Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens
Abstract Background Adult non-neoplastic hyperinsulinemic hypoglycemia (ANHH), also known as adult-onset nesidioblastosis, is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. This disease is characterized by diffuse hyperplasia of pancreatic endocrine cells and is diagnosed by a p...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Diagnostic Pathology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13000-023-01403-y |
| _version_ | 1797454117892784128 |
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| author | Ryota Nakagawa Sachiko Minamiguchi Tatsuki R. Kataoka Junji Fujikura Toshihiko Masui Masakazu Fujimoto Yosuke Yamada Yasuhide Takeuchi Yuki Teramoto Hiroaki Ito Manduwa Saka Kyohei Kitamura Shinya Otsuki Ryohei Nishijima Hironori Haga |
| author_facet | Ryota Nakagawa Sachiko Minamiguchi Tatsuki R. Kataoka Junji Fujikura Toshihiko Masui Masakazu Fujimoto Yosuke Yamada Yasuhide Takeuchi Yuki Teramoto Hiroaki Ito Manduwa Saka Kyohei Kitamura Shinya Otsuki Ryohei Nishijima Hironori Haga |
| author_sort | Ryota Nakagawa |
| collection | DOAJ |
| description | Abstract Background Adult non-neoplastic hyperinsulinemic hypoglycemia (ANHH), also known as adult-onset nesidioblastosis, is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. This disease is characterized by diffuse hyperplasia of pancreatic endocrine cells and is diagnosed by a pathological examination. While diagnostic criteria for this disease have already been proposed, we established more quantitative criteria for evaluating islet morphology. Methods We measured the number, maximum diameter, total area, and circularity (representing how closely islets resemble perfect spheres) of islets contained in representative sections of ANHH (n = 4) and control cases (n = 5) using the NIS-Elements software program. We also measured the average cell size, percentage of cells with enlarged nuclei, and percentage of cells with recognizable nucleoli for each of three representative islets. We also assessed the interobserver diagnostic concordance of ANHH between five experienced and seven less-experienced pathologists. Results There was no significant difference in the number, maximum diameter, or total area of islets between the two groups, even after correcting for these parameters per unit area. However, the number of islets with low circularity (< 0.71) per total area of the pancreatic parenchyma was significantly larger in ANHH specimens than in controls. We also found that the percentage of cells with recognizable nucleoli was significantly higher in the ANHH group than in the controls. There were no significant differences in the average cell size or the number of cells with enlarged nuclei between the groups. The correct diagnosis rate with the blind test was 47.5% ± 6.12% for experienced pathologists and 50.0% ± 8.63% for less-experienced pathologists, with no significant differences noted. Conclusions Low circularity, which indicates an irregular islet shape, referred to as “irregular shape and occasional enlargement of islets” and “lobulated islet structure” in a previous report, is a useful marker for diagnosing ANHH. An increased percentage of recognizable nucleoli, corresponding to “macronucleoli in β-cells,“ has potential diagnostic value. |
| first_indexed | 2024-03-09T15:32:38Z |
| format | Article |
| id | doaj.art-e631fd30be5b443d81aa2de76a7fb4ae |
| institution | Directory Open Access Journal |
| issn | 1746-1596 |
| language | English |
| last_indexed | 2024-03-09T15:32:38Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Diagnostic Pathology |
| spelling | doaj.art-e631fd30be5b443d81aa2de76a7fb4ae2023-11-26T12:10:53ZengBMCDiagnostic Pathology1746-15962023-10-011811710.1186/s13000-023-01403-yCircularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimensRyota Nakagawa0Sachiko Minamiguchi1Tatsuki R. Kataoka2Junji Fujikura3Toshihiko Masui4Masakazu Fujimoto5Yosuke Yamada6Yasuhide Takeuchi7Yuki Teramoto8Hiroaki Ito9Manduwa Saka10Kyohei Kitamura11Shinya Otsuki12Ryohei Nishijima13Hironori Haga14Department of Diagnostic Pathology, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Pathology, Iwate Medical UniversityDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University HospitalDepartment of Department of Hepatobiliary Pancreatic Surgery and Transplantation, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalDepartment of Diagnostic Pathology, Kyoto University HospitalAbstract Background Adult non-neoplastic hyperinsulinemic hypoglycemia (ANHH), also known as adult-onset nesidioblastosis, is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. This disease is characterized by diffuse hyperplasia of pancreatic endocrine cells and is diagnosed by a pathological examination. While diagnostic criteria for this disease have already been proposed, we established more quantitative criteria for evaluating islet morphology. Methods We measured the number, maximum diameter, total area, and circularity (representing how closely islets resemble perfect spheres) of islets contained in representative sections of ANHH (n = 4) and control cases (n = 5) using the NIS-Elements software program. We also measured the average cell size, percentage of cells with enlarged nuclei, and percentage of cells with recognizable nucleoli for each of three representative islets. We also assessed the interobserver diagnostic concordance of ANHH between five experienced and seven less-experienced pathologists. Results There was no significant difference in the number, maximum diameter, or total area of islets between the two groups, even after correcting for these parameters per unit area. However, the number of islets with low circularity (< 0.71) per total area of the pancreatic parenchyma was significantly larger in ANHH specimens than in controls. We also found that the percentage of cells with recognizable nucleoli was significantly higher in the ANHH group than in the controls. There were no significant differences in the average cell size or the number of cells with enlarged nuclei between the groups. The correct diagnosis rate with the blind test was 47.5% ± 6.12% for experienced pathologists and 50.0% ± 8.63% for less-experienced pathologists, with no significant differences noted. Conclusions Low circularity, which indicates an irregular islet shape, referred to as “irregular shape and occasional enlargement of islets” and “lobulated islet structure” in a previous report, is a useful marker for diagnosing ANHH. An increased percentage of recognizable nucleoli, corresponding to “macronucleoli in β-cells,“ has potential diagnostic value.https://doi.org/10.1186/s13000-023-01403-yAdult non-neoplastic hyperinsulinemic hypoglycemia (ANHH)CircularityDigital pathologyImage analysisIsletsNesidioblastosis |
| spellingShingle | Ryota Nakagawa Sachiko Minamiguchi Tatsuki R. Kataoka Junji Fujikura Toshihiko Masui Masakazu Fujimoto Yosuke Yamada Yasuhide Takeuchi Yuki Teramoto Hiroaki Ito Manduwa Saka Kyohei Kitamura Shinya Otsuki Ryohei Nishijima Hironori Haga Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens Diagnostic Pathology Adult non-neoplastic hyperinsulinemic hypoglycemia (ANHH) Circularity Digital pathology Image analysis Islets Nesidioblastosis |
| title | Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens |
| title_full | Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens |
| title_fullStr | Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens |
| title_full_unstemmed | Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens |
| title_short | Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens |
| title_sort | circularity of islets is a distinct marker for the pathological diagnosis of adult non neoplastic hyperinsulinemic hypoglycemia using surgical specimens |
| topic | Adult non-neoplastic hyperinsulinemic hypoglycemia (ANHH) Circularity Digital pathology Image analysis Islets Nesidioblastosis |
| url | https://doi.org/10.1186/s13000-023-01403-y |
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