RARE DISEASE
Intravascular large B-cell lymphoma
Intravascular large B-cell lymphoma
Intravascular large B-cell lymphoma
Synonyms: Angioendotheliomatosis proliferans systemisata, Angiotropic large cell lymphoma, Intravascular lymphomatosis, Malignant angioendotheliomatosis, Tappeiner-Pfleger disease
Synonyms: Angioendotheliomatosis proliferans systemisata, Angiotropic large cell lymphoma, Intravascular lymphomatosis, Malignant angioendotheliomatosis, Tappeiner-Pfleger disease
Synonyms: Angioendotheliomatosis proliferans systemisata, Angiotropic large cell lymphoma, Intravascular lymphomatosis, Malignant angioendotheliomatosis, Tappeiner-Pfleger disease
Drug discovery
0
drugs
With orphan designations
Overview
Intravascular Large B-Cell Lymphoma (IVLBCL) is a rare, aggressive subtype of diffuse large B-cell lymphoma characterized by malignant B-cell proliferation within blood vessel lumina. Clinical presentation varies widely, often involving fever, neurological deficits, or cutaneous manifestations, with frequent delays in diagnosis due to nonspecific symptoms [1][6][11]. Prognosis has improved with rituximab-based therapies, though central nervous system (CNS) involvement portends worse outcomes [3][8][14].
Population
Therapies
First-line: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with 3-year survival rates ≥60% [2][8][14].
CNS involvement: High-dose methotrexate (HDMTX) or cytarabine (HiDAC) combined with R-CHOP improves outcomes [3][6].
Salvage options: Autologous stem cell transplantation (limited by age/comorbidities) and emerging PD-1/PD-L1 inhibitors [11][16].
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
225 drug discovery papers about Intravascular large B-cell lymphoma, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
225 drug discovery papers about Intravascular large B-cell lymphoma, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-30 | A case of primary prostatic intravascular large B-cell lymphoma misdiagnosed as benign prostatic hyperplasia.
Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive subtype of extranodal large B-cell lymphoma, characterized by the confinement of tumor cells within the lumens of small blood vessels. It most commonly involves the skin, central nervous system, bone marrow, liver, and spleen, with primary involvement of the prostate being particularly rare. This article reports a case of a 71-year-old male patient who presented with progressive urinary difficulty. Imaging suggested severe prostatic hyperplasia, and benign prostatic hyperplasia (BPH) was considered preoperatively. However, histopathological examination of the prostate after transurethral resection revealed numerous proliferating neoplastic lymphocytes within the prostatic blood vessels. The diagnosis of primary prostatic intravascular large B-cell lymphoma was confirmed by immunohistochemistry and molecular pathology and PET-CT scans. The patient received first-line ZR2 chemotherapy (rituximab + lenalidomide + zanubrutinib). However, he developed acute liver failure during the second cycle, which improved after treatment. The patient has survived for 23 months during follow-up. Primary prostatic IVLBCL is clinically rare and often misdiagnosed as a benign condition due to the lack of specific symptoms. Early biopsy and immunohistochemistry are crucial for accurate diagnosis.
2026-04-24 | Intravascular large B-cell lymphoma mimicking an orbital mass lesion and bilateral cavernous sinus syndrome: A case report.
Intravascular large B-cell lymphoma (IVLBCL) is a rare entity that can present with atypical extranodal manifestations, often mimicking other orbital or neurological conditions. A 69-year-old woman presented with rapidly progressive left ptosis and diplopia, which progressed to complete bilateral ophthalmoplegia within several weeks. Magnetic resonance imaging revealed a previously unreported right orbital mass accompanied by bilateral cavernous sinus (CS) enhancement, representing a novel imaging feature of IVLBCL. The diagnosis was established by sphenoid sinus biopsy. The patient achieved near-clinical remission, with almost complete resolution of the orbital mass, following rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) chemotherapy combined with a Bruton tyrosine kinase inhibitor and intravenous high-dose methotrexate. However, diplopia recurred at 3 months post-treatment, indicating that although the patient initially responded well to R-CHOP-based combination therapy, more effective maintenance or consolidation strategies should be actively explored for patients with IVLBCL involving the central nervous system. Clinically, various lymphoma subtypes should be considered in the differential diagnosis of patients presenting with CS and intraorbital lesions.
2026-02-11 | Breaking diagnostic and therapeutic barriers in intravascular large B-cell lymphoma: A 13-year real-world study from China
Abstract Background Intravascular large B-cell lymphoma (IVLBCL) is an ultra-orphan disease (incidence 0.095/million/year) with dismal prognosis due to delayed diagnosis and limited therapeutic options. We aimed to evaluate a novel diagnostic algorithm and the efficacy of zanubrutinib-containing therapy in a real-world Chinese cohort. Methods This single-center retrospective study enrolled 54 IVLBCL patients (2010–2022). Diagnostic approaches evolved from PET/CT-guided biopsy to a combination of serum interleukin-10 (IL-10, cut-off 95.65 pg/mL), random skin biopsy (RSB), and circulating tumor DNA (ctDNA) profiling. Treatment regimens shifted from R-CHOP to methotrexate-based therapy (MTX), then to zanubrutinib plus R-CHOP (ZR-CHOP). Results The cohort exhibited distinct features: 35.2% Asian-variant IVLBCL, 50% CNS involvement, and 22.9% PET/CT negativity. IL-10 combined with RSB enabled the diagnosis of 11 PET/CT-negative patients who would have otherwise remained undiagnosed. ctDNA revealed MYD88 L265P (11/17, 65%) and CD79B (7/17, 41%) variants. ZR-CHOP (n = 22) achieved significantly superior 2-year progression-free survival (PFS) compared to R-CHOP alone (n = 6) (90% vs. 30%; hazard ratio [HR] 0.031, P < 0.0001) and demonstrated 100% central nervous system (CNS) relapse-free survival. The efficacy of ZR-CHOP was comparable to that of methotrexate (MTX)-based therapy (n = 20; 2-year PFS 85%), despite a shorter median follow-up (20.1 vs. 38.0 months). Conclusions In this largest Asian IVLBCL cohort to date, IL-10 + RSB + ctDNA significantly improved diagnostic accuracy. Zanubrutinib demonstrated promising efficacy, particularly in CNS involvement, offering a pragmatic solution for this orphan disease.
