms. About 10% of pNETs arise within endocrine tumor syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1). pNETs affect 30-80% of MEN1 patients, manifesting prevalently as multiple microadenomas. pNETs in patients with MEN1 are particularly difficult to treat due to differences in their growth potential, their multiplicity, the frequent requirement of extensive surgery, the high rate of post-operative recurrences, and the concomitant development of other tumors. MEN1 syndrome is caused by germinal heterozygote inactivating mutation of the gene, encoding the menin tumor suppressor protein. MEN1-related pNETs develop following the complete loss of function of wild-type menin. Menin is a key regulator of endocrine cell plasticity and its loss in these cells is sufficient for tumor initiation. Somatic biallelic loss of wild-type menin in the neuroendocrine pancreas presumably alters the epigenetic control of gene expression, mediated by histone modifications and DNA hypermethylation, as a driver of MEN1-associated pNET tumorigenesis. In this light, epigenetic-based therapies aimed to correct the altered DNA methylation, and/or histone modifications might be a possible therapeutic strategy for MEN1 pNETs, for whom standard treatments fail.
Topics: Animals; Epigenesis, Genetic; Humans; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatic Neoplasms; Signal Transduction
PubMed: 33919851
DOI: 10.3390/ijms22084041 -
Frontiers in Endocrinology 2023
Topics: Humans; Multiple Endocrine Neoplasia Type 1
PubMed: 37635979
DOI: 10.3389/fendo.2023.1266148 -
Clinics (Sao Paulo, Brazil) 2012Primary hyperparathyroidism associated with multiple endocrine neoplasia type I (hyperparathyroidism/multiple endocrine neoplasia type 1) differs in many aspects from... (Meta-Analysis)
Meta-Analysis Review
Primary hyperparathyroidism associated with multiple endocrine neoplasia type I (hyperparathyroidism/multiple endocrine neoplasia type 1) differs in many aspects from sporadic hyperparathyroidism, which is the most frequently occurring form of hyperparathyroidism. Bone mineral density has frequently been studied in sporadic hyperparathyroidism but it has very rarely been examined in cases of hyperparathyroidism/multiple endocrine neoplasia type 1. Cortical bone mineral density in hyperparathyroidism/multiple endocrine neoplasia type 1 cases has only recently been examined, and early, severe and frequent bone mineral losses have been documented at this site. Early bone mineral losses are highly prevalent in the trabecular bone of patients with hyperparathyroidism/multiple endocrine neoplasia type 1. In summary, bone mineral disease in multiple endocrine neoplasia type 1 related hyperparathyroidism is an early, frequent and severe disturbance, occurring in both the cortical and trabecular bones. In addition, renal complications secondary to sporadic hyperparathyroidism are often studied, but very little work has been done on this issue in hyperparathyroidism/multiple endocrine neoplasia type 1. It has been recently verified that early, frequent, and severe renal lesions occur in patients with hyperparathyroidism/multiple endocrine neoplasia type 1, which may lead to increased morbidity and mortality. In this article we review the few available studies on bone mineral and renal disturbances in the setting of hyperparathyroidism/multiple endocrine neoplasia type 1. We performed a meta-analysis of the available data on bone mineral and renal disease in cases of multiple endocrine neoplasia type 1-related hyperparathyroidism.
Topics: Bone Demineralization, Pathologic; Bone Density; Bone and Bones; Follow-Up Studies; Humans; Hyperparathyroidism, Primary; Kidney Diseases; Multiple Endocrine Neoplasia Type 1; Parathyroid Hormone; Treatment Outcome
PubMed: 22584713
DOI: 10.6061/clinics/2012(sup01)17 -
The Journal of Clinical Endocrinology... Apr 2018Multiple endocrine neoplasia type 1 (MEN1) is complex with regard to clinical expressions, management, and molecular pathways. Advances are being made broadly and in... (Review)
Review
INTRODUCTION
Multiple endocrine neoplasia type 1 (MEN1) is complex with regard to clinical expressions, management, and molecular pathways. Advances are being made broadly and in focused aspects. Selected topics are presented for their developments since publication of the most recent MEN1 consensus guidelines 6 years ago.
METHODS
Topics were selected for clinical impact or broad interest or both. For each topic, information was obtained from original reports and reviews.
RESULTS
The selected topics are as follows: tumor behavior and breast cancer in MEN1; foregut neuroectoderm tumor screening, biomarkers periodically to detect tumor emergence of foregut neuroectoderm tumors, 68Ga dotatate positron emission tomography/computed tomography for pancreatic and duodenal neuroectodermal tumor imaging, and glucagon-like peptide-1 receptor scintigraphy for insulinoma; therapy, the size of pancreatic neuroendocrine tumor (NET) as one criterion for surgery, minimally invasive surgery of pancreatic NETs, and 177Lu dotatate therapy; MEN1 gene, the search for the MEN1/menin pathway and MEN1 or GCM2 mutation in familial isolated hyperparathyroidism, and MEN1 mutation-positive vs mutation-negative cases of MEN1 are different.
CONCLUSIONS
MEN1 topics are a rich and fast-moving area. Important highlights stand out, and major and rapid advances will continue into the near future.
Topics: Cell Transformation, Neoplastic; Early Detection of Cancer; Humans; Multiple Endocrine Neoplasia Type 1; Mutation; Nuclear Proteins; Proto-Oncogene Proteins; Transcription Factors
PubMed: 29897580
DOI: 10.1210/jc.2017-02340 -
Clinical and molecular features of four Brazilian families with multiple endocrine neoplasia type 1.Frontiers in Endocrinology 2023Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by its clinical variability and complexity in diagnosis and treatment. We...
OBJECTIVE
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by its clinical variability and complexity in diagnosis and treatment. We performed both clinical and molecular descriptions of four families with MEN1 in a follow-up at a tertiary center in Brasília.
METHODS
From a preliminary review of approximately 500 medical records of patients with pituitary neuroendocrine tumor (PitNET) from the database of the Neuroendocrinology Outpatient Clinic of the University Hospital of Brasília, a total of 135 patients met the criteria of at least two affected family members. From this cohort, we have identified 34 families: only four with a phenotype of MEN1 and the other 30 families with the phenotype of familial isolated pituitary adenoma (FIPA). Eleven patients with a clinical diagnosis of MEN1 from these four families were selected.
RESULTS
Variants in gene were identified in all families. One individual from each family underwent genetic testing using targeted high-throughput sequencing (HTS). All patients had primary hyperparathyroidism (PHPT), and the second most common manifestation was PitNET. One individual had well-differentiated liposarcoma, which has been previously reported in a single case of MEN1. Three variants previously described in the database and a novel variant in exon 2 have been found.
CONCLUSIONS
The study allowed the genotypic and phenotypic characterization of families with MEN1 in a follow-up at a tertiary center in Brasília.
Topics: Humans; Multiple Endocrine Neoplasia Type 1; Brazil; Growth Hormone-Secreting Pituitary Adenoma; Pituitary Neoplasms; Neuroendocrine Tumors
PubMed: 36967793
DOI: 10.3389/fendo.2023.1117873