The incidence and role of EBV and HIV in head and neck lymphomas: an institutional study.

Plasmablastic lymphoma (PBL) is a rare and aggressive, usually CD20-negative, B-cell lymphoma with features between multiple myeloma and diffuse large B-cell lymphoma. Approximately 120 new cases are diagnosed annually in the United States, and there is a strong association with HIV infection and other immunosuppressive states. It affects mostly adult males, though PBL has been diagnosed in children and immunocompetent individuals. Epstein-Barr virus infection, MYC gene rearrangements, and other mechanisms appear to play a role in PBL lymphomagenesis. Given its rarity, PBL poses distinct diagnostic and therapeutic challenges. A timely diagnosis is essential and requires a high clinical suspicion and a thorough pathological evaluation. The clinical course is aggressive, with a high relapse rate and poor survival with standard therapies. More recently, better outcomes have been observed in patients with early-stage disease treated with combination chemotherapy followed by consolidative radiotherapy. Additionally, advanced disease outcomes may improve with the use of targeted agents, such as proteasome inhibitors and anti-CD38 monoclonal antibodies, when added to combination chemotherapy. Participation in clinical trials and multi-institutional collaboration will be essential to continue improving patient outcomes with PBL.

Rare B-cell malignancies pose a unique management challenge because of their rarity and aggressiveness. Given their low incidence, they require a high index of suspicion for diagnosis and necessitate specialized therapeutic approaches. Herein, we discuss 3 of those rare lymphomas: plasmablastic lymphoma, lymphomatoid granulomatosis, and intravascular lymphoma. Plasmablastic lymphoma is aggressive and often linked to immunosuppression, particularly in HIV- infected individuals. It is characterized by plasmablastic morphology lacking CD20 expression, extranodal disease, MYC rearrangement, and frequent Epstein-Barr virus infection. Recent advancements in treatment involve using novel agents like bortezomib, daratumumab, and B-cell maturation antigen-targeted therapy, which are improving outcomes; however, the prognosis for relapsed disease remains poor. Lymphomatoid granulomatosis is a rare, Epstein-Barr virus-driven B-cell disorder defined by angiocentric and angiodestructive infiltrates. It primarily affects the lungs but can also involve skin and the central nervous system, causing systemic symptoms. Treatment and prognosis vary by histologic grade; low-grade cases may be treated with immunomodulation, while high-grade cases generally require chemoimmunotherapy. Intravascular lymphoma involves malignant B cells proliferating in small blood vessels, leading to nonspecific clinical symptoms. Early diagnosis through tissue biopsy is crucial. The best remission chances come from rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy combined with central nervous system-directed treatment. New research is ongoing for relapsed cases.

We report a rare case of plasmablastic lymphoma (PBL) in an HIV-positive patient with nodal and gastric involvement, who also showed intravascular PBL cells within a longstanding Kaposi sarcoma (KS) skin lesion.

Plasmablastic lymphoma: atypical cutaneous presentation

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

The influence of racial, socioeconomic, and geographic disparities in the survival of patients with plasmablastic lymphoma: A population-based analysis from the surveillance, epidemiology, and end Results (SEER) database (2000–2022).

Mitoxantrone hydrochloride liposome, gemcitabine, vinorelbine with or without anti-CD20 antibody (GVM±CD20) in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma: A prospective, multicenter, Phase Ⅱ study

Implementation of a next generation sequencing painel for lymphoid malignancies in Brazil: First report of molecular features in a low-middle income country

Key factors for the success of autologous hematopoietic stem cell transplantation in HIV-infected patients with lymphoproliferative diseases

Abstract Introduction/Objective Plasmablastic lymphoma (PBL) is a rare type of B-cell lymphoma with poor prognosis. They can arise de novo in immune deficiency/dysregulation, associated with transplant or transformation of low grade lymphoma. PBL has been reported with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Methods/Case Report 69-year-old male with CLL/SLL, treated with multiple chemotherapy regimens and was in remission. He developed generalized weaknesses. Radiology showed lymphadenopathy. Pathology was positive for DLBCL without MYC and BCL2 rearrangement. Flow cytometry revealed 1% CD5 and CD23 positive. TP53 is negative and mutated IGHV. The PD-1 was negative, favored de novo DLBCL. PET-CT and biopsy confirmed residual disease. For refractory DLBCL, CAR-T cell therapy was initiated. Patient developed PBL diffusely positive for CD138, MUM1, c-MYC and kappa; negative for CD19, CD20, PAX5, CD10, BCL6 and CD79a. MIB-1 was 90%. EBV and HHV8 were negative. BCMA was >95 %, Teclistamab was initiated. The renal function deteriorated and proceeded with palliative care. Results NA Conclusion The nature of Richter transformation or de novo DLBCL into PBL in the setting of immunomodulation with CAR-T is rare occurrence. Molecular and clonality studies are needed to evaluate the pathways of losing B-cell markers to evade lineage specific therapy.

