Spontaneous Regression of Plasmablastic Lymphoma Associated With Methotrexate After Withdrawal.

Objectives: To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD.Methods: Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development.Results: Twenty-three patients (76.7%) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p = 0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3 mg/w, p = 0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein–Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p = 0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3%) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy.Conclusions: Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.

Gene Expression Analysis Of Plasmablastic Lymphoma Identifies Down Regulation Of B Cell Receptor Signaling and Additional Unique Transcriptional Programs

Clinicopathological Study of Methotrexate-Associated Lymphoproliferative Disorders in Rheumatoid Arthritis Patients: Histological Classification and Predictive Factors for Disease Progression

Methotrexate (MTX), the first-line drug for rheumatoid arthritis, rarely causes malignant lymphomas, which have been reported as MTX-associated lymphoproliferative disorders (MTX-LPD). Herein, report a case of MTX-LPD in the ileum with fistula formation in the small bowel and rectum. At the end of January 2023, an 81-year-old man who had been taking MTX for rheumatoid arthritis since the age of 73 years complained of abdominal pain and was diagnosed with intestinal obstruction at a previous hospital. In the early February 2023, the patient was referred to our hospital for further examination and treatment. A computed tomography scan revealed a thickened terminal ileum wall and enlarged mesenteric lymph nodes. A retrograde double-balloon endoscopy (DBE) detected circumferential ulcerative lesions at the terminal ileum with deep depressions in parts of the ulcer base. In addition, submucosal tumor-like lesions with central depressions were observed in the rectum. Retrograde contrast imaging under DBE confirmed the presence of fistulae between the ileum and rectum. A biopsy of the ulcerative lesion revealed hyperplasia of germinal center cell-like cells, and immunohistochemistry demonstrated CD20 and CD79a positivity, but CD5, CD10, and cyclin D1 negativity. Ki-67 positivity was 90%, indicating B-cell lymphoma. Based on histopathological findings and patient's history, the patient was suspected to have MTX-LPD, resulting in ileal and high anterior rectal resection. Histopathological examination of the resected specimen revealed large atypical lymphocyte proliferation. Immunohistochemistry confirmed CD20 and CD79a positivity;CD5, CD10, and cyclin D1 negativity;a Ki-67 positivity rate of 70%;and Epstein-Barr virus-encoded small RNA in situ hybridization negativity, confirmming the MTX-LPD diagnosis, presenting as diffuse large B-cell lymphoma. Postoperatively, the patient was monitored with MTX discontinuation, and no recurrence occurred. The clinical course remained consistent with MTX-LPD.

Introduction: Although methotrexate-associated lymphoproliferative disorders (MTX-LPDs) often develop in extranodal sites, such as the lungs and skin, their involvement in the eyes is quite rare. We report a case of MTX-LPD with subretinal involvement. Case Presentation: A 66-year-old woman had a 14-year history of rheumatoid arthritis and had been receiving MTX for 8 years. Multiple erythematous nodules had developed on both lower extremities during MTX administration, and the patient was diagnosed with diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS). Since the skin masses disappeared within a couple of months after MTX withdrawal, MTX-LPD was diagnosed. Although no recurrence of LPD was observed for 1 year, she suddenly presented with decreased visual acuity in the right eye. Fundus examination showed a swelling of the optic disc, vitreous opacity, and multiple widespread, subretinal, yellow-white, elevated lesions. Since the cytokine profile of the vitreous fluid indicated that interleukin (IL)-10/6 ratio was >1, relapse of MTX-LPD in the eye was diagnosed. Intravitreal injection of MTX (IVMTX) successfully reduced the LPD and led to improved visual acuity. However, a new mass developed in the left cerebellum. Open biopsy confirmed relapse of DLBCL-NOS, and six cycles of chemotherapy resulted in complete remission (CR). She has had no recurrence for 16 months after the last administration of IVMTX in the eye and other regions. Conclusions: Ocular involvement was observed in patients with MTX-DLBCL-NOS. Although IVMTX is effective for intraocular involvement, careful observation should be considered even after CR is achieved.

Gastrointestinal Plasmoblastic Lymphoma Associated with Wiskott-Aldrich Syndrome: A Case Report

Plasmablastic lymphoma (PBL) is an aggressive lymphoma commonly associated with human immunodeficiency virus (HIV) infection. Herein we describe a rare case of PBL that spontaneously regressed. An 80-year-old man was referred to our hospital owing to an exophytic gingival tumor in the right maxillary second molar region. He had no significant past medical history, and a screening test for HIV was negative. Imaging showed that the tumor measured 26 × 23 × 16 mm and was confined in the alveolar bone. The tumor was histologically comprised of highly proliferative immunoblastic cells positive for CD138 and Epstein-Barr virus (EBV)-encoded RNA. Monoclonal IgH chain gene rearrangement was detected via polymerase chain reaction. After biopsy and diagnosis of PBL, the tumor began to decrease in size and had apparently disappeared at the time of surgery. There was no histological evidence of a residual lesion in the surgical specimen. In conclusion, a minority of immunosenescence-associated PBLs in the elderly should be recognized as a unique clinicopathological entity distinct from common aggressive PBL.

