Fanaroff Rachel E, Yang Soo-Ryum, Tan Kay See, Adusumilli Prasad S, Bodd Francis, Bowman Anita, Chang Jason, Offin Michael D, Reiner Allison, Rekhtman Natasha, Rusch Valerie W, Travis William D, Zauderer Marjorie G, Ladanyi Marc, Sauter Jennifer L
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland.
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Mod Pathol. 2025 May;38(5):100706. doi: 10.1016/j.modpat.2025.100706. Epub 2025 Jan 7.
Histologic features, including architectural patterns, cytologic features, and 2021 World Health Organization nuclear grade have been shown to have prognostic significance in epithelioid diffuse pleural mesothelioma (DPM). Biphasic and sarcomatoid DPM, regardless of morphology, have worse outcomes. These prognostic findings are well established but the correlation of architectural patterns, cytologic features, and nuclear grade with genetic alterations has not been well studied. To investigate relationships between histologic findings and genomic alterations, 128 treatment-naïve DPM specimens (70% epithelioid, 23% biphasic, and 6.3% sarcomatoid) with next-generation sequencing data were retrospectively reviewed. Alterations in BAP1 were the most common genomic alteration (n = 62, 48%), followed by CDKN2A (n = 49, 38%) and NF2 (n = 38, 30%). NF2 alterations were significantly more frequent in biphasic DPM (53% in biphasic vs 25% in sarcomatoid and 22% in epithelioid DPM; P = .005). In epithelioid DPM, TP53 alterations were associated with the presence of prognostically unfavorable histology, including micropapillary or solid architecture, pleomorphic features, and high nuclear grade. Tumors with low tumor-infiltrating lymphocytes (TILs) had a higher rate of BAP1 alterations than tumors with higher levels of TILs (67% vs 30%; P = .002). The findings of this study enhance our understanding of the relationships among prognostically significant histologic and molecular features of DPM and provide preliminary data to support increased integration of these findings in clinical diagnosis of pleural mesothelioma.
组织学特征，包括结构模式、细胞学特征和2021年世界卫生组织核分级，已被证明在上皮样弥漫性胸膜间皮瘤（DPM）中具有预后意义。双相型和肉瘤样DPM，无论形态如何，预后都较差。这些预后结果已得到充分证实，但结构模式、细胞学特征和核分级与基因改变之间的相关性尚未得到充分研究。为了研究组织学结果与基因组改变之间的关系，我们对128例未经治疗的DPM标本（70%为上皮样，23%为双相型，6.3%为肉瘤样）进行了回顾性分析，并获取了二代测序数据。BAP1改变是最常见的基因组改变（n = 62，48%），其次是CDKN2A（n = 49，38%）和NF2（n = 38，30%）。NF2改变在双相型DPM中明显更常见（双相型中为53%，肉瘤样中为25%，上皮样DPM中为22%；P = .005）。在上皮样DPM中，TP53改变与预后不良的组织学特征有关，包括微乳头或实性结构、多形性特征和高核分级。肿瘤浸润淋巴细胞（TILs）水平低的肿瘤比TILs水平高的肿瘤BAP1改变率更高（67%对30%；P = .002）。本研究结果增进了我们对DPM预后相关组织学和分子特征之间关系的理解，并提供了初步数据，以支持将这些结果更多地整合到胸膜间皮瘤的临床诊断中。
