Department of Laboratory Medicine and Pathology.
Division of Pulmonary and Critical Care Medicine.
Am J Surg Pathol. 2018 Feb;42(2):256-263. doi: 10.1097/PAS.0000000000000976.
Distinguishing reactive mesothelial proliferation from malignant mesothelioma (MM) can be difficult, particularly on small biopsies. In this scenario, a diagnosis of atypical mesothelial proliferation might be rendered. However, the distinction between a reactive process and MM is important for prognosis and treatment. Recently, loss of BRCA1-associated protein 1 (BAP1) expression and/or homozygous deletion of CDKN2A were identified in some MM, but not in reactive mesothelial proliferations. We studied 34 cases of atypical mesothelial proliferation from our institutional files (1993 to 2016) for BAP1 expression, deletion of CDKN2A, and clinical outcome. Fifteen of 34 patients (44%) were subsequently diagnosed with MM. BAP1 expression was lost in 6 of these 15 (40%) patients. Ten of 15 (67%) patients died of disease within a median time of 18.2 months. BAP1 expression was also lost in 1 case of probable MM. In this case atypical mesothelial proliferation was identified in the pleura during a lobectomy procedure for lung adenocarcinoma. Follow-up of 57.0 months was remarkable for visceral and parietal pleural thickening with continued unilateral effusion identified on imaging studies but no subsequent definitive diagnosis of MM. CDKN2A studies by fluorescence in situ hybridization (performed in 31 cases) found no homozygous deletion of that gene in any case. In conclusion, loss of BAP1 expression in atypical mesothelial proliferation helps to predict MM and is a useful adjunct test in these cases. Homozygous deletion of CDKN2A in mesothelial cell proliferations did not prove to be useful to predict MM in cases of atypical mesothelial proliferation.
鉴别反应性间皮增生与恶性间皮瘤（MM）可能具有挑战性，尤其是在小活检标本上。在这种情况下，可能会做出非典型间皮增生的诊断。然而，区分反应性过程与 MM 对于预后和治疗很重要。最近，在一些 MM 中发现了 BRCA1 相关蛋白 1（BAP1）表达缺失和/或 CDKN2A 纯合缺失，但在反应性间皮增生中未发现。我们研究了 34 例来自我们机构档案的非典型间皮增生病例（1993 年至 2016 年），检测 BAP1 表达、CDKN2A 缺失和临床结局。其中 15 例（44%）患者随后被诊断为 MM。在这 15 例患者中，有 6 例（40%）BAP1 表达缺失。15 例患者中有 10 例（67%）在中位时间为 18.2 个月内死于疾病。1 例可能的 MM 病例中也观察到 BAP1 表达缺失。在这例病例中，在因肺腺癌行肺叶切除术期间，胸膜中发现了非典型间皮增生。57.0 个月的随访发现内脏和壁层胸膜增厚，影像学研究显示持续单侧胸腔积液，但随后未明确诊断为 MM。荧光原位杂交（FISH）的 CDKN2A 研究在任何病例中均未发现该基因的纯合缺失。总之，非典型间皮增生中 BAP1 表达缺失有助于预测 MM，是这些病例中有用的辅助检测手段。在非典型间皮增生病例中，CDKN2A 在间皮细胞增生中的纯合缺失未能证明对预测 MM 有用。
