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Warthin-like Mucoepidermoid Carcinoma: A Combined Study of Fluorescence In Situ Hybridization and Whole-slide Imaging.

Warthin样黏液表皮样癌:FISH及数字切片的联合研究

Ishibashi K,Ito Y,Masaki A,Fujii K,Beppu S,Sakakibara T,Takino H,Takase H,Ijichi K,Shimozato K,Inagaki H

Abstract

There has been some debate as to whether a subset of metaplastic Warthin tumors (mWTs) harbor the mucoepidermoid carcinoma (MEC)-associated CRTC1-MAML2 fusion. We analyzed 15 tumors originally diagnosed as mWT (mWT-like tumors), 2 of which had concurrent MECs. We looked for the CRTC1/3-MAML2 fusion transcripts and performed immunohistochemistry for p63 and fluorescence in situ hybridization (FISH) for the MAML2 split. To localize MAML2 split-positive cells at the cellular level, whole tumor tissue sections were digitalized (whole-slide imaging [WSI]). The CRTC1-MAML2, but not CRTC3-MAML2 was detected in 5/15 mWT-like tumors. FISH-WSI results showed that all epithelial cells harbored the MAML2 split in fusion-positive mWT-like tumors and were totally negative in fusion-negative mWT-like tumors. A review of the hematoxylin and eosin-stained slides showed that morphology of the "metaplastic" epithelium was virtually indistinguishable between fusion-positive and fusion-negative tumors. However, oncocytic bilayered tumor epithelium, characteristic to typical WT, was always found somewhere in the fusion-negative tumors but not in the fusion-positive tumors. This distinguishing histologic finding enabled 5 pathologists to easily differentiate the 2 tumor groups with 100% accuracy. The age and sex distribution of fusion-positive mWT-like tumor cases was similar to that of fusion-positive MEC cases and significantly different from those of fusion-negative mWT-like tumor and typical WT cases. In addition, only fusion-positive mWT-like tumors possessed concurrent low-grade MECs. In conclusion, a subset of mWT-like tumors were positive for the CRTC1-MAML2 fusion and had many features that are more in accord with MEC than with WT. The term Warthin-like MEC should be considered for fusion-positive mWT-like tumors.

摘要

部分化生性Warthin瘤(mWTs)是否有黏表癌(MEC)相关的CRTC1-MAML2融合,一直存在争议。 我们分析了15例初诊为mWT的肿瘤 (mWT样瘤),其中2例同时有MECs。我们试图寻找CRTC1/3-MAML2融合转录 ,行p63免疫组化染色,用FISH法检测MAML2分裂。在细胞水平定位MAML2分裂阳性细胞,对整个肿瘤组织切片进行数字化成像处理(全切片数字成像[WSI])。15例mWT样瘤有5例检测到CRTC1-MAML2,但未检测到CRTC3-MAML2 。FISH—WSI结果显示融合阳性的mWT样瘤中所有的上皮细胞均有MAML2分裂,而融合阴性的mWT样瘤中完全阴性。复习HE染色的切片,显示融合阳性和融合阴性的肿瘤中化生性上皮成分几乎没有区别。然而,融合阴性的肿瘤中总能发现典型的WT特征:双层嗜酸性上皮,而融合阳性的肿瘤中未见此特征。5名病理学家借此可以很容易鉴别两种肿瘤,准确率100%。融合阳性的mWT样瘤,病人年龄和性别分布与融合阳性的MEC相似,但显著不同于融合阴性的mWT样瘤及典型的WT病例。另外,只有融合阳性的mWT样瘤同时伴发低级别MECs。总之,一部分mWT样瘤CRTC1-MAML2融合阳性,它有很多特征与MEC更一致而不是WT。融合阳性的mWT样瘤应考虑应用“Warthin样MEC”这一术语。

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