No abstract

EBV-associated lymphoproliferative disorders (LPD) include conditions of B, T, and NK cell derivation with a wide clinicopathological spectrum ranging from indolent, self-limiting, and localized conditions to highly aggressive lymphomas. Since the 2016 World Health Organization (WHO) lymphoma classification, progress has been made in understanding the biology of the EBV-associated LPDs. The diagnostic criteria of EBV+ mucocutaneous ulcer and lymphomatoid granulomatosis have been refined, and a new category of EBV-positive polymorphic B cell LPD was introduced to encompass the full spectrum of EBV-driven B cell disorders. The differential diagnosis of these conditions is challenging. This report will present criteria to assist the pathologist in diagnosis. Within the group of EBV-associated T and NK cell lymphomas, a new provisional entity is recognized, namely, primary nodal EBV+ T or NK cell lymphoma. The EBV + T and NK cell LPDs in children have undergone major revisions. In contrast to the 2016 WHO classification, now four major distinct groups are recognized: hydroa vacciniforme (HV) LPD, severe mosquito bite allergy, chronic active EBV (CAEBV) disease, and systemic EBV-positive T cell lymphoma of childhood. Two forms of HV LPD are recognized: the classic and the systemic forms with different epidemiology, clinical presentation, and prognosis. The subclassification of PTLD, not all of which are EBV-positive, remains unaltered from the 2016 WHO classification. This review article summarizes the conclusions and the recommendations of the Clinical Advisory Committee (CAC), which are summarized in the International Consensus Classification of Mature Lymphoid Neoplasms.

PURPOSE Peripheral T-cell lymphoma (PTCL) includes heterogeneous clinicopathologic entities with numerous diagnostic and treatment challenges. We previously defined robust transcriptomic signatures that distinguish common PTCL entities and identified two novel biologic and prognostic PTCL-not otherwise specified subtypes (PTCL-TBX21 and PTCL-GATA3). We aimed to consolidate a gene expression–based subclassification using formalin-fixed, paraffin-embedded (FFPE) tissues to improve the accuracy and precision in PTCL diagnosis. MATERIALS AND METHODS We assembled a well-characterized PTCL training cohort (n = 105) with gene expression profiling data to derive a diagnostic signature using fresh-frozen tissue on the HG-U133plus2.0 platform (Affymetrix, Inc, Santa Clara, CA) subsequently validated using matched FFPE tissues in a digital gene expression profiling platform (nCounter, NanoString Technologies, Inc, Seattle, WA). Statistical filtering approaches were applied to refine the transcriptomic signatures and then validated in another PTCL cohort (n = 140) with rigorous pathology review and ancillary assays. RESULTS In the training cohort, the refined transcriptomic classifier in FFPE tissues showed high sensitivity (> 80%), specificity (> 95%), and accuracy (> 94%) for PTCL subclassification compared with the fresh-frozen–derived diagnostic model and showed high reproducibility between three independent laboratories. In the validation cohort, the transcriptional classifier matched the pathology diagnosis rendered by three expert hematopathologists in 85% (n = 119) of the cases, showed borderline association with the molecular signatures in 6% (n = 8), and disagreed in 8% (n = 11). The classifier improved the pathology diagnosis in two cases, validated by clinical findings. Of the 11 cases with disagreements, four had a molecular classification that may provide an improvement over pathology diagnosis on the basis of overall transcriptomic and morphological features. The molecular subclassification provided a comprehensive molecular characterization of PTCL subtypes, including viral etiologic factors and translocation partners. CONCLUSION We developed a novel transcriptomic approach for PTCL subclassification that facilitates translation into clinical practice with higher precision and uniformity than conventional pathology diagnosis.