SH2D1A基因突变的淋巴瘤患儿6例病例系列报告

背景：SH2D1A 基因突变的儿童淋巴瘤临床罕见且有其特殊的临床特征及疾病预后。 目的：总结伴SH2D1A基因突变的儿童淋巴瘤临床表现、病理特点、治疗方案和预后。 设计：病例系列报告。 方法：纳入2017年6月至 2022年7月于首都医科大学附属儿童医院（我院）初诊为淋巴瘤且年龄＜18岁，经高通量全外显子基因测序提示SH2D1A 基因突变的连续住院病例。根据病理诊断确定治疗方案：侵袭性成熟B细胞淋巴瘤基于改良的LMB89方案治疗；成熟T细胞淋巴瘤合并家族性噬血细胞综合征（HLH）患儿先以HLH方案控制病情，确诊后予SMILE方案化疗。化疗2~3个月行中期疗效评估。化疗结束后3个月评估超声和PET/CT，化疗结束第1、2年内每3个月评估瘤灶超声、肝功能、LDH和免疫功能。 主要结局指标：SH2D1A基因突变淋巴瘤患儿的临床特征和预后。 结果6例伴SH2D1A基因突变淋巴瘤患儿，均为男性；中位发病年龄5（4~12）岁。瘤灶累及胃肠道3例，中枢神经系统、头颈部和多脏器浸润各1例；临床分期：Ⅱ期1例，Ⅲ期3例，Ⅳ期2例；病理类型：3例弥漫大B细胞淋巴瘤，1例高级别成熟B细胞淋巴瘤，1例伴11q异常的伯基特样淋巴瘤，1例儿童系统性EB病毒阳性T细胞淋巴瘤。5例患儿体液免疫和/或细胞免疫指标下降。5例病初全血和血浆EBV DNA均阴性，其中2例病程中复测全血EBV DNA上升至≥105拷贝数/mL；1例病初合并HLH，多次全血EBV DNA为106拷贝数/mL。6例均提示SH2D1A基因突变，2例完善SAP蛋白检测未见异常；1例染色体异常。3例完成化疗，2例因HLH死亡，1例予利妥昔单抗免疫治疗。 结论：SH2D1A基因突变的淋巴瘤患儿临床少见，病理形态多表现为非霍奇金淋巴瘤（成熟B细胞淋巴瘤），预后较差，在合适时机考虑行异基因造血干细胞移植可改善疾病预后。

6 cases of childhood lymphoma with SH2D1A gene mutation: A case series report

Background: Childhood lymphoma with SH2D1A gene mutation is rare in clinical practice and has special clinical features and prognosis. Objective:To summarize the clinical manifestations, pathological features, treatment and prognosis of childhood lymphoma with SH2D1A gene mutation. Design:Case series report. Methods:Consecutive hospitalized patients who were newly diagnosed with lymphoma under the age of 18 and had SH2D1A gene mutation indicated by high throughput whole exon gene sequence were enrolled from Beijing Children's Hospital affiliated to Capital Medical University between June 2017 and July 2022. The treatment plan was determined according to the pathological diagnosis. Invasive mature B cell lymphoma was treated based on the modified LMB89 regimen. Mature T cell lymphoma complicated with hemophagocytic syndrome(HLH) was first controlled by the HLH regimen, and chemotherapy was given after the diagnosis by the SMILE regimen. The efficacy was evaluated in the middle period after 2 to 3 months of chemotherapy. Ultrasound and PET/CT were performed at 3 months after chemotherapy. Tumor ultrasound, liver function, LDH and immune function were tested every 3 months within 1 and 2 years after chemotherapy. Main outcome measures:Clinical characteristics and prognosis of children lymphoma with SH2D1A gene mutation. Results:A total of six male patients of childhood lymphoma with SH2D1A gene mutation were summarized. The median age of onset was 5(4 12) years. The tumor lesions involved the gastrointestinal tract in 3 cases, central nervous system, head and neck, and multiple organs in 1 case each. In terms of clinical stages, there was 1 case of stage Ⅱ, 3 cases of stage Ⅲ, and 2 cases of stage Ⅳ. For pathological types, 3 cases were for diffuse large B cell lymphoma, 1 case for high grade mature B cell lymphoma, 1 case for Burkitt like lymphoma with 11q abnormality, and 1 case for systemic Epstein Barr virus positive T cell lymphoma in children. Humoral immunity and/or cellular immunity decreased in 5 cases. Whole blood and plasma EBV DNA were negative in 5 cases at the beginning of the disease, and whole blood EBV DNA increased to ≥105 copy number /mL during the course of the disease in 2 of them. One patient had familial HLH at the beginning of the disease, with multiple whole blood EBV DNA of 106 copies/mL. Six cases showed SH2D1A gene mutation, among which 2 cases showed no abnormal SAP protein detection; 1 case had chromosomal abnormality; 3 cases completed chemotherapy; 2 cases died due to hemophagocytic syndrome, and 1 case received rituximab immunotherapy. Conclusion:Lymphoma in children with SH2D1A gene mutation is rare in clinical practice. The main pathological manifestation is non Hodgkin lymphoma (mature B cell lymphoma), and the prognosis is poor. Allogeneic hematopoietic stem cell transplantation may improve the prognosis of the disease when there is a need.