A 58-year-old Japanese woman with rheumatoid arthritis (RA) presented with the sudden onset of cognitive dysfunction. A random skin biopsy revealed intravascular large B-cell lymphoma (IVLBCL), which resolved spontaneously with methotrexate withdrawal. However, four months later, the disease relapsed with liver injury. After completion of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy, both RA and IVLBCL remained in remission for two years. Among the pathological subtypes of RA-associated lymphoproliferative diseases, reports on IVLBCL are limited, and little is known about its clinical course. Our literature review summarizes the clinical course and mortality of 11 patients with RA-IVLBCL.

This study aimed to establish a standard treatment for disseminated extranodal large B-cell lymphoma, including intravascular large B-cell lymphoma (DEN-LBCL/IVL), and to validate the clinical diagnostic criteria we proposed. Between 2006 and 2016, 22 patients were enrolled in a clinical trial conducted by the Hokuriku Hematology Oncology Study Group. The first cycle of chemotherapy consisted of dose-reduced cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with delayed administration of rituximab. From the second to the sixth cycle, patients received conventional rituximab and CHOP therapy. The primary endpoint was overall survival (OS), while the secondary endpoints included the complete response (CR) rate and time to treatment failure (TTF). The results showed a CR rate of 73%, a median OS of 65 months, and a median TTF of 45 months. These findings indicate that patients with DEN-LBCL/IVL were effectively treated with our new chemoimmunotherapy regimen. Our clinical diagnostic criteria are useful for identifying patients who require early intervention.

This is a case of hemophagocytic intravascular large B-cell lymphoma (IVLBCL) with central nervous system (CNS) involvement. Although R-CHOP chemotherapy regimen has been shown significant improvement in survival rate. The prognosis and outcomes remain unsatisfactory, which is identified as outstanding challenges and need solutions. Gene and molecular profiling studies may provide new therapeutic strategies, especially the BCR/TLR/IL-1R/NF-κB signaling pathway in IVLBCL. Here, we treated the hemophagocytic IVLBCL CNS-involved patient with the Bruton tyrosine kinase inhibitor (BTKi) to block NF-κB pathway, and indicated that the second-generation BTKi zanubrutinib-based treatment was feasible and efficient.

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of extranodal large B-cell lymphoma characterized by the growth of lymphoma cells within lumina of blood vessels, especially capillaries, which aggregate to form clots, resulting in organ ischemia. In Caucasians, it predominantly involves the central nervous system (CNS) and the skin, with the cutaneous variant carrying a better prognosis. Whereas in Asians it preferentially involves the bone marrow, liver, and spleen and is associated with hemophagocytic syndrome. We report a case of a young Asian male with neurological, pulmonary, and hepatosplenic involvement. He presented with recurrent strokes, chronic cough, and unintentional weight loss. The chest radiograph (CXR) on admission was clear. Magnetic resonance imaging (MRI) of the brain showed acute multifocal infarcts, and a whole-body computed tomography (CT) scan revealed upper-lobe predominant pulmonary ground glass opacities (GGOs) with mediastinal lymphadenopathy. Interestingly, a CXR performed one week after the CT scan remained clear. The positron emission tomography-computed tomography (PET-CT) showed hepatosplenic and adrenal involvement. The diagnosis was confirmed via a bronchoscopic approach. The patient received chemotherapy consisting of MR-CHOP (methotrexate, rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone), high-dose methotrexate, and intrathecal cytarabine, which led to complete remission. Subsequently, he underwent an autologous peripheral blood stem cell transplant. At the time of writing this case report, the patient is still in complete remission for three years after the initial diagnosis. As IVLBCL has a non-specific clinicoradiological presentation, it is important to suspect IVLBCL in patients with an atypical neurological and pulmonary presentation in the presence of raised serum lactate dehydrogenase (LDH) and to consider a CT scan of the thorax if CXR is normal.

The diagnosis of intravascular large B-cell lymphoma (IVLBCL) is often challenging owing to its nonspecific clinical manifestations and imaging findings. Herein, we present a rare case of IVLBCL in which seizure was the initial symptom, and unilateral hemispheric hyperperfusion on arterial spin labeling (ASL) was the only abnormal finding observed on brain magnetic resonance imaging (MRI). A 68-year-old male with a history of hypertension and type 2 diabetes was transferred to the emergency room owing to the sudden onset of altered consciousness and abnormal behavior. Upon arrival, the patient was disoriented and confused, and cerebrospinal fluid analysis revealed pleocytosis and elevated protein level. Even after the administration of acyclovir and antiepileptic drugs, his consciousness remained impaired, with repeated transient right hemiparesis indicating a focal seizure. The initial and follow-up MRI scans showed no obvious abnormalities in diffusion-weighted imaging (DWI), T2-weighted imaging, or susceptibility-weighted imaging (SWI); however, ASL revealed markedly increased blood flow to the left hemisphere. Subsequently, the rapid elevation of serum lactate dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) levels after admission led to the diagnosis of IVLBCL by random skin biopsy and bone marrow examination. Despite the initiation of chemotherapy, the patient developed tumor lysis syndrome and succumbed to multiple organ failure. This case underscores the importance of considering IVLBCL in adult patients with refractory seizures and highlights the potential utility of ASL on MRI for early diagnosis.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. Patients with hemophagocytic lymphohistiocytosis (HLH)-associated IVLBCL variants exhibit significantly poor survival. Cytokines play pivotal roles in malignancy-associated HLH as well as in capillary leak syndrome (CLS). The pathogenesis of CLS involves hyperpermeability and transient endothelial dysfunction. Here, we report the first case of HLH-associated IVLBCL variant complicated with CLS. The patient presented with fever, refractory hypoproteinemia, hypotension and severe edema, followed by telangiectasias. Treatment with etoposide and dexamethasone and hydroxyethyl starch-based artificial colloid led to transient improvement. The diagnosis of IVLBCL was confirmed after the sixth bone marrow biopsy. Subsequently, the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone) regimen was administered and resulted in prompt alleviation of CLS and HLH symptoms. The patient has survived for more than 6 years after combination of immunochemotherapy and autologous peripheral stem-cell transplantation. This case provides some insights into the mechanism and clinical management of IVLBCL complicated with HLH and CLS. Similar cases concerning lymphoma-associated CLSs were also reviewed.

