The recognition of typical and variant histological categories of Nodular lymphocyte predominant Hodgkin lymphoma/B-cell lymphoma have high reproducibility, but challenges in classifying each variant remain

Abstract Background: Nodular lymphocyte predominant Hodgkin Lymphoma/B-cell lymphoma (NLPHL/NLPBL) comprises around 5% of Hodgkin Lymphomas. It is characterized by the presence of lymphocyte predominant cells scattered throughout nodular areas of neoplastic follicles. Six morphological growth patterns with prognostic impact are recognized and grouped as “typical” (“A” and “B”) and “variant” (“C”, “D”, “E”, and ”F”) patterns. These patterns also aid in distinct differential diagnosis considerations. Due to its rarity, morphological and immunohistochemical studies are essential to make progress in the classification of such patterns . The study aims to describe the growth patterns of NLPHL/NLPBL diagnosed in a Brazilian Cancer Center, including immunoarchitectural characteristics of both the tumor cells and the microenvironment, and evaluate reproducibility of typical versus variant pattern diagnosis by general pathologists. Methods : Retrospective histopathological study with cases diagnosed as NLPHL/NLPBL between 2014 and February 2022. Histopathological review for diagnostic confirmation and evaluation of growth patterns was performed by two general pathologists, and a Cohen’s kappa concordance level was evaluated. Cases with major diagnostic discordance were reviewed during a consensus meeting by one or two hematopathologists. Results : Fifty cases of 45 patients were retrieved, including excisional biopsies (36/50, 72,0%) and core biopsies (14/50, 28,0%). Typical growth patterns were the most frequently encountered primary pattern (27/47, 57,4%); among the variant patterns, pattern “E” was the most frequent (9/20, 45,0%). Pattern “F” was not identified, and 3 core biopsies could not be evaluated. Cohen’s kappa was 0.894. There were 3 discordant cases, where challenges were related to small sampling in incisional biopsies and difficulties in differentiating pattern “C” from pattern “E”. T-cell PD1 + rosettes were seen in 92,6% of cases (25/27), being positive for CD4 (16/19, 84,2%) and BCL6 (24/31, 77,4%). Conclusion: The identification of typical and variant growth patterns of NLPHL/NLPBL is highly reproducible by general pathologists. These patterns characterize distinct prognostic subgroups and aid in differential diagnostic considerations for specific immunoarchitectural scenarios. Further studies are needed to deepen the understanding of the different microenvironment of each pattern at the molecular level, aiming to uncover novel diagnostic and prognostic markers.