What are the characteristics and treatment options for intravascular lymphoma?

Features of Intravascular Lymphoma

Intravascular lymphoma (IVL) is a rare, aggressive form of non-Hodgkin lymphoma characterized by malignant lymphoid cells growing almost exclusively within the lumina of small to medium-sized blood vessels, typically presenting with neurological and cutaneous manifestations and requiring prompt diagnosis and treatment with systemic chemotherapy.

Clinical Presentation

IVL has a highly variable clinical presentation, which often leads to delayed diagnosis. Key features include:

Common Clinical Manifestations

• Neurological symptoms:

  • Central nervous system involvement is frequent and often rapid 1
  • Cauda equina syndrome 2
  • Progressive lethargy 3
  • Bizarre neurological manifestations 4

• Cutaneous manifestations:

  • Diffuse telangiectasia 2
  • Skin lesions (often the most accessible site for diagnostic biopsy)

• Constitutional symptoms:

  • Unexplained fever 2
  • Weight loss 2
  • Edema of lower limbs and trunk 2

• Hematologic abnormalities:

  • Hemolytic anemia 3
  • Hemophagocytic syndrome 2, 1

• Other organ involvement:

  • Splenomegaly 4
  • Bone marrow infiltration 4
  • Potentially any organ can be affected due to the intravascular nature of the disease 5

Pathological Features

Histopathology

• Proliferation of neoplastic lymphoid cells within the lumen of small and medium-sized blood vessels 2, 1, 4
• Minimal or no extravascular extension of tumor cells
• Intrasinusoidal bone marrow infiltration may be present 4

Immunophenotype

• Most cases (approximately 90%) are of B-cell origin 2, 1
• Rare cases of NK/T-cell lineage have been reported 5
• Proper immunophenotyping combined with clonality testing is essential for accurate diagnosis 5

Molecular Features

• NK/T-cell variants are strongly linked to Epstein-Barr virus (EBV) 5
• EBV may play a role in tumorigenesis and aggressive behavior in some cases 5
• Dysfunction of cell-endothelial interaction affecting adhesion molecules has been suggested in pathogenesis 2

Diagnosis

The diagnosis of IVL is challenging and often delayed due to its nonspecific clinical presentation:

• Tissue biopsy is essential for diagnosis:

  • Skin biopsy (most accessible)
  • Muscle biopsy
  • Bone marrow biopsy (may show intrasinusoidal infiltration) 4

• Immunohistochemistry is crucial for proper classification

  • B-cell markers (CD20) for B-cell IVL
  • NK/T-cell markers for rare variants

• Molecular studies:

  • Clonality testing
  • EBV testing in suspected NK/T-cell variants 5

Treatment

IVL is an aggressive disease with poor prognosis if not treated promptly:

• Systemic chemotherapy is the mainstay of treatment:

  • R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) for B-cell variants
  • Early initiation of therapy is critical for improved outcomes 1

• High-dose chemotherapy followed by autologous stem cell transplantation may be considered in eligible patients 1

• Corticosteroid therapy may be used initially, followed by combination chemotherapy 2

Prognosis

• Generally poor prognosis with reported median survival of 5-7 months without treatment 1
• Favorable responses to chemotherapy have been observed with early diagnosis and treatment 2
• Rapid progression to CNS involvement is common 1
• Death often occurs within months of diagnosis if not treated appropriately 1

Differential Diagnosis

IVL must be distinguished from:

• Other EBV-related entities such as extranodal NK/T-cell lymphoma
• EBV-positive primary nodal T/NK-cell lymphoma
• Aggressive NK-cell leukemia 5
• Other causes of hemophagocytic syndrome

Key Pitfalls to Avoid

1. Delayed diagnosis due to nonspecific symptoms - maintain high index of suspicion in patients with unexplained neurological symptoms and fever
2. Inadequate biopsy - ensure sufficient tissue sampling from affected organs
3. Incomplete immunophenotyping - comprehensive panel is necessary for proper classification
4. Delayed treatment initiation - prompt therapy is essential for improved outcomes
5. Misdiagnosis as systemic inflammatory disease - consider IVL in patients with multisystem involvement not responding to conventional therapy