BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood.
OBJECTIVE: We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years.
METHODS: We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI).
RESULTS: The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively.
CONCLUSIONS: This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.

OBJECTIVE: To analyze the risk factors of Epstein-Barr virus (EBV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its impact on survival.
METHODS: The clinical data of 347 patients who underwent their first allo-HSCT in our hospital from January 2014 to June 2021 were retrospectively analyzed. Patients were divided into EBV (n =114) and Non-EBV (n =233) groups according to whether they were infected with EBV. The incidence of EBV infection after allo-HSCT was calculated, and the risk factors of EBV infection were analyzed.
RESULTS: A total of 114(32.8%) patients presented EBV infection (all peripheral blood EBV-DNA were positive). EBV infection occurred in 88 patients within 100 days after transplantation, which accounted for 77.2% of all patients with EBV infection. 5 cases (1.44%) were confirmed as post-transplant lymphoproliferative disorder (PTLD). The median onset time of patients was 57(7-486) days after transplantation. Multivariate analysis showed that the use of ATG/ATG-F, occurrence of CMV viremia, and grade III-IV aGVHD were risk factors for EBV infection. Furthermore, compared to BUCY, the use of intensified preconditioning regimens containing FA/CA was significantly increased the risk of EBV infection.
CONCLUSIONS: EBV infection is a common complication after allo-HSCT. Intensified preconditioning regimens, use of ATG/ATG-F, CMV viremia and grade III to IV aGVHD increase the risk of EBV infection after allo-HSCT.
UNASSIGNED: 异基因造血干细胞移植术后EB病毒感染的临床分析.
UNASSIGNED: 分析异基因造血干细胞移植（allo-HSCT）后EB病毒（EBV）感染发生的危险因素及对生存的影响。.
UNASSIGNED: 回顾性分析2014年1月-2021年6月于本院进行首次allo-AHCT患者的临床资料。共纳入347例接受allo-HSCT的患者，根据是否感染EB病毒(EBV)将其分为EBV组（n =114）和Non-EBV组（n =233）。统计患者allo-HSCT术后EBV感染的发生情况并分析EBV感染的危险因素。.
UNASSIGNED: 有114例（32.8%）患者发生EBV感染（外周血EBV-DNA均阳性），其中，88例（77.2%）发生在移植后100 d内。5例（1.44%）确诊为PTLD (post-transplant lymphoproliferative disorder)。中位发病时间为移植后57（7-486）d。多因素分析结果显示，ATG/ATG-F的使用、CMV血症和III-IV度aGVHD的发生是EBV感染的危险因素；此外，相对于BuCy，应用包含FA/CA的强化预处理方案者EBV感染的风险显著增高。.
UNASSIGNED: EBV感染是allo-HSCT术后常见并发症，强化预处理方案、ATG/ATG-F的使用、CMV血症和III-IV度aGVHD的发生会增加allo-HSCT后EBV感染的风险。.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder. With the method of indirect immunofluorescence assay (IIF), more anti-NMDAR encephalitis patients have been discovered when its first onset. But it was rare that anti-NMDAR encephalitis overlapped with multiple sclerosis (MS) documented in literatures. Here, we present a case who initially developed anti-NMDAR encephalitis and MS. Furthermore, we concluded the characteristics of patients who were diagnosed as anti-NMDAR encephalitis overlapping with MS. Additionally, due to the relapsing process, mycophenolate mofetil and sequentially fingolimod for the treatment were taken, which subsequently led to the development of a lymphoproliferative disease in his brain and other organs. This case illustrates the complex role of immunosuppressive agents.

