肾上腺血管内大B细胞淋巴瘤的临床病理学特征分析

Clinicopathological analysis of adrenal intravascular large B-cell lymphoma

背景与目的:原发性肾上腺血管内大B细胞淋巴瘤(intravascular large B-cell lymphoma,IVLBCL)是一种罕见的高侵袭性淋巴瘤,目前对其仍缺乏充分认识。本研究旨在探讨肾上腺IVLBCL的临床病理学特征、分子遗传学特征及预后。方法:收集复旦大学附属肿瘤医院病理科2012—2023年诊断的肾上腺IVLBCL病例,回顾性分析其临床及组织病理学特征、免疫表型、治疗和预后,并采用靶向二代测序(next-generation sequencing,NGS)技术探讨其分子遗传学特点。本研究已通过复旦大学附属肿瘤医院伦理委员会审查(伦理编号:050432-4-2307E)。结果:5例肾上腺IVLBCL患者均为男性,中位年龄为52岁(年龄范围50~82岁)。2例因低热而就诊,1例表现为腹痛,1例为体检发现,1例未获得相关信息。外周血检查示2例有血清乳酸脱氢酶升高,2例出现肾上腺功能异常。影像学检查显示,肾上腺增大或占位性病变伴氟代脱氧葡萄糖(fluorodeoxyglucose,FDG)摄取增高;其中4例累及双侧肾上腺,1例累及右侧肾上腺。显微镜下可见异型大淋巴细胞局限于血管腔内,部分病例血管腔内见纤维素性坏死。免疫组织化学染色显示,所有(5/5)病例的肿瘤细胞CD20阳性,Ki-67增殖指数均较高(>80%),80%(4/5)病例呈非生发中心B细胞样(non-germinal-center B-cell-like,non-GCB)表型,100%(4/4)呈MYC/BCL2双表达;血管内皮细胞标志物染色显示,肿瘤细胞绝大多数位于血管内。3例患者获得治疗和随访信息,其中1例仅接受手术切除的患者确诊后5个月死亡,1例经手术切除后接受R-CHOP方案治疗的患者获得完全缓解,1例穿刺活检确诊后接受R-CHOP方案治疗的患者获得部分缓解;1年总生存率为66.7%,总生存期为5~87个月。1例行NGS检测,结果显示,MYD88 V217F、TP53、CDH1、ARID1B、MSH3、MLH3、PTPRK、CD22和FLCN等基因错义突变。结论:肾上腺IVLBCL发病率低,好发于中老年男性,本组病例以non-GCB为主且常伴MYC/BCL2双表达,并存在MYD88非L265P突变。肾上腺IVLBCL由于其临床症状多样化且缺乏特异性导致早期确诊困难,积累更多病例深入了解其临床病理学特征及分子遗传学特征,有助于早期诊断、及时治疗并改善患者预后,为深入认识疾病发生、发展机制、探索治疗靶点提供理论基础。

Background and purpose:Primary adrenal intravascular large B-cell lymphoma(IVLBCL)is rare and highly aggressive.Unfortunately,comprehensive and sufficient understanding of the disease is lacking.This study investigated the clinicopathological and molecular genetic characteristics of adrenal IVLBCL.Methods:Adrenal IVLBCL cases diagnosed from 2012 to 2023 were collected from Department of Pathology,Fudan University Shanghai Cancer Center.The clinical and histopathological features,immunophenotype,treatment and prognosis were analyzed.The molecular genetic characteristics were detected using nextgeneration sequencing(NGS).This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethics number:050432-4-2307E).Results:All of the 5 patients were male,with median age 52 years(ranged 50-82 years).Two cases had low-grade fever,1 case had abdominal pain,1 case was found by physical examination,and the information of the remaining one was unknown.Peripheral blood test showed elevated serum lactate dehydrogenase in 2 cases and adrenal dysfunction in 2 cases.On initial diagnosis,imaging tests displayed adrenal enlargement or masses with increased fluorodeoxyglucose(FDG)uptake.Bilateral adrenal glands were involved in 4 cases and only the right adrenal gland was involved in the other case.Morphologically,large atypical lymphocytes were confined to blood vessels,and fibrinous necrosis was observed in some cases.Immunohistochemical study revealed that CD20 was positive in all cases.Ki-67 proliferation index was high,all above 80%.80%(4/5)of the cases were of non-germinal-center B-cell-like(non-GCB)phenotype,100%(4/4)of the cases had MYC/BCL2 double expression.Endothelial cell markers staining indicated that most of the tumor cells were confined within the blood vessels in all cases.Follow-up data were available in 3 patients.One patient who underwent only surgical resection died 5 months after diagnosis,one achieved complete remission after surgery plus R-CHOP,and the other diagnosed by biopsy achieved a partial remission after R-CHOP.The 1-year overall survival rate was 66.7%,and overall survival was 5-87 months.NGS testing in 1 case showed missense mutations in MYD88 V217F,TP53,CDH1,ARID1B,MSH3,MLH3,PTPRK,CD22 and FLCN.Conclusion:Adrenal IVLBCL is rare and tends to occur in the middle-aged and elderly male.The majority of our patients were non-GCB phenotype,often accompanied by MYC/BCL2 double expression,and MYD88 non-L265P mutation was detected.Early diagnosis of adrenal IVLBCL is difficult due to its diverse clinical symptoms and lack of specificity.It is of great importance to accumulate more cases and further understand the clinicopathological and molecular genetic characteristics of this rare disease,which might not only help with early diagnosis,timely treatment and improvement of prognosis,but also provide a theoretical basis for further understanding the pathogenesis and development of the disease and exploring therapeutic targets.