SAT-470 Histological Fingerprint of Bilateral Macronodular Adrenocortical Disease (BMAD) Associated with ARMC5
Notice bibliographique
Résumé
Abstract Disclosure: H.L. Charchar: None. F. Ledesma: None. A.W. Kuhn: None. B.M. Mariani: None. M.Y. Nishi: None. M.Q. Almeida: None. V. Victor Srougi: None. F.Y. Tanno: None. J. Chambô: None. A. Latronico: None. M.A. Pereira: None. B.B. Mendonca: None. M.B. Fragoso: None. Introduction: Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing’s syndrome. Recent discoveries of clonal molecular alterations have highlighted the neoplastic nature of the disease, leading to the proposed term bilateral macronodular adrenocortical disease (BMAD). BMAD is characterized by the presence of functional adrenal macronodules with variable cortisol secretion. It can occur in association with genetic syndromes or present in isolated forms, such as familial or apparently sporadic cases. Since 2013, mutations in the ARMC5 gene have been recognized as a major genetic cause of BMAD. Objective: This study aims to investigate the histological features that enhance our understanding of patients with BMAD. Methods: A total of 19 patients who underwent surgery for BMAD at HCFMUSP between 2006 and 2021 were included in this study, all of whom were sequenced for ARMC5 germline pathogenic variants. Macroscopic photographs and H&E-stained slides were reviewed by a pathologist (FL), who was blinded to the clinical and genetic data. Results: Twelve patients (63.2%) carried germline pathogenic variants in ARMC5. Among them, three were apparently sporadic cases, while nine were familial cases, comprising six unrelated index cases and three relatives. A total of 11 distinct ARMC5 germline variants were identified, including 8 previously reported (p.Arg654; p.Leu365Pro; Ile58Asnfs45; p.His808Pro; p.Pro662Hist; p.Leu318Val; p.Gly323Asp) and 3 novel variants (p.Leu900Serfs12; p.Leu131Phefs7; p.Ser94Valfs8). In addition, nine different somatic alterations were described (p.Glu442Glyfs19; p.Arg366Leufs7; p.Leu526Alafs9; p.Cys657Trp; p.Leu685del; p.Ala854_Val855del; p.Ala83Argfs51; p.Pro695Serfs20; p.Arg271Glyfs7). Patients carrying ARMC5 germline pathogenic variants (Group 1) exhibited distinct microscopic features, including extensive areas of extracapsular extravasation; trabecular and pseudoglandular patterns; reverse polarity with nuclei positioned away from the basement membrane; and absence of adjacent adrenal parenchyma. In contrast, the seven patients without ARMC5 germline pathogenic variants (Group 2; 36.8%) displayed a slight predominance of clear cells interspersed with compact cells, occasionally showing moderate cytoplasm and lightly eosinophilic nodular outlines. Other findings included areas of adipose metaplasia and frequent lymphoid aggregates, which were sometimes confluent. Conclusion: This study presents a cohort of index and relative patients, proposing a histological fingerprint classification for BMAD associated with ARMC5 germline pathogenic variants. Remarkably, blinded pathologists accurately identified patients with ARMC5 germline pathogenic variants with 100% accuracy, highlighting the distinct histological features linked to this genetic alteration. Presentation: Saturday, July 12, 2025
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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