Double expressor and double/triple hit status among primary cutaneous diffuse large B-cell lymphoma: a comparison between leg type and NOS Subtypes

Primary cutaneous diffuse large B-cell lymphomas (pcDLBCL) are rare hematological neoplasms. pcDLBCL category includes primary cutaneous large B-cell lymphoma "leg type" (pcDLBCL-LT), characterized by a particularly unfavorable outcome, and primary cutaneous large B-cell lymphoma "not otherwise specified" (pcDLBCL-NOS), a widely debated sub-entity with a more indolent course. The negative prognostic impact of double expressor status (DE status, given by coexpression of MYC and BCL2) and double/triple hit status (DH/TH status, given by translocations of MYC and BCL2 and/or BCL6) in nodal DLBCL is well-known; however, no unanimous conclusions regarding relevance of DE and DH/TH status have been reached in pcDLBCL. Therefore, our purpose has been to investigate the presence and prognostic relevance of DE and DH/TH status among a retrospective multicentric cohort of 16 pcDLBCL-LT and 17 pcDLBCL-NOS. All cases were thoroughly re-evaluated, both on a morphological and immunoistochemical level, and tested by means of fluorescence hybridization in situ for MYC, BCL2 and BCL6 rearrangements. DE status was observed in 69% of pcDLBCL-LT and in 24% of pcDLBCL-NOS; however, it did not impact on prognosis in any of the groups examined. Combining molecular results, we highlighted a relevant fraction of DH pcDLBCL (three pcDLBCL-LT and one pcDLBCL-NOS) and the very first case of TH pcDLBCL-LT reported to date. All DH cases were characterized by MYC and BCL6 rearrangements. Overall, DH/TH cases represented 15% (5/33) of all pcDLBCLs and were mostly pcDLBCL-LTs. DH/TH status and DH status alone were associated with poorer OS and DSS (both p<0,05) among all pcDLBCLs, without reaching statistical significance in pcDLBCL-LT and pcDLBCL-NOS groups. In conclusion, MYC, BCL2 and BCL6 cytogenetical testing could be useful in identifying a putative subset of more aggressive pcDLBCLs, although this observation has to be confirmed by further studies.