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Endocrine Nov 2023Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome that combines endocrine and non-endocrine tumors. Thymic neuroendocrine tumors are uncommon components that...
BACKGROUND
Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome that combines endocrine and non-endocrine tumors. Thymic neuroendocrine tumors are uncommon components that predict poor prognosis in patients with MEN1. We aimed to summarize the clinical characteristics of thymoma in MEN1 by reviewing the current reports from the literature.
METHODS
A patient with multiple endocrine neoplasia type 1 (parathyroid hyperplasia, pituitary adenoma, and insulinoma) was found to have a 2 × 1.5 cm thymic mass during long-term follow-up. Thoracoscope surgery was performed, and a histopathology examination revealed WHO Type B3 thymoma. A pathogenic mutation of c.783 + 1G > A in the MEN1 gene was identified. We further searched PubMed and EMBASE for thymoma in association with MEN1.
RESULTS
A comprehensive overview of the literature concerning characteristics of MEN1-related thymoma was summarized. Clinical characteristics and differences between thymoma and thymic carcinoid are highlighted.
CONCLUSIONS
Besides carcinoid, other tumors, including thymoma, need to be identified for thymic space-occupying lesions in MEN1 patients. The impact of thymoma on the long-term prognosis of MEN1 patients needs further investigation.
Topics: Humans; Multiple Endocrine Neoplasia Type 1; Thymoma; Thymus Neoplasms; Carcinoid Tumor; Pancreatic Neoplasms
PubMed: 37668926
DOI: 10.1007/s12020-023-03440-5 -
Frontiers in Endocrinology 2024Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic, but PNETs also occur in hereditary syndromes, primarily multiple endocrine neoplasia type 1 (MEN1). The Knudson hypothesis stated a second, somatic hit in as the cause of PNETs of MEN1 syndrome. In the recent years, reports on genetic somatic events in both sporadic and hereditary PNETs have emerged, providing a basis for a more detailed molecular understanding of the pathophysiology. In this systematic review and meta-analysis, we made a collation and statistical analysis of aggregated frequent genetic alterations and potential driver events in human grade G1/G2 PNETs.
METHODS
A systematic search was performed in concordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guidelines of 2020. A search in Pubmed for published studies using whole exome, whole genome, or targeted gene panel (+400 genes) sequencing of human G1/G2 PNETs was conducted at the 25 of September 2023. Fourteen datasets from published studies were included with data on 221 patients and 225 G1/G2 PNETs, which were divided into sporadic tumors, and hereditary tumors with pre-disposing germline variants, and tumors with unknown germline status. Further, non-functioning and functioning PNETs were distinguished into two groups for pathway evaluation. The collated genetical analyses were conducted using the 'maftools' R-package.
RESULTS
Sporadic PNETs accounted 72.0% (162/225), hereditary PNETs 13.3% (30/225), unknown germline status 14.7% (33/225). The most frequently altered gene was , with somatic variants and copy number variations in overall 42% (95/225); hereditary PNETs (germline variations in , , , , , , and/or ) 57% (16/30); sporadic PNETs 36% (58/162); unknown germline status 64% (21/33). The point mutations/indels were distributed throughout . Overall, (16%, 37/225) and -variants (12%, 27/225) were also abundant with missense mutations clustered in mutational hotspots associated with histone binding, and translocase activity, respectively. mutations occurred more frequently in PNETs with mutations, p<0.05. While functioning PNETs shared few variated genes, non-functioning PNETs had more recurrent variations in genes associated with the Phosphoinositide 3-kinase, Wnt, NOTCH, and Receptor Tyrosine Kinase-Ras signaling onco-pathways.
DISCUSSION
The somatic genetic alterations in G1/G2 PNETs are diverse, but with distinct differences between sporadic vs. hereditary, and functional vs. non-functional PNETs. Increased understanding of the genetic alterations may lead to identification of more drivers and driver hotspots in the tumorigenesis in well-differentiated PNETs, potentially giving a basis for the identification of new drug targets. (Funded by Novo Nordisk Foundation, grant number NNF19OC0057915).
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Sequence Analysis, DNA; Mutation
PubMed: 38868744
DOI: 10.3389/fendo.2024.1351624 -
Annales D'endocrinologie Aug 2023
Topics: Humans; Astrocytoma; Brain Neoplasms; Magnetic Resonance Imaging; Pituitary Gland; Multiple Endocrine Neoplasia Type 1; Male; Adolescent
PubMed: 37169283
DOI: 10.1016/j.ando.2023.04.004