Mlika Mona, Lamzibri Oumeima, Bacha Saoussen, Laabidi Soumeya, Haddouchi Chokri, Mezni Faouzi El
a Department of Pathology, Abderrahman Mami Hospital , Tunis , Tunisia.
b Universite Tunis El Manar , Faculty of Medicine of Tunis , Tunis , Tunisia.
J Immunoassay Immunochem. 2018;39(3):263-273. doi: 10.1080/15321819.2018.1472606. Epub 2018 May 14.
malignant pleural mesothelioma (MPM) is a rare tumor with a challenging diagnosis. Even if, clinical data are mandatory to suspect the diagnosis, the positive diagnosis is based on microscopic features. Morphologic features are still the port of call of the diagnosis but their non specific character and the multiplicity of differential diagnoses made the immunohistochemical markers mandatory for the diagnosis. Many antibodies with a positive diagnostic value including claretinin, mesothelin, WT1 and antibodies with a negative diagnostic value including TTF1, EMA, CD15 are recommended by the scientific societies. This is due to the diagnostic limits of every antibody which necessitate the association of multiple antibodies. In the diagnostic demarch, pathologists deal with different antibodies and clones. Even if many recommendations are available, every pathology lab has to experiment its own antibodies in order to optimize the routine diagnostic demarch especially in low-income country. Our aim was to assess the diagnostic value of different antibodies available in our lab and to recommend a decisional flowchart.
we conducted a retrospective study about 30 MPM diagnosed over a 20-year-period. The different techniques were realized manually. The different antibodies used were anti-calretinin, anti-Epithelial Membrane Antigen (EMA), anti-mesothelin, anti-Thyroid Transcription Factor 1 (TTF1), anti-ACE, anti-cytokeratin, anti-vimentin, anti-CD15, anti-cytokeratin 5/6, anti-bcl2, and anti-CD99 and anti-CD34 antibodies. The sensitivity and specificity of these antibodies were assessed.
the microscopic exam concluded to an epithelioid mesothelioma (EM) in 17 cases, sarcomatoid mesothelioma (SM) in four cases and biphasic mesothelioma (BM) in nine cases. The immunohistochemical study was performed in all cases. A mean of eight antibodies was used in every case, average 4 to 20 antibodies. The immunohistochemical study was repeated from 2 to 5 times in 15 cases and concerned a mean of 3 antibodies per case. In EM and BM, the antibodies with positive predictive value and highest sensitivity were calretinin, EMA, cytokeratin, and vimentin reaching respectively a sensitivity of 86.2%, 89.7%, 92.9% and 89.3%. The most valuable antibodies with negative predictive value were TTF1, CD15 and ACE that presented a specificity reaching respectively 100%. In sarcomatoid mesothelima, the most sensitive antibody was the cytokeratin antibody.
these results yielded to a diagnostic flowchart that we can use in routine practice and that is in accordance with the literature findings. Many diagnostic and technical pitfalls have to be known by pathologists when dealing with MPM.
恶性胸膜间皮瘤（MPM）是一种罕见肿瘤，诊断颇具挑战性。即便临床数据对于怀疑诊断至关重要，但确诊仍基于微观特征。形态学特征仍是诊断的关键依据，但其非特异性以及鉴别诊断的多样性使得免疫组化标志物成为诊断的必要手段。科学协会推荐了许多具有阳性诊断价值的抗体，包括钙网膜蛋白、间皮素、WT1，以及具有阴性诊断价值的抗体，包括甲状腺转录因子1（TTF1）、上皮膜抗原（EMA）、CD15。这是因为每种抗体都有诊断局限性，需要多种抗体联合使用。在诊断过程中，病理学家会处理不同的抗体和克隆。尽管有许多建议可供参考，但每个病理实验室都必须试验自己的抗体，以优化常规诊断流程，尤其是在低收入国家。我们的目的是评估本实验室现有不同抗体的诊断价值，并推荐一个决策流程图。
我们对20年间确诊的30例MPM进行了回顾性研究。不同技术均手动完成。使用的不同抗体包括抗钙网膜蛋白、抗上皮膜抗原（EMA）、抗间皮素、抗甲状腺转录因子1（TTF1）、抗血管紧张素转换酶（ACE）、抗细胞角蛋白、抗波形蛋白、抗CD15、抗细胞角蛋白5/6、抗bcl2、抗CD99和抗CD34抗体。评估了这些抗体的敏感性和特异性。
显微镜检查诊断为上皮样间皮瘤（EM）17例，肉瘤样间皮瘤（SM）4例，双向性间皮瘤（BM）9例。所有病例均进行了免疫组化研究。每个病例平均使用8种抗体，平均4至20种抗体。15例病例免疫组化研究重复进行2至5次，每个病例平均涉及3种抗体。在EM和BM中，具有阳性预测价值且敏感性最高的抗体是钙网膜蛋白、EMA、细胞角蛋白和波形蛋白，敏感性分别达到86.2%、89.7%、92.9%和89.3%。具有阴性预测价值最有价值的抗体是TTF1、CD15和ACE，特异性分别达到100%。在肉瘤样间皮瘤中，最敏感的抗体是细胞角蛋白抗体。
这些结果产生了一个我们可在常规实践中使用且与文献结果相符的诊断流程图。病理学家在处理MPM时必须了解许多诊断和技术陷阱。
