Clinico-Pathological, Cytogenetic and Molecular Profiles of Primary Cutaneous Diffuse Large B-Cell Lymphomas

: We analyzed the clinico-pathological, cytogenetic and molecular features of 18 Primary Cutaneous Diffuse Large B-Cell Lymphoma (PCDLBCL), and 15 DLBCL secondarily localized to the skin (SCDLBCL), highlighting biologic similarities and differences between the two groups. PCDLBCL were sub classified after histopathological review as PCDLBCL-Leg type (PCDLBCL-LT, 10 cases) and the PCDLBCL-not otherwise specified (PCDLBCL, NOS, 8 cases). Immunohistochemistry for Hans' algorithm markers, BCL2, and MYC was performed. The molecular study included the determination of the cell of origin (COO) by Lymph2Cx assay on Nano string platform, FISH analysis of IgH, BCL2, BCL6, and MYC genes, as well as the mutation analysis of MYD88 gene. At immunohistochemistry, BCL2 and MYC hyper expression was more frequent in LT than in NOS cases and, according to Hans' algorithm, PCDLBCL LT were mostly of the non-GC type (8/10), whereas in PCDLBCL NOS the GC type prevailed (6/8). The determination of COO using Lymph2Cx supported and further confirmed these results. At FISH analysis, all but one LT cases versus 5 out of 8 PCDLBCL NOS showed at least one gene rearrangement among IgH, BCL2, MYC or BCL6. In addition, MYD88 mutations were more frequently present in LT than in NOS subtypes. Interestingly, MYD88- mutated patients were older, with a non-GC phenotype and had worse OS, compared to MYD88 WT cases. Overall, SCDLBCL did not show, at the genetic and expression level, different profiles than PCDLBCL, even if they bear a significantly worse prognosis. At survival analysis, the most important prognostic factors in PCDLBCL patients were age and MYD88 mutation, whereas relapse and high Ki67 expression were relevant in SCDLBCL patients. Our study comprehensively analyzed the clinico-pathological and molecular features of PCDLBCL LT, PCDLBCL-NOS, and SCDLBCL, underlining the differnces among them and the importance of properly identifying these entities at the time of diagnosis.