Abstract Introduction/Objective Plasmablastic lymphoma (PBL) is an aggressive large B-cell neoplasm with a terminal B-cell differentiation phenotype that typically arises in immunocompromised patients. In the current literature, a majority of cases involve concurrent HIV infection, while fewer cases discuss other causes of immunodeficiency. This case features a patient with a germline mutation who ultimately developed a PBL. Methods/Case Report A 41-year-old male with a biallelic STXBP2 mutation resulting in hypogammaglobulinemia and monogenic Crohn’s disease, treated with extensive immunotherapy, presented with hemorrhagic ostomy pouch contents. A colonoscopy revealed a partially obstructing mass. Biopsies and subsequent proctocolectomy sections demonstrated sheets of large, pleomorphic, plasmacytoid cells with vesicular nuclei and prominent nucleoli. These cells were positive for CD3, CD138, MUM-1, and EBER, but negative for CD20, PAX-5, CD34, CD117, and HHV8. The Ki67 proliferative index was high. These findings were consistent with an EBV-positive plasmablastic lymphoma. Results NA Conclusion This study highlights a case of PBL in an HIV-negative patient with both acquired and inborn errors of immunity. While STXBP2 mutations are historically associated with hemophagocytic lymphohistiocytosis, minimal case reports describe a connection with lymphomas. With the progressive advancements in molecular sequencing, additional research is necessary to elucidate the relationship between this hereditary mutation and subsequent development of hematologic malignancies.

ABSTRACTPlasmablastic lymphoma (PBL), a rare aggressive B‐cell malignancy linked to HIV, is increasingly noted in extraoral sites beyond its traditional oral cavity presentation. This case report details a 48‐year‐old HIV‐positive woman with prior cerebral toxoplasmosis, presenting with facial swelling, pain, proptosis, and dysphagia despite antiretroviral therapy and cotrimoxazole prophylaxis (CD4 120 cells/μL, suboptimal viral suppression). Imaging identified a sinonasal mass with nasopharyngeal involvement and lymphadenopathy, with immunohistochemistry confirming PBL (MUM1+, weakly CD79a+, CD20‐, CD138‐, EBER‐). Treatment comprised six cycles of dose‐adjusted EPOCH with bortezomib (1.3 mg/m2 on days 1, 8, 15), intrathecal prophylaxis, and supportive care for recurrent neutropenia, achieving a complete metabolic response on interim FDG‐PET/CT after three cycles, with follow‐up CT showing pansinusitis. The patient is now eligible for autologous stem cell transplantation and consolidative radiotherapy, highlighting the diagnostic complexity of CD138‐negative extraoral PBL and the efficacy of bortezomib‐augmented EPOCH in this high‐risk case.

Abstract Introduction/Objective The classification systems for hematolymphoid neoplasms recognize ALK-Positive Large B-cell Lymphoma (ALK+ LBCL) as having plasmablastic morphology and a rearrangement of the ALK gene, resulting in ligand independent activation of ALK kinase. We report an ALK-positive plasmablastic neoplasm by immunohistochemistry (IHC) which did not show an ALK rearrangement by break-apart fluorescent in-situ hybridization (FISH). The neoplastic cells showed increased mitotic activity, morphology ranging from plasmablastic to bizarre, and IHC positivity for CD138 (partial), MUM1, ALK(D5F3), kappa, and CD79a(partial). They were negative for PAX5, CD20, CD19, CD30, lambda, EBER, and HHV8. The case was later clinically matched more closely to a plasma cell myeloma with plasmablastic morphology, and treated as such. We learned that there is evidence supporting that the ALK clone we use in our laboratory (D5F3) is more sensitive but less specific than ALK1 (the other commonly used clone). This discrepancy should be noted when making diagnoses of plasmablastic neoplasms, especially in extramedullary sites. In our particular case, there was also an unusual clinical presentation given the patient’s young age for myeloma, extramedullary involvement, concurrent lymphadenopathy, low level of paraprotein in serum, and lack of other common clinical manifestations of myeloma (i.e. renal deficiency, anemia, hypercalcemia (CRAB)). Methods/Case Report Our patient is a 46 year-old previously healthy male who developed progressive pain and edema in the right knee and tibia. MRI revealed a 10cm osteolytic mass involving bone and soft tissue, which was biopsied. At the time of diagnosis, complete blood count (CBC) was normal and serum protein electrophoresis (SPEP) showed an IgA kappa monoclonal band at 0.6 g/dL. He also had mild inguinal lymphadenopathy (21mm max dimension). A bone marrow biopsy showed involvement by a plasmacytic neoplasm expressing ALK by IHC, albeit not as strongly as in the tissue biopsy. After the FISH was negative for ALK rearrangement, the clinical decision to treat the patient with a myeloma regiment was made (daratumumab, lenalidomide, dexamethasone, and bortezomib, (Dara-VRD)). Additionally the patient received 2500cGy of radiation to the right tibial mass. After 5 cycles of treatment, the patient’s SPEP is no longer detectable and the mass in the right tibia decreased in size considerably. However, the patient developed massive edema in the lower extremities bilaterally. He also developed osseus lesions in the spine which were presumed to be residual/relapsed disease. He has not yet achieved complete remission. Results N/A Conclusion There is a histologic and clinical overlap between the different plasmablastic neoplasms. Relying solely on ancillary testing for classification can lead to misdiagnoses. Multiple myeloma is commonly a disease of older patients with CRAB symptoms which can have plasmablastic morphology. Instead, our patient was relatively young, with normal CBC and calcium levels, and normal renal function who’s presenting symptoms were related to a large tibial/soft tissue mass. In addition the patient’s imaging showed mild lymphadenopathy (in retrospect most likely reactive). ALK+ LBCL is a rare disease with a median age of 38 and aggressive clinical course. It involves lymph nodes and extramedullary sites and is defined by the rearrangement in ALK, which we did not have. However, the ALK expression by IHC could have led us to a misdiagnosis. Other entities with plasmablastic morphology and immunophenotype include plasmablastic lymphoma, seen in HIV/immunodeficient patients and often EBER positive (unlike our case), and HHV8-associated neoplasms (negative in our case). We conclude that IHC, especially the D5F3 ALK clone, is insufficient for diagnosing ALK+ LBCL since it is not specific and since the plasmablastic neoplasms share many clinicopathologic features. FISH and concordance with the clinical data are necessary for definitive evaluation.

