Histopathological stratification of primary aldosteronism using the
CYP11B2
size ratio: first evaluation in clinical routine
Adam Stenman, Tim Nilsson, Henrik Falhammar, C. Christofer Juhlin Background
In primary aldosteronism (PA), the HISTALDO framework classifies aldosterone‐producing lesions as ‘classical’ (solitary nodule) or ‘non‐classical’ (multinodular or diffuse) based on CYP11B2 immunohistochemistry, but interpretation is complicated by frequent micronodules, even in patients without PA. The CYP11B2 size ratio (B2R), a quantitative measure of size disproportion between CYP11B2‐positive nodules, offers an objective way to assess lesion architecture and has shown value in predicting cure versus relapse. In this study, diagnostic classification was intentionally B2R‐guided, generating a modified HISTALDO B2R system in clinical routine.
Objective
Prospective evaluation of the prognostic value of B2R‐guided classification in routine pathology and assessment of postoperative outcomes across B2R‐defined subgroups.
Methods
Specimens of 70 adrenalectomies underwent multisection CYP11B2 staining; 61 patients had at least 6 months of follow‐up (mean age 53 years, 54% were females). All had adrenal vein sampling and confirmatory testing before unilateral laparoscopic adrenalectomy. Imaging showed unilateral findings in 51%, bilateral in 8% and no detectable nodules in 41%. A B2R ≥8.1 defined classical lesions; B2R < 8.1 non‐classical. Outcomes at 6–12 months were assessed using PASO criteria, which classify biochemical and clinical success as absent, partial or complete.
Results
Biochemical cure was achieved in 95% of patients with classical B2R morphology, compared with 40% of those with non‐classical B2R morphology ( p < 0.001). Complete clinical success was also significantly more frequent in the classical B2R group than in the non‐classical group (57% versus 25%, p = 0.0235). Medication‐based measures supported these findings: patients with classic histology showed a trend towards reductions in antihypertensive medication expressed as defined daily doses (DDD) (median ΔDDD 2.83 versus 2.00, p = 0.1254), and a significantly greater reduction in potassium supplementation (median ΔDDD 1.25 versus 0.00, p < 0.001) compared to those with non‐classical histology.
Conclusions
B2R‐guided HISTALDO yields biologically distinct subgroups with clear prognostic separation. Earlier work using the original HISTALDO definition reported ~40%–45% persistent biochemical aldosteronism in non‐classical cases. Our findings reproduce this poor non‐classical outcome profile in a larger and more consistently defined B2R‐classified cohort. Importantly, incorporating B2R reduces misclassification of tumours as non‐classical when background nodularity is present despite a dominant CYP11B2‐positive lesion.