A rare type of diffuse large B-cell lymphoma, intravascular large B-cell lymphoma primarily affects the middle-aged to elderly population, with a slight predominance in men. By the time of presentation, most patients have advanced, disseminated disease, and often the diagnosis is made at autopsy. Patients may present with any of a myriad of symptoms, with any tissue potentially being infiltrated. Central nervous system and cutaneous involvement is common, as is the presence of B symptoms including fever, weight loss, and night sweats. Morphologically, growth of neoplastic cells is restricted to the lumen of small vessels. The cells are large, with 1 or more prominent nucleoli, scant cytoplasm, and frequent mitotic figures, and are commonly positive for cluster of differentiation markers 79a, 20, and 19, as well as MUM1/IRF4 and Bcl-2. Intravascular large B-cell lymphoma is aggressive, and without treatment is rapidly fatal.

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Intravascular Large B-Cell Lymphoma

Patients with intravascular lymphoma (IVL) frequently have neurological signs and symptoms. Prompt diagnosis and treatment is therefore crucial for their survival. However, the spectrum of neurological presentations and their respective frequencies have not been adequately characterized. Our aim is to document the spectrum of clinical symptoms and their respective frequencies and to create a clinical framework for the prompt diagnosis of IVL. A comprehensive meta-analysis of 654 cases of IVL published between 1957 and 2012 was performed to provide better insight into the neurological presentations of this disease. Neurologic complications were mainly divided into central nervous system (CNS) and peripheral nervous system (PNS) presentations. There were no differences in occurrences of CNS IVL based on gender or geographic locations (Asian Vs non-Asian). However, most patients with CNS IVL were younger than 70 years of age (p < 0.05). Our limited data do not support the treatment efficacy of methotrexate. CNS symptoms were seen in 42 % of all cases. The most common CNS complications identified were cognitive impairment/dementia (60.9 %), paralysis (22.2 %), and seizures (13.4 %). PNS complications were seen in 9.5 % of cases. Out of these, muscle weakness (59.7 %), neurogenic bladder (37.1 %), and paresthesia (16.1 %) were the most common presentations. CNS complications are more common among IVL patients. Out of these, dementia and seizures outnumber stroke-like presentations.

/pdf/neurological-presentations-of-intravascular-lymphoma-ivl-k463pvc077.pdf

Neurological presentations of intravascular lymphoma (IVL): meta-analysis of 654 patients

IVL is characterized by a propensity for intravascular tumor cell proliferation. Premortem diagnosis of IVL is difficult because of its nonspecific clinical, laboratory, and imaging manifestations. This study examined cerebral MR imaging patterns of IVL and their changes with and without chemotherapy. Nine of 11 patients studied presented with abnormal findings. We define 5 patterns of abnormal MR imaging findings: 1) infarctlike lesions, 2) nonspecific white matter lesions, 3) meningeal enhancement, 4) masslike lesions, and 5) hyperintense lesions in the pons on T2WI. Seven patients presented with only 1 pattern, while 2 patients presented with multiple patterns. Lesions in 7 treated patients responded to chemotherapy. Pathologic specimens revealed intravascular tumor cell infiltration with associated infarctions, necrosis, congestion, demyelination, vasculitis, and tumor cell extravasation. We conclude that MR imaging patterns can be possible manifestations of intravascular-dominant infiltration by tumor cells with associated occlusion or inflammation, depending on the level of affected vessels.