2025-10-13 | Severe lactic acidosis in association with CD5+ large B-cell lymphoma
Lactic acidosis is classified into type A and type B. In cases of type B lactic acidosis, it is important to consider underlying lymphomas, mostly B-cell types, such as intravascular large B-cell lymphoma (IVLBCL) or diffuse large B-cell lymphoma. Cluster of differentiation (CD) 5+ large B-cell lymphoma (LBCL) is well-known for its aggressive nature. We report here two cases of CD5+ LBCL that showed severe lactic acidosis (11.2 mmol/L and 15.9 mmol/L, respectively; reference range: 0.6–1.7) with hypoglycemia. Case 1 was a 79-year-old female who presented with multiple organ failure. CD5+ IVLBCL was diagnosed through a random skin biopsy in this patient. Case 2 was a 78-year-old female with bone marrow involvement by CD5+ LBCL cells and liver failure. The patient was also diagnosed pathologically as IVLBCL by liver biopsy. Both patients were under ventilator management and high-flow continuous hemodialysis and filtration. Plasma exchange was also employed. An anti-lymphoma regimen (a 50% dose-reduced etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) was introduced on day 11 and day 2 of hospitalization for cases 1 and 2, respectively. In Case 1, lactic acidosis was normalized within day 17, and the patient survived longer than 8 weeks, while in Case 2, lactic levels did not improve until her death on day 16 of hospitalization. In conclusion, prompt recognition of type B lactic acidosis and early diagnostic biopsy are essential for improving outcomes in aggressive CD5+ IVLBCL, highlighting the need for novel therapeutic strategies.
2025-08-22 | Case report: A case of intravascular large B-cell lymphoma and related literature review
Intravascular large B-cell lymphoma (IVLBCL) presents with a wide range of clinical symptoms, making clinical diagnosis challenging. It is often misdiagnosed or overlooked, leading to delays in treatment for affected patients. We present a case of a patient exhibiting clinical symptoms such as chest tightness, dyspnea, fever, and edema, who was later diagnosed with secondary hemophagocytic syndrome (HPS). Laboratory tests indicated persistent hypoalbuminemia, significantly elevated lactate dehydrogenase levels, thrombocytopenia, and splenomegaly, with no evidence of lymphadenopathy. During the treatment for HPS, the patient developed a rash on both lower limbs and abdomen and was ultimately diagnosed as IVLBCL after a skin biopsy. Following four cycles of zanubrutinib in combination with the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the patient achieved complete resolution of both dermatological manifestations and systemic symptoms. Laboratory parameters, including complete blood count, serum albumin levels, and lactate dehydrogenase, were normalized. Additionally, ultrasonography demonstrated a marked reduction in splenic size. However, the patient exhibited suboptimal adherence to the prescribed treatment plan and did not complete the intended number of cycles. During a subsequent telephone follow-up, the patient was confirmed to be alive; however, the status of the disease could not be evaluated. As of the latest follow-up, the patient has survived for 2 years.
cell therapies
2026-08-05 | A 13-Year Review of Non-Diffuse Large B Cell Lymphomas of the Central Nervous System at a Tertiary Hospital: A Case Series Study.
Non-diffuse large B-cell lymphomas (non-DLBCL) of the central nervous system (CNS) are rare and diagnostically challenging. This study aims to characterize the clinical, radiological, and pathological features of non-DLBCL CNS lymphomas diagnosed at a tertiary care center over 13 years, highlighting diagnostic pitfalls. A retrospective review was conducted of non-DLBCL CNS lymphoma cases diagnosed at Sunnybrook Health Sciences Centre, Toronto, from 2010 to 2022. Clinical, demographic, and radiological data were extracted from medical records. Imaging was reviewed by a neuroradiologist, and histopathological slides and molecular data were re-evaluated by a pathology team. Additional tests were performed to update classifications per the 5th edition of the WHO Classification of Haematolymphoid Tumors. Seventeen cases were identified (11 males, 6 females; age 38-76), compared to 72 DLBCL cases during the same period. Nine cases were extra-axial and eight intra-axial. Eight were primary and nine secondary CNS lymphomas. B-cell lymphomas (n = 13) included extra-nodal marginal zone lymphoma (n = 6), follicular lymphoma, mantle cell lymphoma, CLL, intravascular large B-cell lymphoma (n = 2), EBV+ LBCL, and polymorphic PTLD. T-cell lymphomas (n = 4) included PTCL, NOS (n = 2), ALK-negative ALCL, and secondary mycosis fungoides. Imaging revealed four major patterns, and symptoms were largely due to mass effect. This case series emphasizes the considerable heterogeneity of non-DLBCL CNS lymphomas and the diagnostic challenges they present. It highlights key features that can aid recognition and improve diagnostic accuracy for these rare CNS entities. Trial Registration: SUN-5771.