BACKGROUND: Epstein-Barr virus-associated lymphoproliferative disorders (EBV-LPDs) are a group of disorders involving lymphoid tissues or lymphocytes. The epidemiology and economic burden of hospitalized children with EBV-LPDs in China have not been well studied. This study aimed to reveal the epidemic characteristics and disease burden of EBV-LPDs among the Chinese hospitalized children, providing strategies for the prevention and management.
METHODS: This study was based on the FUTang Updating medical REcords (FUTURE) database of China and collected the medical records from 27 tertiary children\'s hospitals between January 2016 and December 2021 in China, counting five types of EBV-LPDs, namely EBV-positive T-cell lymphoproliferative disease, NK/T cell lymphoma, extranodal NK/T-cell lymphoma (nasal type), systemic EBV-positive T-cell lymphoproliferative disease of childhood and posttransplant lymphoproliferative disorders. We conducted a retrospective syhthesis and analysis of the epidemiological characteristics, expenses, length of stay (LOS), as well as complications among hospitalized children diagnosed with five types of EBV-LPDs and compared parameters using appropriate statistical tests.
RESULTS: The study described 153 children aged 0-18 years hospitalized with EBV-LPDs from 2016 to 2021 in the FUTURE database. The male-to-female ratio was 1.10:1, and more than half of the age distribution was in the 6-12 y group. Among EBV-LPDs cases, EBV+ T-LPD accounted for the largest proportion (65.36%). Complications were presented in 93 children with EBV-LPDs, mainly hemophagocytic lymphohistiocytosis (HLH). The median LOS of NKTL was 26.5 days [interquartile range (IQR) = 3-42], which was the longest among EBV-LPDs. The median hospitalization cost of PTLD was 10 785.74 United States dollars (IQR = 7 329.38-16 531.18), which was the heaviest among EBV-LPDs.
CONCLUSIONS: Compared with the total number of hospitalized children in China during the same period and in the same age group, the proportion of EBV-LPD is very low. EBV-LPD can develop in all age groups, but it is more common in school-age children. Among 5 EBV-LPDs, the disease with the highest proportion is EBV+ T-LPD. The overall disease burden of EBV-LPD was heavy, especially the economic burden. HLH was one of the most common complications, which could directly affect the burden of patients because of prolonged hospitalization. These data are taken from a very large database, illustrating the epidemiological and economic burden of EBV-LPDs hospitalized children in China, which enriched the existing epidemiological and disease burden content of EBV-LPDs.

ITK突变引起的原发性免疫缺陷的淋巴增殖性疾病比较罕见，及时诊断是改善原发性免疫缺陷病的结局并降低其病死率的重要因素。本文报道1例罕见的ITK杂合突变的原发性免疫缺陷的患儿，腹股沟肿块及颈部淋巴结活检提示Burkitt淋巴瘤及淋巴增殖性疾病。临床特征表现为全身淋巴结肿大、严重的EB病毒感染、CD4+T细胞持续减少、双阴性T细胞增加、IgG水平升高、血小板及中性粒细胞减少、低纤维蛋白原血症及高γ球蛋白血症。此病例具有自身免疫性淋巴细胞增生综合征样疾病的临床表现及实验室特征。.

Objective: To investigate the clinicopathological features and differential diagnosis of primary mucosal CD30-positive T-cell lymphoproliferative disorders (pmCD30+TLPD). Methods: Eight cases of pmCD30+TLPD diagnosed from 2013 to 2023 at the Department of Pathology, Beijing Friendship Hospital Affiliated to Capital Medical University and Beijing Ludaopei Hospital were retrospectively collected. The immunophenotype, EBV infection status and T-cell receptor (TCR) clonability of tumor cells were examined. The clinicopathological features were analyzed and related literatures were reviewed. Results: There were 5 females and 3 males, aged 28 to 73 years, without B symptoms, lack of trauma and autoimmune diseases. Seven cases occurred in oral mucosa and one in anal canal mucosa. Submucosal nodules with ulcerations were presented in all cases except one, which only submucosal nodule. Morphologically, there was different distribution of allotypic lymphocytes in inflammatory background. Four cases showed \"kidney-shaped\", \"embryonic\" and \"horseshoe-shaped\" cells, and one case resembled Hodgkin and Reed/Sternberg (HRS) cells. Allotypic lymphocytes expressed CD3 (7/8), CD4+/CD8-(7/8) and CD4-/CD8-(1/8). CD30 was uniformly strongly positive while ALK and CD56 were negative. In situ hybridization of EBER was negative in five cases (5/5). Clonal TCR gene rearrangement was positive in two cases. Four patients did not receive radiotherapy or chemotherapy. All the seven patients survived without disease except one died due to concurrent leukopenia. Conclusions: pmCD30+TLPD had a broad morphological spectrum and could be easily confused with primary cutaneous CD30+TLPD and systemic ALK-negative anaplastic large cell lymphoma involving mucosa, which may lead to misdiagnosis. Although the majority of the cases had a favorable prognosis, a few cases relapsed or progressed to lymphoma.
目的： 探讨原发黏膜CD30阳性T细胞淋巴组织增殖性疾病（pmCD30+TLPD）的临床病理特征及鉴别诊断。 方法： 回顾性收集首都医科大学附属北京友谊医院及北京陆道培医院2013至2023年会诊的8例pmCD30+TLPD，检测该病的免疫表型、EB病毒感染状态和T细胞受体（TCR）克隆性，分析患者的临床病理特征并复习相关文献。 结果： 患者男性3例，女性5例，年龄28~73岁；均无B症状，缺乏创伤和自身免疫性疾病。7例发生于口腔黏膜，1例为肛管黏膜。所有病例表现为黏膜结节，除1例外均伴溃疡。形态学上，于炎性背景中分布多少不等的异型淋巴细胞，4例呈“肾形”“胚胎样”及“马蹄铁样”细胞；1例类似霍奇金淋巴瘤HRS细胞。异型淋巴细胞表达CD3（7/8）、CD4+/CD8-（7/8）、CD4-/CD8-（1/8）；CD30均匀强阳性，不表达间变性淋巴瘤激酶（ALK）和CD56。5/5例EB病毒原位杂交阴性。2例TCR基因重排阳性。4例未进行放化疗。除1例因同时伴有白细胞减少症而死亡外，7例均无病生存。 结论： pmCD30+TLPD形态学谱系较宽，容易与原发皮肤CD30阳性T细胞淋巴组织增殖性疾病和累及黏膜的系统性ALK阴性间变性大细胞淋巴瘤相混淆，从而造成误诊。预后良好，少数病例复发或进展为淋巴瘤。.

