原发性中枢神经系统恶性淋巴瘤MR表现及其病理学基础

目的 研究原发性中枢神经系统恶性淋巴瘤(PCNSL)的MR表现及其病理学基础。方法 分析13例手术病理证实的原发性中枢神经系统恶性淋巴瘤的临床病理及MR表现。结果 13例中单发肿瘤4例，多发肿瘤9例，共计36个病灶。13例病变均累及幕上，其中8例病灶位于深部脑白质近脑室旁。肿瘤平均最大径为3．2cm。T1WI略低信号28个，T2WI等信号24个。28个病灶呈均匀强化。肿瘤水肿及占位效应相对较轻。2例PCNSL行MR动态增强扫描，早期强化均不明显，时间-信号强度曲线呈缓慢上升型。病理上肿瘤细胞弥漫分布，瘤细胞大小较一致，细胞质少，细胞核大，染色质颗粒粗，可见瘤细胞围绕血管呈袖套样浸润，少见明显的出血及片状坏死，未见钙化，病理均为非霍奇金淋巴瘤。结论 原发性中枢神经系统恶性淋巴瘤的病理基础决定其MR增强形态、占位程度以及肿瘤发生部位具有一定特征，运用不同的MR影像学检查方法和技术，在多数情况下可以做出术前正确诊断。     

中枢神经系统原发性弥漫大B细胞淋巴瘤中EZH2蛋白的表达和意义

目的探讨组蛋白甲基转移酶EZH2在中枢神经系统原发性弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达及意义。方法采用免疫组化法检测33例中枢神经系统原发性DLBCL中EZH2的表达,分析其与临床病理学特征之间的关系。结果 33例中枢神经系统原发性DLBCL中20例为中心母细胞型,4例为免疫母细胞型,6例为中间型细胞组成,3例为间变亚型。免疫表型上,25例为非生发中心B细胞样型(non-germinal centre B-cell-like,non-GCB)型,8例为生发中心B细胞样型(germinal centre B-cell-like,GCB)型。全部病例均过表达EZH2蛋白,但不同形态学和免疫表型的DLBCL中EZH2蛋白表达无差异,28例80%~100%肿瘤细胞呈EZH2蛋白强阳性,5例50%~79%肿瘤细胞呈EZH2蛋白中等程度~强阳性。24例患者获得随访,中位生存时间为12.5个月,其中Non-GCB型和GCB型患者的中位生存时间分别为11个月和25个月,EZH2蛋白表达与患者预后无相关性。结论 EZH2在中枢神经系统原发性DLBCL中过表达,提示将来可能用EZH2抑制剂治疗这种高度恶性DLBCL。     

原发性中枢神经系统弥漫性大B细胞淋巴瘤主要为活化B细胞亚型

目的 对原发性中枢神经系统弥漫性大B细胞淋巴瘤分型,并探讨其组织起源和预后相关意义.方法 应用免疫组织化学EnVision二步法,检测CD10、bcl-6、MUM-1、CD138和FOXP1在47例原发性中枢神经系统弥漫性大B细胞淋巴瘤中的表达情况.结果 CD10、bcl-6、MUM-1、CD138和FOXPI表达率分别为6.4%、53.2%、91.5%、0和93.6%.47例中有43例(91.5%)为活化B细胞表型:21例(44.7%)为活化的生发中心亚型,22例(46.8%)为活化的非生发中心亚型.该分型及FOXP1的表达与预后无明显相关性(P=0.279和P=0.154).结论 原发性中枢神经系统弥漫性大B细胞淋巴瘤绝大多数为活化B细胞亚型,是系统性弥漫性大B细胞淋巴瘤中一种相对同质性的亚型,推测其组织起源是生发中心末期至后生发中心早期的B细胞.     