2026-05-18 | Supplemental Table S1. Full clinicopathologic characteristics of IVLBCL and DLBCL cases with cutaneous recurrence
Supplemental Table S1 containing full clinicopathologic characteristics of intravascular large B-cell lymphoma (IVLBCL) and diffuse large B-cell lymphoma (DLBCL) cases with cutaneous recurrence. This file accompanies the associated JAAD Case Reports manuscript "Systemic intravascular large B-cell lymphoma relapsing as an extravascular cutaneous large B-cell lymphoma after eight years from initial diagnosis."
2026-05-01 | Progressive bilateral leg edema due to intravascular large B-cell lymphoma
An 81-year-old woman presented with subacute progressive bilateral leg edema without fever or weight loss. Laboratory tests showed elevated C-reactive protein (4.89 mg/dL) and lactate dehydrogenase (1314 U/L) levels. A random skin biopsy revealed intravascular large B-cell lymphoma (IVLBCL). Intravascular large B-cell lymphoma can cause isolated bilateral leg edema without fever or weight loss and should be suspected in cases of unexplained edema accompanied by a high lactate dehydrogenase level. A random skin biopsy is useful for confirming the diagnosis.
2026-03-25 | WCN26-2682 Intravascular Large B-cell Lymphoma Diagnosed by Renal Biopsy Presenting with Nephrotic Syndrome
Intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive subtype of extranodal diffuse large B-cell lymphoma characterized by selective proliferation of neoplastic lymphoid cells within small vessels. Its features are heterogeneous and nonspecific, often including fever of unknown origin (FUO) and organ dysfunction, leading to delayed diagnosis. We report a case of IVLBCL diagnosed by renal biopsy in a patient presenting with nephrotic syndrome and unexplained fever.
2026-03-06 | Clear cell renal cell carcinoma combined with intravascular large B-cell lymphoma: a case report and review of the literature.
Clear cell renal cell carcinoma (ccRCC) combined with intravascular large B-cell lymphoma (IVLBCL) is an extremely rare collision tumor, and its coexistence is often missed or misdiagnosed, making clinical diagnosis and treatment notably difficult. We present the case of a 68-year-old male, in whom imaging revealed a nodular soft tissue density shadow in the parenchyma of the left kidney. Immunohistochemistry and molecular testing confirmed the combination of ccRCC and IVLBCL. Following surgery, the patient underwent comprehensive examinations, including bone marrow biopsy and cytology, to rule out systemic lymphoma involving the kidneys. The patient received postoperative chemotherapy and was still in a favorable condition after 16 months of follow-up. In the ccRCC combined with IVLBCL, the lymphoma component is confined within the blood vessels of the RCC, making it extremely prone to misdiagnosis, which can lead to a poor prognosis. This case report presents an incidental finding of ccRCC combined with IVLBCL, aiming to raise physician awareness and provide valuable clinical references.
antibodies
2026-05-20 | Immunological rationale for PD-1 blockade in intravascular large B-cell lymphoma harboring a PD-L1 structural variant
Abstract: The efficacy of immune checkpoint inhibitors (ICIs) in the treatment of malignant lymphomas has been limited to histological subtypes such as classic Hodgkin lymphoma, which frequently harbors genomic amplification of programmed death-ligand 1 ( PD-L1 ). Intravascular large B-cell lymphoma (IVLBCL), a rare type of extranodal large B-cell lymphoma, is characterized by recurrent structural variants within the 3′ untranslated regions of PD-L1/PD-L2 , leading to their overexpression. These genomic features suggest potential vulnerability to PD-1/PD-L1 blockade; however, the immunological basis for ICI responsiveness in IVLBCL remains unknown. To investigate the biological plausibility of PD-1 blockade in PD-L1–altered B-cell lymphoma, we established immune-humanized mouse models using major histocompatibility complex class I/II–deficient NOD.Cg- Prkdc scid Il2rg tm1Sug /ShiJic mice engrafted with patient-derived xenograft (PDX) cells from IVLBCL. In a model developed from a patient with relapsed/refractory IVLBCL, treatment with nivolumab was associated with reduced tumor burden across multiple organs. Residual tumor sites were characterized by prominent infiltration of CD8 + T cells. Immunophenotypic analyses revealed an expansion of CD28 + PD-1 + CD8 + T-cell subsets following PD-1 blockade consistent with immunohistochemical detection of CD28 expression within tumor-infiltrating lymphocytes. Further assessment using ex vivo stimulation of peripheral blood mononuclear cells from healthy donors showed that CD28 + PD-1 + CD8 + T cells tended to exhibit the highest interferon gamma–producing capacity among CD8 + T-cell subsets. Collectively, these findings provide immunological insights for PD-1 blockade in B-cell lymphomas with PD-L1 structural alterations, using IVLBCL as a model disease. Our immune-humanized PDX platform offers a translational framework for evaluating immune checkpoint–based strategies in rare lymphomas.
2026-03-07 | Pulmonary intravascular large B-cell lymphoma misdiagnosed as allergic pneumonia: a case report and literature review.
