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Journal ArticleDOI

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

01 Jan 2014-Journal of investigative medicine high impact case reports (SAGE Publications)-Vol. 2, Iss: 1, pp 2324709614526702-2324709614526702
TL;DR: The fact that this case showed evidence of EBV infection lends support to the association of this diagnosis to viral illness, and it is important to consider this diagnosis in the appropriate settings because patients may achieve durable remissions with therapy.
Abstract: 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.
Citations
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Journal ArticleDOI
TL;DR: Intravascular large B-cell lymphoma is aggressive, and without treatment is rapidly fatal, with a slight predominance in men.
Abstract: 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.

81 citations


Cites background from "Intravascular Large B-Cell Lymphoma..."

  • ...The World Health Organization reports neoplastic cells will be found within the lumina of small and intermediatesized vessels, with prominent nucleoli, scant cytoplasm, and frequent mitotic figures.(3) Some variability of IVLBCL cell characteristics has been observed, particularly including cases with coarse nuclear chromatin and irregular nuclei, cells of sizes smaller than expected, limited extravasation of neoplastic cells, involvement of larger veins and arteries than expected, and involvement of the walls of major vessels....

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  • ...The Asian form of IVLBCL has been historically described as occurring predominantly in Japan, characterized by multi-organ failure, hepatosplenomegaly, pancytopenia, and hemophagocytic syndrome.(3) Some have suggested that concomitant presence or absence of Figure 1....

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  • ...Intravascular lymphoma is most frequently a disease of B lymphocytes, although rare cases of thymus-cell (T-cell) and natural killer–cell disease have been reported;(6) the World Health Organization considers these cases to be a separate entity.(3) Intravascular large B-cell lymphoma is aggressive, and has historically been a rapidly fatal malignancy when diagnosis and treatment is delayed....

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Journal ArticleDOI
TL;DR: CNS complications are more common among IVL patients and dementia and seizures outnumber stroke-like presentations, and limited data do not support the treatment efficacy of methotrexate.
Abstract: 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.

66 citations

Journal ArticleDOI
Asako Yamamoto1, Y. Kikuchi, K. Homma, T. O'uchi, S. Furui 
TL;DR: It is concluded 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.
Abstract: 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.

59 citations


Cites background from "Intravascular Large B-Cell Lymphoma..."

  • ...IVL is a rare subtype of extranodal diffuse large B-cell lymphoma.(1) It is characterized by a propensity for intravascular proliferation of tumor cells in small vessels with a predilection for the central nervous system and skin....

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Journal ArticleDOI
TL;DR: 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.
Abstract: 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.

49 citations


Cites background or methods from "Intravascular Large B-Cell Lymphoma..."

  • ...Intravascular large B-cell lymphoma (IVLBCL) is a distinct type of extranodal diffuse large B-cell lymphoma (DLBCL) characterized by selective growth of lymphoma cells within the lumen of small blood vessels (Nakamura et al, 2008; Nakamura et al, 2017)....

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  • ...We retrospectively reviewed the records of patients who were diagnosed with IVLBCL according to the 2008 World Health Organization criteria (Nakamura et al, 2008) and its revision (Nakamura et al, 2017)....

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Journal ArticleDOI
14 Mar 2019-Blood
TL;DR: Diagnosis of IVLBCL is often challenging because of the heterogeneity of the cells within the vascular lumen, especially within capillaries.

48 citations

References
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Book
29 Sep 2017
TL;DR: Thank you very much for reading who classification of tumours of haematopoietic and lymphoid tissues, and maybe you have knowledge that, people have look hundreds of times for their chosen readings like this, but end up in malicious downloads.
Abstract: WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , WHO CLASSIFICATION OF TUMOURS OF HAEMATOPOIETIC AND LYMPHOID TISSUES , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

