Intravascular large B-cell lymphoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2] Syed Musadiq Ali M.B.B.S.[3]

Synonyms and keywords: Intravascular lymphomatosis, angiotropic large cell lymphoma, angio-endotheliotropic (intravascular) lymphoma, angioendotheliomatosis proliferans systematisata, malignant angioendotheliomatosis

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[1].

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.

Micrograph showing an intravascular large B-cell lymphoma in a blood vessel of the brain. H&E stain.
Micrograph showing an intravascular large B-cell lymphoma.


Causes

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

Differentiating Intravascular Large B-Cell Lymphoma from other Diseases

Intravascular large B-cell lymphoma must be differentiated from other lymphomas with the help of clincal, morphological, immunophenotypic and genetic data as the treatment of all these conditions are different from each other.[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][23][28][29]

Differential Diagnosis Cytogenetics Morphological Features Immunophenotype

Splenic marginal zone lymphoma

Splenic diffuse red pulp lymphoma

  • Uncommon: 7q deletion, trisomy 18, 17p deletion ( TP53)

Hairy cell leukemia variant

  • Common: Deletion 17p ( TP53),
  • Uncommon: 5q gain, deletion 7q
  • Gene mutation: MAP2K1

Hairy cell leukemia

  • Uncommon: 5q gain, 7q deletion
  • gene mutation: BRAF V600E

Lymphoplasmacytic lymphoma

  • Common: 6q deletion,
  • Uncommon: 13q deletion, 7q deletion
  • Gene mutation: MYD88 L265P

Chronic lymphocytic leukemia

Follicular lymphoma

Mantle cell lymphoma

Epidemiology and Demographics

Age

The incidence of intravascular large B-cell lymphoma increases with age; the median age at diagnosis is 67 years.[30]

Gender

Intravascular large B-cell lymphoma affects men and women equally.[30]

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).[30]
  • Hemophagocytic syndrome causes:

Diagnosis

Staging

Staging for Intravascular large B-cell lymphoma is provided in the following table:[31]

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:[30]

Physical Examination

Vitals

Skin

  • Skin rash

HEENT

Thorax

Abdomen

Extremities

Intravascular large B-cell lymphoma clinical features based on organ involvement
Organ Involved Clinical features
Central nervous system
Cutaneous Involvement
  • Maculopapular eruptions, nodules, plaques, tumors, hyperpigmented patches, palpable purpura, ulcers, and infiltrative “peau d’orange”

Laboratory Findings

Laboratory tests for intravascular large B-cell lymphoma include:[30]

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.

Treatment

Medical Therapy

Treatment of intravascular large B-cell lymphoma[34]
Therapy[35] Description
Chemotherapy
  • Combination therapy :
Radiation therapy

References

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