RARE DISEASE
Plasmablastic lymphoma
Plasmablastic lymphoma
Plasmablastic lymphoma
Synonyms: PBL
Synonyms: PBL
Synonyms: PBL
Drug discovery
1
drug
With orphan designation
Overview
Plasmablastic lymphoma (PBL) is a rare, aggressive CD20-negative large B-cell lymphoma associated with immunodeficiency (e.g., HIV, organ transplantation, or age-related immune decline). Characterized by plasmablastic morphology, high Ki-67 proliferation (often >90%), and frequent EBV association, it commonly presents with extranodal involvement (oral cavity, GI tract). Diagnosis requires immunohistochemistry showing plasma cell markers (CD138+) and lacks CD20 expression. Prognosis remains poor due to high relapse rates and chemoresistance.
Therapies
First-line: Intensive regimens (EPOCH, DA-EPOCH, hyper-CVAD) over CHOP due to better outcomes [5][6][9]
Novel agents: Bortezomib ± chemotherapy, lenalidomide, or checkpoint inhibitors (limited evidence) [5][9][12]
Adjunctive: ART for HIV-positive patients, CNS prophylaxis with intrathecal chemotherapy, autologous stem cell transplant in remission [1][5][6]
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
290 drug discovery papers about Plasmablastic lymphoma, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
290 drug discovery papers about Plasmablastic lymphoma, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-05-15 | Plasmablastic Lymphoma: 2026 Update on Diagnosis, Risk Stratification, and Management.
Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with poor prognosis when treated with standard treatment options. Although PBL is associated with HIV infection and other immunosuppressed states, it can also affect immunocompetent individuals. The diagnosis of PBL requires a high clinical suspicion and pathological confirmation. EBV-encoded RNA (EBER) expression and MYC gene rearrangements are frequently detected in the malignant cells. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma (DLBCL), extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others. Age ≥ 60 years, advanced clinical stage, and high International Prognostic Index scores are associated with worse survival. Combination chemotherapy regimens, such as infusional EPOCH, are recommended. The addition of bortezomib or daratumumab might improve outcomes. B-cell maturation antigen-targeted therapies have shown early efficacy. The participation of patients with PBL in prospective clinical trials is warranted.
2026-05-01 | A69-35 When Pneumonia Isn’t Just Pneumonia: Pulmonary Plasmablastic Lymphoma in a Newly Diagnosed HIV Patient
Abstract Introduction Pulmonary complications are frequent in patients with Human Immunodeficiency Virus (HIV) infection, most often due to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP) or tuberculosis. However, malignant etiologies, including Plasmablastic Lymphoma (PBL) - a rare, aggressive variant of diffuse large B-cell lymphoma - can mimic infection both clinically and radiographically. Early recognition is critical given its poor prognosis and distinct therapeutic approach. Case Report A 40-year-old male with no prior medical history presented with three weeks of cough, intermittent hemoptysis, pleuritic chest pain, fever, night sweats, and weight loss. Physical examination revealed bilateral cervical and axillary lymphadenopathy and diffuse rhonchi. Initial chest radiograph demonstrated multifocal patchy consolidative opacities concerning for multifocal pneumonia (Figure 1). Computed tomography (CT) of the chest showed extensive peribronchovascular flame-shaped consolidations, perilymphatic nodularity, and diffuse mediastinal and axillary lymphadenopathy, suggestive of an atypical infection or lymphoproliferative process.HIV-1 testing was positive with a CD4 count of 149 cells/µL. Noninvasive workup, including Pneumocystis jirovecii, fungal, and Mycobacterium tuberculosis testing, was negative. The patient was initiated on antiretroviral therapy (bictegravir/emtricitabine/tenofovir alafenamide). Given persistent abnormalities, bronchoscopy with bronchoalveolar lavage, brushings, and endobronchial ultrasound-guided (EBUS) transbronchial biopsies was performed. The airways were noted to be irregular and narrowed in the left upper and lower lobes, with bulky subcarinal lymphadenopathy. Pathology revealed sheets of plasmablast-like cells positive for CD138, MUM1, CD38, and Epstein-Barr virus-encoded RNA (EBER), but negative for CD20 and PAX5, consistent with Plasmablastic Lymphoma. Following the procedure, the patient developed a small left apical pneumothorax, managed conservatively with supplemental oxygen. He subsequently initiated dose-adjusted EPOCH chemotherapy alongside antiretroviral therapy. Discussion This case highlights pulmonary PBL as a rare but important cause of diffuse pulmonary infiltrates in HIV-positive patients. Its radiographic presentation can closely resemble opportunistic infection or Kaposi sarcoma, delaying diagnosis. A high index of suspicion and early tissue sampling via bronchoscopy are essential for accurate diagnosis. Prompt recognition and initiation of combined chemotherapy and antiretroviral therapy are crucial for improved outcomes in this highly aggressive lymphoma. Figure 1: Chest CT showing multifocal patchy airspace opacities predominantly in the perihilar and lower lung zones. References: 1. Castillo JJ et al. Plasmablastic lymphoma: a systematic review. Lancet Oncol. 2008;9(6):559-567. 2. Loghavi S et al. Pulmonary plasmablastic lymphoma: a diagnostic pitfall in HIV-positive patients. Am J Surg Pathol. 2015;39(4):543-551. 3. Morscio J et al. Clinicopathologic comparison of plasmablastic lymphoma in HIV-positive and HIV-negative patients. Histopathology. 2014;65(2):230-242. This abstract is funded by: none
2026-03-26 | Case Report: From multiple myeloma to plasmablastic lymphoma - a diagnostic dilemma in unraveling a rare transformation.
Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of diffuse large B-cell lymphoma. Its transformation from multiple myeloma (MM) is an exceptionally rare event, with only nine cases reported in the literature. Differentiating PBL from plasmablastic myeloma (PBM) is a significant diagnostic challenge due to overlapping morphological and immunophenotypic features, yet it is critical for determining the appropriate treatment regimen. We report the case of a woman in her 50s with a seven-year history of kappa-restricted MM who presented with a right leg mass. Biopsy confirmed a lambda-restricted plasmacytoma, indicating an extramedullary relapse. Two months after initiating therapy for myeloma relapse, she developed right inguinal lymphadenopathy. A lymph node biopsy revealed lambda-restricted plasmablasts positive for CD138, CD56, C-MYC, and Ki67 (100%), and negative for CD79a and EBER. In the absence of systemic MM-related end-organ damage and the presence of nodal disease, a diagnosis of PBL was favored over PBM. The patient was subsequently treated with DA-EPOCH chemotherapy (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), leading to significant regression of disease on interim PET scan. This case represents the 10th reported transformation of MM to PBL and highlights the diagnostic dilemma posed by these entities. It underscores the importance of clinical context, the potential for clonal evolution (evidenced by a light-chain switch), and the efficacy of lymphoma-specific chemotherapy in this setting.
2026-03-24 | Prognosis and treatment of plasmablastic lymphoma in the United States: a multicenter retrospective study.
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.
2026-03-06 | HIV-associated lymphoproliferative disorders: Single-center experience.
