Intravascular large B-cell lymphoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2]

Synonyms and keywords: Intravascular lymphomatosis; Malignant angioendotheliomatosis; Intravascular lymphoma; Angiotropic large-cell lymphoma; Angiotropic lymphoma; IVLBCL

Overview

Intravascular large B-cell lymphoma is a very rare subtype of diffuse large B-cell lymphoma (DLBCL). It is also considered a distinct type of non-Hodgkin lymphoma (NHL) in the World Health Organization (WHO) classification system. Intravascular large B-cell lymphoma affects small blood vessels. It is a rare and aggressive variant of intravascular proliferation of clonal lymphocytes with little to no parenchymal involvement. Based on the clinical presentation, intravascular large B-cell lymphoma may be classified into either Western variant or Asian variant. On microscopic histopathological analysis, diffuse infiltrate of large atypical cells with irregular nuclear contours, vesicular chromatin, and occasional prominent nucleoli are characteristic findings of intravascular large b-cell lymphoma. The incidence of intravascular large B-cell lymphoma increases with age; the median age at diagnosis is 67 years. Intravascular large B-cell lymphoma affects men and women equally. People with this type of lymphoma often have a poor prognosis. Symptoms of the intravascular large B-cell lymphoma include fever, weight loss, night sweats, chest pain, abdominal pain, bone pain, and painless swellings in the neck, axilla, groin, thorax, and abdomen. Lymph node biopsy is diagnostic of intravascular large B-cell lymphoma. CT, MRI, and PET scan may be helpful in the diagnosis of intravascular large B-cell lymphoma. The predominant therapy for intravascular large B-cell lymphoma is chemotherapy. Adjunctive radiotherapy may be required.

Classification

Based on the clinical presentation, intravascular large B-cell lymphoma may be classified into either Western variant or Asian variant.

Intravascular large B-cell lymphoma classification

Name	Description
Western variant	Western variant characterized by symptoms related to the main organ involved, predominantly neurological or cutaneous
Asian variant	Asian variant in which the patients present with multi-organ failure, hepatosplenomegaly, pancytopenia, and hemophagocytic syndrome. This is an aggressive lymphoma which responds poorly to chemotherapy. The poor prognosis reflects in part frequent delays in diagnosis because of a lack of detectable tumor masses.

Pathophysiology

Intravascular large B-cell lymphoma is characterized by a massive intravascular proliferation of atypical mononuclear cells which lodged in the lumina of small or intermediate vessels in many organs. The neoplastic lymphoid cells are large with prominent nucleoli and frequent mitotic figures. Fibrin thrombi, haemorrhage and necrosis may be seen.

Microscopic Pathology

On microscopic histopathological analysis, diffuse infiltrate of large atypical cells with irregular nuclear contours, vesicular chromatin, and occasional prominent nucleoli are characteristic findings of intravascular large b-cell lymphoma.

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  At autopsy, many of the organs showed involvement by intravascular diffuse large B-cell lymphoma. The alveolar wall showed large atypical cells in the capillaries that were positive for CD20. Within the arteriole wall of the lung were these atypical cells as well.

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  At autopsy, many of the organs showed involvement by intravascular diffuse large B-cell lymphoma.The myocardium also showed these large atypical cells in the vessel lumen.

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  Retrospective evaluation of the bone marrow also showed inconspicuous large cells in clusters.

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  Retrospective evaluation of the bone marrow also showed inconspicuous large cells in clusters highlighted with CD20 (inset).

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  Hematoxylin-eosin staining of pulmonary interstitium intravascular lymphoma (100X).

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  Hematoxylin-eosin staining of pulmonary interstitium intravascular lymphoma (400X),the the alveolar septae was widen and filled with tumour cells showed in high power field.

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  CD20 immunostain of the neoplastic intravascular B lymphocytes (400X).

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  CD34 immunostain shows the neoplastic lymphocytes located in the alveolar capillaries,(200X).

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  KI-67 immunostain highlights the proliferation of intravascular lymphoma cells, (200X).