http://www.ajnr.org/content/ajnr/33/2/292.full.pdf

Characteristics of Intravascular Large B-Cell Lymphoma on Cerebral MR Imaging

This study aimed to clarify the comprehensive clinical, laboratory, pathological and imaging features of intravascular large B‐cell lymphoma (IVLBCL) using data on 42 IVLBCL patients diagnosed at our hospital over the past 20 years. The majority of patients were diagnosed via random skin biopsy (29/42, 69·0%) followed by bone marrow biopsy alone (8/42, 19·0%). Characteristic features included persistent fever (41/42, 97·6%), decreased performance status (≥2) (100%), hypoxaemia (32/40, 80·0%), impaired consciousness (19/42, 45·2%), hypoalbuminemia (42/42, 100%) and extreme elevation of lactate dehydrogenase and soluble interleukin 2 receptor levels. Brain magnetic resonance imaging showed abnormal findings in 32/37 patients (86·4%). Hyperintense lesion in the pons was a peculiar finding that was unrelated to the neurological deficits. Positron emission tomography‐computed tomography revealed a high incidence of bone marrow (26/34, 76·5%), spleen (19/34, 55·9%) and adrenal gland (9/34, 26·5%) involvement. Neurolymphomatosis was noted in 6 patients during the course of the disease. About 60% of IVLBCL patients in whom in vivo diagnosis was possible survived more than 5 years with combination chemotherapy. Our observations provide additional insight into the diagnosis of IVLBCL and indicate that early disease recognition via random skin biopsy combined with imaging, enables in vivo diagnosis of the disease and improved survival for many patients.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.16081

Diagnosis of intravascular large B cell lymphoma: novel insights into clinicopathological features from 42 patients at a single institution over 20 years.

Sensitivity and specificity of incisional random skin biopsy for diagnosis of intravascular large B-cell lymphoma.

Case Presentation. A 69-year-old Hispanic male, with a past history of diabetes and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks duration. Physical examination showed a disoriented patient with multiple ecchymoses, possible ascites, and bilateral scrotal swelling. Hemoglobin was 6.7, prothrombin time (PT) 21.4 seconds with international normalized ratio 2.1, partial thromboplastin time (PTT) 55.6 seconds, fibrin split 10 µg/L, and lactate dehydrogenase (LDH) 1231 IU/L. Except for a positive DNA test for Epstein-Barr virus (EBV) infection, extensive diagnostic workup for infections, malignancy, or a neurological cause was negative. Mixing studies revealed a nonspecific inhibitor of PT and PTT but Factor VIII levels were normal. The patient was empirically treated with antibiotics but developed hypotension and died on day 27 of admission. At autopsy, patient was found to have intravascular diffuse large B-cell lymphoma involving skin, testes, lung, and muscles. The malignant cells were positive for CD20, CD791, Mum-1, and Pax-5 and negative for CD3, CD5, CD10, CD30, and Bcl-6. The malignant cells were 100% positive for Ki-67. Discussion. Intravascular large cell B-cell lymphoma (IVLBCL) is rare form of diffuse large B-cell lymphoma and tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules. The cause of its affinity for vascular bed remains unknown. In many reports, IVLBCL was associated with HIV, HHV8, and EBV infections. The fact that our case showed evidence of EBV infection lends support to the association of this diagnosis to viral illness. The available literature on this subject is scant, and in many cases, the diagnosis was made only at autopsy. The typical presentation of this disorder is with B symptoms, progressive neurologic deficits, and skin findings. Bone marrow, spleen, and liver are involved in a minority of patients. Nearly all patients have elevated LDH, and about 65% are anemic. About 20% have hepatic and renal dysfunction. The treatment consists of systemic chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone plus rituximab (CHOP-R) and central nervous system prophylaxis. Retrospective data suggests that, with treatment, 51% to 82% of the patients achieve a complete remission and 27% to 56% are alive at 2-year follow-up. Conclusion. IVLBCL is a difficult diagnosis to make as the disease remains confined to the vascular lumen. It may be associated with certain viral illnesses, and this association needs to be explored further. It is important to consider this diagnosis in the appropriate settings because patients may achieve durable remissions with therapy.

https://journals.sagepub.com/doi/pdf/10.1177/2324709614526702

Maria S. Khan

Papers

Intravascular Large B-Cell Lymphoma: A Difficult Diagnostic Challenge.