Survival rates of human immunodeficiency virus-positive subjects improved in recent years, especially due to innovations in current lymphoma treatments and the addition of combination antiretroviral therapy (cART). This study presents demographic and clinical characteristics, prognosis, and survival data of acquired immune deficiency syndrome (AIDS)-related lymphoma patients as a single-center experience. This retrospective study included 16 patients with AIDS-related lymphoma treated at our center between August 2010 and March 2022. Demographic data, clinical information, treatment details, and survival analysis of the patients were retrospectively reviewed from the relevant clinical archives. Fifteen out of 16 patients were males with a median age of 46.5 years (range, 24-71 years). The diagnoses were as follows: diffuse large B-cell lymphoma in 6, Burkitt lymphoma in 4, Hodgkin lymphoma in 3, plasmablastic lymphoma in 1, primary central nervous system lymphoma in 1, and chronic lymphocytic leukemia in 1 out of 16 patients. Fifteen patients presented with an advanced stage at diagnosis. Diagnosis of AIDS preceded the onset of lymphoma in 11 patients. The time from human immunodeficiency virus infection to diagnosis of lymphoma was 23.8 months (range, 1-185 months). All patients received cART during lymphoma treatment. The treatment response was evaluated in all patients who completed the initial treatment. Eleven patients (68.8%) are still alive with a complete response. Antitumour treatments administered in conjunction with cART have a favorable impact on survival and response rates in this aggressive group of patients.
gene therapies
2022-02-28 | Hematologic cancers in individuals infected by HIV.
HIV infection increases cancer risk and is linked to cancers associated to infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. Lymphomas represent one of the most frequent malignancies among individuals infected by HIV. Diffuse large B-cell lymphoma remains a leading cancer after the introduction of combined antiretroviral therapy (cART). The incidence of other lymphomas including Burkitt lymphoma, primary effusion lymphomas, and plasmablastic lymphoma of the oral cavity remain stable, whereas the incidence of Hodgkin lymphoma and Kaposi sarcoma-associated herpesvirus (KSHV)-associated multicentric Castleman disease has increased. The heterogeneity of lymphomas in individuals infected by HIV likely depends on the complexity of involved pathogenetic mechanisms (ie, HIV-induced immunosuppression, genetic abnormalities, cytokine dysregulation, and coinfection with the gammaherpesviruses Epstein-Barr virus and KSHV) and the dysregulation of the immune responses controlling these viruses. In the modern cART era, standard treatments for HIV-associated lymphoma including stem cell transplantation in relapsed/refractory disease mirror that of the general population. The combination of cART and antineoplastic treatments has resulted in remarkable prolongation of long-term survival. However, oncolytic and immunotherapic strategies and therapies targeting specific viral oncogenes will need to be developed.
2004-01-06 | Oral Plasmablastic Lymphomas in AIDS Patients Are Associated With Human Herpesvirus 8
Human herpes virus type 8 (HHV8) has been strongly associated with Kaposi sarcoma, primary effusion lymphoma (PEL), and Castleman's disease. To our knowledge, infection by this virus has not been strongly associated with other hematopathologic malignancies. We examined five oral cavity lymphomas from men with AIDS for HHV8 and HIV-1 by reverse transcriptase in situ polymerase chain reaction, as well as for Epstein-Barr virus (EBV) (EBER-1, -2) using in situ hybridization and HHV8 protein with immunohistochemistry. Four of these tumors were plasmablastic lymphomas; the final case was diffuse large B-cell lymphoma. Most of the neoplastic cells in these five lymphomas contained HHV8 RNA and protein. Further, the four plasmablastic lymphoma cases had tumor cells that contained EBV. HIV-1 RNA was not detected in the tumor cells but was noted in surrounding benign T cells. In comparison, HHV8 RNA was not detected in any of the five oral cavity lymphomas from people who did not have acquired immunosuppression nor in five lymphomas from AIDS patients that were located at a site other than the oral cavity. It is concluded that oral cavity lymphomas from people with AIDS are strongly associated with infection by HHV8 and EBV. Given the poor prognosis of oral cavity lymphomas in immunocompromised patients, therapy directed against the HHV8 and EBV infection may be of therapeutic value.
antibodies
2026-06-02 | Case Report: Synchronous Manifestations of Kaposi Sarcoma Herpesvirus-Associated Disorders.
Kaposi sarcoma herpes virus (KSHV) is associated with multiple clinical manifestations, including primary effusion lymphoma, an aggressive CD38+ B cell lymphoma with a plasmablastic phenotype. This case describes an antiretroviral therapy-adherent person with HIV who presented with concurrent KSHV-related disorders of Kaposi sarcoma (KS), multicentric Castleman disease (MCD), and extracavitary primary effusion lymphoma (EC-PEL). Single-cell RNAseq (scRNAseq) and multiplex immunohistochemistry (mIHC) provide detailed insights into differences in cellular composition and viral and cellular transcriptomic differences between these diseases. Moreover, the case describes a long-term remission with single-agent anti-CD38 antibody, daratumumab, in a chemotherapy-refractory case. This case highlights the differing clinical manifestations of KSHV and the efficacy of immunotherapy in KSHV-associated primary effusion lymphoma.
2026-03-23 | Haematuria As the Initial Manifestation of Bladder Plasmablastic Lymphoma: A Report of a Rare Case and Literature Review
Plasmablastic lymphoma (PBL) is an aggressive and uncommon variant of diffuse large B-cell lymphoma, most frequently associated with immunocompromised states. Although extranodal disease is characteristic, involvement of the urinary bladder is exceptionally rare and may mimic primary urothelial malignancy both clinically and histologically. We report the case of a 62-year-old man with a previous history of high-grade diffuse large B-cell lymphoma in remission who presented with acute gross haematuria. Imaging demonstrated bladder wall thickening with associated hydronephrosis. Transurethral resection of the bladder lesion, followed by detailed histopathological and immunohistochemical analysis, confirmed plasmablastic large B-cell lymphoma involving the bladder. This case underscores the importance of maintaining a broad differential diagnosis in patients presenting with haematuria, particularly those with a prior history of haematologic malignancy. A review of the literature highlights the rarity of bladder involvement and the diagnostic challenges associated with this entity.
2026-03-03 | Targeting BCMA in Plasmablastic Lymphoma With Teclistamab: A Case Study of Three Patients.
Plasmablastic lymphoma (PBL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited standard therapeutic options and poor outcomes. PBL typically lacks expression of the B-cell antigens CD20 or CD19 and, accordingly, has not benefited from the incorporation of B-cell-targeted antibodies. However, recent reports demonstrate that B-cell maturation antigen (BCMA) is expressed in most patients with PBL. BCMA is an established therapeutic target in multiple myeloma. Herein, we describe the clinical course of 3 patients with PBL found to express BCMA by immunohistochemistry who were treated with the BCMA×CD3 bispecific antibody teclistamab after developing disease refractory to at least 2 lines of standard therapy. A complete response was observed in 2 patients: 1 patient remains in remission after 2 years of teclistamab treatment, while the second achieved a complete response after 1 cycle of teclistamab, subsequently underwent allogeneic stem cell transplantation, and developed relapsed PBL 3 months post-transplant. The third patient developed a small bowel obstruction and transitioned to hospice care after 1 cycle of teclistamab. This case series adds to the growing evidence that BCMA is expressed in a considerable subset of patients with PBL and suggests that BCMA may serve as a potential molecular biomarker in PBL for further investigation of available BCMA-directed therapies.
