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Abstract：
Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis (HLH) but factors associated with variable manifestations remain undetermined. To evaluate clinical variations and associated factors in SPTCL and/or HLH with/without HAVCR2 mutations, we performed direct sequencing of HAVCR2 exon 2 using DNA from patients with SPTCL or idiopathic HLH/HLH-like systemic illnesses, defined by HLH alone without secondary causes. The systematic review and individual patient data (IPD) level meta-analysis which included the present and previously published studies reporting HAVCR2 mutations in SPTCL with/without HLH populations was subsequently conducted using random-effects meta-analysis and multivariate logistic regression. Among 34 patients enrolled, ten of 28 SPTCL patients developed HLH/HLH-like systemic illnesses. Six cases with HAVCR2Y82C mutation manifested with HLH without panniculitis. Male sex (P=0.03) and age <18 years (P=0.04) were associated with HLH, corresponding to the inverse correlation between age and HLH-2004 score (r=-0.40; P=0.02). Homozygous HAVCR2Y82C mutation was more common in the presence of HLH compared with the absence (75.0% vs. 44.4%; P=0.02). Using IPD from the present and the other three eligible cohorts (N=127), male sex, heterozygous and homozygous/compound heterozygous HAVCR2 mutations were associated with HLH by the adjusted odds ratio of 2.93 (95% confidence interval [CI]: 1.22-7.06), 4.77 (95% CI: 1.05-21.63) and 8.48 (95% CI: 2.98-24.10), respectively. Patients with male sex and/or germline HAVCR2 mutations showed an increased risk of developing HLH. Younger patients tended to manifest with HLH, while older patients typically presented with SPTCL with less frequent HLH/HLH-like systemic illnesses.
摘要：
在有/没有噬血细胞性淋巴组织细胞增多症（HLH）的皮下脂膜炎样T细胞淋巴瘤（SPTCL）患者中经常检测到种系HAVCR2突变，但与可变表现相关的因素仍未确定。为了评估有/没有HAVCR2突变的SPTCL和/或HLH的临床变异和相关因素，我们使用来自SPTCL或特发性HLH/HLH样系统性疾病患者的DNA对HAVCR2外显子2进行直接测序，由无次要原因的单独HLH定义。随后使用随机效应荟萃分析和多变量逻辑回归进行了系统评价和个体患者数据（IPD）水平的荟萃分析，其中包括当前和先前发表的报告有/无HLH人群中HAVCR2突变的SPTCL。在34名患者中，28名SPTCL患者中有10名发展为HLH/HLH样全身性疾病。6例HAVCR2Y82C突变表现为HLH无脂膜炎。男性（p=0.03）和年龄。