Pulmonary intravascular large B-cell lymphoma (PIVLBCL) is an extremely rare subtype of extranodal diffuse large B-cell lymphoma (DLBCL). This hematologic malignancy exhibits nonspecific radiological features, including ground glass opacities (GGOs), often leading to misdiagnosis as interstitial lung disease (ILD). We present a 51-year-old female hairdresser with progressive dyspnea and 20 years of occupational hair dye exposure. Initially, she was misdiagnosed with chronic bronchitis due to a persistent dry cough. Then her initial chest CT demonstrated diffuse bilateral GGOs with isolated diffusion capacity of the lungs for carbon monoxide (DLCO) reduction (46.1% predicted) and normal spirometry, which led to a second misdiagnosis as hypersensitivity pneumonitis (HP). Despite initial improvement with corticosteroids, respiratory deterioration occurred during tapering. Finally, transbronchial lung cryobiopsy (TBCB) confirmed PIVLBCL, showing intravascular lymphoid proliferation (CD20+/BCL-6+/Ki-67≈80%). The R-CHOP chemotherapy treatment led to a complete remission for her, and the DLCO improved to 68% of the predicted value at the 6-month follow-up. A literature review of 75 PIVLBCL patients revealed that fever (74.7%) and dyspnea (65.3%) were the predominant presentations. GGOs were observed in 54.7% of cases, with frequent misdiagnosis as ILD (31.8%) or pneumonia (31.8%). TBCB provided definitive diagnostic evidence, demonstrating its clinical utility in resolving ambiguous pulmonary opacities. Clinicians should maintain high suspicion for PIVLBCL when encountering diffuse GGOs with isolated DLCO reduction, even without classic risk factors.
2025-09-30 | Intravascular large B-cell lymphoma presenting as encephalomyelitis diagnosed by renal biopsy: a case report.
The assessment of patients with multifocal lesions in the brain and spinal cord is complicated. A comprehensive neurologic workup requires extensive imaging evaluation, lumbar puncture, and sometimes a stereotactic biopsy to identify the final diagnosis. We report a case of intravascular large B-cell lymphoma (IVLBCL) manifesting as encephalomyelitis, which was diagnosed via percutaneous renal biopsy. IVLBCL should be considered as a differential diagnosis in cases with brain and spinal cord involvement. A 43-year-old man with no significant medical history presented with mild dysuresia and recurrent sudden-onset numbness of the right limbs over one month. Initial brain Magnetic Resonance Imaging (MRI) showed hyperintensities in the right frontal lobe, left parietal lobe, and bilateral centrum semiovale on diffusion-weighted images (DWI). He was diagnosed as cerebral embolism, but thrombolysis treatment was ineffective. Follow-up brain MRI revealed extension of the lesions and an intramedullary non-enhancing lesion was observed at the T1-T2 level on spinal cord MRI. Lumbar puncture was performed, and a diagnosis of inflammatory encephalomyelitis was considered. However, his symptoms worsened despite four months of glucocorticoid treatment. Subsequently, the patient underwent an 18F-FDG PET-CT scan. It showed diffuse increased FDG uptake in bilateral kidneys, but no specific increased FDG uptake was observed in the brain. To establish the final diagnosis, stereotactic brain biopsy was advised; however, the patient's poor general condition precluded this procedure. Instead, we conducted a percutaneous kidney biopsy due to the abnormality of kidneys on PET-CT. The final diagnosis was intravascular large B-cell lymphoma with predominant involvement of the kidneys, brain, and spinal cord. He was treated with five cycles of intravenous chemotherapy. His neurological symptoms recovered almost completely. Repeat MRIs of the brain and spinal cord demonstrated marked improvement. This case highlights the importance of awareness of IVLBCL. It should be a differential diagnosis in cases with brain and spinal cord involvement. Early diagnosis is crucial for patient outcomes.
2025-07-29 | Intravascular Lymphoma: A Unique Pattern Underlying a Protean Disease.
Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence of tumor masses or lymphadenopathies often lead to diagnostic delays and poor outcomes. IVLBCL can manifest in classic, hemophagocytic syndrome-associated (HPS), or cutaneous variants, with extremely variable organ involvement including the central nervous system (CNS), skin, lungs, and endocrine system. Diagnosis requires histopathologic identification of neoplastic intravascular lymphoid cells via targeted or random tissue biopsies. Tumor cells are highly atypical and display a non-GCB B-cell phenotype, often expressing CD20, MUM1, BCL2, and MYC; molecularly, they frequently harbor mutations in MYD88 and CD79B, defining a molecular profile shared with ABC-type DLBCL of immune-privileged sites. Therapeutic approaches are based on rituximab-containing chemotherapy regimens (R-CHOP), often supplemented with CNS-directed therapy due to the disease's marked neurotropism. Emerging strategies include autologous stem cell transplantation (ASCT) and novel immunotherapeutic approaches, potentially exploiting the frequent expression of PD-L1 by tumor cells. A distinct but related entity, intravascular NK/T-cell lymphoma (IVNKTCL), is an exceedingly rare EBV-associated lymphoma, showing unique own histologic, immunophenotypic, and molecular features and an even poorer outcome. This review provides a comprehensive overview of the current understandings about clinicopathological, molecular, and therapeutic landscape of IVL, emphasizing the need for increased clinical awareness, standardized diagnostic protocols, and individualized treatment strategies for this aggressive yet intriguing malignancy.
2025-04-28 | In the era of targeted therapy and immunotherapy: advances in the treatment of large B-cell lymphoma of immune-privileged sites.
