Hist-O-07 - Classification of primary cutaneous large B-cell lymphomas according to cell of origin is clinically relevant

Abstract

Primary cutaneous large B-cell lymphomas (PCLBCL) correspond to either PCLBCL, leg type (PCLBCL, LT) or to primary cutaneous follicle centre lymphoma, large cell (PCFCL, LC). Patients with PCFCL, LC are mostly treated by local approaches such as radiotherapy or when multiple lesions by rituximab only. Alternatively, PCLBCL, LT have an aggressive course, requiring a combination of rituximab and polychemotherapy as first line therapy. The combination of clinico-pathological criteria according to WHO-EORTC guidelines permit to classify most cases but those with discordant findings may fall in a not otherwise specified (PLBCL, NOS) category without therapeutic guidelines. Moreover, the expected rate of the NOS diagnosis may vary between centers. We used an already well-characterized retrospective series with long-term follow-up data to evaluate the cell of origin classification of PCLBCL as either germinal center (GC)-type or non-germinal center (NGC)-type using either an immunohistochemical profiling or a reverse transcriptase multiplex ligation assay (RT-MLPA). This cohort contained 21 PCFCL, LC cases, 27 PCLBCL, LT cases and 7 PCLBCL, NOS cases for which the review of clinical data, morphology and immunophenotype could not achieve categorization. The Hans algorithm classified 21 PCFCL, LC cases as GC-type and 27 PCLBCL, LT as NGC-type. Accordingly, the RT-MLPA analysis classified 21 PCFCL, LC cases as GC-type and 25 out of 27 PCLBCL, LT as NGC-type with two undetermined or non-contributive cases containing less than 20% tumoral cells. A concordant profiling between the two techniques permitted to reclassify 4 of the 7 PCLBCL, NOS into either PCFCL, LC (n=2) or PCLBCL, LT (n=2). RT-MLPA profiling was also concordant with lymphopanel mutational analysis providing an integrative categorization of PCLBCL especially in 6 out of 7 NOS cases categorized as PCFCL, LC (n=3) or PCLBCL, LT (n=3). A single case with a discordant profiling remained as NOS and presented with leg involvement, a GC RT-MLPA profile, no mutation and a complete remission. Survival analyses confirmed the clinical relevance of the cell of origin and molecular classifications of PCLBCL reducing the NOS diagnosis to only one case. Primary cutaneous large B-cell lymphomas (PCLBCL) correspond to either PCLBCL, leg type (PCLBCL, LT) or to primary cutaneous follicle centre lymphoma, large cell (PCFCL, LC). Patients with PCFCL, LC are mostly treated by local approaches such as radiotherapy or when multiple lesions by rituximab only. Alternatively, PCLBCL, LT have an aggressive course, requiring a combination of rituximab and polychemotherapy as first line therapy. The combination of clinico-pathological criteria according to WHO-EORTC guidelines permit to classify most cases but those with discordant findings may fall in a not otherwise specified (PLBCL, NOS) category without therapeutic guidelines. Moreover, the expected rate of the NOS diagnosis may vary between centers. We used an already well-characterized retrospective series with long-term follow-up data to evaluate the cell of origin classification of PCLBCL as either germinal center (GC)-type or non-germinal center (NGC)-type using either an immunohistochemical profiling or a reverse transcriptase multiplex ligation assay (RT-MLPA). This cohort contained 21 PCFCL, LC cases, 27 PCLBCL, LT cases and 7 PCLBCL, NOS cases for which the review of clinical data, morphology and immunophenotype could not achieve categorization. The Hans algorithm classified 21 PCFCL, LC cases as GC-type and 27 PCLBCL, LT as NGC-type. Accordingly, the RT-MLPA analysis classified 21 PCFCL, LC cases as GC-type and 25 out of 27 PCLBCL, LT as NGC-type with two undetermined or non-contributive cases containing less than 20% tumoral cells. A concordant profiling between the two techniques permitted to reclassify 4 of the 7 PCLBCL, NOS into either PCFCL, LC (n=2) or PCLBCL, LT (n=2). RT-MLPA profiling was also concordant with lymphopanel mutational analysis providing an integrative categorization of PCLBCL especially in 6 out of 7 NOS cases categorized as PCFCL, LC (n=3) or PCLBCL, LT (n=3). A single case with a discordant profiling remained as NOS and presented with leg involvement, a GC RT-MLPA profile, no mutation and a complete remission. Survival analyses confirmed the clinical relevance of the cell of origin and molecular classifications of PCLBCL reducing the NOS diagnosis to only one case.