Department of Diagnostic Pathology, Kobe University Hospital, Address: 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe, 650-0017, Japan.
Division of Pathology for Regional Communication, Kobe University Graduate School of Medicine, Address: 7-5-2 Kusunoki-Cho, Chuo-Ku, Kobe, 650-0017, Japan.
Diagn Pathol. 2023 Nov 28;18(1):126. doi: 10.1186/s13000-023-01416-7.
Overlapping morphological features of mesothelial cells have been rendered it difficult to distinguish between reactive and malignant conditions. The development of methods based on detecting genomic abnormalities using immunohistochemistry and fluorescence in situ hybridization have contributed markedly to solving this problem. It is important to identify bland mesothelioma cells on cytological screening, perform efficient genomic-based testing, and diagnose mesothelioma, because the first clinical manifestation of pleural mesothelioma is pleural effusion, which is the first sample available for pathological diagnosis. However, certain diagnostic aspects remain challenging even for experts.
This report describes a case of a 72-year-old man with a history of asbestos exposure who presented with pleural effusion as the first symptom and was eventually diagnosed as mesothelioma. Mesothelioma was suspected owing to prominent cell-in-cell engulfment in mesothelial cells on the first cytological sample, and the diagnosis of mesothelioma in situ was confirmed by histology. Unexpectedly, sarcomatoid morphology of mesothelioma was found in the second pathology samples 9 months after the first pathological examination. Both the mesothelioma in situ and invasive lesion showed immunohistochemical loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) on fluorescence in situ hybridization. The patient received medication therapy but died of disease progression 12 months after the diagnosis of the sarcomatoid morphology of mesothelioma.
Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early formation to invasive lesions and/or sarcomatoid morphology. We believe that it is important to consider genetic abnormalities when deciding on individual patient management. Furthermore, cases of mesothelioma, even those of an in situ lesion, with MTAP loss and/or CDKN2A deletion should be carefully followed up or subjected to early treatment.
间皮细胞重叠的形态特征使得区分反应性和恶性状态变得困难。使用免疫组织化学和荧光原位杂交检测基因组异常的方法的发展极大地有助于解决这个问题。在细胞学筛查中识别良性间皮瘤细胞、进行有效的基于基因组的检测以及诊断间皮瘤非常重要，因为胸膜间皮瘤的首次临床表现是胸腔积液，这是用于病理诊断的第一个样本。然而，即使对于专家来说，某些诊断方面仍然具有挑战性。
本报告描述了一例 72 岁男性，有石棉暴露史，以胸腔积液为首发症状，最终被诊断为间皮瘤。由于第一次细胞学样本中间皮细胞的显著细胞内吞噬现象，怀疑为间皮瘤，组织学证实为原位间皮瘤。出乎意料的是，在第一次病理检查 9 个月后，第二次病理样本中发现间皮瘤肉瘤样形态。原位和侵袭性病变均显示免疫组织化学缺失甲基硫腺苷磷酸化酶（MTAP）和细胞周期蛋白依赖性激酶抑制剂 2A（CDKN2A）纯合缺失，荧光原位杂交。患者接受了药物治疗，但在诊断出间皮瘤肉瘤样形态后 12 个月因疾病进展而死亡。
我们的病例表明，在核异型性不明显且多核细胞较少的早期间皮瘤中，细胞内吞噬现象可能很明显。此外，MTAP 缺失和 CDKN2A 纯合缺失的存在可能涉及到从早期原位病变到侵袭性病变和/或肉瘤样形态的形成。我们认为，在决定患者个体管理时，考虑遗传异常非常重要。此外，对于 MTAP 缺失和/或 CDKN2A 缺失的间皮瘤病例，即使是原位病变，也应仔细随访或进行早期治疗。