2026-02-24 | Clinicopathological Analysis of Plasmablastic Lymphoma Cases: A Cross-sectional Study from a Tertiary Care Cancer Centre in Kerala, India
Introduction: Plasmablastic Lymphoma (PBL) is an aggressive lymphoid neoplasm composed of large atypical B cells with plasmablastic or immunoblastic morphology and a terminal B-cell differentiation phenotype predominantly presenting at extranodal sites. PBL is rare comprising 1% of large B-cell lymphomas. Most PBLs occur in the context of immune deficiency/dysregulation. Aim: To analyse the morphology, immunophenotype, clinical details and diagnostic challenges in cases diagnosed as PBL. Materials and Methods: The present study was a crosssectional cohort study analysing cases of PBL diagnosed during 2011 to 2021 in the Department of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India. Morphology and Immunohistochemistry (IHC) (CD45, CD3, CD5, CD20, CD79a, Pax5, CD38, CD138, MUM1, EMA, Kappa, Lambda, CD56, CD30, Alk-1, Ki-67) of tumour cells were reviewed. Epstein-Barr Virus (EBV) by Rapid in Situ Hybridisation (RISH) was also documented. Clinical details including patients age, sex, clinical presentation were elaborated using descriptive statistics. Treatment details and overall survival also noted. Results: During the study period there were a total of 36 cases. The median age at presentation was 57 years (range: 10 to 85 years). Six cases (16.7%) had associated HIV, 26 cases (72.2%) had extranodal disease. Tumour cells in all cases were positive for CD138 and MUM1, and negative for CD20, PAX5, and T-cell markers with a high Ki-67 proliferation index (80-95%). Leukocyte Common Antigen (LCA) were negative in 22 cases (61.11%) or weakly positive in 14 cases (38.9%), CD 79a was faintly positive in one case (2.8%) and weak Pax5 positivity was seen in two cases (5.6%). EBV was positive in 21 cases (58.3%) Median overall survival was 17.5% for 3-year in the present study. Conclusion: PBL is a rare aggressive lymphoma having association with HIV, predominant extranodal location, and characteristic IHC pattern. Lymphoproliferative neoplasms with plasmablastic morphology share many morphologic and immunophenotypic similarities and diagnosis requires integration of clinical morphological and IHC findings.
2026-02-14 | Differential Expression of CD79B, CD19, and PD-L1 in de Novo and Transformed CD20-Negative Large B-Cell Lymphomas.
CD20-negative large B-cell lymphomas exhibit aggressive behavior and are ineligible for rituximab-containing therapy. To identify antigens targeted by treatment, we analyzed CD79B and CD19 expression in 108 samples from 75 patients with CD20-negative large B-cell lymphomas using H-score. Diffuse-strong (H-score 300) CD79B and CD19 expression was observed in 51% and 57% of samples, and low/negative (H-score ≤ 100) in 35% and 30%, respectively. CD79B expression was significantly lower in de novo CD20-negative diffuse large B-cell lymphoma (DLBCL) than in CD20-negative DLBCL changed from CD20-positive DLBCL after rituximab-containing therapy and in CD20-negative DLBCL transformed from CD20-positive low-grade B-cell lymphoma after rituximab-containing therapy (H-score ≤ 100 in 79% vs. 27% vs. 10%, p < 0.001). CD19 expression was lower in de novo CD20-negative DLBCL than in transformed DLBCL (H-score ≤ 100 in 43% vs. 3%, p = 0.006). Of 12 patients with plasmablastic lymphoma, CD79B and CD19 were negative in 83% and 66% of cases, respectively. Among 46 CD20-negative large B-cell lymphomas with low CD79B and/or CD19 expression, the tumor proportion score for programmed death-ligand 1 was positive (≥ 1%) in 33% of cases. The combined positive score for programmed death-ligand 1 was positive in 52% of programmed death-ligand 1 tumor proportion score-negative samples. In conclusion, CD79B and CD19 were variably expressed in CD20-negative large B-cell lymphomas, but lower in de novo DLBCL, and especially in plasmablastic lymphoma. Programmed cell death protein 1/programmed death-ligand one inhibitors may represent a treatment option.
cell therapies
2026-09-25 | Autologous hematopoietic stem cell transplantation in patients with HIV and lymphoproliferative disorders
Background. Human immunodeficiency virus (HIV) associated lymphomas remain a leading cause of death among people living with HIV, despite the advances in antiretroviral therapy. Autologous hematopoietic stem cell transplantation (auto-HSCT) is considered an effective consolidation strategy; however, data on its safety and feasibility in HIV-infected patients are limited. Aim. To evaluate the feasibility, safety, and efficacy of mobilization, collection of peripheral blood hematopoietic stem cells, and subsequent auto-HSCT in HIV-positive patients with aggressive relapsed B-cell lymphomas. Materials and methods. This single-center retrospective study included 9 patients (median age 43 years) with HIV infection and lymphomas (Hodgkin lymphoma – 3, plasmablastic lymphoma – 4, diffuse large B-cell lymphoma – 2) who underwent high-dose chemotherapy followed by auto-HSCT. Peripheral blood hematopoietic stem cells mobilization was performed using the HD-Cy / HD-Ara-C regimen combined with granulocyte colony-stimulating factor; plerixafor (n = 1) or empegfilgrastim (n = 2) was added in cases of insufficient response. The conditioning regimen was Benda-EAM. Mandatory inclusion criteria were complete virological suppression (HIV RNA 50 copies / mL), CD4+ lymphocyte count 100 / μL, and continued antiretroviral therapy. Results. The median harvested CD34+ cell dose was 3.64 × 106 / kg. The median time to neutrophil recovery 0.5 × 109 / L was 11 days, and to platelet recovery 20 × 109 / L – 14 days. Early post-transplant complications included febrile neutropenia (33.3 %), fatal septicemia (11.1 %), grade I–III mucositis (33.3 %), enterocolitis (22.2 %), and cytomegalovirus infection (11.1 %). Non-relapse mortality at 100 days was 11.1 %. No HIV reactivation was observed. At a median follow-up of 15.4 months, only one progression occurred – in a patient with plasmablastic lymphoma who underwent auto-HSCT in partial remission. The estimated 12-month overall survival and progression-free survival were 76.2 and 77.8 %, respectively. Conclusion. Auto-HSCT demonstrates promising results in HIV-infected patients with lymphomas, provided that complete remission is achieved, virological suppression is maintained, and adequate supportive care is delivered. Further follow-up and multicenter studies are warranted to confirm long-term efficacy.
2026-08-21 | A Giant Intra-Abdominal Plasmablastic Neoplasm Favoring Lymphoma Mimicking an Exacerbation of Severe Fistulizing Crohn’s Disease: A Case Report
Objective:Rare coexistence of disease or pathology Background:Plasmablastic lymphoma (PBL) is a rare, aggressive large B-cell lymphoma associated with immunosuppression.In Crohn's disease, it can mimic disease exacerbation or infection.We describe a rapidly enlarging intraabdominal plasmablastic neoplasm in a medically complex patient, emphasizing diagnostic vigilance without inferring a causal association with biological therapy. Case Report:A 44-year-old woman with severe fistulizing Crohn's disease treated sequentially with adalimumab, infliximab, and ustekinumab developed progressive systemic deterioration despite partial intestinal stabilization.Her course included portal hypertension secondary to portal vein thrombosis, refractory ascites, severe malnutrition, and recurrent systemic and multidrug-resistant infections.In September 2023 imaging showed a rapidly enlarging intra-abdominal/pelvic mass measuring more than 22 cm.Core-needle biopsy demonstrated a plasmablastic neoplasm positive for CD38, CD138, MUM1, and c-MYC, with equivocal CD10 and negative CD45, favoring PBL.Epstein-Barr virus-encoded RNA in situ hybridization, CD20, PAX5, Ki-67, anaplastic lymphoma kinase, human herpesvirus 8, and tissue light-chain restriction were unavailable.Bone marrow examination, serum and urine immunofixation, complete monoclonal-protein assessment, and whole-body skeletal imaging were not performed; therefore, plasmablastic myeloma could not be definitively excluded.Intensive chemotherapy was not feasible because her Eastern Cooperative Oncology Group performance status was at least 3 and she had multiorgan dysfunction, severe malnutrition, and active infections.The patient was transitioned to palliative care and subsequently died. Conclusions:Discordance between apparent intestinal control and systemic deterioration should prompt urgent tissue diagnosis.The findings favor PBL within the spectrum of plasmablastic neoplasms but neither establish drug-specific causation nor definitively exclude plasmablastic myeloma.
