Operative Unit of Pathologic Anatomy, Local Health Authority of Romagna, Infermi Hospital, Rimini, Italy.
Operative Unit of Pathologic Anatomy, Local Health Authority of Romagna, St Maria delle Croci Hospital, Ravenna, Italy.
Cancer Cytopathol. 2021 Apr;129(4):275-282. doi: 10.1002/cncy.22368. Epub 2020 Oct 12.
The distinction between mesothelioma with epithelioid features and metastatic carcinoma may be challenging, particularly on cytology. A novel 2-hit Claudin-4 and BRCA-associated protein 1 (BAP1) panel was investigated.
The objective of this study was to determine the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the panel on cytology from pleural effusions and matched biopsies, including 49 malignant mesotheliomas on cytology with 43 matched biopsies, 49 normal/reactive mesothelial proliferations, and 49 pleural metastatic carcinomas from different primaries with 21 matched pleural biopsies. The diagnostic role of the 4 categories obtained by crossing the immunostaining results was analyzed.
Claudin-4 strongly stained all metastatic carcinomas and tested completely negative in normal mesothelium, benign reactive mesothelial hyperplasia, and malignant mesothelioma. All normal and benign mesothelial proliferations and all carcinomas except 1 were immunoreactive for BAP1, whereas BAP1 loss was observed in 88% of malignant mesotheliomas. The expression of Claudin-4 alone excluded all benign and malignant mesothelial growth, consistently characterizing all metastatic carcinomas. Double negativity was evident in all malignant mesotheliomas, and double positivity was observed in all metastatic carcinomas. BAP1-positive/Claudin-4-negative status was observed only in malignant mesotheliomas and benign mesothelial proliferations. A single metastatic anal squamous cell carcinoma had BAP1-negative/Claudin-4-positive staining.
Claudin-4 expression was completely specific and sensitive for metastatic carcinoma, excluding mesothelial proliferations. BAP1 staining characterized 98% of metastatic carcinomas and 100% of benign mesothelial proliferations, whereas negativity was observed almost exclusively in mesotheliomas. This 2-hit panel is probably the best compromise for differentiating malignant mesothelioma and metastatic carcinoma on either cytology or biopsy specimens.
间皮瘤伴上皮样特征与转移性癌的鉴别可能具有挑战性，尤其是在细胞学检查中。本研究旨在评估 Claudin-4 和 BRCA 相关蛋白 1（BAP1）双免疫组化在胸腔积液细胞学和配对活检中的敏感性、特异性、阳性预测值、阴性预测值和准确性，包括 49 例细胞学诊断的恶性间皮瘤及其 43 例配对活检、49 例正常/反应性间皮增生和 49 例来自不同原发灶的胸腔转移癌及其 21 例配对胸膜活检。分析了免疫组化结果交叉获得的 4 种分类的诊断作用。
Claudin-4 染色所有转移性癌均呈强阳性，而正常间皮、良性反应性间皮增生和恶性间皮瘤均完全阴性。所有正常和良性间皮增生以及除 1 例以外的所有癌均为 BAP1 阳性，而 88%的恶性间皮瘤存在 BAP1 缺失。Claudin-4 单独表达可排除所有良性和恶性间皮生长，一致地特征性地表现为所有转移性癌。双阴性在所有恶性间皮瘤中均可见，双阳性在所有转移性癌中均可见。BAP1 阳性/Claudin-4 阴性仅见于恶性间皮瘤和良性间皮增生。1 例转移性肛门鳞状细胞癌为 BAP1 阴性/Claudin-4 阳性染色。
Claudin-4 表达对转移性癌具有完全的特异性和敏感性，可排除间皮增生。BAP1 染色可特征性地表现 98%的转移性癌和 100%的良性间皮增生，而其阴性几乎仅见于间皮瘤。该 2 点免疫组化检测可能是区分细胞学和活检标本中恶性间皮瘤和转移性癌的最佳折衷方案。
