TESTICULAR DIFFUSE LARGE B‐CELL LYMPHOMA: CLINICO‐BIOLOGICAL CHARACTERIZATION, EVALUATION OF TREATMENT RESPONSE AND SURVIVAL

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Background: Testicular diffuse large B-cell lymphoma (T-DLBCL) is an infrequent and aggressive lymphoma accounting for 1-2% of all non-Hodgkin's lymphomas. Although prognosis improved with the introduction of rituximab, the outcome of these patients is still poor. This study aimed to analyze the clinical features and outcome of a series of T-DLBCL as well as to characterize their genomic profile. Methods: We collected 62 patients with T-DLBCL diagnosed between 2002 and 2020. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) tissue biopsies. Copy number alterations (CNA) were studied using OncoScanTM CNV FFPE arrays (Thermofisher) (n = 17) and gene mutations by a B-cell malignancy-oriented targeted next-generation sequencing (NGS) panel containing 121 genes (SureSelectXT, Agilent Technologies) (n = 15). The genomic status of BCL2, BCL6, MYC, and JAK2 locus was also investigated by FISH in 33 cases. Results: Median age at diagnosis was 69 (30-89) years. Sixty-seven percent of the cases had stages I/II, 72% low- or low-intermediate-risk IPI, and 84% (32/39) showed a non-germinal center phenotype (Hans algorithm). In 15 patients with available NGS, the most frequently mutated genes were MYD88 L265P (67%), PIM1 (60%), KMT2D (60%), CD79B (40%), CREBBP (33%), and TBL1XR1 (47%) (Figure 1A). Of note, none of the patients with localized stages had CIITA mutations (p = 0.011). MYC, BCL2, and BCL6 rearrangements were observed in 0%, 9%, and 31% of cases by FISH, respectively. We detected CNA in all samples with a median of 13 alterations per case (range, 1-33), including a median of 6 gains (1-25), 6 losses (0-13), and 3 copy neutral loss of heterozygosity (CN-LOH) (0-8). The most frequent CNA were trisomy 7 (18%) and 18 (18%); gains of 1q (47%), 3 (35%), 6p (29%), 9p24.3-p24.1 (18%), 9p13.2 (29%), 12p13.33-q21.1 (18%), 17q (24%), 18q (29%), and 19q13.32-q14.43 (35%); and losses of 9p21.3 (CDNK2A/B) (59%), 6q21 (PRDM1) (76%), 6q22.31-q24.3 (TNFAIP3) (65%), 13q14.2 (DLEU2) (18%) and 17p (TP53) (35%) (Figure 1B). CN-LOH of 9p region was recurrent in 35% of cases. Moreover, using FISH for JAK2 (9p24) we detected gain in one additional case, corresponding to a total of 4 cases (24%). All but five patients received first-line treatment with immunochemotherapy, mostly R-CHOP (86%), followed by radiotherapy in 63%. Central nervous system prophylaxis was performed in 79% of the patients. Complete response rate was 78%. With a median follow-up of 8 years, eleven patients relapsed, 3 at CNS. Progression-free survival at 5 years was 45% (95% CI: 32-62). Thirty-three (53%) patients died. Overall survival at 5 years was 50% (95% CI: 37-67). The research was funded by: This work was supported by the Instituto de Salud Carlos III, the Ministerio de Ciencia e Innovación and the European Regional Development Fund “Una manera de hacer Europa” [grants numbers PI16/00420 and PI19/00887 to ALG and EG and PI17/01061 to SB ]; CIBERONC [grants numbers CB16/12/00334 and CB16/12/00225]; Fundación AECC/CIBER [grant number PROYE18020BEA]. CL is supported by Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) [grant number 2018-BP-00055]. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Extranodal non-Hodgkin lymphoma, Pathology and Classification of Lymphomas No conflicts of interest pertinent to the abstract.

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