Primary large B-cell lymphomas of immune-privileged sites (IP-LBCLs) include primary central nervous system large B-cell lymphoma (PCNSL), primary vitreoretinal large B-cell lymphoma (PVRL), and primary testicular large B-cell lymphoma (PTL). These tumors not only have a unique anatomical distribution but also exhibit specific biological and clinical characteristics. Given the high biological overlap between intravascular large B-cell lymphoma (IVLBCL) and IP-LBCLs, and the fact that IVLBCL is confined to the intravascular microenvironment, IVLBCL is currently included in the category of IP-LBCLs. IP-LBCLs are associated with suboptimal prognosis. However, advancements in biomarker detection technologies have facilitated novel therapeutic approaches for this disease entity. This review aims to summarize and analyze the latest research progress in IP-LBCLs, with a focus on new treatment strategies in the era of targeted therapy and immunotherapy. It is intended to further understand the biological characteristics, treatment, and latest advancements of this disease.
small molecules
2026-06-30 | A case of primary prostatic intravascular large B-cell lymphoma misdiagnosed as benign prostatic hyperplasia.
Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive subtype of extranodal large B-cell lymphoma, characterized by the confinement of tumor cells within the lumens of small blood vessels. It most commonly involves the skin, central nervous system, bone marrow, liver, and spleen, with primary involvement of the prostate being particularly rare. This article reports a case of a 71-year-old male patient who presented with progressive urinary difficulty. Imaging suggested severe prostatic hyperplasia, and benign prostatic hyperplasia (BPH) was considered preoperatively. However, histopathological examination of the prostate after transurethral resection revealed numerous proliferating neoplastic lymphocytes within the prostatic blood vessels. The diagnosis of primary prostatic intravascular large B-cell lymphoma was confirmed by immunohistochemistry and molecular pathology and PET-CT scans. The patient received first-line ZR2 chemotherapy (rituximab + lenalidomide + zanubrutinib). However, he developed acute liver failure during the second cycle, which improved after treatment. The patient has survived for 23 months during follow-up. Primary prostatic IVLBCL is clinically rare and often misdiagnosed as a benign condition due to the lack of specific symptoms. Early biopsy and immunohistochemistry are crucial for accurate diagnosis.
2026-04-24 | Intravascular large B-cell lymphoma mimicking an orbital mass lesion and bilateral cavernous sinus syndrome: A case report.
Intravascular large B-cell lymphoma (IVLBCL) is a rare entity that can present with atypical extranodal manifestations, often mimicking other orbital or neurological conditions. A 69-year-old woman presented with rapidly progressive left ptosis and diplopia, which progressed to complete bilateral ophthalmoplegia within several weeks. Magnetic resonance imaging revealed a previously unreported right orbital mass accompanied by bilateral cavernous sinus (CS) enhancement, representing a novel imaging feature of IVLBCL. The diagnosis was established by sphenoid sinus biopsy. The patient achieved near-clinical remission, with almost complete resolution of the orbital mass, following rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) chemotherapy combined with a Bruton tyrosine kinase inhibitor and intravenous high-dose methotrexate. However, diplopia recurred at 3 months post-treatment, indicating that although the patient initially responded well to R-CHOP-based combination therapy, more effective maintenance or consolidation strategies should be actively explored for patients with IVLBCL involving the central nervous system. Clinically, various lymphoma subtypes should be considered in the differential diagnosis of patients presenting with CS and intraorbital lesions.
2026-02-11 | Breaking diagnostic and therapeutic barriers in intravascular large B-cell lymphoma: A 13-year real-world study from China
Abstract Background Intravascular large B-cell lymphoma (IVLBCL) is an ultra-orphan disease (incidence 0.095/million/year) with dismal prognosis due to delayed diagnosis and limited therapeutic options. We aimed to evaluate a novel diagnostic algorithm and the efficacy of zanubrutinib-containing therapy in a real-world Chinese cohort. Methods This single-center retrospective study enrolled 54 IVLBCL patients (2010–2022). Diagnostic approaches evolved from PET/CT-guided biopsy to a combination of serum interleukin-10 (IL-10, cut-off 95.65 pg/mL), random skin biopsy (RSB), and circulating tumor DNA (ctDNA) profiling. Treatment regimens shifted from R-CHOP to methotrexate-based therapy (MTX), then to zanubrutinib plus R-CHOP (ZR-CHOP). Results The cohort exhibited distinct features: 35.2% Asian-variant IVLBCL, 50% CNS involvement, and 22.9% PET/CT negativity. IL-10 combined with RSB enabled the diagnosis of 11 PET/CT-negative patients who would have otherwise remained undiagnosed. ctDNA revealed MYD88 L265P (11/17, 65%) and CD79B (7/17, 41%) variants. ZR-CHOP (n = 22) achieved significantly superior 2-year progression-free survival (PFS) compared to R-CHOP alone (n = 6) (90% vs. 30%; hazard ratio [HR] 0.031, P < 0.0001) and demonstrated 100% central nervous system (CNS) relapse-free survival. The efficacy of ZR-CHOP was comparable to that of methotrexate (MTX)-based therapy (n = 20; 2-year PFS 85%), despite a shorter median follow-up (20.1 vs. 38.0 months). Conclusions In this largest Asian IVLBCL cohort to date, IL-10 + RSB + ctDNA significantly improved diagnostic accuracy. Zanubrutinib demonstrated promising efficacy, particularly in CNS involvement, offering a pragmatic solution for this orphan disease.
