Intravascular Lymphoma with Progressive CNS Hemorrhage and Multiple Dissections

Peripheral Nerve Involvement (Neurolymphomatosis) as a Manifestation of Intravascular Large B-Cell Lymphoma

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of non- Hodgkin lymphoma characterized by a disseminated intravascular proliferation of tumor cells in the lumina of small vessels. Although the kidney is one of the target organs of IVLBCL, lymphoma cells that localize only in glomeruli are extremely rare. We report a 55-year-old Chinese patient diagnosed as glomerular-limited IVLBCL by percutaneous renal biopsy. The patient was referred to our institution for further examination of mild proteinuria and anemia without lymphoma symptoms. He had daily urinary excretion of 0.65 g proteins with normal renal function. Percutaneous renal biopsy showed that lymphoid cell accumulation was encircled within the glomerular capillary lumina only in certain glomeruli, resulting in marked obstruction of capillary structure. However, almost all of the peritubular capillary and tubulointerstitium were intact. Immunohistochemical analysis confirmed the diagnosis of intravascular large B-cell lymphoma. Extensive systemic examinations showed no other organ involvement. With these characteristic changes, glomerularlimited IVLBCL were considered as an exceptional renal manifestation of intravascular lymphoma diagnosised by percutaneous renal biopsy.

Intravascular large B cell lymphoma (IVL) is a rare subtype of diffuse large B cell lymphoma confined to small blood vessels with a predilection for CNS involvement. The prognosis of IVL with CNS involvement (CNS-IVL) is extremely poor. The optimal treatment for CNS-IVL is not well defined. Thus, we report three patients with CNS-IVL successfully treated with a CNS-centric approach consisting of high-dose methotrexate (HDMTX) and high-dose Ara-C (HiDAC) based CNS-directed chemoimmunotherapy (CIT) alternating with anthracycline-based CIT. Our rationale for intensifying the CNS-directed therapy is the presence of intracerebral bleeding in two of our patients which would result in extravasation of lymphoma cells into the cerebral parenchyma with the development of CNS lymphoma. All three patients have achieved excellent therapeutic outcomes. Two patients with intracerebral bleeding have been in complete remission (CR) for about 11 years and 4 years. One patient was successfully induced into CR about 10 months ago and currently is in CR. This unique therapeutic approach should be further explored for CNS-IVL.

Hypercalcaemia in intravascular large B-cell lymphoma (IVLBCL) is extremely rare, occurring more often in other non-Hodgkin's lymphomas (NHL). A 68-year-old man was admitted with a fever of unknown origin, mild disturbance of consciousness and respiratory failure. Laboratory findings showed hypercalcaemia with elevated parathyroid hormone-related protein (PTHrP) and decreased intact parathyroid hormone and 1,25-dihydroxyvitamin D. The patient was diagnosed with IVLBCL via random skin biopsy. Chemotherapy resulted in complete remission and normalised PTHrP levels. More than half of all cases of hypercalcaemia in NHL are not associated with PTHrP or 1,25-dihydroxyvitamin D, and the cause of the hypercalcaemia is unknown. However, PTHrP levels are elevated in most cases of IVLBCL with hypercalcaemia, which may present as humoral hypercalcaemia of malignancy. Intravascular large B-cell lymphoma, a rare, clinically aggressive type of B-cell non-Hodgkin's lymphoma, is prone to central nervous system disturbances, including altered consciousness.Hypercalcaemia, which causes impaired consciousness, is extremely rare in intravascular large B-cell lymphoma, occurring more often in other non-Hodgkin's lymphomas.Parathyroid hormone-related protein is elevated in most cases of intravascular large B-cell lymphoma with hypercalcaemia, which may present as humoral hypercalcaemia of malignancy.

Rational:Intravascular large B-cell lymphoma (IVLBCL) is a rare condition with a poor prognosis. The clinical presentation of primary lymphoma of the prostate is non-specific and it is difficult to distinguish from other prostatic diseases. The primary prostate IVLBCL is very rare, the diagnosis and treatment of which remains unclear. We reported a rare case to explore the diagnosis and treatment for the primary prostate IVLBCL.Patients concerns:This report described a case of a 71-year-old male diagnosed as primary prostate IVLBCL who presented with prostatic hyperplasia.Diagnosis:The patient first visited an outpatient clinic of urinary surgery because of urinary urgency and frequency and was diagnosed as benign prostatic hyperplasia in about January 2010. Four years later, the symptoms worsened quickly within two months. The diagnosis was still prostatic hyperplasia according to the physical examination and imaging. However, histopathology showed IVLBCL of prostate after transurethral resection of the prostate.Interventions:With the clear diagnosis of primary prostate stage I IVLBCL, the patient received immunochemotherapy of R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone) for 4 cycles and intensity-modulated radiation therapy (IMRT) including the region of prostate with the dose of 45Gy/25f.Outcomes:The response was complete remission after all treatment. The last follow-up time of the patient was June 20th, 2019, and no evidence of disease progression was observed. The progression-free survival of the patient was about 49 months until now.Lessons:The biopsy of prostate by prostatectomy plays an important role in the diagnosis and removal of the original lesion of primary prostate lymphoma. There is no consensus on therapeutic modalities for the treatment of primary prostate IVLBCL till now. Individual treatments include immunochemotherapy and/or radiotherapy according to the National Comprehensive Cancer Network (NCCN) practice guideline of diffuse large B cell lymphoma (DLBCL) based on the performance status and tumor staging of the patient. Timely and accurate diagnosis as well as the appropriate treatment may improve the clinical outcome.

