{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:40:12Z","timestamp":1790138412264,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"abstract":"\n Background<\/jats:title>\n In primary aldosteronism (PA), the HISTALDO framework classifies aldosterone\u2010producing lesions as \u2018classical\u2019 (solitary nodule) or \u2018non\u2010classical\u2019 (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\u2010positive 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\u2010guided, generating a modified HISTALDO B2R system in clinical routine.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n Prospective evaluation of the prognostic value of B2R\u2010guided classification in routine pathology and assessment of postoperative outcomes across B2R\u2010defined subgroups.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Specimens of 70 adrenalectomies underwent multisection CYP11B2 staining; 61 patients had at least 6\u2009months of follow\u2010up (mean age 53\u2009years, 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 \u22658.1 defined classical lesions; B2R\u2009<\u20098.1 non\u2010classical. Outcomes at 6\u201312\u2009months were assessed using PASO criteria, which classify biochemical and clinical success as absent, partial or complete.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Biochemical cure was achieved in 95% of patients with classical B2R morphology, compared with 40% of those with non\u2010classical B2R morphology (\n p<\/jats:italic>\n \u2009<\u20090.001). Complete clinical success was also significantly more frequent in the classical B2R group than in the non\u2010classical group (57% versus 25%,\n p<\/jats:italic>\n \u2009=\u20090.0235). Medication\u2010based measures supported these findings: patients with classic histology showed a trend towards reductions in antihypertensive medication expressed as defined daily doses (DDD) (median \u0394DDD 2.83 versus 2.00,\n p<\/jats:italic>\n \u2009=\u20090.1254), and a significantly greater reduction in potassium supplementation (median \u0394DDD 1.25 versus 0.00,\n p<\/jats:italic>\n \u2009<\u20090.001) compared to those with non\u2010classical histology.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n B2R\u2010guided HISTALDO yields biologically distinct subgroups with clear prognostic separation. Earlier work using the original HISTALDO definition reported ~40%\u201345% persistent biochemical aldosteronism in non\u2010classical cases. Our findings reproduce this poor non\u2010classical outcome profile in a larger and more consistently defined B2R\u2010classified cohort. Importantly, incorporating B2R reduces misclassification of tumours as non\u2010classical when background nodularity is present despite a dominant CYP11B2\u2010positive lesion.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/his.70254","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:58:59Z","timestamp":1785833939000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Histopathological stratification of primary aldosteronism using the\n CYP11B2<\/scp>\n size ratio: first evaluation in clinical routine"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3248-7629","authenticated-orcid":false,"given":"Adam","family":"Stenman","sequence":"first","affiliation":[{"name":"Department of Breast, Endocrine Tumors and Sarcoma Karolinska University Hospital Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1777-839X","authenticated-orcid":false,"given":"Tim","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Breast, Endocrine Tumors and Sarcoma Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-6987","authenticated-orcid":false,"given":"Henrik","family":"Falhammar","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden"},{"name":"Department of Endocrinology Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5945-9081","authenticated-orcid":false,"given":"C. Christofer","family":"Juhlin","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet Stockholm Sweden"},{"name":"Department of Pathology and Cancer Diagnostics Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S0140-6736(21)01330-1","article-title":"Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: A pooled analysis of 1201 population\u2010representative studies with 104 million participants","volume":"398","author":"Zhou B","year":"2021","journal-title":"Lancet"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1016\/j.jacc.2017.01.052","article-title":"Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice","volume":"69","author":"Monticone S","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S2213-8587(17)30319-4","article-title":"Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: A systematic review and meta\u2010analysis","volume":"6","author":"Monticone S","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"R45","DOI":"10.1530\/EJE-18-0704","article-title":"Management of endocrine disease: The role of confirmatory tests in the diagnosis of primary aldosteronism","volume":"180","author":"Morera J","year":"2019","journal-title":"Eur. J. 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Endocrinol."},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","DOI":"10.1007\/s12022-026-09912-4","article-title":"Increased frequency and distinct genotypic patterns of somatic aldosterone\u2010driver mutations in aldosterone\u2010producing micronodules from primary aldosteronism patients","volume":"37","author":"Lim JS","year":"2026","journal-title":"Endocr. Pathol."},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jsbmb.2019.04.010","article-title":"Expression of aldosterone synthase CYP11B2 was inversely correlated with longevity","volume":"191","author":"Hayashi T","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1055\/a-1139-2079","article-title":"Immunohistochemistry of the human adrenal CYP11B2 in Normal individuals and in patients with primary aldosteronism","volume":"52","author":"Gomez\u2010Sanchez CE","year":"2020","journal-title":"Horm. Metab. 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Kidney Found."},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","first-page":"18935","DOI":"10.1038\/s41598-025-03912-w","article-title":"Novel predictive factors scoring model for persistent hypertension after adrenalectomy in patients with primary aldosteronism","volume":"15","author":"Harirugsakul K","year":"2025","journal-title":"Sci. Rep."}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70254","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.70254","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.70254","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:59:03Z","timestamp":1785833943000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.70254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":25,"alternative-id":["10.1111\/his.70254"],"URL":"https:\/\/doi.org\/10.1111\/his.70254","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"assertion":[{"value":"2026-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"his.70254"}}