2026-08-15 | Oral plasmablastic lymphoma in an HIV-negative immunocompetent patient: a rare case report
Background: Plasmablastic lymphoma (PBL) is an uncommon and highly aggressive variant of diffuse large B-cell lymphoma, which was first recognized in association with human immunodeficiency virus (HIV). Although an increasing number of cases occurring in HIV-negative immunocompetent individuals have been described, thereby expanding the clinical picture of this tumor. Methods: We present a case of a 27-year-old HIV negative, medically fit male who came with a rapidly enlarging gingival mass. Clinical, radiographic, and histopathological assessments were done, plus immunohistochemical staining for plasma cell and B-cell markers. We also checked for Epstein-Barr virus (EBV) and then the Ki‑67 proliferation index, basically. Results: The patient had about a 2-week history of progressive swelling on the left lower jaw. On examination, there was a lobulated 1.5 × 2.0 cm red to violaceous mass, sitting on the buccal gingiva. Radiographs suggested minimal involvement of the bone. Histopathology showed a diffuse sheet-like infiltrate of atypical plasmablastic cells. In immunohistochemistry, the tumor was positive for CD138, CD38, c‑Myc, and EBV, with loss of CD20 expression. The Ki‑67 index was above 90%. Altogether, this confirmed the diagnosis of oral PBL. Conclusion: Although it is an uncommon entity and usually occurs in patients with HIV infection, oral PBL should be included when comparing treatments for gingival masses that rapidly harden, even in people who do not have AIDS. Patients will have a favorable outcome if they can be identified early, definitely diagnosed by pathologists, and then treated promptly with the proper therapy for this aggressive malignancy.
2026-07-11 | Aggressive Mandibular Plasmablastic Lymphoma in an HIV-Negative Patient: Clinicopathologic and Immunophenotypic Insights From a Rare Oral Case.
Plasmablastic lymphoma (PBL) is a rare and highly aggressive subtype of diffuse large B-cell lymphoma characterized by plasmacytic differentiation and a distinct immunophenotypic profile. It is most frequently associated with human immunodeficiency virus (HIV) infection and typically involves the oral cavity. However, PBL may also occur in immunocompetent individuals, representing a diagnostic and clinical challenge. This report describes a rare case of PBL affecting the mandible of an HIV-negative patient who presented with a rapidly progressive ulcerated oral lesion. Histopathological examination revealed a diffuse proliferation of large atypical cells with plasmablastic morphology and a high mitotic rate. Immunohistochemical analysis demonstrated strong expression of plasma cell markers, including CD138 and MUM1, along with negativity for conventional B-cell markers such as CD20 and CD79a. The Ki-67 proliferation index was approximately 90%, confirming the aggressive biological behavior of the neoplasm. Based on these findings, a diagnosis of PBL was established. Despite prompt referral for oncologic management and initiation of chemotherapy, the disease showed rapid progression with an unfavorable outcome. This case highlights the importance of including PBL in the differential diagnosis of aggressive oral lesions, even in HIV-negative and immunocompetent patients, and emphasizes the critical role of histopathological and immunohistochemical evaluation for accurate diagnosis.
2026-06-23 | Autologous Stem Cell Transplantation Of HIV-Positive Plasmablastic Lymphoma - Case Series.
Plasmablastic lymphoma (PBL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) commonly associated with immunosuppressed conditions, such as HIV infection. Historically, HIV-positive patients were not considered candidates for aggressive systemic therapies due to the risk of life-threatening opportunistic infections. However, with the advent of highly active antiretroviral therapy (HAART), the management of HIV-associated lymphomas has improved, allowing for more intensive treatments, including autologous stem cell transplantation (ASCT). This case series explores the safety and efficacy of ASCT in HIV-positive patients with PBL as consolidation at first complete response (CR1) following first-line chemotherapy. Patients who underwent ASCT for PBL at CR1 after first-line chemotherapy were selected from the Bone Marrow Transplant (BMT) registry from January 2015 to December 2024. Clinical details, transplant specific details and outcomes were collected from the case records. Three cases of HIV-positive patients diagnosed with PBL underwent ASCT as consolidation therapy were included in the case series. ASCT was done after achieving complete metabolic response (CMR) following induction chemotherapy. All patients received dose-adjusted EPOCH chemotherapy along with HAART. HAART was temporarily withheld during conditioning chemotherapy. Prophylactic medications were administered to prevent infections. Complications during the peri-transplant period included febrile neutropenia and mucositis, but no opportunistic infections were reported. CD4 counts dropped during the transplant period but stabilized post-transplant, with no significant long-term decline. ASCT is a safe and effective treatment option for HIV-positive patients with PBL who achieve CMR after induction chemotherapy. The procedure is well-tolerated, with manageable complications and favourable long-term outcomes. ASCT should be considered as a consolidation therapy for eligible HIV-positive patients with PBL, offering the potential for prolonged disease-free survival.
other
2026-06-24 | Abstract A034: Unlocking BCMA in aggressive lymphomas: A native receptor-targeted peptide for theranostic applications
Abstract Background Plasmablastic lymphoma (PBL) and related Diffuse Large B-cell Lymphoma (DLBCL) variants with plasmablastic differentiation are aggressive malignancies characterized by high BCMA (TNFRSF17) expression, yet BCMA-targeted therapies remain largely unexplored in this setting despite poor outcomes with standard approaches. These tumors frequently present with extramedullary disease, poor vascularity, and profound immunosuppression – features that reduce the efficacy of Fc-dependent biologics and underscore the need for Fc-independent targeting approaches. Aim We aimed to identify small BCMA-binding peptide ligands (≈1–5 kDa) for theranostic applications in plasmablastic lymphomas. Our strategy focused on targeting the native BCMA receptor on intact tumor cells to preserve its physiological conformation, including its cysteine-rich ectodomain and membrane-associated lipid environment, which is critical for genuine epitope recognition and binding interactions. Methods We performed phage display screening to identify BCMA-binding peptides using large combinatorial peptide libraries displayed on M13 phage, through three iterative rounds of positive selection on BCMA-positive NCI-H929 cells and negative selection on induced BCMA-negative NCI-H929 cells. We subsequently performed in silico characterization of the binding mechanisms of selected peptides, including protein-peptide docking analyses using the HADDOCK server and binding free energy estimation with the PRODIGY tool. Results We identified three peptide scaffolds capable of binding BCMA in its native form on BCMA-positive cells. Peptide pBCMA_7 was selected because of its clonal prevalence and its binding affinity toward BCMA-positive tumor cells. Docking and free energy studies suggest a configuration in which the peptide associates with a surface-accessible region of BCMA, forming extensive interactions through both backbone and side-chain atoms. Molecular dynamics simulations further indicate a stable and consistent binding mode within an exposed pocket of the receptor. Notably, pBCMA_7 exhibited strong binding (-11.2 kcal/mol) across a range of plasmablastic lymphoma cell lines (DB, Pfeiffer, SU-DHL-2, U-2932, Karpas 422) as well as multiple myeloma cell lines (NCI-H929, U266 and IM9). Conclusion We report the identification of BCMA-binding peptide ligands with demonstrated activity in plasmablastic lymphomas and related large B-cell lymphomas with plasmablastic differentiation. These peptide scaffolds constitute a versatile theranostic toolkit supporting Fc-independent patient stratification, therapy monitoring and delivery of imaging and therapeutic agents. By establishing phage display against native receptors as a tractable strategy for ligand discovery in an unexplored oncological setting, this work opens a wide therapeutic space for BCMA-directed precision targeting in aggressive lymphomas. Citation Format: Elisabetta Pingitore, Khushboo Fatima, Selena Mimmi, Valentina Crapella, Anna Maria Zimbo, Antonio Lupia, Alessia Onali, Domenico Maisano, Francesco Bertoni, Alessandra Scagliola, Federica Melle, Maria Carmela Vegliante, Doriana Gramegna, Michele Guida, Sabino Ciavarella, Enrico Iaccino. Unlocking BCMA in aggressive lymphomas: A native receptor-targeted peptide for theranostic applications [abstract]. In: Proceedings of the Fifth AACR International Meeting on Advances in Malignant Lymphoma: From Discovery to Clinical Impact; 2026 Jun 24-27; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2026;7(3_Suppl):Abstract nr A034.
small molecules
2026-05-15 | Plasmablastic Lymphoma: 2026 Update on Diagnosis, Risk Stratification, and Management.
Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with poor prognosis when treated with standard treatment options. Although PBL is associated with HIV infection and other immunosuppressed states, it can also affect immunocompetent individuals. The diagnosis of PBL requires a high clinical suspicion and pathological confirmation. EBV-encoded RNA (EBER) expression and MYC gene rearrangements are frequently detected in the malignant cells. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma (DLBCL), extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others. Age ≥ 60 years, advanced clinical stage, and high International Prognostic Index scores are associated with worse survival. Combination chemotherapy regimens, such as infusional EPOCH, are recommended. The addition of bortezomib or daratumumab might improve outcomes. B-cell maturation antigen-targeted therapies have shown early efficacy. The participation of patients with PBL in prospective clinical trials is warranted.
2026-05-01 | A69-35 When Pneumonia Isn’t Just Pneumonia: Pulmonary Plasmablastic Lymphoma in a Newly Diagnosed HIV Patient
Abstract Introduction Pulmonary complications are frequent in patients with Human Immunodeficiency Virus (HIV) infection, most often due to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP) or tuberculosis. However, malignant etiologies, including Plasmablastic Lymphoma (PBL) - a rare, aggressive variant of diffuse large B-cell lymphoma - can mimic infection both clinically and radiographically. Early recognition is critical given its poor prognosis and distinct therapeutic approach. Case Report A 40-year-old male with no prior medical history presented with three weeks of cough, intermittent hemoptysis, pleuritic chest pain, fever, night sweats, and weight loss. Physical examination revealed bilateral cervical and axillary lymphadenopathy and diffuse rhonchi. Initial chest radiograph demonstrated multifocal patchy consolidative opacities concerning for multifocal pneumonia (Figure 1). Computed tomography (CT) of the chest showed extensive peribronchovascular flame-shaped consolidations, perilymphatic nodularity, and diffuse mediastinal and axillary lymphadenopathy, suggestive of an atypical infection or lymphoproliferative process.HIV-1 testing was positive with a CD4 count of 149 cells/µL. Noninvasive workup, including Pneumocystis jirovecii, fungal, and Mycobacterium tuberculosis testing, was negative. The patient was initiated on antiretroviral therapy (bictegravir/emtricitabine/tenofovir alafenamide). Given persistent abnormalities, bronchoscopy with bronchoalveolar lavage, brushings, and endobronchial ultrasound-guided (EBUS) transbronchial biopsies was performed. The airways were noted to be irregular and narrowed in the left upper and lower lobes, with bulky subcarinal lymphadenopathy. Pathology revealed sheets of plasmablast-like cells positive for CD138, MUM1, CD38, and Epstein-Barr virus-encoded RNA (EBER), but negative for CD20 and PAX5, consistent with Plasmablastic Lymphoma. Following the procedure, the patient developed a small left apical pneumothorax, managed conservatively with supplemental oxygen. He subsequently initiated dose-adjusted EPOCH chemotherapy alongside antiretroviral therapy. Discussion This case highlights pulmonary PBL as a rare but important cause of diffuse pulmonary infiltrates in HIV-positive patients. Its radiographic presentation can closely resemble opportunistic infection or Kaposi sarcoma, delaying diagnosis. A high index of suspicion and early tissue sampling via bronchoscopy are essential for accurate diagnosis. Prompt recognition and initiation of combined chemotherapy and antiretroviral therapy are crucial for improved outcomes in this highly aggressive lymphoma. Figure 1: Chest CT showing multifocal patchy airspace opacities predominantly in the perihilar and lower lung zones. References: 1. Castillo JJ et al. Plasmablastic lymphoma: a systematic review. Lancet Oncol. 2008;9(6):559-567. 2. Loghavi S et al. Pulmonary plasmablastic lymphoma: a diagnostic pitfall in HIV-positive patients. Am J Surg Pathol. 2015;39(4):543-551. 3. Morscio J et al. Clinicopathologic comparison of plasmablastic lymphoma in HIV-positive and HIV-negative patients. Histopathology. 2014;65(2):230-242. This abstract is funded by: none
2026-03-26 | Case Report: From multiple myeloma to plasmablastic lymphoma - a diagnostic dilemma in unraveling a rare transformation.
Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of diffuse large B-cell lymphoma. Its transformation from multiple myeloma (MM) is an exceptionally rare event, with only nine cases reported in the literature. Differentiating PBL from plasmablastic myeloma (PBM) is a significant diagnostic challenge due to overlapping morphological and immunophenotypic features, yet it is critical for determining the appropriate treatment regimen. We report the case of a woman in her 50s with a seven-year history of kappa-restricted MM who presented with a right leg mass. Biopsy confirmed a lambda-restricted plasmacytoma, indicating an extramedullary relapse. Two months after initiating therapy for myeloma relapse, she developed right inguinal lymphadenopathy. A lymph node biopsy revealed lambda-restricted plasmablasts positive for CD138, CD56, C-MYC, and Ki67 (100%), and negative for CD79a and EBER. In the absence of systemic MM-related end-organ damage and the presence of nodal disease, a diagnosis of PBL was favored over PBM. The patient was subsequently treated with DA-EPOCH chemotherapy (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), leading to significant regression of disease on interim PET scan. This case represents the 10th reported transformation of MM to PBL and highlights the diagnostic dilemma posed by these entities. It underscores the importance of clinical context, the potential for clonal evolution (evidenced by a light-chain switch), and the efficacy of lymphoma-specific chemotherapy in this setting.
2026-03-24 | Prognosis and treatment of plasmablastic lymphoma in the United States: a multicenter retrospective study.
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.
2026-03-06 | HIV-associated lymphoproliferative disorders: Single-center experience.
Survival rates of human immunodeficiency virus-positive subjects improved in recent years, especially due to innovations in current lymphoma treatments and the addition of combination antiretroviral therapy (cART). This study presents demographic and clinical characteristics, prognosis, and survival data of acquired immune deficiency syndrome (AIDS)-related lymphoma patients as a single-center experience. This retrospective study included 16 patients with AIDS-related lymphoma treated at our center between August 2010 and March 2022. Demographic data, clinical information, treatment details, and survival analysis of the patients were retrospectively reviewed from the relevant clinical archives. Fifteen out of 16 patients were males with a median age of 46.5 years (range, 24-71 years). The diagnoses were as follows: diffuse large B-cell lymphoma in 6, Burkitt lymphoma in 4, Hodgkin lymphoma in 3, plasmablastic lymphoma in 1, primary central nervous system lymphoma in 1, and chronic lymphocytic leukemia in 1 out of 16 patients. Fifteen patients presented with an advanced stage at diagnosis. Diagnosis of AIDS preceded the onset of lymphoma in 11 patients. The time from human immunodeficiency virus infection to diagnosis of lymphoma was 23.8 months (range, 1-185 months). All patients received cART during lymphoma treatment. The treatment response was evaluated in all patients who completed the initial treatment. Eleven patients (68.8%) are still alive with a complete response. Antitumour treatments administered in conjunction with cART have a favorable impact on survival and response rates in this aggressive group of patients.
gene therapies
2022-02-28 | Hematologic cancers in individuals infected by HIV.
