Onofre Fabiana Botelho de Miranda, Onofre Alexandre Sherlley Casimiro, Pomjanski Natalia, Buckstegge Birgit, Grote Hans Juergen, Böcking Alfred
Institute of Cytopathology, Heinrich-Heine University, Dusseldorf, Germany.
Cancer. 2008 Jun 25;114(3):204-15. doi: 10.1002/cncr.23413.
The diagnosis of malignant mesothelioma (MM) in serous effusions is difficult but may be achieved by the application of adjuvant methods.
The authors cytologically diagnosed 33 effusions as suspicious or positive for MM cells by using DNA-image cytometry (DNA-ICM), immunocytochemistry and AgNOR analysis. The authors further detected 9p21 deletions by chromosomal fluorescence in situ hybridization (FISH). In addition, 31 cases of metastatic carcinomas and 39 of tumor cell-negative effusions were investigated. All diagnoses were confirmed by histologic and/or clinical follow-up.
DNA aneuploidy was found in 71% of MMs, 100% of metastatic carcinomas, and in none of the negative effusions. Calretinin was positive in 100% of MMs, in none of the metastatic carcinomas, and in 94.9% of negative effusions. BerEP4 showed positivity in 15.6% of MMs, 87.1% of metastatic carcinomas, and in none of the negative effusions. With AgNOR analysis, 89.3% of MMs and 96.7% of metastatic carcinomas showed >or=2.5 AgNOR dots as satellites and >or=4.5 as total AgNOR counts. 9p21 deletions were demonstrated in 90.9% of MM cases, 45.2% of metastatic carcinomas, and in none of the negative effusions. By cytology alone, 81.8% of MMs were identified unequivocally. Addition of DNA-ICM improved the prevalence of tumor cell detection to 87.9% and of AgNOR analysis to 97%. The introduction of 9p21 deletions by FISH improved this prevalence to 100%.
Because of these results, the authors propose the sequential application of immunocytochemistry, DNA-ICM, and AgNOR analysis to establish a cytological diagnosis of malignant mesothelioma in serous effusions. In persistent doubtful diagnoses, the authors recommend fluorescence in situ hybridization to analyze the 9p21 deletion.
浆液性积液中恶性间皮瘤（MM）的诊断较为困难，但可通过应用辅助方法实现。
作者通过DNA图像细胞术（DNA-ICM）、免疫细胞化学和AgNOR分析，对33例积液进行细胞学诊断，判定为MM细胞可疑或阳性。作者进一步通过染色体荧光原位杂交（FISH）检测9p21缺失。此外，对31例转移性癌和39例肿瘤细胞阴性积液进行了研究。所有诊断均经组织学和/或临床随访证实。
71%的MM、100%的转移性癌存在DNA非整倍体，而阴性积液中均未发现。钙视网膜蛋白在100%的MM中呈阳性，在转移性癌中均为阴性，在94.9%的阴性积液中呈阳性。BerEP4在15.6%的MM、87.1%的转移性癌中呈阳性，在阴性积液中均为阴性。通过AgNOR分析，89.3%的MM和96.7%的转移性癌显示卫星AgNOR点≥2.5个，总AgNOR计数≥4.5个。90.9%的MM病例、45.2%的转移性癌中显示9p缺失，阴性积液中均未发现。仅通过细胞学检查，81.8%的MM能明确诊断。增加DNA-ICM可将肿瘤细胞检测率提高至87.9%，AgNOR分析提高至97%。通过FISH检测9p21缺失可将该检测率提高至100%。
基于这些结果，作者建议依次应用免疫细胞化学、DNA-ICM和AgNOR分析来建立浆液性积液中恶性间皮瘤的细胞学诊断。对于持续存在疑问的诊断，作者建议采用荧光原位杂交分析9p21缺失情况。