肾脏原发性淋巴瘤临床病理分析

目的 :对肾脏原发性淋巴瘤的临床病理特点、组织学起源、诊断及鉴别诊断等进行初步探讨。方法 :对 1例手术切除的肾脏原发性淋巴瘤标本做HE染色和S P免疫组化染色 ,光镜观察。结果 :左肾脏上极见一 7 5cm× 6cm× 4cm界限不清的肿块。镜下见在肾实质内有弥漫大片淋巴瘤细胞浸润。瘤细胞核呈略不规则形 ,染色质呈凝块状。免疫表型肿瘤细胞表达LCA、L2 6、IgA弥漫阳性。病理诊断为弥漫小核裂细胞型。 结论 :肾脏原发性淋巴瘤甚为罕见。结合文献 ,其主要诊断依据为 :①肾脏内有弥漫大片形态一致的淋巴瘤细胞浸润 ;②肿瘤主要位于肾脏实质内 ,肾包膜及其周围脂肪组织内亦可见瘤细胞浸润 ;③患者浅表淋巴结不肿大 ,CT检查未见胸、腹腔内有肿大的淋巴结 ;④骨髓穿刺涂片和活检未见异常细胞。⑤发现肾脏淋巴瘤至少 3月后未发现其它部位的淋巴瘤。发生于肾脏的淋巴瘤应与肾脏的肉瘤样癌、Wilm瘤、慢性炎症等相鉴别。其主要治疗方法为肾切除加化疗和 (或 )放疗。     

原发CD5阳性弥漫大B细胞淋巴瘤9例临床病理分析

目的探讨原发CD5阳性弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)临床病理特征、诊断及鉴别诊断。方法回顾性分析9例DLBCL临床特点、组织学特征及免疫表型,并进行随访。结果 8例患者为女性,1例为男性,年龄56～83岁,中位年龄70岁。9例均有结外累及,包括骨髓、肺及肾上腺、鼻咽部、回盲部、脾脏、乳腺、胸壁。光镜下见中-大异型淋巴样细胞弥漫浸润,核仁显著。免疫表型:9例CD5、CD20、CD79a呈弥漫阳性,8例BCL-2呈阳性,6例BCL-6呈阳性,5例MUM-1呈阳性,4例CD10呈阳性,Ki-67增殖指数40%～80%。Hans分型:6例为生发中心B细胞(germinal center B-cell,GCB)亚型,3例为活化B细胞(activated B-cell,ABC)亚型。随访6. 5～23. 5个月,1例死亡,6例存活,但病情均进展或复发,2例失访。结论 CD5阳性DLBCL患者的病程呈侵袭性,多见于老人,常累及结外。免疫组化标记BCL-2多为阳性,CD10多为阴性。常规化疗效果不佳,预后较差。     

继发性中枢神经系统淋巴瘤24例临床分析

目的 继发性中枢神经系统淋巴瘤(SCNSL)是非霍奇金淋巴瘤(NHL)继发播散累及到中枢神经系统(CNS)。SCNSL发病率低且预后较差,目前还没有标准的预防及治疗方法。方法 为了进一步了解SCNSL的临床特征和预后,我们回顾性分析了我院2018年1月1日至2022年7月30日收治的24例SCNSL患者的临床特征。结果 24例SCNSL患者的肿瘤组织类型包括17例(70.83%)弥漫性大B细胞淋巴瘤(DLBCL),5例(20.83%)惰性B细胞淋巴瘤,1例(4.17%)外周T细胞淋巴瘤-非特指型淋巴瘤,1例(4.17%)原发纵隔大B细胞淋巴瘤。我们主要关注17例SCNSL(DLBCL)患者的临床特征。起病方式：12例(70.59%)SCNSL(DLBCL)患者为起病时CNS及CNS外同时受累;5例(29.41%)SCNSL(DLBCL)患者为NHL进展时单独CNS受累,而没有同时合并CNS外病灶。病理亚型：13例(76.47%)为非生发中心B细胞来源(non-GCB)亚型。基因分型：11例患者的肿瘤组织进行了二代测序,9例(81.82%)患者的分子亚型为MCD亚型。诊治过程：16例SC...     