Intravascular Large B-cell Lymphoma Successfully Treated with Autologous Transplantation

BackgroundThe 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.Case presentationA 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.ConclusionsThis 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.

Intravascular large B-cell lymphoma (IVLBCL) is a rare variant of diffuse large B-cell lymphoma that is characterized histologically by proliferating mononuclear cells within the lumens of capillaries, venules, arterioles, and small arteries (1,2). This is an aggressive lymphoma with poor prognosis that contributes to delays in diagnosis because of the variable symptoms (1). IVLBCL of the lung is mostly detected at autopsy due to rarity (3). Chest computed tomography (CT) findings of IVLBCL include bilateral diffuse ground glass attenuation (GGA) in the whole lung, but this is nonspecific and can be seen in patients with diverse diseases, which can cause delayed diagnosis of this rapidly progressive and diffuse vascular tumorous condition (3,4). There are no reports about serial chest CT and 18F-fluorodeoxyglucose (FDG) positronemission tomography-CT (PET-CT) findings of IVLBCL, which could help to differentiate this unusual vascular lymphoma from diffuse lung disease.

Diffuse large B-cell lymphoma (DLBCL) accounts for 30-40% of all lymphoma subtypes. More than half of DLBCLs are estimated to arise from extranodal sites, and are called extranodal DLBCLs. Generally, the outcomes of extranodal DLBCL are not different from those of nodal DLBCL. To our knowledge, this report is the first to discuss the concept and the cell of origin of extranodal DLBCL, with the significance of the presence/absence of each involvement site in determining the outcome. Second, the evidence of clinical manifestation and outcomes of several extranodal DLBCLs requiring treatments other than R-CHOP, which is the current standard therapy for this malignancy, are discussed. Most primary central nervous system (CNS) and testicular lymphomas are histologically DLBCLs. Moreover, primary mediastinal and intravascular large B-cell lymphomas are subtypes of DLBCL by definition. Hence, the evidence of high-risk sites for CNS involvement is also described.

Background & Purpose: Cerebrovascular disease (CVD) and peripheral artery disease (PAD) sometimes coexist with each other. We investigated predictive factors for CVD before bypass surgery for PAD. Subjects & Methods: For the present study, 200 consecutive PAD patients who were planned to undergo a bypass surgery for their lower extremity artery were included. Before the surgery, all patients were studied by ankle brachial index (ABI), duplex carotid ultrasonography, magnetic resonance imaging (MRI) including diffusion weighted imaging (DWI), and MR angiography. A stenosis of ≥50% or occlusion of the major intracranial or extracranial cerebral arteries was defined as a significant CVD. We also investigated the predictive factors for significant cerebrovascular lesions. Results: Of the total 200 patients (137 men; 69%, 74±9 years old) studied, a significant CVD of the intracranial or extracranial cerebral arteries was observed in 104 (52%) patients: 57 (29%) in intracranial arteries and 68 (34%) in extracranial arteries. There were asymptomatic ischemic lesions on MRI in 116 (59%) patients. Among them, 13 (7%) patients had asymptomatic high-intense lesions on DWI. In patients with significant CVDs, dyslipidemia (63% vs 47%, p=0.0455), diabetes mellitus (67% vs 37%, p<0.001), prior ischemic stroke (65% vs 48%, p=0.0328), and prior ischemic heart disease (63% vs 46%, p=0.0189) were more frequent, and ABI value was lower (0.34 vs 0.45, p=0.0369) in comparison to patients without CVDs. On ROC curve analysis, the most accurate ABI cut-off value for predicting significant CVDs was 0.46. Prevalence of CVDs tended to increase with the increasing number of risk factors described above (44% in patient with 1, 56% in patient with 2, 71% in patient with 3, 69% in patient with 4, 80% in patient with 5; P<0.0001 for armitage trend). On multivariate analysis, dyslipidemia (OR, 1.93; 95% CI, 1.00-3.81) and diabetes mellitus (OR, 3.06; 95% CI, 1.62-5.86) were independent predictors for significant CVDs. Conclusions: In PAD patients before the bypass surgery, significant CVDs were observed in 52%. Dyslipidemia and diabetes mellitus were independent predictors for significant CVDs. Number of the predictive factors was also important for predicting CVDs.

Hepatic intravascular large B-cell lymphoma (IVL) is a rare disease entity that involves invasion into various organs. Due to the aggressive behavior and poor prognosis of the disease and the difficulty in making an early diagnosis, some cases are diagnosed at autopsy. Early suspicion and the use of imaging studies and liver biopsies are key for diagnosing IVL; however, no reports have described the results of imaging studies due to the limited number of cases. We herein report the results of imaging studies of hepatic IVL, including the findings PET-CT, dynamic-CT, EOB-MRI and CEUS. These results may help physicians to make an early diagnosis and improve the prognosis.

