title: Warthin-like Mucoepidermoid Carcinoma: A Combined Study of Fluorescence In Situ Hybridization and Whole-slide Imaging.
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.
authors.affiliation: *Department of Pathology and Molecular Diagnostics ‡Department of Otolaryngology, Head and Neck Surgery §Core Laboratory, Graduate School of Medical Sciences, Nagoya City University †Department of Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ito
authors.forename: Ayako
authors.initials: A
authors.lastname: Masaki
authors.forename: Kana
authors.initials: K
authors.lastname: Fujii
authors.forename: Shintaro
authors.initials: S
authors.lastname: Beppu
authors.forename: Takeo
authors.initials: T
authors.lastname: Sakakibara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takase
authors.forename: Kei
authors.initials: K
authors.lastname: Ijichi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shimozato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inagaki
mesh_terms: D000235:Adenolymphoma / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D018277:Carcinoma, Mucoepidermoid / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D004268:DNA-Binding Proteins / Q000235:genetics; D003937:Diagnosis, Differential; D050939:Gene Fusion; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008853:Microscopy; D009687:Nuclear Proteins / Q000235:genetics; D010307:Parotid Neoplasms / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D011237:Predictive Value of Tests; D009626:Terminology as Topic; D015534:Trans-Activators; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C500984:CRTC1 protein, human; C495791:CRTC3 protein, human; D004268:DNA-Binding Proteins; C471297:MAML2 protein, human; D009687:Nuclear Proteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins