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Histopathological Classification of Cross-Sectional Image-Negative Hyperaldosteronism
Yuto Yamazaki1, Yasuhiro Nakamura1,2, Kei Omata3,4,5,6,7,8
1Department of Pathology, and.
The Journal of Clinical Endocrinology and Metabolism
|April 8, 2017
Summary
Primary aldosteronism without visible nodules is often due to multiple micronodules (MN) or diffuse hyperplasia (DH). Aldosterone-driver gene mutations are common in these image-negative cases, particularly within MN.
Area of Science:
- Endocrinology
- Pathology
- Genetics
Background:
- Primary aldosteronism (PA) affects many patients with hypertension and/or abnormal hormone levels but lacks detectable nodules on imaging.
- The histopathologic and molecular features of image-negative PA remain poorly understood.
Purpose of the Study:
- To investigate the histopathology, steroidogenic enzyme expression, and gene mutation status in primary aldosteronism cases not visible on routine imaging.
- To classify image-negative PA based on detailed molecular and histological analysis.
Main Methods:
- Retrospective review of 25 image-negative PA cases.
- Immunohistochemistry (IHC) for steroidogenic enzymes (CYP11B2) to assess aldosterone production.
- Next-generation sequencing for somatic mutations in aldosterone-driver genes (ATP1A1, ATP2B3, CACNA1D, KCNJ5) in CYP11B2-positive areas.
Main Results:
- Image-negative PA cases were classified into multiple micronodules (MN; n=13) or diffuse hyperplasia (DH; n=12).
- Somatic mutations in aldosterone-driver genes were found in 81% of CYP11B2-positive micronodules within MN cases, with CACNA1D being the most frequent.
- One DH case showed a CACNA1D mutation in a nodule, but no mutations were found in non-nodular DH areas.
Conclusions:
- Morphological and CYP11B2 IHC analysis can differentiate image-negative PA into MN and DH subtypes.
- Somatic mutations driving aldosterone overproduction are frequent in MN, suggesting a distinct histological entity possibly linked to aldosterone-producing cell clusters.