2025-10-13 | Severe lactic acidosis in association with CD5+ large B-cell lymphoma
Lactic acidosis is classified into type A and type B. In cases of type B lactic acidosis, it is important to consider underlying lymphomas, mostly B-cell types, such as intravascular large B-cell lymphoma (IVLBCL) or diffuse large B-cell lymphoma. Cluster of differentiation (CD) 5+ large B-cell lymphoma (LBCL) is well-known for its aggressive nature. We report here two cases of CD5+ LBCL that showed severe lactic acidosis (11.2 mmol/L and 15.9 mmol/L, respectively; reference range: 0.6–1.7) with hypoglycemia. Case 1 was a 79-year-old female who presented with multiple organ failure. CD5+ IVLBCL was diagnosed through a random skin biopsy in this patient. Case 2 was a 78-year-old female with bone marrow involvement by CD5+ LBCL cells and liver failure. The patient was also diagnosed pathologically as IVLBCL by liver biopsy. Both patients were under ventilator management and high-flow continuous hemodialysis and filtration. Plasma exchange was also employed. An anti-lymphoma regimen (a 50% dose-reduced etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) was introduced on day 11 and day 2 of hospitalization for cases 1 and 2, respectively. In Case 1, lactic acidosis was normalized within day 17, and the patient survived longer than 8 weeks, while in Case 2, lactic levels did not improve until her death on day 16 of hospitalization. In conclusion, prompt recognition of type B lactic acidosis and early diagnostic biopsy are essential for improving outcomes in aggressive CD5+ IVLBCL, highlighting the need for novel therapeutic strategies.
2025-08-22 | Case report: A case of intravascular large B-cell lymphoma and related literature review
Intravascular large B-cell lymphoma (IVLBCL) presents with a wide range of clinical symptoms, making clinical diagnosis challenging. It is often misdiagnosed or overlooked, leading to delays in treatment for affected patients. We present a case of a patient exhibiting clinical symptoms such as chest tightness, dyspnea, fever, and edema, who was later diagnosed with secondary hemophagocytic syndrome (HPS). Laboratory tests indicated persistent hypoalbuminemia, significantly elevated lactate dehydrogenase levels, thrombocytopenia, and splenomegaly, with no evidence of lymphadenopathy. During the treatment for HPS, the patient developed a rash on both lower limbs and abdomen and was ultimately diagnosed as IVLBCL after a skin biopsy. Following four cycles of zanubrutinib in combination with the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the patient achieved complete resolution of both dermatological manifestations and systemic symptoms. Laboratory parameters, including complete blood count, serum albumin levels, and lactate dehydrogenase, were normalized. Additionally, ultrasonography demonstrated a marked reduction in splenic size. However, the patient exhibited suboptimal adherence to the prescribed treatment plan and did not complete the intended number of cycles. During a subsequent telephone follow-up, the patient was confirmed to be alive; however, the status of the disease could not be evaluated. As of the latest follow-up, the patient has survived for 2 years.
cell therapies
2026-08-05 | A 13-Year Review of Non-Diffuse Large B Cell Lymphomas of the Central Nervous System at a Tertiary Hospital: A Case Series Study.
Non-diffuse large B-cell lymphomas (non-DLBCL) of the central nervous system (CNS) are rare and diagnostically challenging. This study aims to characterize the clinical, radiological, and pathological features of non-DLBCL CNS lymphomas diagnosed at a tertiary care center over 13 years, highlighting diagnostic pitfalls. A retrospective review was conducted of non-DLBCL CNS lymphoma cases diagnosed at Sunnybrook Health Sciences Centre, Toronto, from 2010 to 2022. Clinical, demographic, and radiological data were extracted from medical records. Imaging was reviewed by a neuroradiologist, and histopathological slides and molecular data were re-evaluated by a pathology team. Additional tests were performed to update classifications per the 5th edition of the WHO Classification of Haematolymphoid Tumors. Seventeen cases were identified (11 males, 6 females; age 38-76), compared to 72 DLBCL cases during the same period. Nine cases were extra-axial and eight intra-axial. Eight were primary and nine secondary CNS lymphomas. B-cell lymphomas (n = 13) included extra-nodal marginal zone lymphoma (n = 6), follicular lymphoma, mantle cell lymphoma, CLL, intravascular large B-cell lymphoma (n = 2), EBV+ LBCL, and polymorphic PTLD. T-cell lymphomas (n = 4) included PTCL, NOS (n = 2), ALK-negative ALCL, and secondary mycosis fungoides. Imaging revealed four major patterns, and symptoms were largely due to mass effect. This case series emphasizes the considerable heterogeneity of non-DLBCL CNS lymphomas and the diagnostic challenges they present. It highlights key features that can aid recognition and improve diagnostic accuracy for these rare CNS entities. Trial Registration: SUN-5771.
2026-05-18 | Supplemental Table S1. Full clinicopathologic characteristics of IVLBCL and DLBCL cases with cutaneous recurrence
Supplemental Table S1 containing full clinicopathologic characteristics of intravascular large B-cell lymphoma (IVLBCL) and diffuse large B-cell lymphoma (DLBCL) cases with cutaneous recurrence. This file accompanies the associated JAAD Case Reports manuscript "Systemic intravascular large B-cell lymphoma relapsing as an extravascular cutaneous large B-cell lymphoma after eight years from initial diagnosis."
