AIMS: We applied the 2017 WHO classification criteria to categorize a series of 64 primary cutaneous large B-cell lymphomas (PCLBCLs), containing a majority (80%) of large-cells and a proliferative rate 40%, raising the problem of the differential diagnosis between PCLBCLs, leg type (PCLBCLs-LT) or primary cutaneous follicle center lymphomas with large cell morphology (PCFCLs-LC). The aims were to determine reproducibility and prognostic relevance of the 2017 WHO criteria. METHODS AND RESULTS: Morphology and phenotype identified 32 PCLBCLs-LT and 25 PCFCLs-LC; 7 cases (11%) remained unclassified. Morphology was less reproducible than immunophenotype. Pertinent markers for the differential diagnosis were MUM1, FOXP1, CD10 and IgM. BCL2 and BCL6 were expressed by both PCFCLs-LC and PCLBCLs-LT in substantial percentages. Neither Ki67 nor P63 expression had diagnostic value. MYD88 was only found mutated in PCLBCLs-LT (n = 22, 69%). Using Hans/Hans modified algorithms, 23 out of 25 PCFCLs-LC had germinal center (GC) status and the 32 PCLBCLs-LT, non-GC status. Overall survival was poorer for PCLBCLs-LT than PCFCLs-LC (P=0.0002). Non-GC cases had poorer overall survival than GC cases (P=0.0007). In PCLBCLs-LT, MYC expression was associated with cutaneous relapses (P=0.014). Applying GC/non-GC status for unclassified cases, only a single case remained discordant. CONCLUSIONS: Our results support the 2017 WHO classification criteria for PCLBCL diagnosis. The Hans modified algorithm using CD10 and MUM1 distinguished PCFCLs-LC from PCLBCLs-LT with optimal diagnostic value without requiring BCL6 immunolabeling (poor reproducible). Rare unclassified cases may be a provisionally heterogeneous subgroup for which GC/non-GC status (relevant for prognosis) may guide therapeutic decisions. This article is protected by copyright. All rights reserved.< Leer menos