以胸痛为首发症状原发性心脏弥漫大B细胞淋巴瘤1例的临床分析并文献复习

Clinical analysis of a case of primary cardiac diffuse large B-cell lymphoma with chest pain as initial symptom and literature review

目的探讨原发性心脏弥漫大B细胞淋巴瘤(DLBCL)患者的临床特征及诊疗策略。方法选择2019年4月26日南京医科大学附属南京医院收治的1例61岁原发性心脏DLBCL男性患者为研究对象。采用回顾性分析方法,对本例患者病史、临床特征、影像学及病理学检查结果等临床资料进行分析。根据本例患者临床表现、影像学及病理学检查结果对其进行诊断与治疗。本研究对本例患者的随访截至2021年4月28日。本研究以"原发性心脏弥漫大B细胞淋巴瘤""primary cardiac diffuse large B-cell lymphoma"为中、英文关键词,检索中国知网数据库、万方数据知识服务平台及PubMed数据库中相关文献,总结与本研究原发性心脏DLBCL患者相关病例的诊疗资料。文献检索时间设定为2019年1月1日至2021年5月31日。本研究符合2013年修订的《世界医学协会赫尔辛基宣言》要求,并且征得受试者及其家属知情同意。结果①本例患者因"反复胸闷、胸痛3 d"于当地医院就诊,发现心脏占位后转诊至南京医科大学附属南京医院心胸外科,既往无特殊病史。②患者于2019年4月26日入本院后再次突发胸闷、胸痛,伴面色苍白,一过性黑矇,心电监护结果示,心率为45次/min,血压为78 mmHg/45 mmHg(1 mmHg=0.133 kPa),血氧饱和度为70%。遂立即予积极抢救,但是患者仍反复发作,考虑患者为右心房占位导致右心室流出道梗阻,有急诊手术指征,于就诊当日对其进行体外循环下右心房占位切除术。术中见肿瘤位于三尖瓣后瓣及隔瓣交界处与冠状静脉窦之间,与心肌相互融合,阻挡三尖瓣瓣口开放及关闭,但是肿物与心肌组织融合,无法完全切除,遂沿肿瘤突起边缘部分切除肿物,以明确病变性质及解除肿物对三尖瓣活动的影响。术中肿物的免疫组织化学结果示,CD20(+)、CD79a(+)、配对盒蛋白(PAX)-5(+)、CD3(-)、CD5(-)、CD10(-)、多发性骨髓瘤癌基因(MUM)-1(-)、B细胞淋巴瘤/白血病(BCL)-6(-)、BCL-2(+)、c-Myc(-)、CD30(-)、EB病毒编码小RNA(EBER)(-)、CD117(-)、Ki-67(60%)、波形蛋白(+)、CD31(-)、结蛋白(-)、细胞角蛋白(CK)(-),考虑为DLBCL。2019年5月16日本例患者被转至本院血液科,正电子发射计算机体层显像仪(PET/CT)检查结果示,右心房肿瘤部分切除术后,右房内团块状略低密度影,18F-氟代脱氧葡萄糖(18F-FDG)代谢增高[摄取区域大小约为9.2 cm×6.3 cm,最大标准摄取值(SUVmax)为29.03],符合肿瘤改变,心包增厚,并有少量积液本例患者。心脏彩色多普勒超声检查结果示,右心房肿瘤部分切除术后,主动脉瓣反流(轻度),二、三尖瓣反流(轻度),左心室舒张功能异常,左心室收缩功能正常,右心房腔内有大小约为53 mm×43 mm不规则高回声,且与右心房侧壁相连,未见其明显移动或者摆动。本例患者骨髓细胞形态学检查结果示,骨髓增生活跃,粒、红、巨核系三系细胞增生,偶见异常细胞,形似淋巴瘤细胞。③结合本例患者的临床特征、PET/CT、活组织免疫组织化学及骨髓细胞形态学检查结果,于2019年5月16日被确诊为原发性心脏DLBCL[非生发中心型,Ⅳ期A组,淋巴瘤国际预后指数(IPI)为4分,美国国立综合癌症网络(NCCN)-IPI为6分]。遂先予1个疗程减低剂量R-CHOP方案(利妥昔单抗300 mg/d,d1+环磷酰胺600 mg/d,d2+表柔比星50 mg/d,d2+长春地辛6 mg/d,d2+泼尼松60 mg/d,d2~6)化疗,随后对其进行4个疗程R-CHOP方案(利妥昔单抗500 mg/d,d1+环磷酰胺1000 mg/d,d2+表柔比星70 mg/d,d2+长春地辛4 mg/d,d2+泼尼松60 mg/d,d2~6)化疗。本例患者中期疗效评估为完全缓解(CR)。建议对其进行自体造血干细胞移植(auto-HSCT),但患者及其家属拒绝。本例患者再次接受2个疗程R-CHOP方案巩固化疗后停止治疗。截止随访结束本例患者无复发。④按照本研究设定的文献检索策略,共纳入17篇文献,报道17例原发性心脏DLBCL患者,加上本例患者共18例患者被纳入进行原发性心脏DLBCL患者诊疗研究。原发性心脏DLBCL患者常见发病部位为右心房,其次为右心室,起病症状主要表现为心脏相关症状,常用化疗方案为R-CHOP,这18例患者中5例死亡,随访最长时间为24个月,患者未复发。结论本例原发性心脏DLBCL患者诊断及时,疗效尚可。原发性心脏DLBCL是一种临床少见且预后欠佳的恶性肿瘤,早发现、早诊断及早治疗有望改善患者预后。