2026-05-01 | Progressive bilateral leg edema due to intravascular large B-cell lymphoma
An 81-year-old woman presented with subacute progressive bilateral leg edema without fever or weight loss. Laboratory tests showed elevated C-reactive protein (4.89 mg/dL) and lactate dehydrogenase (1314 U/L) levels. A random skin biopsy revealed intravascular large B-cell lymphoma (IVLBCL). Intravascular large B-cell lymphoma can cause isolated bilateral leg edema without fever or weight loss and should be suspected in cases of unexplained edema accompanied by a high lactate dehydrogenase level. A random skin biopsy is useful for confirming the diagnosis.
2026-03-25 | WCN26-2682 Intravascular Large B-cell Lymphoma Diagnosed by Renal Biopsy Presenting with Nephrotic Syndrome
Intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive subtype of extranodal diffuse large B-cell lymphoma characterized by selective proliferation of neoplastic lymphoid cells within small vessels. Its features are heterogeneous and nonspecific, often including fever of unknown origin (FUO) and organ dysfunction, leading to delayed diagnosis. We report a case of IVLBCL diagnosed by renal biopsy in a patient presenting with nephrotic syndrome and unexplained fever.
2026-03-06 | Clear cell renal cell carcinoma combined with intravascular large B-cell lymphoma: a case report and review of the literature.
Clear cell renal cell carcinoma (ccRCC) combined with intravascular large B-cell lymphoma (IVLBCL) is an extremely rare collision tumor, and its coexistence is often missed or misdiagnosed, making clinical diagnosis and treatment notably difficult. We present the case of a 68-year-old male, in whom imaging revealed a nodular soft tissue density shadow in the parenchyma of the left kidney. Immunohistochemistry and molecular testing confirmed the combination of ccRCC and IVLBCL. Following surgery, the patient underwent comprehensive examinations, including bone marrow biopsy and cytology, to rule out systemic lymphoma involving the kidneys. The patient received postoperative chemotherapy and was still in a favorable condition after 16 months of follow-up. In the ccRCC combined with IVLBCL, the lymphoma component is confined within the blood vessels of the RCC, making it extremely prone to misdiagnosis, which can lead to a poor prognosis. This case report presents an incidental finding of ccRCC combined with IVLBCL, aiming to raise physician awareness and provide valuable clinical references.
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2026-05-20 | Immunological rationale for PD-1 blockade in intravascular large B-cell lymphoma harboring a PD-L1 structural variant
Abstract: The efficacy of immune checkpoint inhibitors (ICIs) in the treatment of malignant lymphomas has been limited to histological subtypes such as classic Hodgkin lymphoma, which frequently harbors genomic amplification of programmed death-ligand 1 ( PD-L1 ). Intravascular large B-cell lymphoma (IVLBCL), a rare type of extranodal large B-cell lymphoma, is characterized by recurrent structural variants within the 3′ untranslated regions of PD-L1/PD-L2 , leading to their overexpression. These genomic features suggest potential vulnerability to PD-1/PD-L1 blockade; however, the immunological basis for ICI responsiveness in IVLBCL remains unknown. To investigate the biological plausibility of PD-1 blockade in PD-L1–altered B-cell lymphoma, we established immune-humanized mouse models using major histocompatibility complex class I/II–deficient NOD.Cg- Prkdc scid Il2rg tm1Sug /ShiJic mice engrafted with patient-derived xenograft (PDX) cells from IVLBCL. In a model developed from a patient with relapsed/refractory IVLBCL, treatment with nivolumab was associated with reduced tumor burden across multiple organs. Residual tumor sites were characterized by prominent infiltration of CD8 + T cells. Immunophenotypic analyses revealed an expansion of CD28 + PD-1 + CD8 + T-cell subsets following PD-1 blockade consistent with immunohistochemical detection of CD28 expression within tumor-infiltrating lymphocytes. Further assessment using ex vivo stimulation of peripheral blood mononuclear cells from healthy donors showed that CD28 + PD-1 + CD8 + T cells tended to exhibit the highest interferon gamma–producing capacity among CD8 + T-cell subsets. Collectively, these findings provide immunological insights for PD-1 blockade in B-cell lymphomas with PD-L1 structural alterations, using IVLBCL as a model disease. Our immune-humanized PDX platform offers a translational framework for evaluating immune checkpoint–based strategies in rare lymphomas.
2026-03-07 | Pulmonary intravascular large B-cell lymphoma misdiagnosed as allergic pneumonia: a case report and literature review.
Pulmonary intravascular large B-cell lymphoma (PIVLBCL) is an extremely rare subtype of extranodal diffuse large B-cell lymphoma (DLBCL). This hematologic malignancy exhibits nonspecific radiological features, including ground glass opacities (GGOs), often leading to misdiagnosis as interstitial lung disease (ILD). We present a 51-year-old female hairdresser with progressive dyspnea and 20 years of occupational hair dye exposure. Initially, she was misdiagnosed with chronic bronchitis due to a persistent dry cough. Then her initial chest CT demonstrated diffuse bilateral GGOs with isolated diffusion capacity of the lungs for carbon monoxide (DLCO) reduction (46.1% predicted) and normal spirometry, which led to a second misdiagnosis as hypersensitivity pneumonitis (HP). Despite initial improvement with corticosteroids, respiratory deterioration occurred during tapering. Finally, transbronchial lung cryobiopsy (TBCB) confirmed PIVLBCL, showing intravascular lymphoid proliferation (CD20+/BCL-6+/Ki-67≈80%). The R-CHOP chemotherapy treatment led to a complete remission for her, and the DLCO improved to 68% of the predicted value at the 6-month follow-up. A literature review of 75 PIVLBCL patients revealed that fever (74.7%) and dyspnea (65.3%) were the predominant presentations. GGOs were observed in 54.7% of cases, with frequent misdiagnosis as ILD (31.8%) or pneumonia (31.8%). TBCB provided definitive diagnostic evidence, demonstrating its clinical utility in resolving ambiguous pulmonary opacities. Clinicians should maintain high suspicion for PIVLBCL when encountering diffuse GGOs with isolated DLCO reduction, even without classic risk factors.