HIV infection increases cancer risk and is linked to cancers associated to infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. Lymphomas represent one of the most frequent malignancies among individuals infected by HIV. Diffuse large B-cell lymphoma remains a leading cancer after the introduction of combined antiretroviral therapy (cART). The incidence of other lymphomas including Burkitt lymphoma, primary effusion lymphomas, and plasmablastic lymphoma of the oral cavity remain stable, whereas the incidence of Hodgkin lymphoma and Kaposi sarcoma-associated herpesvirus (KSHV)-associated multicentric Castleman disease has increased. The heterogeneity of lymphomas in individuals infected by HIV likely depends on the complexity of involved pathogenetic mechanisms (ie, HIV-induced immunosuppression, genetic abnormalities, cytokine dysregulation, and coinfection with the gammaherpesviruses Epstein-Barr virus and KSHV) and the dysregulation of the immune responses controlling these viruses. In the modern cART era, standard treatments for HIV-associated lymphoma including stem cell transplantation in relapsed/refractory disease mirror that of the general population. The combination of cART and antineoplastic treatments has resulted in remarkable prolongation of long-term survival. However, oncolytic and immunotherapic strategies and therapies targeting specific viral oncogenes will need to be developed.
2004-01-06 | Oral Plasmablastic Lymphomas in AIDS Patients Are Associated With Human Herpesvirus 8
Human herpes virus type 8 (HHV8) has been strongly associated with Kaposi sarcoma, primary effusion lymphoma (PEL), and Castleman's disease. To our knowledge, infection by this virus has not been strongly associated with other hematopathologic malignancies. We examined five oral cavity lymphomas from men with AIDS for HHV8 and HIV-1 by reverse transcriptase in situ polymerase chain reaction, as well as for Epstein-Barr virus (EBV) (EBER-1, -2) using in situ hybridization and HHV8 protein with immunohistochemistry. Four of these tumors were plasmablastic lymphomas; the final case was diffuse large B-cell lymphoma. Most of the neoplastic cells in these five lymphomas contained HHV8 RNA and protein. Further, the four plasmablastic lymphoma cases had tumor cells that contained EBV. HIV-1 RNA was not detected in the tumor cells but was noted in surrounding benign T cells. In comparison, HHV8 RNA was not detected in any of the five oral cavity lymphomas from people who did not have acquired immunosuppression nor in five lymphomas from AIDS patients that were located at a site other than the oral cavity. It is concluded that oral cavity lymphomas from people with AIDS are strongly associated with infection by HHV8 and EBV. Given the poor prognosis of oral cavity lymphomas in immunocompromised patients, therapy directed against the HHV8 and EBV infection may be of therapeutic value.
antibodies
2026-06-02 | Case Report: Synchronous Manifestations of Kaposi Sarcoma Herpesvirus-Associated Disorders.
Kaposi sarcoma herpes virus (KSHV) is associated with multiple clinical manifestations, including primary effusion lymphoma, an aggressive CD38+ B cell lymphoma with a plasmablastic phenotype. This case describes an antiretroviral therapy-adherent person with HIV who presented with concurrent KSHV-related disorders of Kaposi sarcoma (KS), multicentric Castleman disease (MCD), and extracavitary primary effusion lymphoma (EC-PEL). Single-cell RNAseq (scRNAseq) and multiplex immunohistochemistry (mIHC) provide detailed insights into differences in cellular composition and viral and cellular transcriptomic differences between these diseases. Moreover, the case describes a long-term remission with single-agent anti-CD38 antibody, daratumumab, in a chemotherapy-refractory case. This case highlights the differing clinical manifestations of KSHV and the efficacy of immunotherapy in KSHV-associated primary effusion lymphoma.
2026-03-23 | Haematuria As the Initial Manifestation of Bladder Plasmablastic Lymphoma: A Report of a Rare Case and Literature Review
Plasmablastic lymphoma (PBL) is an aggressive and uncommon variant of diffuse large B-cell lymphoma, most frequently associated with immunocompromised states. Although extranodal disease is characteristic, involvement of the urinary bladder is exceptionally rare and may mimic primary urothelial malignancy both clinically and histologically. We report the case of a 62-year-old man with a previous history of high-grade diffuse large B-cell lymphoma in remission who presented with acute gross haematuria. Imaging demonstrated bladder wall thickening with associated hydronephrosis. Transurethral resection of the bladder lesion, followed by detailed histopathological and immunohistochemical analysis, confirmed plasmablastic large B-cell lymphoma involving the bladder. This case underscores the importance of maintaining a broad differential diagnosis in patients presenting with haematuria, particularly those with a prior history of haematologic malignancy. A review of the literature highlights the rarity of bladder involvement and the diagnostic challenges associated with this entity.
2026-03-03 | Targeting BCMA in Plasmablastic Lymphoma With Teclistamab: A Case Study of Three Patients.
Plasmablastic lymphoma (PBL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited standard therapeutic options and poor outcomes. PBL typically lacks expression of the B-cell antigens CD20 or CD19 and, accordingly, has not benefited from the incorporation of B-cell-targeted antibodies. However, recent reports demonstrate that B-cell maturation antigen (BCMA) is expressed in most patients with PBL. BCMA is an established therapeutic target in multiple myeloma. Herein, we describe the clinical course of 3 patients with PBL found to express BCMA by immunohistochemistry who were treated with the BCMA×CD3 bispecific antibody teclistamab after developing disease refractory to at least 2 lines of standard therapy. A complete response was observed in 2 patients: 1 patient remains in remission after 2 years of teclistamab treatment, while the second achieved a complete response after 1 cycle of teclistamab, subsequently underwent allogeneic stem cell transplantation, and developed relapsed PBL 3 months post-transplant. The third patient developed a small bowel obstruction and transitioned to hospice care after 1 cycle of teclistamab. This case series adds to the growing evidence that BCMA is expressed in a considerable subset of patients with PBL and suggests that BCMA may serve as a potential molecular biomarker in PBL for further investigation of available BCMA-directed therapies.
2026-02-24 | Clinicopathological Analysis of Plasmablastic Lymphoma Cases: A Cross-sectional Study from a Tertiary Care Cancer Centre in Kerala, India
Introduction: Plasmablastic Lymphoma (PBL) is an aggressive lymphoid neoplasm composed of large atypical B cells with plasmablastic or immunoblastic morphology and a terminal B-cell differentiation phenotype predominantly presenting at extranodal sites. PBL is rare comprising 1% of large B-cell lymphomas. Most PBLs occur in the context of immune deficiency/dysregulation. Aim: To analyse the morphology, immunophenotype, clinical details and diagnostic challenges in cases diagnosed as PBL. Materials and Methods: The present study was a crosssectional cohort study analysing cases of PBL diagnosed during 2011 to 2021 in the Department of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India. Morphology and Immunohistochemistry (IHC) (CD45, CD3, CD5, CD20, CD79a, Pax5, CD38, CD138, MUM1, EMA, Kappa, Lambda, CD56, CD30, Alk-1, Ki-67) of tumour cells were reviewed. Epstein-Barr Virus (EBV) by Rapid in Situ Hybridisation (RISH) was also documented. Clinical details including patients age, sex, clinical presentation were elaborated using descriptive statistics. Treatment details and overall survival also noted. Results: During the study period there were a total of 36 cases. The median age at presentation was 57 years (range: 10 to 85 years). Six cases (16.7%) had associated HIV, 26 cases (72.2%) had extranodal disease. Tumour cells in all cases were positive for CD138 and MUM1, and negative for CD20, PAX5, and T-cell markers with a high Ki-67 proliferation index (80-95%). Leukocyte Common Antigen (LCA) were negative in 22 cases (61.11%) or weakly positive in 14 cases (38.9%), CD 79a was faintly positive in one case (2.8%) and weak Pax5 positivity was seen in two cases (5.6%). EBV was positive in 21 cases (58.3%) Median overall survival was 17.5% for 3-year in the present study. Conclusion: PBL is a rare aggressive lymphoma having association with HIV, predominant extranodal location, and characteristic IHC pattern. Lymphoproliferative neoplasms with plasmablastic morphology share many morphologic and immunophenotypic similarities and diagnosis requires integration of clinical morphological and IHC findings.
