Patients with primary central nervous system lymphoma (PCNSL) have a prognosis poorer than that of systemic lymphoma patients. In patients with this condition, TLR4/STAT3 pathway alterations and the MYD88 L265P mutation may be viable targets for therapeutic intervention. The present study was, therefore, designed to identify clinicopathologic correlates of MYD88 mutations and TLR4/STAT3 pathway alterations in PCNSL. We detected TLR4 and p-STAT3 in 41.5% (22/53) and 43.4% (23/53) of PCNSL patients, respectively, while 60.4% of these patients (32/53) were found to harbor the MYD88 L265P mutation. TLR4 expression was found to be significantly associated with the presence of multiple brain lesions, while p-STAT3 expression was significantly linked to advanced age, the presence of multiple brain lesions, non-GCB histological findings, and non-CR status. The presence of the MYD88 L265P mutation was significantly linked to advanced age, the presence of multiple brain lesions, and DLBCL molecular subtype. Multivariate analyses additionally confirmed that elevated TLR4 and p-STAT3 expression levels are associated with a poorer PCNSL patient prognosis. Based on these findings, we hypothesize that signaling through the TLR4/MYD88/STAT3 pathway plays a key role in the pathogenesis of PCNSL.

原发性中枢神经系统淋巴瘤（PCNSL）患者的预后较系统性淋巴瘤患者差。在患有这种疾病的患者中，TLR4 / STAT3途径改变和MYD88 L265P突变可能是治疗干预的可行目标。因此，本研究旨在鉴定PCNSL中MYD88突变和TLR4 / STAT3途径改变的临床病理相关性。我们分别在41.5％（22/53）和43.4％（23/53）的PCNSL患者中检测到TLR4和p-STAT3，而这些患者中有60.4％（32/53）被发现具有MYD88 L265P突变。发现TLR4的表达与多种脑病变的存在显着相关，而p-STAT3的表达与高龄，多种脑病变的存在，非GCB组织学表现和非CR状态显着相关。MYD88 L265P突变的存在与高龄，多发性脑损伤和DLBCL分子亚型显着相关。多变量分析还证实，TLR4和p-STAT3表达水平升高与PCNSL患者预后较差有关。基于这些发现，我们假设通过TLR4 / MYD88 / STAT3途径的信号传导在PCNSL的发病机理中起关键作用。