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Abstract：
BACKGROUND: MYB RNA in situ hybridization (ISH) has emerged as a reliable and accessible marker to support adenoid cystic carcinoma (ACC) diagnosis, though still not well studied. Here, we report our results in a validation and prospective cohort to improve MYB RNA ISH diagnostic accuracy.
METHODS: 79 cases (23 retrospective and 56 prospective) underwent MYB RNA ISH testing (44 ACC and 35 non-ACC). MYB RNA ISH results were initially interpreted based on previously established (original) scoring criteria. Weighted \"i-scores\", percent positive tumor cells, percent tumor cells with large signals (% LS), and staining pattern (abluminal, diffuse, focal non-patterned, or negative) were inputs for logistic regression models. Final model performance characteristics were compared with original scoring criteria and MYB::NFIB FISH results.
RESULTS: An abluminal pattern was characteristic and exclusive to ACC. All i-scores, % LS, and percent positive were significantly higher in ACC. Original scoring criteria yielded a 95.5% sensitivity (Sn), 68.6% specificity (Sp), and 83.5% accuracy. MYB::NFIB FISH yielded a 42.9% sensitivity, 100% specificity, and 60% accuracy. Optimizing for performance, simplicity, and minimal collinearity, our final model was defined as: abluminal pattern and/or % LS > 16.5%, which resulted in a 93.2% Sn, 97.1% Sp, and 94.9% accuracy for ACC diagnosis. False negatives included an ACC with striking tubular eosinophilia and a MYBL1::NFIB translocated ACC. One false positive exclusive to the final model was a nasopharyngeal carcinoma with MYB amplification.
CONCLUSIONS: MYB RNA ISH has a higher Sn than MYB::NFIB FISH while retaining high Sp. Our model provides improvements to specificity compared to original scoring criteria and highlight the importance of abluminal staining pattern and % LS. Nonetheless, alternate fusions remain key false negatives while rare non-ACC with other mechanisms of MYB activation may present as false positives.
METHODS: 79 cases (23 retrospective and 56 prospective) underwent MYB RNA ISH testing (44 ACC and 35 non-ACC). MYB RNA ISH results were initially interpreted based on previously established (original) scoring criteria. Weighted \"i-scores\", percent positive tumor cells, percent tumor cells with large signals (% LS), and staining pattern (abluminal, diffuse, focal non-patterned, or negative) were inputs for logistic regression models. Final model performance characteristics were compared with original scoring criteria and MYB::NFIB FISH results.
RESULTS: An abluminal pattern was characteristic and exclusive to ACC. All i-scores, % LS, and percent positive were significantly higher in ACC. Original scoring criteria yielded a 95.5% sensitivity (Sn), 68.6% specificity (Sp), and 83.5% accuracy. MYB::NFIB FISH yielded a 42.9% sensitivity, 100% specificity, and 60% accuracy. Optimizing for performance, simplicity, and minimal collinearity, our final model was defined as: abluminal pattern and/or % LS > 16.5%, which resulted in a 93.2% Sn, 97.1% Sp, and 94.9% accuracy for ACC diagnosis. False negatives included an ACC with striking tubular eosinophilia and a MYBL1::NFIB translocated ACC. One false positive exclusive to the final model was a nasopharyngeal carcinoma with MYB amplification.
CONCLUSIONS: MYB RNA ISH has a higher Sn than MYB::NFIB FISH while retaining high Sp. Our model provides improvements to specificity compared to original scoring criteria and highlight the importance of abluminal staining pattern and % LS. Nonetheless, alternate fusions remain key false negatives while rare non-ACC with other mechanisms of MYB activation may present as false positives.
摘要：
背景：MYBRNA原位杂交（ISH）已成为支持腺样囊性癌（ACC）诊断的可靠且可访问的标志物，虽然还没有很好的研究。这里,我们在验证和前瞻性队列中报告了我们的结果,以提高MYBRNAISH诊断准确性.
方法：79例（回顾性23例，前瞻性56例）接受了MYBRNAISH检测（44个ACC和35个非ACC）。MYBRNAISH结果最初基于先前建立的(原始)评分标准来解释。加权\"i-scores\",阳性肿瘤细胞百分比，具有大信号的肿瘤细胞百分比(%LS)，和染色模式(近腔，弥漫,无焦点图案，或阴性)是逻辑回归模型的输入。将最终模型性能特征与原始评分标准和MYB::NFIBFISH结果进行比较。
结果：非房型是ACC特有且独有的。所有i分数，%LS,ACC的阳性百分比明显更高。原始评分标准产生了95.5%的灵敏度(Sn)，68.6%特异性（Sp），准确率为83.5%。MYB::NFIBFISH的灵敏度为42.9%，100%特异性,60％的准确性。优化性能，简单，和最小的共线性，我们的最终模型被定义为：近腔模式和/或%LS>16.5%，导致93.2%的锡，97.1%Sp,ACC诊断准确率为94.9%。假阴性包括伴有明显肾小管嗜酸性粒细胞增多的ACC和MYBL1::NFIB易位的ACC。最终模型独有的一个假阳性是具有MYB扩增的鼻咽癌。
结论：MYBRNAISH具有比MYB::NFIBFISH更高的Sn，同时保持高Sp。与原始评分标准相比，我们的模型提供了对特异性的改进，并强调了近腔染色模式和%LS的重要性。尽管如此，替代融合仍然是关键的假阴性,而具有其他MYB激活机制的罕见非ACC可能表现为假阳性.
方法：79例（回顾性23例，前瞻性56例）接受了MYBRNAISH检测（44个ACC和35个非ACC）。MYBRNAISH结果最初基于先前建立的(原始)评分标准来解释。加权\"i-scores\",阳性肿瘤细胞百分比，具有大信号的肿瘤细胞百分比(%LS)，和染色模式(近腔，弥漫,无焦点图案，或阴性)是逻辑回归模型的输入。将最终模型性能特征与原始评分标准和MYB::NFIBFISH结果进行比较。
结果：非房型是ACC特有且独有的。所有i分数，%LS,ACC的阳性百分比明显更高。原始评分标准产生了95.5%的灵敏度(Sn)，68.6%特异性（Sp），准确率为83.5%。MYB::NFIBFISH的灵敏度为42.9%，100%特异性,60％的准确性。优化性能，简单，和最小的共线性，我们的最终模型被定义为：近腔模式和/或%LS>16.5%，导致93.2%的锡，97.1%Sp,ACC诊断准确率为94.9%。假阴性包括伴有明显肾小管嗜酸性粒细胞增多的ACC和MYBL1::NFIB易位的ACC。最终模型独有的一个假阳性是具有MYB扩增的鼻咽癌。
结论：MYBRNAISH具有比MYB::NFIBFISH更高的Sn，同时保持高Sp。与原始评分标准相比，我们的模型提供了对特异性的改进，并强调了近腔染色模式和%LS的重要性。尽管如此，替代融合仍然是关键的假阴性,而具有其他MYB激活机制的罕见非ACC可能表现为假阳性.