The fifth edition of the World Health Organization (WHO) classification of lymphohematopoietic system tumors updated the terminology, types of lesions, diagnostic criteria, nomenclature, and other aspects of lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation. The important updates and main changes in this section were briefly introduced, in order to guide the precise classification of lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation, and standardize pathological reports.
第5版WHO血液淋巴肿瘤分类关于免疫缺陷和失调相关性淋巴组织增殖与淋巴瘤的术语、病变类型及其诊断标准、命名等进行了相应的更新。本文简要介绍这部分内容的重要进展和主要变化，从而指导免疫缺陷和失调相关性淋巴组织增殖与淋巴瘤的精准分类，规范病理报告。.

Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein-Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.

The 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumours used the hierarchical system to classify T-cell and NK-cell lymphoid proliferations and lymphomas (T/NK-LPD/LYM) based on research advances and clinicopathological characteristics of the diseases. In this edition of classification, tumour-like lesions were included, some tumors were added/deleted, the names or terms of certain diseases were refined, and the diagnostic criteria or subtypes of some diseases were revised. This group of diseases was reintegrated from non-clonal hyperplasia to highly aggressive lymphoma, which would further reflect the nature of T/NK-LPD/LYM and benefit to clinical application.
第5版WHO造血与淋巴组织肿瘤分类对T细胞和NK细胞增生性疾病和淋巴瘤（T-cell and NK-cell lymphoid proliferations and lymphomas，T/NK-LPD/LYM）根据研究进展以及疾病的临床病理特征，采用了分级系统进行分类。同时纳入了瘤样病变，引入/删除一些肿瘤，修改某些疾病的名称，并修订一些疾病的诊断标准或亚型，将这组疾病从非克隆性增生到高度侵袭性淋巴瘤进行了重新整合，更体现了T/NK-LPD/LYM的疾病本质，有利于临床应用。.

Objective: To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation. Methods: This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children\'s Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis. Results: Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions: The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.
目的： 总结儿童肝移植后侵袭性成熟B细胞淋巴瘤的临床特点、诊治要点及预后因素。 方法： 回顾性病例总结。以2018年6月至2022年6月上海交通大学医学院附属上海儿童医学中心血液肿瘤科收治的病理诊断明确的肝移植后侵袭性成熟B细胞淋巴瘤患儿18例为研究对象，分析临床特点、治疗过程和预后等数据，采用Kaplan-Meier方法计算总生存率（OS）和无事件生存率（EFS），采用Log-Rank检验进行预后因素分析。 结果： 18例患儿中男6例、女12例，年龄40（35，54）月龄，肿瘤发生于肝移植后21（17，35）个月，其中早发型病例（肝移植1年以内）5例。17例患儿存在腹部病灶，主要临床表现为腹泻、呕吐和腹部包块。所有患儿均为EB病毒相关移植后淋巴组织增生性疾病（PTLD）。18例患儿中1例起病危重个体化治疗，17例接受CP方案（环磷酰胺+甲泼尼龙联合利妥昔单抗）和（或）改良EPOCH方案（泼尼松+依托泊苷+阿霉素+长春新碱+环磷酰胺联合利妥昔单抗）。18例患儿中15例完全缓解，2例部分缓解，1例严重感染死亡。18例患儿2年OS和EFS分别为（94±5）%和（83±8）%。单因素分析显示，年龄、性别和早发型病例等对OS和EFS的影响差异均无统计学意义（均P>0.05）。 结论： PTLD临床表现不典型，推荐肝移植后持续监测血浆EB病毒DNA以发现早期PTLD。针对肝移植术后侵袭性成熟B淋巴瘤患儿，CP和（或）改良EPOCH化疗方案效果较好。.