Poor Outcomes in HIV Negative and HIV Positive Patients with Plasmablastic Lymphoma (PBL) in a Population Based Patient Study

Background Plasmablastic lymphoma (PBL) is a rare aggressive B cell lymphoma that is commonly encountered in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). In this case series, we describe the clinicopathological features of cases of PBL seen at a tertiary care center in South India. Materials and Methods Medical records of patients diagnosed with PBL between January 2009 and November 2017 were reviewed. PBL was defined as per the World Health Organization 2016 classification for hematopoietic and lymphoid neoplasms. The slides were reviewed with hematoxylin and eosin along with immunohistochemistry (IHC) including CD45, CD20, PAX5, CD79a, CD3, CD5, CD138, MUMI, EMA, ALK, and Ki67. Epstein-Barr virus (EBV) association was documented by rapid in situ hybridization (RISH) studies wherever possible. The demographic data, clinical presentation, treatment details, and outcomes are elaborated using descriptive statistics. Results During the study period, nine patients with PBL were identified. The median age at presentation was 47 years (range: 36–54 years). All patients had associated HIV/AIDS, eight (89%) had extranodal disease, and six (66%) had advanced clinical stage (stage III). All biopsies were positive for CD45, CD138, and MUM1, and negative for CD79a and T cell markers with a high Ki67 proliferation index (85–90%); CD20 was faint positive in one patient, and CD56 was positive in one (11%) patient. EBV-RISH was tested in two patients and was positive in one. Bone marrow was uninvolved in all the cases. At the time of last follow-up, three patients were alive. Treatment details were available in six patients. With frontline therapy, four patients achieved a complete remission (CR) and one patient developed progressive disease. Three of four patients in CR are alive till the last follow-up. Conclusion PBL is a rare form of lymphoma with predominant association with HIV, extranodal location, and characteristic IHC pattern.

To study the clinical, pathologic, immunophenotype, molecular characteristics and prognosis of HIV-negative plasmablastic lymphoma (PBL). Twelve cases of HIV-negative PBLs diagnosed between 2005 and 2014 in Guangdong General Hospital were identified according to WHO classification of tumors of haematopoietic and lymphoid tissues (2008). The clinicopathologic features and outcome were analyzed and the relevant literatures were reviewed. The patients were predominantly male (11/12) with a median age of 55.5 years. The tumor cells showed the characteristic combination of immunoblastic/plasmablastic morphology, plasma cell phenotype and high proliferation, no expression of mature B cell markers. 7/10 of the cases were EBER positive. Two cases were positive for C-myc translocation. Four of twelve patients were died. PBL is a rare, aggressive B-cell lymphoma. HIV-negative PBL has lower rate of oral involvement and EBER expression than HIV-positive patients, the differential diagnosis is very challenging, and the prognosis is worse.

Daratumumab for relapsed/refractory primary effusion lymphoma, plasmablastic lymphoma and multicentric castleman disease.

BackgroundMethotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA). Patients with RA have a modestly increased risk of developing lymphoproliferative disorders (LPD). Furthermore, although...

It is not widely known that incorrect use of oral bisphosphonates (BPs), such as chewing the medication, can cause oral ulcers. An 83-year-old woman with dementia was referred to our clinic with multiple oral ulcers. Blood and histopathological examinations were inconclusive. Further questioning revealed that the patient chewed the oral BP, resulting in oral ulceration. Patients with loss of cognitive function, such as dementia, are at risk of oral ulcers caused by incorrect use of BPs.

Daratumumab with dose-adjusted EPOCH feasibility and early efficacy in newly diagnosed plasmablastic lymphoma: AIDS malignancy consortium 105

A 78-year-old man had fatigue and appetite loss for 5 months. He had been receiving low-dose methotrexate for rheumatoid arthritis. Computed tomography revealed multiple pulmonary infiltrations and muddiness of the fatty tissue surrounding the right kidney, ureter wall thickening, and hydroureter/nephrosis, which were suspected retroperitoneal fibrosis. Lung biopsy revealed polymorphic/lymphoplasmacytic lymphoproliferative disorder. Methotrexate withdrawal resulted in spontaneous regression. Therefore, retroperitoneal lesion may account for the diagnosis as having retroperitoneal lymphoproliferative disorder, not retroperitoneal fibrosis.