淋巴瘤样肉芽肿型大B细胞淋巴瘤

目的 探讨淋巴瘤样肉芽肿型大B细胞淋巴瘤(原名淋巴瘤样肉芽肿病，lymphomatoid granulomatosis，LYG)的病理形态特征、病变性质及鉴别诊断要点。方法 对l例LYG的组织形态学、免疫组织化学、EBV原位分子杂交(EBER)结合临床特征进行了分析。结果 l例63岁男性患者，临床上表现为多系统多器官性病变，主要累及肺，表现为双肺内境界清楚的圆形结节，呈孤立性或弥漫性分布，并出现多发性皮下结节，发热、体重减轻、全身无力等症状。皮下结节活检示多个肉芽肿样结构，细胞形态多样，见组织样细胞、非典型淋巴样细胞、小淋巴细胞、浆细胞及散在多核巨细胞，可见一血管壁有淋巴样细胞浸润，未见明显中心粒细胞，可见核分裂象。肺部穿刺组织示弥漫淋巴样细胞浸润，并见灶性坏死，免疫表型示瘤细胞呈CD20 ，CD79α ，CD43 ,CD3-,GraB-，EBV散在 ，CK-，Syn-，原位杂交示EBER 。结论 本例LYG是一种罕见的淋巴瘤样肉芽肿型大B细胞性淋巴瘤，与EBV相关。临床与影像学上与Wegener肉芽肿相似。肺部出现结节状病灶时，临床上易与结核、肉芽肿病、肺癌及炎性假瘤等相混淆，病理上须与结核、非特异性肉芽肿病、结外的外周T细胞淋巴瘤等相鉴别，形态学、免疫表型结合临床特征可明确诊断。     

原发性中枢神经系统淋巴瘤107例临床病理观察

目的：对原发性中枢神经系统淋巴瘤（PCNSLs）进行临床与病理观察，进一步认识其病理特性。方法：分析107例PCNSLs的临床资料，行HE染色与免疫组化（ABC法）LCA、L26、UCHL－1、Lyso、α1－AT、MAC、GFAP、S－100蛋白、EMA等标记，并区分T、B细胞类型。结果：该肿瘤以40岁以上中老年人多见，以颅内压力增高或肢体麻瘫为主要表现，肿瘤可发生于中枢神经系统的任何部位，以侵犯大脑半球（尤以额、颞叶）较多，PCNSLs的组织学特征为淋巴瘤的瘤细胞形态较单一，如体躯性淋巴瘤胞质常少；病灶周边区瘤细胞常围绕血管形成袖套状，病灶中央的瘤细胞呈片状分布伴灶性坏死和出血，肿瘤侵及脑膜可引起胶原纤维增多，免疫组化染色的33例中，有29例（占84.8%）为B细胞型，其中1例为富T的B细胞型；4例（15.2%）为T细胞型。结论：PCNSLs为高度恶性肿瘤，临床上起病急，主要表现为颅内压力增高、肢体乏力、瘫痪和神经精神症状；瘤细胞形态相似于体躯性淋巴瘤肿瘤周边部瘤细胞，有向血管性，以血管为中心，侵犯血管壁开成袖套状，中心部瘤细胞呈温分布，有坏死、出血，免疫组化显示为B细胞型与T细胞型，患者预后差。     

原发性中枢神经系统淋巴瘤VEGF、MVD与影像学对比研究

目的 :分析原发性中枢神经系统淋巴瘤 (PCNSL)的VEGF表达分布和测量其微血管密度 (MVD) ,旨在提高PCNSL早期诊断率和判断预后 ,同时为影像学提供理论依据。方法 :对 2 2例PCNSL临床 (包括影像学 )病理资料分析 ,同时行VEGF及CD34免疫组化标记 ,并测量MVD ,以 12例胶质瘤作为对照。结果 :2 2例PCNSL中单发者 17例 (占 77 2 7% ) ;多发者 4例 ,共有病灶 10处 ;1例为弥漫浸润型。肿瘤位于脑白质深部者 15例 (占 5 5 5 6 % )、脑表面及灰白质交界区者 8例、胼胝体者4例。CT示肿瘤为边界清楚的高密度结节或肿块。组织病理学示瘤细胞弥漫分布 ,瘤细胞大小较一致 ,胞质少 ,核大 ,可见瘤细胞围绕血管呈“袖套样”浸润。淋巴瘤MVD值 (2 1 8± 11 6 )与恶性胶质瘤组 (44 4± 16 8)的差异有非常显著性 (t =3 374 ,P <0 0 1)。VEGF表达无特异性 ,与对照组比较无统计学意义。结论 :病理学基础决定了影像学的特征。血管生成活性的不同 ,有助于PCNSL与恶性胶质瘤的鉴别 ,并对其预后的判断有一定帮助 ,VEGF可能是恶性肿瘤重要的促血管生成因子 ,但对于鉴别诊断无特异性。     

睾丸原发性弥漫大B细胞淋巴瘤中EZH2蛋白的表达及其意义

目的探讨睾丸原发性弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)中EZH2蛋白的表达、临床病理特征及意义。方法采用免疫组化Ventana Ultra View两步法检测17例睾丸原发性DLBCL中EZH2蛋白的表达,并结合文献分析其病理形态、诊断及鉴别诊断。采用Sanger法检测EZH2 641位点酪氨酸(Y641)突变。结果 11例肿瘤细胞类似中心母细胞,3例肿瘤细胞类似免疫母细胞,3例肿瘤细胞具有间变亚型特点。免疫组化标记显示14例为非生发中心B细胞样(non germinal centre B cell like,non-GCB)型,3例为生发中心B细胞样(germinal centre B cell like,GCB)型;其中15例肿瘤细胞核强阳性表达EZH2蛋白,2例约70%肿瘤细胞核中等强度表达EZH2蛋白;未检测到EZH2 Y641点突变。随访9例患者,中位生存时间35个月,EZH2蛋白的表达与患者预后无相关性。结论睾丸原发性DLBCL属于少见的非霍奇金淋巴瘤,具有独特的临床病理学特征,绝大部分为non-GCB型;EZH2蛋白在睾丸原发性DLBCL过表达,其有望成为肿瘤诊断及治疗的新靶点。     

Clinicopathological features of primary diffuse large B‐cell lymphoma of the central nervous system – strong EZH2 expression implying diagnostic and therapeutic implication

Primary diffuse large B‐cell lymphoma of the central nervous system (CNS DLBCL) is a rare entity which is difficult to diagnose and treat. The histone methyltransferase EZH2 was reported to be involved in the tumorigenesis of systemic DLBCL but has not been implicated in primary CNS DLBCL. The clinicopathological features of 33 cases of primary CNS DLBCL and expression of EZH2 and Y641 mutation were assessed. The tumor cells of the majority cases resembled centroblasts, and intriguingly, three cases of rare anaplastic variant were observed. Immunophenotypically, 25/33 (75.8%) cases were non‐germinal center B‐cell‐like type. Several cases (10/33; 30.3%) co‐expressed BCL2 and MYC, 6/33 (18.2%) expressed both BCL6 and MYC, and 5/33 (15.2%) expressed BCL2, BCL6, and MYC. MYC expression alone and BCL2/MYC co‐expression were associated with poor prognosis. EZH2 was strongly expressed in all 33 cases independent of Y641 mutation and was significantly associated with the tumor proliferative index Ki67. However, no association was found between the level of EZH2 expression and outcomes of patients. In summary, the clinicopathological features including three rare anaplastic variant of primary CNS DLBCL are described. Strong expression of EZH2 in all the primary CNS DLBCL and association with high proliferative index provides further information for treatment and diagnosis of this distinctive entity.     

Diffuse large B-cell lymphoma involving the central nervous system

Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell-like and nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype.     

Primary central nervous system B cell lymphoma with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma

B cell lymphoma with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma (DLBCL/BL) is a new lymphoma entity which is recognized in the current World Health Organization (WHO) classification (2008). We report a case of a primary central nervous system lymphoma (PCNSL) with findings consistent with DLBCL/BL. It is characterized by a very aggressive clinical course, and a widespread multifocal involvement of the CNS. Our case shows that a DLBCL/BL can manifest in the CNS alone without any systemic involvement.     

MYC protein expression is associated with poor prognosis in primary diffuse large B‐cell lymphoma of the central nervous system

MYC and BCL2 gene translocations and protein expression have recently demonstrated to be of prognostic significance in systemic diffuse large B‐cell lymphoma (DLBCL). However, their role in primary central nervous system DLBCL (CNS‐DLBCL) prognosis has been scarcely analyzed. We studied the immunophenotype, the status of the MYC, BCL2, and BCL6 genes and the clinical features of a series of 42 CNS‐DLBCL and evaluated their prognostic significance. We found high MYC protein expression in 43% of cases, and this was associated with lower overall survival (OS). Cases with concurrent expression of MYC and BCL2 showed a lower OS, although the difference did not reach statistical significance. Translocations involving the MYC or BCL2 genes were not detected. The BCL6 gene was frequently translocated, but was unrelated to survival. We conclude that MYC protein expression detected by immunohistochemistry identifies a CNS‐DLBCL subset with worse prognosis and may contribute to a more accurate risk stratification of CNS‐DLBCL patients.     

Array‐based profiling of the lymphoma cell DNA methylome does not unequivocally distinguish primary lymphomas of the central nervous system from non‐CNS diffuse large B‐cell lymphomas

Primary lymphomas of the central nervous system (PCNSL) are diffuse large B‐cell lymphomas (DLBCLs) confined to the central nervous system (CNS). We here performed array‐based DNA methylation analyses of 26 PCNSL and 78 DLBCL and validated our findings in an independent dataset. We identified 2847 CpGs differentially methylated between PCNSL and non‐CNS‐DLBCL. Neither a supervised analysis using these CpGs nor application of 3 CpG classifiers selected for class separation unambiguously separated PCNSL from non‐CNS‐DLBCL. Remarkably, 6/78 non‐CNS‐DLBCL consistently segregated with PCNSL, which displayed molecular features typical for PCNSL. Our findings suggest that a subset of non‐CNS‐DLBCL exists which molecularly resembles PCNSL.     

Aggressive B cell lymphomas in the 2017 revised WHO classification of tumors of hematopoietic and lymphoid tissues

The recent 2017 update of the World Health Organization classification of lymphomas has significant changes from the previous edition. Subtypes of large B cell lymphoma and related aggressive B cell lymphomas are addressed. Clinicopathological features of entities as related to morphology, immunophenotype, cell of origin, and molecular/genetic findings are reviewed with emphasis on changes or updates in findings. Specific subtypes addressed include: T cell/histiocyte-rich large B cell lymphoma, primary diffuse large B cell lymphoma (DLBCL) of the CNS, primary cutaneous DLBCL leg-type, EBV-positive DLBCL, NOS, DLBCL associated with chronic inflammation, primary mediastinal large B cell lymphoma, intravascular large B cell lymphoma, ALK-positive large B cell lymphoma, plasmablastic lymphoma, primary effusion lymphoma, HHV8-positive diffuse large B-cell lymphoma, NOS, Burkitt lymphoma, Burkitt-like lymphoma with 11q aberration, high-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, high grade B cell lymphoma, NOS, B cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma and large B cell lymphoma with IRF4 translocation. In addition, EBV positive mucocutaneous ulcer is addressed.     

Comparative clinicopathological study of primary CNS diffuse large B-cell lymphoma and intravascular large B-cell lymphoma

Primary CNS diffuse large B-cell lymphoma (CNS DLBCL) is confined to the CNS, and constitutes a distinct entity. In the present study a series of 40 Japanese patients with CNS DLBCL who presented with neurological, but not systemic symptoms, was reviewed. Median survival was 18.7 months. CD5, CD10, Bcl-6, MUM-1, and Bcl-2 were positive in 30%, 10%, 84%, 100%, and 93% of patients, respectively. All CD10-negative patients had non-germinal center B-cell type. There was no significant difference in survival among the immunophenotypic subgroups. CNS DLBCL appeared to be homogenous as a group, which prompted the comparison with another distinct extranodal entity, intravascular large B-cell lymphoma (IVLBCL) in Japanese patients. CNS DLBCL patients did not differ in age, sex, or immunophenotype, including CD5 positivity, from IVLBCL patients, but were significantly less likely to have poor prognostic parameters than IVLBCL patients: the international prognostic index score was low or low–intermediate in 86% of CNS DLBCL patients and high or high–intermediate in 98% of IVLBCL patients. Notably, despite this difference, their survival curves almost overlapped. The present study highlights the issue of clinical distinctiveness of aggressive extranodal lymphomas, the peculiar migration and localization of which should be further clarified.     

