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

Am J Surg Pathol. 2015 Nov;39(11):1479-87. doi: 10.1097/PAS.0000000000000507.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenolymphoma / chemistry
  • Adenolymphoma / classification
  • Adenolymphoma / genetics*
  • Adenolymphoma / pathology*
  • Adenolymphoma / surgery
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Biopsy
  • Carcinoma, Mucoepidermoid / chemistry
  • Carcinoma, Mucoepidermoid / classification
  • Carcinoma, Mucoepidermoid / genetics*
  • Carcinoma, Mucoepidermoid / pathology*
  • Carcinoma, Mucoepidermoid / surgery
  • DNA-Binding Proteins / genetics
  • Diagnosis, Differential
  • Gene Fusion
  • Humans
  • Image Interpretation, Computer-Assisted
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence*
  • Microscopy*
  • Nuclear Proteins / genetics
  • Parotid Neoplasms / chemistry
  • Parotid Neoplasms / classification
  • Parotid Neoplasms / genetics*
  • Parotid Neoplasms / pathology*
  • Parotid Neoplasms / surgery
  • Predictive Value of Tests
  • Terminology as Topic
  • Trans-Activators
  • Transcription Factors / analysis
  • Transcription Factors / genetics
  • Tumor Suppressor Proteins / analysis

Substances

  • Biomarkers, Tumor
  • CRTC1 protein, human
  • CRTC3 protein, human
  • DNA-Binding Proteins
  • MAML2 protein, human
  • Nuclear Proteins
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins