Lymphoma & related disorders

Mature B cell neoplasms

Large B cell lymphomas-special subtypes

Intravascular



Minor changes: 21 January 2022

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PubMed Search: intravascular large B cell lymphoma [title] review[ptyp]

Kathryn Gibbons, M.D.
Anamarija M. Perry, M.D.
Page views in 2021: 1,154
Page views in 2022 to date: 67
Cite this page: Gibbons K, Perry AM. Intravascular. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomadiffuseintra.html. Accessed January 23rd, 2022.
Definition / general
  • Extranodal large B cell lymphoma characterized by lymphoma cells, predominantly within lumina of blood vessels, especially capillaries, with the exclusion of larger arteries and veins
  • Few to no circulating lymphoma cells in peripheral blood
Essential features
  • Rare, mature B cell lymphoma limited to intravascular spaces
  • Most common in skin and central nervous system
  • Classical variant most common clinical presentation (neurological and cutaneous manifestations)
  • Neoplastic cells are located in lumina of small to intermediate sized vessels
  • Lymphoma cells are large with prominent nucleoli and vesicular chromatin
  • Pan B cell markers positive, as well as BCL2 and MUM1
  • Aggressive behavior with short overall survival
Terminology
  • Intravascular large B cell lymphoma (ILBCL)
  • Malignant angioendotheliomatosis, angioendotheliomatosis proliferans syndrome, intravascular lymphomatosis, angioendothelilotropic lymphoma (all obsolete)
ICD coding
  • ICD-O: 9712/3 - intravascular large B cell lymphoma
Epidemiology
Sites
  • Selective growth within lumina of small blood vessels, particularly capillaries
  • Extranodal sites, including bone marrow, with sinusoidal or perivascular involvement
  • Most common sites of involvement: skin, nervous system, kidneys, lungs, endocrine glands
  • Lymph node involvement rare (Blood 2018;132:1561)
Pathophysiology
  • Localization to blood vessel lumens partially explained by lack of CD29 (β1 integrin) and CD54 (ICAM1), both of which are important for transvascular lymphocyte migration (Blood 2018;132:1561)
Etiology
  • Unknown
Clinical features
  • Classic / western form:
    • Clinical presentation ranges from a few mild symptoms (fever of unknown origin, pain, organ specific local symptoms) to severe symptoms (B symptoms and signs of multiorgan failure) (Cancer Sci 2021;112:3953)
    • CNS involvement (present in 35%) with heterogeneous symptoms, including sensory and motor deficits or neuropathies, meningoradiculitis, paresthesias, hemiparesis, seizures and altered mental state
    • Skin lesions (present in 40%) are heterogeneous, including painful indurated erythematous eruptions, cellulitis, peau d’orange, small red palpable spots, nodules with or without ulceration, tumors and erythematous and desquamated plaques (Blood 2018;132:1561)
    • Lymphadenopathy typically absent
    • May present with disseminated intravascular coagulation leading to critical bleeding after biopsy (Cancer Sci 2021;112:3953)
  • Cutaneous variant:
    • 25% of patients
    • More frequent in western countries
    • Patients usually younger, with a median age of 59
    • Single or multiple skin lesions; no other sites involved
    • Disease progression is less aggressive and associated with better overall survival (Blood 2018;132:1561)
  • Hemophagocytic syndrome associated form:
    • Presents in Asian populations with multiorgan failure, hepatosplenomegaly and pancytopenia
    • Bone marrow infiltration common
    • Skin and CNS involvement are rare
    • Rapid aggressive onset and progression with median survival of 2 - 8 months (Blood 2018;132:1561)
Diagnosis
Laboratory
  • Anemia, leukopenia, thrombocytopenia and unexplained hypoxemia are most frequently observed
  • Low levels of serum albumin
  • High LDH and ferritin (Br J Haematol 2019;187:328)
Radiology description
  • Lung involvement presents with ground glass appearance and nodules (Blood 2018;132:1561)
  • Organ enlargement (liver, spleen, kidney and adrenal gland) is common (Cancer Sci 2021;112:3953)
  • Brain MRI shows hyperintense lesions in pons, nonspecific white matter lesions, infarct-like lesions or meningeal enhancement
  • PET CT can detect bone marrow involvement (Br J Haematol 2019;187:328)
Prognostic factors
  • Median overall survival of 105 months, with chemotherapy 135 months
  • 5 year survival of approximately 50 - 60% (Br J Haematol 2019;187:328)
Case reports
Treatment
Microscopic (histologic) description
  • Lymphoma cells can be found in any organ vessel lumina (Br J Haematol 2019;187:328)
  • Lymphoma cells are large with high nuclear to cytoplasmic ratio with single or multiple prominent nucleoli and scant cytoplasm
  • Morphologic spectrum from centroblasts to immunoblasts / plasmablasts, including rare forms with anaplastic morphology
  • Different growth patterns:
    • Discohesive - lymphoma cells are preferentially within the central portion of the blood vessels with a free floating appearance
    • Cohesive pattern - lymphoma cells almost completely fill the lumen to the point that assessment of vascular structure tends to be difficult
    • Marginating pattern - less frequent, lymphoma cells preferentially adhere to endothelium, leaving the central portion of the lumen free (Blood 2018;132:1561)
  • Infiltration patterns in bone marrow:
    • Pure intrasinusoidal infiltration - neoplastic cells are confined within the intrasinusoidal spaces
    • Intrasinusoidal infiltration with extravasation - neoplastic cells proliferate within intrasinusoidal space but with extravasation
    • Diffuse interstitial infiltration - neoplastic cells proliferate diffusely within bone marrow (Br J Haematol 2019;187:328)
Microscopic (histologic) images

