Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Mod Pathol. 2023 Sep;36(9):100237. doi: 10.1016/j.modpat.2023.100237. Epub 2023 Jun 8.
Primary pericardial mesotheliomas are extremely rare, accounting for <1% of all mesotheliomas, and their molecular genetic features and predisposing factors remain to be determined. Here, we report the clinicopathologic, immunohistochemical, and molecular genetic findings of 3 pericardial mesotheliomas without pleural involvement. Three cases diagnosed between 2004 and 2022 were included in the study and analyzed by immunohistochemistry and targeted next-generation sequencing (NGS); corresponding nonneoplastic tissue was sequenced in all cases. Two patients were female and 1 was male, aged between 66 and 75 years. Two patients each had prior asbestos exposure and were smokers. Histologic subtypes were epithelioid in 2 cases and biphasic in 1 case. Immunohistochemical staining identified expression of cytokeratin AE1/AE3 and calretinin in all cases, D2-40 in 2 cases, and WT1 in 1 case. Staining for tumor suppressors revealed loss of p16, MTAP, and Merlin (NF2) expression in 2 cases and loss of BAP1 and p53 in 1 case. Abnormal cytoplasmic BAP1 expression was observed in an additional case. Protein expression abnormalities correlated with NGS results, which showed concurrent complete genomic inactivation of CDKN2A/p16, CDKN2B, MTAP, and NF2 in 2 mesotheliomas and of BAP1 and TP53 in 1 mesothelioma each, respectively. In addition, 1 patient harbored a pathogenic BRCA1 germline mutation, which resulted in biallelic inactivation in the mesothelioma. All mesotheliomas were mismatch repair proficient and showed several chromosomal gains and losses. All patients died from disease. Our study demonstrates that pericardial mesotheliomas share common morphologic, immunohistochemical, and molecular genetic features with pleural mesothelioma, including recurrent genomic inactivation of canonical tumor suppressors. Our study adds new insights into the genetic landscape of primary pericardial mesothelioma and highlights BRCA1 loss as a potential contributing factor in a subset of cases, thereby contributing to refined precision diagnostics for this rare cancer.
原发性心脏包膜间皮瘤极为罕见,占所有间皮瘤的<1%,其分子遗传特征和易患因素仍有待确定。在这里,我们报告了 3 例无胸膜受累的心脏包膜间皮瘤的临床病理、免疫组织化学和分子遗传学发现。这项研究纳入了 2004 年至 2022 年期间诊断的 3 例病例,并通过免疫组织化学和靶向下一代测序(NGS)进行了分析;所有病例均对相应的非肿瘤组织进行了测序。2 例患者为女性,1 例为男性,年龄在 66 岁至 75 岁之间。2 例患者均有石棉暴露史且为吸烟者。组织学亚型 2 例为上皮样,1 例为双相型。免疫组织化学染色显示所有病例均表达细胞角蛋白 AE1/AE3 和钙视网膜蛋白,2 例表达 D2-40,1 例表达 WT1。肿瘤抑制因子染色显示 2 例病例存在 p16、MTAP 和 Merlin(NF2)表达缺失,1 例病例存在 BAP1 和 p53 缺失。在另一个病例中观察到细胞质 BAP1 表达异常。蛋白表达异常与 NGS 结果相关,2 例间皮瘤中同时存在 CDKN2A/p16、CDKN2B、MTAP 和 NF2 的完全基因组失活,1 例间皮瘤中分别存在 BAP1 和 TP53 的失活。此外,1 例患者携带致病性 BRCA1 种系突变,导致间皮瘤中 BRCA1 基因的双等位基因失活。所有间皮瘤均为错配修复功能完整,表现出多种染色体增益和缺失。所有患者均死于疾病。我们的研究表明,心脏包膜间皮瘤与胸膜间皮瘤具有共同的形态学、免疫组织化学和分子遗传学特征,包括经典肿瘤抑制因子的反复基因组失活。我们的研究为原发性心脏包膜间皮瘤的遗传特征提供了新的见解,并强调了 BRCA1 缺失是部分病例的潜在促成因素,从而为这种罕见癌症的精确诊断提供了帮助。