2026-02-14 | Differential Expression of CD79B, CD19, and PD-L1 in de Novo and Transformed CD20-Negative Large B-Cell Lymphomas.
CD20-negative large B-cell lymphomas exhibit aggressive behavior and are ineligible for rituximab-containing therapy. To identify antigens targeted by treatment, we analyzed CD79B and CD19 expression in 108 samples from 75 patients with CD20-negative large B-cell lymphomas using H-score. Diffuse-strong (H-score 300) CD79B and CD19 expression was observed in 51% and 57% of samples, and low/negative (H-score ≤ 100) in 35% and 30%, respectively. CD79B expression was significantly lower in de novo CD20-negative diffuse large B-cell lymphoma (DLBCL) than in CD20-negative DLBCL changed from CD20-positive DLBCL after rituximab-containing therapy and in CD20-negative DLBCL transformed from CD20-positive low-grade B-cell lymphoma after rituximab-containing therapy (H-score ≤ 100 in 79% vs. 27% vs. 10%, p < 0.001). CD19 expression was lower in de novo CD20-negative DLBCL than in transformed DLBCL (H-score ≤ 100 in 43% vs. 3%, p = 0.006). Of 12 patients with plasmablastic lymphoma, CD79B and CD19 were negative in 83% and 66% of cases, respectively. Among 46 CD20-negative large B-cell lymphomas with low CD79B and/or CD19 expression, the tumor proportion score for programmed death-ligand 1 was positive (≥ 1%) in 33% of cases. The combined positive score for programmed death-ligand 1 was positive in 52% of programmed death-ligand 1 tumor proportion score-negative samples. In conclusion, CD79B and CD19 were variably expressed in CD20-negative large B-cell lymphomas, but lower in de novo DLBCL, and especially in plasmablastic lymphoma. Programmed cell death protein 1/programmed death-ligand one inhibitors may represent a treatment option.
cell therapies
2026-09-25 | Autologous hematopoietic stem cell transplantation in patients with HIV and lymphoproliferative disorders
Background. Human immunodeficiency virus (HIV) associated lymphomas remain a leading cause of death among people living with HIV, despite the advances in antiretroviral therapy. Autologous hematopoietic stem cell transplantation (auto-HSCT) is considered an effective consolidation strategy; however, data on its safety and feasibility in HIV-infected patients are limited. Aim. To evaluate the feasibility, safety, and efficacy of mobilization, collection of peripheral blood hematopoietic stem cells, and subsequent auto-HSCT in HIV-positive patients with aggressive relapsed B-cell lymphomas. Materials and methods. This single-center retrospective study included 9 patients (median age 43 years) with HIV infection and lymphomas (Hodgkin lymphoma – 3, plasmablastic lymphoma – 4, diffuse large B-cell lymphoma – 2) who underwent high-dose chemotherapy followed by auto-HSCT. Peripheral blood hematopoietic stem cells mobilization was performed using the HD-Cy / HD-Ara-C regimen combined with granulocyte colony-stimulating factor; plerixafor (n = 1) or empegfilgrastim (n = 2) was added in cases of insufficient response. The conditioning regimen was Benda-EAM. Mandatory inclusion criteria were complete virological suppression (HIV RNA 50 copies / mL), CD4+ lymphocyte count 100 / μL, and continued antiretroviral therapy. Results. The median harvested CD34+ cell dose was 3.64 × 106 / kg. The median time to neutrophil recovery 0.5 × 109 / L was 11 days, and to platelet recovery 20 × 109 / L – 14 days. Early post-transplant complications included febrile neutropenia (33.3 %), fatal septicemia (11.1 %), grade I–III mucositis (33.3 %), enterocolitis (22.2 %), and cytomegalovirus infection (11.1 %). Non-relapse mortality at 100 days was 11.1 %. No HIV reactivation was observed. At a median follow-up of 15.4 months, only one progression occurred – in a patient with plasmablastic lymphoma who underwent auto-HSCT in partial remission. The estimated 12-month overall survival and progression-free survival were 76.2 and 77.8 %, respectively. Conclusion. Auto-HSCT demonstrates promising results in HIV-infected patients with lymphomas, provided that complete remission is achieved, virological suppression is maintained, and adequate supportive care is delivered. Further follow-up and multicenter studies are warranted to confirm long-term efficacy.
2026-08-21 | A Giant Intra-Abdominal Plasmablastic Neoplasm Favoring Lymphoma Mimicking an Exacerbation of Severe Fistulizing Crohn’s Disease: A Case Report
Objective:Rare coexistence of disease or pathology Background:Plasmablastic lymphoma (PBL) is a rare, aggressive large B-cell lymphoma associated with immunosuppression.In Crohn's disease, it can mimic disease exacerbation or infection.We describe a rapidly enlarging intraabdominal plasmablastic neoplasm in a medically complex patient, emphasizing diagnostic vigilance without inferring a causal association with biological therapy. Case Report:A 44-year-old woman with severe fistulizing Crohn's disease treated sequentially with adalimumab, infliximab, and ustekinumab developed progressive systemic deterioration despite partial intestinal stabilization.Her course included portal hypertension secondary to portal vein thrombosis, refractory ascites, severe malnutrition, and recurrent systemic and multidrug-resistant infections.In September 2023 imaging showed a rapidly enlarging intra-abdominal/pelvic mass measuring more than 22 cm.Core-needle biopsy demonstrated a plasmablastic neoplasm positive for CD38, CD138, MUM1, and c-MYC, with equivocal CD10 and negative CD45, favoring PBL.Epstein-Barr virus-encoded RNA in situ hybridization, CD20, PAX5, Ki-67, anaplastic lymphoma kinase, human herpesvirus 8, and tissue light-chain restriction were unavailable.Bone marrow examination, serum and urine immunofixation, complete monoclonal-protein assessment, and whole-body skeletal imaging were not performed; therefore, plasmablastic myeloma could not be definitively excluded.Intensive chemotherapy was not feasible because her Eastern Cooperative Oncology Group performance status was at least 3 and she had multiorgan dysfunction, severe malnutrition, and active infections.The patient was transitioned to palliative care and subsequently died. Conclusions:Discordance between apparent intestinal control and systemic deterioration should prompt urgent tissue diagnosis.The findings favor PBL within the spectrum of plasmablastic neoplasms but neither establish drug-specific causation nor definitively exclude plasmablastic myeloma.