This case report describes a rare case of intravascular large B-cell lymphoma (IVLBCL), initially presenting with nonspecific symptoms of fever and fatigue, and tentatively diagnosed as disseminated carcinomatosis of the bone marrow originating from urothelial cancer in an 80-year-old woman. The patient\'s journey began with symptoms treated as common ailments and progressed through multiple differential diagnoses, including giant cell arteritis, TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) syndrome, and disseminated carcinomatosis of the bone marrow originating from urothelial cancer due to the presence of systemic inflammation, anasarca, and elevated soluble interleukin 2 receptor levels, indicative of an intense immunological response. Despite initial treatments, her condition deteriorated, leading to further investigations that ultimately revealed the presence of malignant cells in the urine and bone marrow, confirming the diagnosis of IVLBCL. This case underscores the diagnostic challenges faced when elderly patients present with systemic inflammation and the critical need for thorough investigation beyond initial impressions. It highlights the importance of considering differentiation between disseminated carcinomatosis of the bone marrow and IVLBCL in the differential diagnosis of persistent inflammation, especially in cases where common causes have been excluded and the primary malignancy is not immediately apparent.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal, diffuse, large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumen of small blood vessels, with no lymphadenopathy or masses. Herein, we report a cutaneous variant of IVLBCL that is rare in Asia. A healthy 73-year-old Japanese woman presented to our hospital with painful erythematous indurations and telangiectasia of the lower extremities, which was confirmed on dermoscopy. Physical examination revealed no systemic involvement, and laboratory parameters were within normal ranges. No abnormal fluorodeoxyglucose (FDG) uptake was detected on 18FDG positron emission tomography/computed tomography. Histopathological examination revealed proliferation and dilatation of blood vessels in the subcutis layer, occluded by CD20-positive atypical lymphoid cells. Thus, the patient was diagnosed with a cutaneous variant of IVLBCL without systemic symptoms. In conclusion, it is important to confirm telangiectasia using dermoscopy and perform skin biopsies in patients presenting with sudden-onset erythematous induration.

Hemophagocytic lymphohistiocytosis (HLH) has been recognized as a rare adverse event following the coronavirus disease 2019 (COVID-19) vaccination. We report a case of neuropsychiatric symptoms and refractory HLH in a woman with systemic lupus erythematosus (SLE) after receiving her COVID-19 vaccine treated with belimumab, later found to have intravascular large B-cell lymphoma (IVLBCL) at autopsy. A 61-year-old woman with SLE was referred to our hospital because of impaired consciousness and fever. One month prior to consulting, she received her second COVID-19 vaccine dose. Afterward, her consciousness level decreased, and she developed a high fever. She tested negative for SARS-CoV-2. Neuropsychiatric SLE was suspected; therefore, glucocorticoid pulse therapy was initiated on day 1 and 8. She had thrombocytopenia, increased serum ferritin levels and hemophagocytosis. The patient was diagnosed with HLH and treated with etoposide, dexamethasone and cyclosporine. Despite treatment, the patient died on day 75; autopsy report findings suggested IVLBCL as the underlying cause of HLH. Differentiating comorbid conditions remains difficult; however, in the case of an atypical clinical presentation, other causes should be considered. Therefore, we speculate that the COVID-19 vaccination and her autoimmune condition may have expedited IVLBCL development.

Intravascular large B-cell lymphoma (IVLBCL), a rare subtype of malignant lymphoma, is diagnosed by observation of intravascular proliferation of tumor cells in samples taken from affected organs. However, diagnosis of IVLBCL is usually difficult due to the lack of mass formation. IVLBCL may be fatal when the diagnosis is delayed, so an accurate early diagnosis is the key to successful treatment. Random skin biopsy (RSB), in which specimens are sampled from normal-appearing skin, has been reported as useful. However, the specific method of RSB remains controversial, with individual institutions using either the punch method or the incisional method. Research has shown that the incisional method has higher sensitivity than the punch method. We discuss whether this difference might owe to the collection of punch specimens from an insufficient depth and whether the punch method might result in false negatives. For RSB, we recommend taking specimens not only from normal-appearing skin, but also from any lesional skin, because lesions may reflect micro IVLBCL lesions. To ensure accurate diagnosis, both dermatologists and hematologists should know the proper method of RSB. This review summarizes the appropriate biopsy method and sites for RSB.