Lymphoma is one of the causative factors of hypothalamus-pituitary dysfunction, and intravascular large B-cell lymphoma (IVLBCL) is a subtype of primary extranodal neoplasm. A 69-year-old woman visited our hospital because of general fatigue. We diagnosed her with presumable non-functional primary pituitary adenoma and subsequent dysfunction. Eight months after, the patient revisited our hospital because of dyspnea. Though we conducted systemic investigations including chest and abdomen enhanced computer tomography, transbronchial lung biopsy, and bone marrow biopsy, the diagnosis was not confirmed. Inadvertently, a breast cancer was found, and the surgical specimen proved that the patient had double cancer-adenocarcinoma and IVLBCL. Rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone regimen was initiated, and complete remission was achieved. Notably, the sellar mass returned to normal size with improved function. We reviewed 32 patients with primary parasellar lymphoma. In affected sites, both sellar and pituitary stalk (6.7%), both hypothalamus and pituitary stalk (6.7%), only sellar (63.3%), only pituitary stalk (6.7%), only hypothalamus (13.3%), and only clivus (3.3%) were observed. In hypothalamus-pituitary dysfunction, both anterior and posterior dysfunction (20.7%), only anterior dysfunction (58.6%), only posterior dysfunction (3.4%), and no dysfunction (17.2%) were observed. It seemed that hypothalamic lesion is related to both anterior and posterior dysfunction, while sellar lesion is related to mainly anterior dysfunction. In cranial nerve dysfunction, 2nd nerve dysfunction (45.2%) and 6th nerve dysfunction (35.5%) were frequently observed. It seemed that sellar lesion is related to both 2nd and 6th nerve dysfunction, while hypothalamic lesion is related to mainly 2nd nerve dysfunction.

Intravascular lymphomatosis (IVL) is a rare type of B-cell non-Hodgkin lymphoma (BCNHL), which can mimic many other diseases. Fever, neurological symptoms, and skin findings are the most frequent clinical findings. Intravascular lymphomatosis may be associated with genetic factors and infection with human immunodeficiency virus (HIV), human herpesvirus 8 (HHV-8), human T-lymphotropic virus 1 (HTLV1), Epstein-Barr virus (EBV), and hepatitis B virus (HBV). A 50-year-old man was hospitalized with recalcitrant hyponatremia of unknown cause. He had also telangiectatic, indurated, slightly erythematous plaques on his trunk for the last 10 days. His past medical history was unremarkable, although he was a carrier of hepatitis B. Multiple skin biopsies were performed and were considered to be diagnostic of IVL. The hyponatremia was unresponsive to water restriction and hypertonic solution support but it resolved with B cell directed chemotherapy. A final diagnosis was made as syndrome of inappropriate antidiuretic hormone (SIADH) in the setting of IVL. This case had a relatively early diagnosis with just 10-days of skin lesions. Intravascular lymphomatosis is a very rare disease and is usually difficult to diagnose. An even more uncommon presentation is IVL complicated by a paraneoplastic syndrome. There are prior reported cases of SIADH in the setting of IVL. However, this case underscores the importance of evaluating patients with SIADH for potential IVL.

To determine the value of color Doppler sonography (CDUS) in the diagnosis and follow-up of patients with extracranial and intracranial vertebral artery (VA) dissection. Thirty-three patients aged 42 +/- 12 years with 40 VADS confirmed via digital subtraction angiography (DSA) (n = 37) and magnetic resonance angiography (MRA) (n = 3) were included in the study. All patients were investigated with extracranial CDUS and transcranial CDUS (TCCDUS) over a mean +/- SD follow-up period of 42 +/- 24 months and occurrence of new ischemic symptoms was assessed. Sonographic results were compared with initial and follow-up angiographic results. At presentation, 24/33 (73%) patients had suffered an ischemic stroke, 5/33 (15%) had a transient ischemic attack (TIA), and 4/33 (12%) were asymptomatic. Two patients had a recurrent vertebrobasilar TIA; there was no recurrent stroke. The initial DSA findings consisted of 14 stenoses, 20 tapered occlusions, and 6 pseudoaneurysms. During follow-up, 63% of the vessels recanalized. Sonographic findings were consistent with angiographic findings in 80% at the initial examination and in 86% during follow-up. The main reason for discordant results was the failure of CDUS to detect pseudoaneurysms. No recurrence occurred in the vertebral arteries (VA), but 1 patient had an asymptomatic carotid artery dissection during follow-up. Recurrent TIA or stroke after VAD appears to be extremely rare, independent of recanalization or persistent occlusion of the affected artery. CDUS and TCCDUS provide reliable follow-up of VAD in all patients presenting with stenosis or occlusion, but do not allow for detection of pseudoaneurysms of the VA.

Primary lung intravascular large B-Cell lymphoma clinically mimicking sarcoidosis: A rare case report and review of literature