Causes

There are no established causes for intravascular large B-cell lymphoma.

Differentiating type page name here from other Diseases

Intravascular large B-cell lymphoma must be differentiated from other diseases such as:

• Hepatosplenic T-cell lymphoma
• B-cell chronic lymphocytic leukemia
• Mantle cell lymphoma
• Splenic marginal zone lymphoma

Epidemiology and Demographics

Age

The incidence of intravascular large B-cell lymphoma increases with age; the median age at diagnosis is 67 years.

Gender

Intravascular large B-cell lymphoma affects men and women equally.

Risk Factors

There are no established risk factors for intravascular large B-cell lymphoma.

Natural History, Complications and Prognosis

• Intravascular large B-cell lymphoma usually affects the small blood vessels in many organs, including: central nervous system, kidneys, lungs, and skin. However, almost any site can be affected.
• People with intravascular large B-cell lymphoma have a variety of symptoms. The symptoms will depend on the tissue or organ affected when the blood vessels become occluded. This type of lymphoma is often difficult to diagnose because the symptoms can be so varied.
• Intravascular large B-cell lymphoma is a fast-growing (aggressive) lymphoma.
• People with this type of lymphoma often have a poor prognosis.
• People with this type of lymphoma can also develop a very serious condition where certain parts of the immune system are activated (hemophagocytic syndrome).
• Hemophagocytic syndrome causes:

• Fever
• Enlarged liver and spleen (hepatosplenomegaly)
• A lower number of red blood cells, white blood cells and platelets in the blood (pancytopenia)

Diagnosis

Staging

Staging for Intravascular large B-cell lymphoma is provided in the following table:

Revised staging system for primary nodal lymphomas (Lugano classification)

Stage	Involvement	Extranodal (E) status
Limited
Stage I	One node or a group of adjacent nodes	Single extranodal lesions without nodal involvement
Stage II	Two or more nodal groups on the same side of the diaphragm	Stage I or II by nodal extent with limited contiguous extranodal involvement
Stage II bulky	II as above with "bulky" disease	Not applicable
Advanced
Stage III	Nodes on both sides of the diaphragm; nodes above the diaphragm with spleen involvement	Not applicable
Stage IV	Additional noncontiguous extralymphatic involvement	Not applicable

Symptoms

People with intravascular large B-cell lymphoma have a variety of symptoms. The symptoms will depend on the tissue or organ affected when the blood vessels become occluded. This type of lymphoma is often difficult to diagnose because the symptoms can be so varied. Most common symptoms of the intravascular large B-cell lymphoma include:

• Fever
• Weight loss
• Night sweats
• Painless swellings in the neck, axilla, groin, thorax, and abdomen
• Pain in the chest, abdomen, or bones

Physical Examination

Vitals

• Fever is often present

Skin

• Skin rash

HEENT

• Cervical lymphadenopathy

Thorax

• Thoracic masses suggestive of central lymphadenopathy

Abdomen

• Abdominal masses suggestive of central lymphadenopathy
• Hepatosplenomegaly

Extremities

• Peripheral lymphadenopathy

Laboratory Findings

Laboratory tests for intravascular large B-cell lymphoma include:

• Complete blood count (CBC): pancytopenia
• Blood chemistry studies:
• Cytogenetic analysis
• Flow cytometry
• Immunohistochemistry
• Immunophenotyping

Biopsy

Lymph node biopsy is diagnostic of intravascular large B-cell lymphoma.

Other Imaging Findings

CT, MRI, and PET scan may be helpful in the diagnosis of intravascular large B-cell lymphoma.

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  Computed tomography (CT) scan of the chest showed diffuse interstitial thickening and ground glass opacities.

Treatment

Medical Therapy

Treatment of intravascular large B-cell lymphoma

Therapy	Description
Chemotherapy	Combination therapy : CHOP – Cyclophosphamide AND Doxorubicin AND Vincristine AND Prednisone
Radiation therapy	External beam radiation therapy may be used.

Related Chapters

• Richter's transformation
• T-cell lymphoma

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