Immunohistochemical analysis of cleaved caspase-3 detects high level of apoptosis frequently in diffuse large B-cell lymphomas of the central nervous system

The purpose of the present paper was to examine the level of apoptosis and the relationships among apoptosis, apoptosis-associated proteins, and proliferating potential in lymphoma tissues to clarify the characteristics of apoptosis in diffuse large B-cell lymphomas (DLBCL) of the central nervous system (CNS). The formalin-fixed, paraffin-embedded tissues of CNS and non-CNS DLBCL (20 cases each) were studied by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) and immunohistochemistry, using antibodies against single-stranded DNA (ssDNA), cleaved caspase-3, bcl-2, bax, p53, Fas and Ki-67. The cleaved caspase-3 immunohistochemistry detected apoptosis of the lymphoma cells most sensitively compared to TUNEL and ssDNA immunohistochemistry. High expression (grade + + or + + +) of cleaved caspase-3 was found more frequently in CNS DLBCL (11 cases, 55%) than non-CNS DLBCL (three cases, 15%; P = 0.009). Bax-positivity of lymphoma cells was increased in six cases of CNS DLBCL, which also showed high positivity of cleaved caspase-3. There was no significant correlation between the cleaved caspase-3-positivity and the Ki-67 positivity. The present study indicates that the number of apoptotic cells and expression level of cleaved caspase-3 were significantly higher in CNS DLBCL than non-CNS DLBCL, and that the correlation of bax and cleaved caspase-3 expression was often present in CNS DLBCL.     

Primary breast diffuse large B-cell lymphoma shows an activated B-cell-like phenotype

Patients with diffuse large B-cell lymphoma (DLBCL) can be divided into germinal center B-cell-like subtype (GCB-DLBCL) and activated B-cell-like type (ie non-GCB-DLBCL) and with a prognostic value based on the cell of origin of the tumor as determined by microarray analysis, as well as by immunostain algorithms. To stratify primary breast DLBCL, according to immunostain algorithms of Hans, Choi, and Meyer (Tally), the reason why primary breast DLBCL possesses a poor clinical outcome was further elucidated. Twenty-two cases of primary breast DLBCL, diagnosed according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues, were retrospectively studied. Immunochemical study was performed, and follow-up information was analyzed. The histopathologic and immunophenotypic features of all cases were summarized. Among these 22 cases, most (17, 16, and 17, respectively) were assigned to the activated B-cell-like subtypes, few (5, 6, and 5, respectively) were classified as GCB-DLBCL subtype. Fourteen of these 22 cases expressed high proliferative activity (≥40% Ki-67 labeling). Most primary breast DLBCLs have activated B-cell-like subtype characteristics and high proliferative activity; these features might be a significant factor.     

Secondary parenchymal CNS involvement by lymphoma including rare types: Follicular and EBV-positive NK/T cell lymphoma,nasal type

BackgroundSecondary CNS involvement by systemic lymphomas (SCNSL) is uncommon, but when it occurs, is usually due to diffuse large B cell lymphoma (DLBCL). Three recent unusual cases serve to highlight diagnostic challenges.ObjectiveTo report SCNSL from DLBCL and two unusual lymphoma types: follicular lymphoma with high-grade transformation to DLBCL and NK/T cell lymphoma, nasal type (ENKL), nasal type.ResultsSCNSL in the DLBCL case occurred at 7-year interval from primary in a 54-year-old woman who presented with stroke-like symptoms and a right postcentral gyrus 2.6 × 2.9 × 2.6 cm. mass. The follicular lymphoma occurred at 6-month interval in a 69-year-old woman with 1 month of diplopia and 2 weeks of cognitive decline; multifocal lesions involved temporal lobe, subependymal periventricular areas, brainstem, cerebellum, hypothalamus, corpus callosum and gyrus rectus. The ENKL occurred at 25-month interval from nasal biopsy in a 45-year-old man with 1 week of altered mental status; multifocal cerebral and brainstem lesions were identified. Histological features in cases 1 and 3 were identical to the primary lymphoma, with high-grade transformation to DLBCL in the follicular lymphoma.ConclusionUnusual features in our series include longer interval from primary to relapse in case 1 with DLBCL (usually <2 years of diagnosis), and SCNSL occurring from either follicular lymphoma or EKNL, nasal type (<6% of cases). Pathologists play an important role in excluding infectious, especially in cases with parenchymal lesions and characterizing the lymphoma type in SCNSL.