S4659 A Case of Primary Anorectal Plasmablastic Lymphoma, a Rare and Unexpected Endoscopy Finding in a Patient With HIV and Rectal Adenocarcinoma

Plasmablastic Lymphoma of maxilla in an HIV-negative, immunocompetent patient: A case report on unusual occurrence

Plasmablastic lymphoma (PBL) is a rare, aggressive AIDS-related lymphoma observed in patients with immunosuppressed states as well as in immunocompetent individuals. We sought to determine survival outcomes, prognostic factors, and optimal treatment regimens in a large, contemporary cohort of patients with PBL in the United States. We performed a multicenter, retrospective cohort study, including 344 patients diagnosed with PBL between 2005 and 2022. Patients were stratified into cohorts according to underlying immune status. Survival outcomes were calculated using Kaplan-Meier statistics, with cohort-specific survival outcomes adjusted using propensity score-based weighting. Factors associated with outcomes were assessed via multivariable models using multiple imputation. The median age at diagnosis was 53 years, most patients were male (n = 270), and many had HIV (n = 164). The median OS was 5.0 years, with a median PFS of 1.4 years. Patients living with HIV had the best outcomes, whereas patients with prior organ transplantation had the worst outcomes. Use of higher intensity chemotherapy regimens and use of a proteasome inhibitor in the frontline setting did not show survival benefit. While there was no clear optimal treatment approach in the frontline setting, the median OS of 5.0 years is dramatically improved compared with historical controls.

Plasmablastic lymphoma (PBL) of the oral cavity is a rare, aggressive subtype of Non-Hodgkin lymphoma, predominantly seen in immunocompromised patients, particularly those with chronic Human Immunodeficiency Virus (HIV) infection. This malignancy is closely associated with Epstein-Barr virus (EBV), highlighting its oncogenic role. We present 11 cases of oral cavity PBL (OPBL) managed at our institution, detailing clinical, radiological, pathological, and therapeutic features, as well as patient outcomes. We also conducted a comprehensive literature review to synthesize current evidence. Since 2008, 645 OPBL cases have been reported. The disease primarily affects men with underlying immunodeficiency, particularly HIV. The maxillary alveolar ridge was the most frequent subsite, typically associated with osteolytic bone lesions. Most patients presented at a localized stage. Although chemotherapy remains the mainstay of treatment, novel targeted therapies are emerging. Prognosis, however, remains poor. OPBL should be systematically considered when evaluating oral cavity malignancy, especially in immunocompromised patients with submucosal lesion.

HIV-associated lymphoma (HAL) is an aggressive malignancy directly linked to HIV infection and accounts for more than 30% of cancer-related deaths in people living with HIV (PLWH). HAL subtypes, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), primary effusion lymphoma (PEL), and plasmablastic lymphoma (PBL), exhibit five to ten times higher incidence rates and distinct molecular profiles compared to HIV-negative lympho-mas. Pathogenesis involves HIV-driven CD4+ T-cell depletion, chronic B-cell activation, and on-cogenic viral coinfection. First-line therapy combines antiretroviral therapy (ART) with chemo-therapy, achieving complete remission rates of 60-70% for DLBCL using R-EPOCH and 50-60% for BL with CODOX-M/IVAC. Relapsed/refractory cases show durable responses to CD19-CAR-T therapy; however, only 10% of HAL patients are enrolled in pivotal immunotherapy tri-als. Severe immunosuppression necessitates PET-CT-guided de-escalation and nanoparticle-based drug delivery systems to minimize toxicity. Emerging strategies include PD-1 inhibitors and broad-spectrum antivirals targeting HIV reservoirs, underscoring the need for precision med-icine that integrates tumor genomics and viral dynamics.

Deep learning differentiates multiple myeloma from plasmablastic lymphoma