Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.
目的： 探讨睾丸弥漫大B细胞淋巴瘤（DLBCL）的临床病理特征及预后。 方法： 回顾性分析2001年10月至2020年4月上海交通大学医学院附属瑞金医院收治的68例睾丸DLBCL患者的临床病理资料，采用靶向测序（55个淋巴瘤相关基因）评估患者的基因突变情况，同时进行生存和预后因素分析。 结果： 68例睾丸DLBCL中，原发睾丸DLBCL患者45例（66.2%），继发睾丸DLBCL患者23例（33.8%）。继发睾丸DLBCL患者Ann Arbor分期Ⅲ~Ⅳ期（P<0.001）、LDH升高（P<0.001）、ECOG评分≥2分（P＝0.005）、IPI评分3~5分（P<0.001）的比例高于原发睾丸DLBCL患者。62例（91%）患者接受以R-CHOP（利妥昔单抗+环磷酰胺+阿霉素+长春新碱+泼尼松）方案为基础的治疗，54例（79%）患者在化疗前接受睾丸切除术。继发睾丸DLBCL患者的预期5年无进展生存（PFS）率（16.5%对68.1%，P<0.001）及预期5年总生存（OS）率（63.4%对74.9%，P＝0.008）低于原发睾丸DLBCL患者，继发睾丸DLBCL患者的完全缓解率（57%对91%，P＝0.003）也低于原发患者。ECOG评分≥2分（PFS：P＝0.018；OS：P<0.001）、Ann Arbor分期Ⅲ~Ⅳ期（PFS：P<0.001；OS：P＝0.018）、LDH升高（PFS：P＝0.015；OS：P＝0.006）、多结外受累（PFS：P<0.001；OS：P＝0.013）是睾丸DLBCL患者的不良预后因素。20例睾丸DLBCL患者的靶向测序结果显示，突变频率≥20%的突变基因为PIM1（12例，60%）、MYD88（11例，55%）、CD79B（9例，45%）、CREBBP（5例，25%）、KMT2D（5例，25%）、ATM（4例，20%）、BTG2（4例，20%），继发睾丸DLBCL患者KMT2D突变发生率高于原发睾丸DLBCL患者（66.7%对7.1%，P＝0.014），且与睾丸DLBCL患者较低的5年PFS率相关（P＝0.019）。 结论： 继发睾丸DLBCL患者的PFS和OS较原发睾丸DLBCL患者更差。ECOG评分≥2分、Ann Arbor分期Ⅲ~Ⅳ期、LDH升高和多结外受累为睾丸DLBCL的不良预后因素。PIM1、MYD88、CD79B、CREBBP、KMT2D、ATM、BTG2是睾丸DLBCL中常见的突变，KMT2D突变患者预后不佳。.
Keywords: Gene expression profiling; Lymphoma, large B-cell, diffuse; Pathology, clinical; Prognosis; Testis.