Objective To investigate clinical symptoms,diagnosis and treatment strategies of patients with primary cardiac diffuse large B-cell lymphoma(DLBCL).Methods On April 26,2019,one case of 61 year-old male patient with primary cardiac DLBCL admitted to Nanjing First Hospital was selected as research subject.Clinical data such as medical history,clinical features,imaging and pathology and other examination results were retrospectively analyzed.Patient was diagnosed and treated according to their clinical manifestations,imaging and pathology examination results.The patient was followed up until April 28,2021.With"primary cardiac diffuse large B-cell lymphoma"as the key word in English and Chinese,relevant literature on primary cardiac DLBCL were searched in China National Knowledge Infrastructure database,Wanfang Data Knowledge Service Platform and PubMed database,and clinical characteristics,diagnosis,treatment and prognosis of patients reported in the literature were analyzed and summarized.Literature search period was from January 1,2019 to May 31,2021.This study was line with the requirements of the World Medical Association Declaration of Helsinki revised in 2013,and informed consent was obtained from the subject and their families.Results①This patient was referred to the Cardiothoracic Surgery Department of Nanjing First Hospital for"recurrent chest tightness and chest pain for 3 d"after consultation with a local hospital and was found to have a cardiac occupancy with no previous specific medical history.②The patient was admitted to our hospital on April 26,2019,and then he suddenly experienced chest distress and pain again,accompanied by pale face and amaurosis fugax.Results of electrocardiograph monitoring showed the heart rate was 45 times/min,the blood pressure was 78 mmHg/45 mmHg(1 mmHg=0.133 kPa),and the saturation of peripheral oxygen was 70%.Active rescue was given immediately,but the patient still had recurrent episodes.Considering that the right atrial mass of the patient might lead to right ventricular outflow tract obstruction,there were indications for emergency surgery.This patient underwent right atrial occupancy resection under extracorporeal circulation on April 26,2019.Intraoperatively,the tumor was seen to be located between the posterior tricuspid valve and septal valve junction and coronary sinus,which was fused with the myocardium and blocked the opening and closing of the tricuspid valve,but it could not be completely removed because of the fusion of the mass with the myocardial tissue.The tumor was partially removed along the edge of the tumor protrusion to clarify the nature of the lesion and to relieve the impact of the mass on tricuspid valve motion.Immunohistochemical results of the tumor were CD20(+),CD79a(+),paired box(PAX)-5(+),CD3(-),CD5(-),CD10(-),multiple myeloma oncogene(MUM)-1(-),B cell lymphoma/leukemia(BCL)-6(-),BCL-2(+),c-Myc(-),CD30(-),Epstein-Barr virus encoded RNA(EBER)(-),CD117(-),Ki-67(60%),vimentin foci(+),CD31(-),desmin(-),cytokeratin(CK)(-),and was considered as DLBCL.On May 16,2019,the patient was referred to Department of Hematology,and positron emission tomography and computed tomography(PET/CT)result showed that after partial resection of the right atrial tumor,there was a slightly hypodense focus of mass in the right atrium with increased metabolism of 18F-fluorodeoxyglucose(18F-FDG)[the size of uptake area was approximately 9.2 cm×6.3 cm,and maximum standardized uptake value(SUVmax)was 29.03],which was consistent with tumor changes.Pericardium was thickened with a small amount of fluid.Cardiac color Doppler ultrasonography results showed a right atrial tumor after partial resection and there was mild aortic regurgitation,mild bicuspid and tricuspid regurgitation,abnormal diastolic function of the left ventricle,normal systolic function of the left ventricle,and an irregular hypoechoic sound of about 53 mm×43 mm in the right atrial cavity that was connected to the lateral wall of the right atrium,and did not move or oscillate significantly.Bone marrow cytomorphology showed active bone marrow hyperplasia,with proliferation of granulocytes,erythrocytes,and megakaryocytes,and occasional abnormal cells that resembled lymphoma cells.③This patient was diagnosed with primary cardiac DLBCL[non-germinal center type,stageⅣgroup A,international prognostic index(IPI)scores of 4,National Comprehensive Cancer Network(NCCN)-IPI scores of 6]on May 16,2019.So he was given a reduced dose of R-CHOP regimen(rituximab 300 mg/d,d1+cyclophosphamide 600 mg/d,d2+epirubicin 50 mg/d,d2+vindesine 6 mg/d,d2+prednisone 60 mg/d,d2-6)for 1 course of treatment,followed by 4 courses of adequate R-CHOP regimen(rituximab 500 mg/d,d1+cyclophosphamide 1000 mg/d,d2+epirubicin 70 mg/d,d2+vindesine 4 mg/d,d2+prednisone 60 mg/d,d2-6),and the interim assessment was complete remission(CR),but the patient and his family refused to undergo autologous hemapoietic stem cell transplantation(auto-HSCT),so they continued to receive 2 courses of adequate R-CHOP regimen chemotherapy and then stopped the treatment.By the end of follow-up,the patient had no recurrence.④According to the literature search strategy set in this study,a total of 17 related articles were included,involving 18 cases of primary cardiac DLBCL patients included the patient in this study for diagnosis and treatment research of primary cardiac DLBCL.Most common site of primary cardiac DLBCL patients was the right atrium,followed by the right ventricle.Onset symptoms were mainly heart-related symptoms and the commonly used therapeutic regimen was R-CHOP.Five of the 18 patients who could be counted died,and the longest follow-up was 24 months without recurrence.Conclusions This patient was diagnosed in a timely manner during treatment and had a good outcome.Primary cardiac DLBCL is a rare malignant tumor with poor prognosis,which is expected to improve the early detection,diagnosis and treatment.