Are there EWSR1 rearranged cutaneous hidradenomas and mucoepidermoid carcinomas of salivary glands? A FISH study and review of the literature

Abstract

MAML2 rearrangements have been previously described for hidradenomas and mucoepidermoid carcinomas (MEC). However, one report showed EWSR1 rearrangement in both tumours. In this study, EWSR1 and MAML2 translocation were investigated in hidradenomas and MECs. Specimens from thirteen MECs of the salivary glands and twenty hidradenomas of the skin were evaluated. Fluorescence in situ hybridisation (FISH) studies with EWSR1 and MAML2 break-apart probes were used. Forty percent of hidradenomas and 84.6% of MECs showed a positive MAML2 break signal. EWSR1 break signal was absent in hidradenomas. Only two MECs showed positive EWSR1 signal and were, thus, reclassified as clear cell carcinoma (CCC). A statistically significant relationship was also observed between clear cells containing hidradenomas and the FISH status. Despite the previous study, EWSR1 translocations could not be established in hidradenomas and MECs. The study further suggests that evaluation of EWSR1 might be obligatory for the correct diagnosis of MAML2-negative MECs to exclude the chance of CCCs. The present study also supports the notion that MAML2 can be used as a marker for hidradenomas and MECs.

MAML2 Gene Rearrangement Occurs in Nearly All Hidradenomas: A Reappraisal in a Series of 20 Cases

“…The rate of MAML2 translocation in hidradenomas has believed thought to be in the 50% range. 5,[15][16][17] The significant Winnes et al 6 Krypchova et al 15 Kuma et al 16 Bozdogan et al 17 Sekine et al 19 Behboudi et al 13 Seethala et al 14 Roden et al 24 Bean et al 25 Antonescu et al 30 Vivero et al 31 Zhao et al 32 BAP, break-apart probe; RT-PCR, reverse-transcription polymerase chain reaction.…”

“…The rate of MAML2 translocation in hidradenomas has believed thought to be in the 50% range. 5,15–17 The significant fraction of apparently translocation-negative hidradenomas raised the question of whether there might exist alternate pathways of molecular pathogenesis in hidradenomas. Indeed, we initially intended to identify and then further characterize MAML2 -negative hidradenomas.…”

“…13,14 Studies in hidradenomas have suggested that approximately half possess the translocation, with a range of 40%–59%. 6,15–17 This lack of homogeneity has not been explained. One possibility is that hidradenomas represent a molecularly heterogeneous tumor type, and that some fraction of bona fide hidradenomas operates through distinct molecular pathways, although, to date, no such alternative pathway has been identified.…”

Recent Advances on Immunohistochemistry and Molecular Biology for the Diagnosis of Adnexal Sweat Gland Tumors

“…Discordant or controversial data: EWSR1::POU5F1 fusion has been described in tumors diagnosed as hidradenoma in a single report [58] but has not been further confirmed [59]. A subsequent study has shown that this fusion defined a subset of myoepithelial tumors that can be mistaken for hidradenoma due to an extensive clear cell morphology [60] (cf.…”

“…Discordant or controversial data: EWSR1::POU5F1 translocation is frequent in a subset of myoepithelial tumors with frequent extensive clear cell morphology that can be mistaken for hidradenoma [60]. In this context and before the description of this fusion in clear cell myoepithelial neoplasms, EWSR1::POU5F1 had been reported in tumors diagnosed as hidradenoma in a single report [58] but was not confirmed afterwards [59] (cf. : hidradenoma).…”