Contributed by Kathryn Gibbons, M.D.
ILBCL involving skin and subcutaneous tissue

ILBCL involving skin and subcutaneous tissue

Large lymphoma cells in small vessels

Large lymphoma cells in small vessels

ILBCL involving the brain parenchyma

ILBCL involving the brain parenchyma

Vessel with involvement by ILBCL

Vessel with involvement by ILBCL


Large lymphoma cells in the vessels

Large lymphoma cells in the vessels

CD20

CD20

BCL6

BCL6

MUM1

MUM1

Virtual slides

Images hosted on other servers:

Lymphoma cells in blood vessels of subcutaneous adipose tissue

Lymphoma cells limited to lumina of blood vessels

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Skin, left thigh, punch biopsy:
    • Intravascular large B cell lymphoma (see comment)
    • Comment: Biopsy shows large atypical CD20 positive B cells present within vascular spaces in the subcutaneous fat. These cells coexpress CD5, BCL6 and MUM1 and are negative for CD10 and CD3. Overall, these findings are consistent with intravascular large B cell lymphoma.
Differential diagnosis
Board review style question #1

The image shown above is from a brain biopsy in a patient with fever and seizures. Large cells are strongly positive for CD20. What is the correct diagnosis?

  1. CNS vasculitis
  2. Intravascular large B cell lymphoma
  3. Marginal zone lymphoma
  4. Plasmablastic lymphoma
Board review style answer #1
B. Intravascular large B cell lymphoma

Comment Here

Reference: Intravascular large B cell lymphoma
Board review style question #2
Which of the following combinations of immunohistochemical stains is most consistent with immunophenotypic profile of intravascular large B cell lymphoma?

  1. CD20+, CD3-, CD5-, CD10+, BCL6+, BCL2+, c-MYC+
  2. CD20+, CD5+, Cyclin D1+
  3. CD20+, PAX5+, MUM1+, BCL2+
  4. CD20-, CD2+, CD3+, CD5-, CD7+, CD56+
Board review style answer #2
C. CD20+, PAX5+, MUM1+, BCL2+

Comment Here

Reference: Intravascular large B cell lymphoma
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