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.

BACKGROUND: Epstein-Barr virus-positive mucocutaneous ulcer is one of the mature B-cell lymphoproliferative diseases occurring in patients with immune dysfunction including those with immunosuppressive treatment such as methotrexate.
METHODS: A Japanese elderly man in his 80s with rheumatoid arthritis on methotrexate was admitted to our hospital complaining persistent pharyngeal pain. Laboratory tests revealed severe pancytopenia, elevated C-reactive protein, and increased creatinine levels. An otolaryngological examination showed ulceration of the right tonsil, from which diagnostic biopsy was performed. The diagnosis of Epstein-Barr virus-positive mucocutaneous ulcer was made and bone marrow aspiration revealed hypocellularity and megaloblastic changes. Pancytopenia was improved after discontinuing methotrexate, and repeated bone marrow aspiration test revealed recovery of normal cellularity and disappearance of dysplasia, confirming the diagnosis of methotrexate intoxication. Tonsil ulcer was improved only with discontinuation of methotrexate, which strongly supported the diagnosis of EBV-MCU.
CONCLUSIONS: Our case suggested that even this best prognosis form of lymphoproliferative disease could lead to fatal complications if not appropriately managed.

A rare lymphoproliferative disorder involving thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), renal dysfunction (R), and organomegaly (O), called TAFRO syndrome, was first reported in 2010. Considered a variant of idiopathic multicentric Castleman\'s disease, the recent discovery and rarity of this syndrome pose challenges to diagnosis and management. Herein, we review three pediatric cases, including an infant, that illustrate the heterogeneity of TAFRO syndrome. Despite differences in presentation and treatment responses, all patients experienced excellent outcomes. This multi-institutional case series highlights the need to work toward earlier diagnosis and improved long-term management recommendations for patients with TAFRO syndrome.

Dermatomyositis (DM) and polymyositis are idiopathic inflammatory myopathies (IIMs), most associated with solid organ malignancies, and less commonly hematological malignancies. We discuss a case of DM associated with diffuse large B-cell lymphoma, followed by a review of literature on the pathogenesis, clinical course, treatment, and prognosis. Various challenges with the diagnosis and management of underlying lymphoproliferative disorders (LPDs) in patients with IIM are discussed. The case demonstrates the importance of being vigilant of the association between IIM and LPD. Cancer screening in patients with IIM is discussed, including the recently published International Guideline for IIM-Associated Cancer Screening. More research is required to address knowledge gaps in cancer screening in IIM.

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.

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。.

Lymphocytic interstitial pneumonia (LIP) is a rare but largely benign interstitial lung disease, most frequently associated with HIV and autoimmune conditions. It is infrequently found to be an idiopathic condition. Diagnosis is complex and can require numerous invasive tests as evidenced in the case presented. The diagnosis is made from a combination of clinical, radiological, and histological features but the unusual radiological and clinical features meant diagnosis in our case required surgical biopsy. There is minimal evidence around best treatment although largely involves targeting the underlying cause. There is a small risk of transformation to lymphoma and fibrosis. Immunosuppression with steroids is the most common therapeutic strategy however in our case the radiographic changes spontaneously resolved. We present a case of an immunocompetent male presenting with significant radiological and histopathological findings of LIP, without significant symptomatology, that spontaneously resolved without intervention suggesting a monitoring approach may be a valid management strategy.

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.

As of the most recent WHO classification of immunodeficiency diseases, lymphoproliferative disorders that occur during treatment with immunosuppressive drugs are classified as \"other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs)\" other than post-transplant lymphoproliferative disorders. Most patients with OIIA-LPD have rheumatoid arthritis as the underlying disease. Research indicates that approximately half of people diagnosed with OIIA-LPD see a remission of their lesion after stopping treatment with methotrexate (MTX), a drug used in rheumatoid arthritis treatment. Hereby, we present the case of an 81-year-old woman with rheumatoid arthritis who developed OIIA-LPD at the bilateral lingual margins. The patient had been receiving MTX for the preceding 10 years. After determining that OIIA-LPD was MTX-related, the patient underwent MTX withdrawal and was treated conservatively. The lesion resolved one month after MTX withdrawal. This case report confirms immunosuppressive drug withdrawal as a potentially effective treatment for multiple OIIA-LPDs of the oral mucosa.

A 67-year-old man underwent renal transplantation in his twenties. He developed refractory pleural effusion, with many large lymphocytes with severe atypia and mitosis in the effusion, indicating malignant lymphoma. He finally died of respiratory failure. An autopsy revealed atypical lymphocytes positive for CD3, CD4, and CD30 and negative for CD8, CD20, PAX5, human herpesvirus (HHV) 8, and Epstein-Barr virus-encoded small RNAs by immunohistochemistry and in situ hybridization. Atypical lymphocytes also had T-cell receptor gene rearrangements Jβ2, Jγ2, and Jδ1 and chromosomal aberrations der(8)t(1;8)(q21;p21), add(13)(q12), add(14)(q32), and add(16)(q12-13). A few atypical lymphocytes were present at other sites. We finally diagnosed this case as monomorphic T-cell post-transplant lymphoproliferative disorder with features of HHV8-negative primary effusion lymphoma. A literature review only identified six cases (four HHV8-negative, two HHV8-positive) of effusion lymphoma of T-cell type, including the present case. Interestingly, about half of HHV8-negative and HHV8-positive cases had a history of renal transplantation in their twenties. All cases showed tumor CD30 expression, whereas CD4 and CD8 expressions were inconsistent. These findings indicated that this lymphoma may be associated with post-transplant lymphoproliferative disorder by renal transplantation at a young age, although further cases need to be analyzed.