CRTC1-MAML2 and CRTC3-MAML2 Fusions Were Not Detected in Metaplastic Warthin Tumor and Metaplastic Pleomorphic Adenoma of Salivary Glands

Abstract

The recurrent translocations t(11;19) and t(11;15) resulting in CRTC1-MAML2 or CRTC3-MAML2 fusion oncogenes, respectively, are identified in a large proportion of mucoepidermoid carcinomas (MECs) of the salivary gland and have impact on prognosis. However, there are conflicting data on the specificity of this translocation, in particular, on its putative occurrence in Warthin tumor (WT) of the parotid gland as reported in few previous cases. It was speculated that extensive squamous metaplasia could explain the presence of t(11;19) translocation in a subset of WTs. We evaluated 76 salivary gland tumors, including 16 cases of metaplastic WT and 8 cases of pleomorphic adenoma (PA) with squamous and/or mucinous metaplasia, extensive enough morphologically to mimic MEC. Detection of CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts and MAML2 gene break was performed using nested reverse transcription-polymerase chain reaction and fluorescence in situ hybridization (FISH), respectively. None of 16 analyzed metaplastic WTs showed positivity for fusion transcripts CRTC1-MAML2 or CRTC3-MAML2, and none showed rearrangement of the MAML2 gene by FISH. Similarly, we did not detect these transcripts or break of MAML2 gene in any case of PA with extensive squamous/mucinous metaplasia. For comparison, 40 cases of low-grade MEC were also evaluated. CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts were detected in 17 and 5 cases, respectively. The FISH method using break-apart probe demonstrated the MAML2 gene rearrangement in 25 cases of low-grade MEC. In contrast to low-grade MEC, neither metaplastic WTs nor metaplastic PAs harbored translocations t(11;19) and anticipated t(11;15) resulting in CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts, respectively, and/or MAML2 gene rearrangement.

Warthin Tumour

“…Warthin tumours which are known to histologically overlap considerably with mucoepidermoid carcinoma [ 35 ]. CRTC1-MAML2 and CRTC3-MAML2 fusions were not detected in WT [ 97 ].…”

“…There have been some reports indi- cating that some cells in areas of squamous metaplasia in WT possibly had MAML2 rearrangement. However, a large recent study by Skalova and associates included 16 cases of metaplastic WT, but CRTC1-MAML2 and CRTC3-MAML2 fusions were not detected [ 97 ] (see also Chaps. 7 and 16 ).…”

Translocation-associated Salivary Gland Tumors

“…28 These were considered suspicious for MEC by the authors. Martins et al, 18 Seethala et al, 21 and Skalova et al, 29 have all found no WTs with the MAML2 fusion in a large number of cases, including metaplastic examples. 27 However, another interpretation could be that these represent the "Warthin-like" MECs with prominent lymphoid stroma that have rarely been described 25 and that there was never a benign component in these cases.…”

Thymic Mucoepidermoid Carcinoma

“…25 According to a series of cutaneous MECs, these rare tumors apparently can exhibit CRTC1 rearrangements but not MAML2 aberrations nor t (11;19). 26 [15][16][17]20,27 A recent article by Roden et al 28 describes the presence of MAML2 rearrangement in 2 TMECs and its absence in potential mimics-namely, thymic squamous cell carcinoma (TSCC) and thymic adenosquamous carcinoma (TADS). Herein, we describe a case of TMEC with fluorescence in situ hybridization (FISH) analysis for MAML2 rearrangement as well as reverse transcriptase polymerase chain reaction (RT-PCR) for CRTC1/CRTC3-MAML2 fusion products.…”