Primary Aldosteronism

The introduction of CYP11B2 (aldosterone synthase) immunohistochemistry has revolutionized the diagnosis and classification of Primary Aldosteronism (PA). 

The HISTALDO Classification: Modern pathology now categorizes PA into Classical histology (solitary adenomas/nodules) and non-classical histology (multiple micronodules or diffuse hyperplasia). The 2022 WHO Classification of Adrenal Cortical Tumors (5th Edition) formally endorses the HISTALDO nomenclature. More recent studies also proposed a B2R histology system to refine the HISTALDO classification of CYP11B2 pathology in clinical practice. B2R (B2 Ratio) Criteria is the size ratio of the largest to the second-largest CYP11B2-positive nodule. A B2 ratio ≥8.1 is a reliable indicator of classical histology, even when background micronodules are present, and correlate strongly with complete clinical response. 

Predicting Cure vs. Recurrence: Classical Histology (solitary adenomas or nodules) is associated with an excellent prognosis, with a biochemical recurrence risk of <5%. Non-classical Histology (multiple micronodules or diffuse hyperplasia) is associated with a significantly higher risk of biochemical recurrence, estimated at approximately 42%. 

Guiding Post-Surgical Management: It helps clinicians determine which patients are likely cured after a unilateral adrenalectomy and which require aggressive long-term monitoring for potential bilateral or recurrent diseases.

Identifying "Silent" Sources: CYP11B2 IHC allows pathologists to identify tiny, functional aldosterone-producing micronodules (APMs) that are often invisible on standard H&E staining or radiological imaging, ensuring the true source of hormone excess is correctly identified.

Differentiating Unilateral from Bilateral Disease: The classification aids proper subclassification of PA, helping distinguish a unilateral surgical target from a more diffuse, bilateral process that might require medical management rather than surgery.