Multiple endocrine neoplasia type 1 with Zollinger–Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistry
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 mul...
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1221514/full |
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| author | Noriko Kimura Noriko Kimura Yasuji Hirata Nozomu Iwashiro Hiroshi Kijima Shinobu Takayasu Satoshi Yamagata Satoshi Yamagata Satoru Sakihara Satoru Sakihara Shinya Uchino Masanori Ohara |
| author_facet | Noriko Kimura Noriko Kimura Yasuji Hirata Nozomu Iwashiro Hiroshi Kijima Shinobu Takayasu Satoshi Yamagata Satoshi Yamagata Satoru Sakihara Satoru Sakihara Shinya Uchino Masanori Ohara |
| author_sort | Noriko Kimura |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T19:40:15Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-11T19:40:15Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-1ea0a8a8732c4ae0adbf27117c7bb8d92023-10-06T12:45:16ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-10-011410.3389/fendo.2023.12215141221514Multiple endocrine neoplasia type 1 with Zollinger–Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistryNoriko Kimura0Noriko Kimura1Yasuji Hirata2Nozomu Iwashiro3Hiroshi Kijima4Shinobu Takayasu5Satoshi Yamagata6Satoshi Yamagata7Satoru Sakihara8Satoru Sakihara9Shinya Uchino10Masanori Ohara11Department of Clinical Research, National Hospital Organization Hakodate Hospital, Hakodate, Hokkaido, JapanDepartment of Diagnostic Pathology, National Hospital Organization Hakodate Hospital, Hakodate, Hokkaido, JapanDepartment of Hematology and Oncology, National Hospital Organization Hakodate Hospital, Hakodate, Hokkaido, JapanDepartment of Surgery, National Hospital Organization Hakodate Hospital, Hakodate, Hokkaido, JapanDepartment of Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, JapanDepartment of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine and Hospital, Hirosaki, Aomori, JapanDepartment of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine and Hospital, Hirosaki, Aomori, JapanInstitute of Human Nutrition, Columbia University Irving Medical Center, New York, NY, United StatesDepartment of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine and Hospital, Hirosaki, Aomori, JapanDivision of Diabetes and Endocrinology, Aomori Rosai Hospital, Aomori, JapanDepartment of Endocrine Surgery, Noguchi Thyroid Clinic and Hospital Foundation, Beppu, Oita, JapanDepartment of Surgery, National Hospital Organization Hakodate Hospital, Hakodate, Hokkaido, JapanBackgroundMultiple 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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1221514/fullmultiple endocrine neoplasia type 1Zollinger-Ellison syndromeneuroendocrine tumorpulmonary atypical carcinoidmetastasisprognosis |
| spellingShingle | Noriko Kimura Noriko Kimura Yasuji Hirata Nozomu Iwashiro Hiroshi Kijima Shinobu Takayasu Satoshi Yamagata Satoshi Yamagata Satoru Sakihara Satoru Sakihara Shinya Uchino Masanori Ohara Multiple endocrine neoplasia type 1 with Zollinger–Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistry Frontiers in Endocrinology multiple endocrine neoplasia type 1 Zollinger-Ellison syndrome neuroendocrine tumor pulmonary atypical carcinoid metastasis prognosis |
| title | Multiple endocrine neoplasia type 1 with Zollinger–Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistry |
| title_full | Multiple endocrine neoplasia type 1 with Zollinger–Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistry |
| title_fullStr | Multiple endocrine neoplasia type 1 with Zollinger–Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistry |
| title_full_unstemmed | Multiple endocrine neoplasia type 1 with Zollinger–Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistry |
| title_short | Multiple endocrine neoplasia type 1 with Zollinger–Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistry |
| title_sort | multiple endocrine neoplasia type 1 with zollinger ellison syndrome clinicopathological analysis of a japanese family with focus on menin immunohistochemistry |
| topic | multiple endocrine neoplasia type 1 Zollinger-Ellison syndrome neuroendocrine tumor pulmonary atypical carcinoid metastasis prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1221514/full |
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