13,835 citations

Journal ArticleDOI
TL;DR: It emerged that IVLBCL may have additional Histopathologic/cytologic definition criteria with respect to those currently recommended, some clinical features are not randomly distributed worldwide, recent therapeutic approaches, such as anti-CD20-containing regimens, may improve outcome, and kidney, spleen, and liver involvement may show peculiar histopathologic features.
Abstract: Intravascular large B-cell lymphoma (IVLBCL) is a rare form of diffuse LBCL characterized by preferential intravascular growth of malignant lymphocytes, aggressive behavior, and an often fatal course. IVLBCL usually affects elderly patients with poor performance status, elevated lactic dehydrogenase serum levels, anemia, and B symptoms. It displays some differences in clinical presentation among diverse geographical areas, mostly between patients diagnosed in Western countries and Japan. In addition, data from the literature suggest that pathologic diagnostic criteria as well as clinical features of this disease may be broader than described in current classification scheme(s). Under the sponsorship of the International Extranodal Lymphoma Study Group, clinicians and pathologists with interest in IVLBCL, coming from Western and Eastern countries, joined to reach a consensus on defining features as well as to focus on the most urgent unresolved issues in IVLBCL. To this end, a representative group of IVLBCL patients coming from both the aforementioned geographical areas were collectively analyzed. Additional features of IVLBCL were proposed both under clinical and pathologic stand points. At the meeting, it emerged that IVLBCL may have additional histopathologic/cytologic definition criteria with respect to those currently recommended, some clinical features are not randomly distributed worldwide, recent therapeutic approaches, such as anti-CD20-containing regimens, may improve outcome, and kidney, spleen, and liver involvement may show peculiar histopathologic features. Finally, a provisional practical diagnostic approach to hemophagocytosis-associated patients and a proposal for the most useful criteria in the settings of differential diagnosis are included.

416 citations

Journal ArticleDOI
15 Jan 2007-Blood
TL;DR: Multivariate analysis in IVLBCL revealed that a lack of anthracycline-based chemotherapies, age older than 60 years, and thrombocytopenia less than 100x10(9)/L were independently unfavorable prognostic factors; CD5 positivity was not.

362 citations


"Intravascular Large B-Cell Lymphoma..." refers background in this paper

  • ...The most commonly involved sites in this lymphoma are skin and brain, but it can involve any organ.(5) It has 2 major subtypes: “Western” subtype with skin and neurologic involvement and “Asian” subtype that presents as a hemophagocytic syndrome with multiorgan involvement....

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Journal Article
01 Aug 1959-Hautarzt

268 citations


"Intravascular Large B-Cell Lymphoma..." refers background in this paper

  • ...IVLBCL, also known as angiotropic large cell lymphoma,1,2 was first described in 1959 by Pfleger and Tappeiner.3 It was formerly known as “malignant angioendotheliomatosis.”...

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  • ...IVLBCL, also known as angiotropic large cell lymphoma,(1,2) was first described in 1959 by Pfleger and Tappeiner.(3) It was formerly known as “malignant angioendotheliomatosis....

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Journal ArticleDOI
TL;DR: The success achieved with the anti-CD20 chimeric monoclonal antibody, rituximab, represents an important milestone in the clinical practice of B-cell lymphoma and an advantage of adding ritUXimab to conventional chemotherapies has been shown.
Abstract: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of non-Hodgkin lymphoma according to the current WHO classification. This rare form of B-cell lymphoma is characterised by selective growth of tumour cells in the lumina of small vessels of various organs. Strange characteristics of IVLBCL, including the absence of marked lymphoadenopathy and the usually aggressive clinical behaviour, result in the delay of timely and accurate diagnosis and fatal complications. Thus, the prognosis of IVLBCL is extremely poor. The success achieved with the anti-CD20 chimeric monoclonal antibody, rituximab, represents an important milestone in the clinical practice of B-cell lymphoma. An advantage of adding rituximab to conventional chemotherapies has been shown, in the process of increasing our understanding of the clinical and pathological manifestations for IVLBCL. This Review describes the cutting edge of research on IVLBCL, and discusses the unsolved issues from biological and clinical perspectives to provide a better understanding of this rare lymphoma.

240 citations


"Intravascular Large B-Cell Lymphoma..." refers background in this paper

  • ...Intravascular large cell B-cell lymphoma (IVLBCL) is a malignancy confined to the lumina of small blood vessels without any extravascular tumor mass or circulating lymphoma cells in the peripheral blood or bone marrow.(1) IVLBCL is rare, and as of 2007, only about 300 cases have been reported, mostly involving B cells (IVLBCL)....

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