2025-09-30 | Intravascular large B-cell lymphoma presenting as encephalomyelitis diagnosed by renal biopsy: a case report.
The assessment of patients with multifocal lesions in the brain and spinal cord is complicated. A comprehensive neurologic workup requires extensive imaging evaluation, lumbar puncture, and sometimes a stereotactic biopsy to identify the final diagnosis. We report a case of intravascular large B-cell lymphoma (IVLBCL) manifesting as encephalomyelitis, which was diagnosed via percutaneous renal biopsy. IVLBCL should be considered as a differential diagnosis in cases with brain and spinal cord involvement. A 43-year-old man with no significant medical history presented with mild dysuresia and recurrent sudden-onset numbness of the right limbs over one month. Initial brain Magnetic Resonance Imaging (MRI) showed hyperintensities in the right frontal lobe, left parietal lobe, and bilateral centrum semiovale on diffusion-weighted images (DWI). He was diagnosed as cerebral embolism, but thrombolysis treatment was ineffective. Follow-up brain MRI revealed extension of the lesions and an intramedullary non-enhancing lesion was observed at the T1-T2 level on spinal cord MRI. Lumbar puncture was performed, and a diagnosis of inflammatory encephalomyelitis was considered. However, his symptoms worsened despite four months of glucocorticoid treatment. Subsequently, the patient underwent an 18F-FDG PET-CT scan. It showed diffuse increased FDG uptake in bilateral kidneys, but no specific increased FDG uptake was observed in the brain. To establish the final diagnosis, stereotactic brain biopsy was advised; however, the patient's poor general condition precluded this procedure. Instead, we conducted a percutaneous kidney biopsy due to the abnormality of kidneys on PET-CT. The final diagnosis was intravascular large B-cell lymphoma with predominant involvement of the kidneys, brain, and spinal cord. He was treated with five cycles of intravenous chemotherapy. His neurological symptoms recovered almost completely. Repeat MRIs of the brain and spinal cord demonstrated marked improvement. This case highlights the importance of awareness of IVLBCL. It should be a differential diagnosis in cases with brain and spinal cord involvement. Early diagnosis is crucial for patient outcomes.
2025-07-29 | Intravascular Lymphoma: A Unique Pattern Underlying a Protean Disease.
Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence of tumor masses or lymphadenopathies often lead to diagnostic delays and poor outcomes. IVLBCL can manifest in classic, hemophagocytic syndrome-associated (HPS), or cutaneous variants, with extremely variable organ involvement including the central nervous system (CNS), skin, lungs, and endocrine system. Diagnosis requires histopathologic identification of neoplastic intravascular lymphoid cells via targeted or random tissue biopsies. Tumor cells are highly atypical and display a non-GCB B-cell phenotype, often expressing CD20, MUM1, BCL2, and MYC; molecularly, they frequently harbor mutations in MYD88 and CD79B, defining a molecular profile shared with ABC-type DLBCL of immune-privileged sites. Therapeutic approaches are based on rituximab-containing chemotherapy regimens (R-CHOP), often supplemented with CNS-directed therapy due to the disease's marked neurotropism. Emerging strategies include autologous stem cell transplantation (ASCT) and novel immunotherapeutic approaches, potentially exploiting the frequent expression of PD-L1 by tumor cells. A distinct but related entity, intravascular NK/T-cell lymphoma (IVNKTCL), is an exceedingly rare EBV-associated lymphoma, showing unique own histologic, immunophenotypic, and molecular features and an even poorer outcome. This review provides a comprehensive overview of the current understandings about clinicopathological, molecular, and therapeutic landscape of IVL, emphasizing the need for increased clinical awareness, standardized diagnostic protocols, and individualized treatment strategies for this aggressive yet intriguing malignancy.
2025-04-28 | In the era of targeted therapy and immunotherapy: advances in the treatment of large B-cell lymphoma of immune-privileged sites.
Primary large B-cell lymphomas of immune-privileged sites (IP-LBCLs) include primary central nervous system large B-cell lymphoma (PCNSL), primary vitreoretinal large B-cell lymphoma (PVRL), and primary testicular large B-cell lymphoma (PTL). These tumors not only have a unique anatomical distribution but also exhibit specific biological and clinical characteristics. Given the high biological overlap between intravascular large B-cell lymphoma (IVLBCL) and IP-LBCLs, and the fact that IVLBCL is confined to the intravascular microenvironment, IVLBCL is currently included in the category of IP-LBCLs. IP-LBCLs are associated with suboptimal prognosis. However, advancements in biomarker detection technologies have facilitated novel therapeutic approaches for this disease entity. This review aims to summarize and analyze the latest research progress in IP-LBCLs, with a focus on new treatment strategies in the era of targeted therapy and immunotherapy. It is intended to further understand the biological characteristics, treatment, and latest advancements of this disease.
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