Unusual Clinical and Pathological Presentation of a Neuroendocrine Tumor in a Patient with Multiple Endocrine Neoplasia Type 1

Sakurai, Akihiro; Murakami, Akiko; Sakai, Kenji; Uchino, Shigehiko; Fukushima, Yoshimitsu

doi:10.1507/endocrj.k09e-126

Cited by 6 publications

(1 citation statement)

References 34 publications

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“…Although there was positive staining in the menin protein, menin is a nuclear protein, and localization to the cellular membrane, as shown in Fig. 2(C) , is evidence of an abnormal protein [ 12 ]. VHL staining appears predominantly cytoplasmic in normal tissue [ 13 ].…”

Section: Case Descriptionmentioning

confidence: 99%

Somatic VHL Mutation in a Patient With MEN1-Associated Metastatic Pancreatic Neuroendocrine Tumor Responding to Sunitinib Treatment: A Case Report

Shell

Patel

Powers

et al. 2017

Journal of the Endocrine Society

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Multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau (VHL) are autosomal-dominant diseases caused by germline mutations in tumor-suppressor genes. A patient with a germline MEN1 mutation and a somatic VHL mutation in the tumor has not been reported. Herein, we report on a patient with MEN1 and a metastatic nonfunctioning pancreatic neuroendocrine tumor (PNET) with a somatic VHL mutation. This patient underwent a pancreaticoduodenectomy for a grade 2 PNET obstructing her pancreatic duct. The patient developed liver and regional lymph node metastases as well as growth of a PNET in the remnant pancreas. As part of a clinical trial for mutation-targeted therapy, a biopsy of the metastatic tumor was obtained. The clinical diagnosis, confirmed by OncoVAR-NET and molecular profiling analysis, revealed MEN1 with a germline deletion in exon 2 and a c.402 deletion C, p.Phe134LeufsX51. In addition, a somatic mutation in the VHL gene—a nonsense mutation, c.529A>T, p.Arg177Ter—was identified by hybrid capture sequencing. The mutations were confirmed by Sanger sequencing. Comparative genomic hybridization showed loss of heterozygosity in both the MEN1 and VHL genes. The patient was treated with sunitinib and had a partial response to treatment. This case illustrates not only that a second hit occurs in tumor suppressor genes but that somatic mutations are also possible in additional tumor suppressor genes. This suggests that targeted therapy selection should include analysis of somatic mutations even when the susceptibility gene is known.

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Section: Case Descriptionmentioning

confidence: 99%

Somatic VHL Mutation in a Patient With MEN1-Associated Metastatic Pancreatic Neuroendocrine Tumor Responding to Sunitinib Treatment: A Case Report

Shell

Patel

Powers

et al. 2017

Journal of the Endocrine Society

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The MENX Syndrome and p27: Relationships with Multiple Endocrine Neoplasia

Molatore

Pellegata

2010

Neuroendocrinology - Pathological Situations and Diseases

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Multiple endocrine neoplasia type 1 with Zollinger–Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistry

Kimura,

Hirata,

Iwashiro

et al. 2023

Front. Endocrinol.

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BackgroundMultiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of multiple epithelial neuroendocrine tumors (NETs) and non-NETs in various organs. MEN1 encodes a 610-amino acid-long tumor suppressor protein, menin. The optimal treatment for multiple tumors, identification of the most critical tumors for patient prognosis, and menin immunohistochemistry findings remain controversial. Therefore, we aimed to elucidate these issues through a histological analysis of tumors and tumor-like lesions in a Japanese family, comprising a father and his two sons, who had MEN1 with Zollinger–Ellison syndrome (ZES).Patients and methodsAll family members had a germline alteration in exon 10, c.1714-1715 del TC of MEN1, and exhibited multiple synchronous and metachronous tumors. The patients had pulmonary NETs, hyperparathyroidism, hypergastrinemia, pituitary adenomas, pancreaticoduodenal NETs, adrenocortical adenoma with myelolipoma, nodular goiter of the thyroid, lipomas, and angiofibroma. Most tumors were resected and histologically examined. We compared their clinical courses and tumor histology, and conducted menin immunohistochemistry (IHC).ResultsTwo patients died of pulmonary NET G2. One patient who underwent pancreaticoduodenectomy was cured of ZES; however, the two other patients who did not undergo pancreaticoduodenectomy suffered persistent ZES despite treatment with octreotide. Menin IHC revealed varying NET intensities, ranging from positive to negative stains.ConclusionPancreaticoduodenectomy is the most effective treatment for ZES. Long-term follow-up is essential for pulmonary NET G2 owing to the risk of distant metastasis and/or multiplicity. Moreover, the variability of menin IHC in MEN1-related tumors may indicate the pattern of tumor formation rather than the diagnostic utility of menin in MEN1.

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Unusual Clinical and Pathological Presentation of a Neuroendocrine Tumor in a Patient with Multiple Endocrine Neoplasia Type 1

Cited by 6 publications

References 34 publications

Somatic VHL Mutation in a Patient With MEN1-Associated Metastatic Pancreatic Neuroendocrine Tumor Responding to Sunitinib Treatment: A Case Report

Somatic VHL Mutation in a Patient With MEN1-Associated Metastatic Pancreatic Neuroendocrine Tumor Responding to Sunitinib Treatment: A Case Report

The MENX Syndrome and p27: Relationships with Multiple Endocrine Neoplasia

Multiple endocrine neoplasia type 1 with Zollinger–Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistry

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