Warthin-like Mucoepidermoid Carcinoma

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.

MAML2 rearrangement as a useful diagnostic marker discriminating between Warthin tumour and Warthin-like mucoepidermoid carcinoma

“…What is more, our WT cohort comprised no patients younger than 38 years, while all below 45 years were heavy smokers. Similar observations were reported before [9]. Therefore, the status of MAML2 rearrangement should be investigated when a WT is considered in a young, non-smoking, female patient.…”

“…Only newly reported cases of MEC with Warthin-like morphology were included in the analysis; thus, 7 studies reporting 20 cases were included (Table 1 [8][9][10][11][12][13][14]). Similarly, the PubMed database was searched using "Warthin MAML2" and "Warthin t(11;19)" queries (performed on 6 February 2019); subsequently, the reference lists of the included studies were also searched for further articles.…”

“…Originally, García et al reported a series of 12 oncocytic MECs in 2011 [8]. Among these, 5 were described as having Warthin-like histology (all such cases reported to date are summarized in Table 1 [8][9][10][11][12][13][14]) and harboured a mastermindlike transcriptional coactivator 2 (MAML2) rearrangement. This alteration occurs in > 50% of MECs and correlates with low-/intermediate-grade histology and a better prognosis [15].…”

“…Its most common underlying mechanism is t(11;19) translocation, producing CREB-regulated transcription coactivator 1 (CRTC1)-MAML2 gene fusion. Subsequently, Ishibashi et al coined a new term: Warthin-like MEC (WL-MEC) for a subset of tumours characterized by prominent lymphoid stroma and MAML2 rearrangement [9]. The distinction between true WT and Warthin-like MEC is crucial as it carries vital clinical consequences.…”

Intra-Cystic (In Situ) Mucoepidermoid Carcinoma: A Clinico-Pathological Study of 14 Cases

“…Despite its high specificity, MAML2 testing is no longer considered a useful prognostic indicator for already diagnosed MECs, and may be avoided when the diagnosis of MEC is reached straightforwardly, based on typical morphologic features [34,35,37]. Consequently, MAML2 testing as an ancillary diagnostic tool should be reserved for MECs showing unusual histological appearances [38,39], such as the oncocytic variant of MEC, to rule out oncocytoma and oncocytic carcinoma; and the Whartin-like variant and the recently described ciliated MEC variant, to rule out benign developmental cysts and ciliated, HPV-related squamous cell carcinomas [40,41].…”