Bronchopulmonary Neuroendocrine Neoplasms and Their Precursor Lesions in Multiple Endocrine Neoplasia Type 1

2015 ◽  
Vol 103 (3-4) ◽  
pp. 240-247 ◽  
Author(s):  
Detlef K. Bartsch ◽  
Max B. Albers ◽  
Caroline L. Lopez ◽  
Jonas C. Apitzsch ◽  
Eduard M. Walthers ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Neuroendocrine Neoplasms ◽  
Precursor Lesions ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

scholarly journals Multiple Endocrine Neoplasia Type 1 (MEN1) Phenocopy Due to a Cell Cycle Division 73 (CDC73) Variant

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Kate E Lines ◽  
Lisa B Nachtigall ◽  
Laura E Dichtel ◽  
Treena Cranston ◽  
Hannah Boon ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Endocrine Neoplasia ◽  
Kinase Inhibitor ◽  
Multiple Endocrine Neoplasia Type ◽  
Neuroendocrine Neoplasm ◽  
Neuroendocrine Neoplasms ◽  
Autosomal Dominant Disorder ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

Abstract Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid tumors, pituitary adenomas, and pancreatic neuroendocrine neoplasms (PNENs). MEN1 is caused by germline MEN1 mutations in > 75% of patients, and the remaining 25% of patients may have mutations in unidentified genes or represent phenocopies with mutations in genes such as cell cycle division 73 (CDC73), the calcium sensing receptor (CASR), and cyclin-dependent kinase inhibitor 1B (CDKN1B), which are associated with the hyperparathyroidism-jaw tumor syndrome, familial hypocalciuric hypercalcemia type 1, and MEN4, respectively. Here, we report a heterozygous c.1138C>T (p.Leu380Phe) CDC73 germline variant in a clinically diagnosed MEN1 patient, based on combined occurrence of primary hyperparathyroidism, acromegaly, and a PNEN. Characterization of the PNEN confirmed it was a neuroendocrine neoplasm as it immuno-stained positively for chromogranin and glucagon. The rare variant p.Leu380Phe occurred in a highly conserved residue, and further analysis using RNA-Scope indicated that it was associated with a significant reduction in CDC73 expression in the PNEN. Previously, CDC73 mutations have been reported to be associated with tumors of the parathyroids, kidneys, uterus, and exocrine pancreas. Thus, our report of a patient with PNEN and somatotrophinoma who had a CDC73 variant, provides further evidence that CDC73 variants may result in a MEN1 phenocopy.

scholarly journals SUN-116 The Role of 68Gallium DOTATATE PET/CT Versus 18F-FDOPA PET/CT in the Imaging of Neuroendocrine Neoplasms in Patients with Multiple Endocrine Neoplasia Type 1 (MEN1)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Aisha Tepede ◽  
Maya Lee ◽  
James Welch ◽  
Adel Mandl ◽  
Rashika Bansal ◽  
...  
Keyword(s):  
Nuclear Medicine ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Neuroendocrine Neoplasms ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Pet Ct ◽  
Significant Difference ◽  
Ct And Mri

Abstract Background: Neuroendocrine neoplasms (NEN) are a heterogenous group of tumors. Patients with the multiple endocrine neoplasia type 1 (MEN1) syndrome often manifest with simultaneous functional and non-functional NEN in various endocrine glands. In MEN1, nuclear medicine plays an important role in the diagnostic work-up and localization of NEN. Little is known about the comparative efficacy of 68Ga-Dotatate PET/CT (DOTA) versus 18F-FDOPA PET/CT (FDOPA) and both versus non-nuclear medicine imaging (CT and MRI) in the identification of primary and metastatic NEN. Methods: This prospective MEN1 cohort study evaluated 15 germline MEN1 mutation-positive patients. Subjects were imaged using CT, MRI, DOTA and 18F-FDOPA. Radiological review with a multidisciplinary team was performed for each patient. Results: One-hundred twenty-nine total lesions were identified using any of the four scans. DOTA sensitivity was 69% (89/129; 95% CI 61% to 76%) with a mean standardized uptake value (SUV) of 33.9 ± 30.1, FDOPA sensitivity was 18% (23/129; 95% CI 12% to 25%) with mean SUV of 12.1 ± 15.16. DOTA identified an additional 50 lesions not seen on CT (of which MRI detected 8 lesions with an average size 0.95 cm ± 0.48; 3 pancreatic, 2 duodenal, 2 liver, and 1 lymph node) and identified 55 lesions not seen on MRI (of which CT identified 13 with a mean size of 1.1 cm ± 0.45; 1 lung, 4 pancreatic, 2 duodenal, 1 liver, and 5 lymph nodes). Overall, CT detected 51.2% (66/129) of lesions (mean 0.61 cm ± 0.73; 95% CI 43% to 60%) and MRI detected 39.5% (51/129; 0.47 cm ± 0.71; 95% CI 32% to 48%), and there was no significant difference in the size of lesions detected (p=0.18). Analysis by organ NEN revealed equal sensitivity between FDOPA and DOTA for lung carcinoid, detecting 33% (4/12) of lesions, while CT detected 92% (11/12) of lesions. In the duodenum, DOTA identified 100% (11 /11) of lesions, while FDOPA had poor sensitivity (9%) in this location. Within the pancreas, DOTA has a sensitivity of 81% (31/38), while FDOPA had a sensitivity of 21% (8/38). CT localized 42% (16/38) of pancreatic lesions, of which MRI missed 6. Interestingly, DOTA missed 7 pancreatic lesions all approximately 1cm or larger, which is previously unrecognized (range 0.9 - 1.8cm). Twenty-three liver metastases were detected on anatomic imaging (CT identified 14, while MRI detected 15, with only 9 overlapping lesions). DOTA identified 60% (14/23) of lesions, of which 3 lesions were missed by CT and MRI. However, DOTA was more sensitive in the liver than FDOPA which only detected 2 lesions. FDOPA detected one lesion in the adrenal (0.9cm) that was not seen on DOTA. Conclusion: DOTA imaging proved to be superior to FDOPA, CT and MRI overall in detecting NENs in MEN1, specifically in the duodenum. Pancreatic NEN missed by DOTA may represent higher grade tumors and may benefit from 18FDG PET/CT imaging.

Precursor Lesions in Patients With Multiple Endocrine Neoplasia Type 1--Associated Duodenal Gastrinomas

2005 ◽  
Vol 128 (5) ◽  
pp. 1187-1198 ◽  
Author(s):  
Martin Anlauf ◽  
Aurel Perren ◽  
Cora Lu Meyer ◽  
Sonja Schmid ◽  
Parvin Saremaslani ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Precursor Lesions ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

scholarly journals Pancreatic Neuroendocrine Neoplasms in Multiple Endocrine Neoplasia Type 1

2021 ◽  
Vol 22 (8) ◽  
pp. 4041
Author(s):  
Francesca Marini ◽  
Francesca Giusti ◽  
Francesco Tonelli ◽  
Maria Luisa Brandi
Keyword(s):  
Histone Modifications ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Growth Potential ◽  
Neuroendocrine Neoplasms ◽  
Wild Type ◽  
Control Of Gene Expression ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

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 MEN1 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.

Multiple endocrine neoplasia type 1 (MEN-1) and neuroendocrine neoplasms (NENs)

2021 ◽  
Author(s):  
Grigoris Effraimidis ◽  
Ulrich Knigge ◽  
Maria Rossing ◽  
Peter Oturai ◽  
Åse Krogh Rasmussen ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Neuroendocrine Neoplasms ◽  
Men 1 ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type
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