2026-08-15 | Oral plasmablastic lymphoma in an HIV-negative immunocompetent patient: a rare case report
Background: Plasmablastic lymphoma (PBL) is an uncommon and highly aggressive variant of diffuse large B-cell lymphoma, which was first recognized in association with human immunodeficiency virus (HIV). Although an increasing number of cases occurring in HIV-negative immunocompetent individuals have been described, thereby expanding the clinical picture of this tumor. Methods: We present a case of a 27-year-old HIV negative, medically fit male who came with a rapidly enlarging gingival mass. Clinical, radiographic, and histopathological assessments were done, plus immunohistochemical staining for plasma cell and B-cell markers. We also checked for Epstein-Barr virus (EBV) and then the Ki‑67 proliferation index, basically. Results: The patient had about a 2-week history of progressive swelling on the left lower jaw. On examination, there was a lobulated 1.5 × 2.0 cm red to violaceous mass, sitting on the buccal gingiva. Radiographs suggested minimal involvement of the bone. Histopathology showed a diffuse sheet-like infiltrate of atypical plasmablastic cells. In immunohistochemistry, the tumor was positive for CD138, CD38, c‑Myc, and EBV, with loss of CD20 expression. The Ki‑67 index was above 90%. Altogether, this confirmed the diagnosis of oral PBL. Conclusion: Although it is an uncommon entity and usually occurs in patients with HIV infection, oral PBL should be included when comparing treatments for gingival masses that rapidly harden, even in people who do not have AIDS. Patients will have a favorable outcome if they can be identified early, definitely diagnosed by pathologists, and then treated promptly with the proper therapy for this aggressive malignancy.
2026-07-11 | Aggressive Mandibular Plasmablastic Lymphoma in an HIV-Negative Patient: Clinicopathologic and Immunophenotypic Insights From a Rare Oral Case.
Plasmablastic lymphoma (PBL) is a rare and highly aggressive subtype of diffuse large B-cell lymphoma characterized by plasmacytic differentiation and a distinct immunophenotypic profile. It is most frequently associated with human immunodeficiency virus (HIV) infection and typically involves the oral cavity. However, PBL may also occur in immunocompetent individuals, representing a diagnostic and clinical challenge. This report describes a rare case of PBL affecting the mandible of an HIV-negative patient who presented with a rapidly progressive ulcerated oral lesion. Histopathological examination revealed a diffuse proliferation of large atypical cells with plasmablastic morphology and a high mitotic rate. Immunohistochemical analysis demonstrated strong expression of plasma cell markers, including CD138 and MUM1, along with negativity for conventional B-cell markers such as CD20 and CD79a. The Ki-67 proliferation index was approximately 90%, confirming the aggressive biological behavior of the neoplasm. Based on these findings, a diagnosis of PBL was established. Despite prompt referral for oncologic management and initiation of chemotherapy, the disease showed rapid progression with an unfavorable outcome. This case highlights the importance of including PBL in the differential diagnosis of aggressive oral lesions, even in HIV-negative and immunocompetent patients, and emphasizes the critical role of histopathological and immunohistochemical evaluation for accurate diagnosis.
2026-06-23 | Autologous Stem Cell Transplantation Of HIV-Positive Plasmablastic Lymphoma - Case Series.
Plasmablastic lymphoma (PBL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) commonly associated with immunosuppressed conditions, such as HIV infection. Historically, HIV-positive patients were not considered candidates for aggressive systemic therapies due to the risk of life-threatening opportunistic infections. However, with the advent of highly active antiretroviral therapy (HAART), the management of HIV-associated lymphomas has improved, allowing for more intensive treatments, including autologous stem cell transplantation (ASCT). This case series explores the safety and efficacy of ASCT in HIV-positive patients with PBL as consolidation at first complete response (CR1) following first-line chemotherapy. Patients who underwent ASCT for PBL at CR1 after first-line chemotherapy were selected from the Bone Marrow Transplant (BMT) registry from January 2015 to December 2024. Clinical details, transplant specific details and outcomes were collected from the case records. Three cases of HIV-positive patients diagnosed with PBL underwent ASCT as consolidation therapy were included in the case series. ASCT was done after achieving complete metabolic response (CMR) following induction chemotherapy. All patients received dose-adjusted EPOCH chemotherapy along with HAART. HAART was temporarily withheld during conditioning chemotherapy. Prophylactic medications were administered to prevent infections. Complications during the peri-transplant period included febrile neutropenia and mucositis, but no opportunistic infections were reported. CD4 counts dropped during the transplant period but stabilized post-transplant, with no significant long-term decline. ASCT is a safe and effective treatment option for HIV-positive patients with PBL who achieve CMR after induction chemotherapy. The procedure is well-tolerated, with manageable complications and favourable long-term outcomes. ASCT should be considered as a consolidation therapy for eligible HIV-positive patients with PBL, offering the potential for prolonged disease-free survival.
other
2026-06-24 | Abstract A034: Unlocking BCMA in aggressive lymphomas: A native receptor-targeted peptide for theranostic applications
Abstract Background Plasmablastic lymphoma (PBL) and related Diffuse Large B-cell Lymphoma (DLBCL) variants with plasmablastic differentiation are aggressive malignancies characterized by high BCMA (TNFRSF17) expression, yet BCMA-targeted therapies remain largely unexplored in this setting despite poor outcomes with standard approaches. These tumors frequently present with extramedullary disease, poor vascularity, and profound immunosuppression – features that reduce the efficacy of Fc-dependent biologics and underscore the need for Fc-independent targeting approaches. Aim We aimed to identify small BCMA-binding peptide ligands (≈1–5 kDa) for theranostic applications in plasmablastic lymphomas. Our strategy focused on targeting the native BCMA receptor on intact tumor cells to preserve its physiological conformation, including its cysteine-rich ectodomain and membrane-associated lipid environment, which is critical for genuine epitope recognition and binding interactions. Methods We performed phage display screening to identify BCMA-binding peptides using large combinatorial peptide libraries displayed on M13 phage, through three iterative rounds of positive selection on BCMA-positive NCI-H929 cells and negative selection on induced BCMA-negative NCI-H929 cells. We subsequently performed in silico characterization of the binding mechanisms of selected peptides, including protein-peptide docking analyses using the HADDOCK server and binding free energy estimation with the PRODIGY tool. Results We identified three peptide scaffolds capable of binding BCMA in its native form on BCMA-positive cells. Peptide pBCMA_7 was selected because of its clonal prevalence and its binding affinity toward BCMA-positive tumor cells. Docking and free energy studies suggest a configuration in which the peptide associates with a surface-accessible region of BCMA, forming extensive interactions through both backbone and side-chain atoms. Molecular dynamics simulations further indicate a stable and consistent binding mode within an exposed pocket of the receptor. Notably, pBCMA_7 exhibited strong binding (-11.2 kcal/mol) across a range of plasmablastic lymphoma cell lines (DB, Pfeiffer, SU-DHL-2, U-2932, Karpas 422) as well as multiple myeloma cell lines (NCI-H929, U266 and IM9). Conclusion We report the identification of BCMA-binding peptide ligands with demonstrated activity in plasmablastic lymphomas and related large B-cell lymphomas with plasmablastic differentiation. These peptide scaffolds constitute a versatile theranostic toolkit supporting Fc-independent patient stratification, therapy monitoring and delivery of imaging and therapeutic agents. By establishing phage display against native receptors as a tractable strategy for ligand discovery in an unexplored oncological setting, this work opens a wide therapeutic space for BCMA-directed precision targeting in aggressive lymphomas. Citation Format: Elisabetta Pingitore, Khushboo Fatima, Selena Mimmi, Valentina Crapella, Anna Maria Zimbo, Antonio Lupia, Alessia Onali, Domenico Maisano, Francesco Bertoni, Alessandra Scagliola, Federica Melle, Maria Carmela Vegliante, Doriana Gramegna, Michele Guida, Sabino Ciavarella, Enrico Iaccino. Unlocking BCMA in aggressive lymphomas: A native receptor-targeted peptide for theranostic applications [abstract]. In: Proceedings of the Fifth AACR International Meeting on Advances in Malignant Lymphoma: From Discovery to Clinical Impact; 2026 Jun 24-27; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2026;7(3_Suppl):Abstract nr A034.
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Drug Discovery Landscape
1 orphan drug designation for Plasmablastic lymphoma.
1 orphan drug designation for Plasmablastic lymphoma.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
nanatinostat and valganciclovir | small molecules | FDA | Epirare Therapeutics |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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