CRTC1 rearrangements in the absence of t(11;19) in primary cutaneous mucoepidermoid carcinoma

SummaryBackground Mucoepidermoid carcinoma (MEC) of the skin is an uncommon neoplasm with a remarkable resemblance to MEC of the salivary glands. The latter has been shown to harbour an oncogenic translocation resulting in a fusion gene consisting of exon 1 of CRTC1/MECT1/TORC1 at 19p and exons 2-5 of MAML2 at 11q. Objectives While t(11;19) and rearrangements of the involved loci have been demonstrated in MEC of the salivary gland and other sites, it remains to be determined if morphological similarities in cutaneous MEC are reflected at the molecular level. Methods Cases of cutaneous MEC were defined by three histopathological features: (i) cystic dermal nodule with (ii) overlying intact epidermis and (iii) presence of three cell types (squamoid, intermediate, mucinous), and characterized by reverse transcription-polymerase chain reaction (RT-PCR), interphase fluorescent in situ hybridization (FISH) and immunohistochemistry. Results Eight primary cutaneous MECs were analysed. All informative cases showed CRTC1 rearrangements; none of the cases had MAML2 rearrangements or the presence of t(11;19) by RT-PCR. One case of primary MEC of the breast showed amplification of MAML2 in the absence of CRTC1 or t(11;19). Two MECs metastatic to the skin, histologically identical to primary cutaneous MEC, were included, one of which harboured the CRTC1-MAML2 fusion gene by RT-PCR, verified by interphase FISH and sequencing. Conclusions MEC of the skin harbours CRTC1 rearrangements, a molecular finding that reflects morphological similarities between glandular and cutaneous MEC. The absence of oncogenic t(11;19) or MAML2 aberrations in our series, which is the largest reported, may explain the innocuous clinical behaviour of this uncommon adnexal tumour.