Neurosurgery notes/Tumours/Haematolymphoid and histiocytic tumours/Lymphomas/Immunodeficiency-associated CNS lymphomas

Immunodeficiency-associated CNS lymphomas

View Details
Status
Done
logo
Parent item
Lymphomas
 

General

  • Immunodeficiency-associated CNS lymphomas comprise a family of lymphomas arising in patients with inherited or acquired immunodeficiency.
  • This includes conditions related to Acquired Immunodeficiency Syndrome (AIDS) and iatrogenic disease.
      • Immune status
      Groups
      Disorders/syndromes
      Incidence/risk of PCNSL
      Competent
      ㅤ
      ㅤ
      ~0.5 in 100,000
      Compromised
      Acquired
      HIV-associated (AIDS)
      2–6% incidence in HIV infected
      ㅤ
      Iatrogenic (PTLD)
      Renal, cardiac, lung, liver transplant
      1–7% of transplant recipients
      ㅤ
      Congenital
      SCID, Wiskott–Aldrich syndrome, ataxia-telangiectasia
      4% risk

Definition

  • Essential:
    • A B-cell lymphoma confined to the Central Nervous System (CNS) at presentation, in a patient who is immunodeficient.
    • EBV positivity of tumour cells demonstrated by immunohistochemistry or in situ hybridisation.
  • Desirable:
    • Demonstration of a clonal B-cell population by PCR (in diagnostically difficult cases).

WHO Grade

  • A malignant tumour (lymphoma) but do not assign a specific numerical CNS WHO grade (1–4).

Histopathology

Macroscopic

  • Multiple lesions occur more frequently than in CNS lymphoma of immunocompetent patients.
  • The tumours exhibit a tendency to contain large areas of necrosis.
  • Tumours may simulate necrotizing cerebral toxoplasmosis, which can occur concomitantly.

Microscopic

  • The tumours are typically EBV-related.
  • The lymphoma cells express B-cell markers including CD19, CD20, and CD79a.
  • The tumour cells also express EBV-associated proteins such as EBNA1-6, LMP1, and EBV-encoded small RNAs 1 and 2 (EBER1 and EBER2).
  • AIDS-related diffuse large B-cell lymphoma of the CNS (CNS-DLBCL) shares the characteristics of CNS-DLBCL found in immunocompetent patients.

Aetiology of immunodeficiency

  • Inherited
    • Ataxia-telangiectasia
    • Wiskott-Aldrich syndrome
    • IgA deficiency.
  • Acquired
    • Autoimmune disorders (e.g. systemic lupus erythematosus and Sjogren syndrome)
    • Iatrogenic immunosuppression
      • Organ transplantation
      • Due to treatment with drugs such as methotrexate, azathioprine, or mycophenolate for a wide variety of other diseases)
    • AIDS-positive diffuse large B-cell lymphoma
      • Shares the morphological features of primary CNS lymphoma in immunocompetent patients + the following features
        • More frequent multifocal presentation,
        • EBV association
        • A tendency to contain more and larger areas of necrosis.
          • These areas of necrosis may simulate necrotizing cerebral toxoplasmosis, which may occur concomitantly
      • HIV-associated primary CNS lymphoma has become rarer with the introduction of HAART therapy
    • Immune system senescence are associated with an increased risk of CNS lymphoma
      • EBV+ diffuse large B-cell lymphoma, NOS
        • Affect the CNS in elderly patients with no known immunodeficiency.
        • Lymphomagenesis is attributed to the immunosenescence that can develop with advancing age

Pathogenesis

  • The pathogenesis of AIDS- related PCNSL appears to occur when the CD4 + lymphocyte count falls below 100 cells/ µl
  • Pathogenesis is different from its immunocompetent counterpart.
  • It is perhaps due to impaired T- cell responses and malignant transformation of activated B cells.
  • High levels of EBV DNA were detected in the CSF of almost 100% of HIV- positive patients with PCNSL in a study by Knowles (2003).
  • The pathogenesis is closely linked to EBV infection, as most associated lymphomas are viral-related.
    • EBV-positive diffuse large B-cell lymphoma expresses the following
      • EBNA1-6
      • LMP1
      • EBER1
      • EBER2

Clinical Features

  • The clinical presentation and imaging features may be similar to those of CNS lymphoma in immunocompetent patients.
  • Work up
    • Is similar to immunocompetent
    • The potential morbidity faced by the patient and the potential risks towards the healthcare workers justifies pursuing a less invasive work- up for this group of patients in the first instance.
    • A positive CSF PCR for EBV DNA in the setting of typical MR features of PCNSL, coupled with demonstration of a hypermetabolic lesion on PET is highly likely to represent PCNSL
    • A negative response to a trial of antitoxoplasmosis treatment is suggestive of PCNSL
      • But there are opponents to this approach for a few reasons.
        • A definitive histological diagnosis is not obtained.
        • The diagnosis is delayed and further neurological deterioration is common.
        • Both toxoplasmosis and PCNSL may coexist

Treatment

  • Corticosteroids and WBRT form the mainstay of treatment.
  • HAART (Highly Active Anti- Retroviral Therapy)
    • In the treatment naïve patients, or a change in the drug combination, has been associated with an improvement in disease control and overall survival.
  • The treatment of the acquired and congenitally immunosuppressed associated PCNSL follows the same principle
    • Improvement or elimination of the immunosuppressive state.
    • This needs to be carefully balanced with the risks of transplant rejection and disease progression.
  • Other forms of treatment such as chemotherapy and reduced- dose WBRT (rdWBRT), although promising, should only be offered as part of investigational studies in appropriate tertiary centres.
  • CSF EBV DNA levels act as a surrogate tumour marker to measure response to chemotherapy.
  • Jacomet et al. (1997) studied HD- MTX as sole therapy in HIV- associated PCNSL and demonstrated improved survival rates of 9.7 months.
    • Ideal patients for this form of treatment are those in good neurological condition and without active opportunistic infection.

Prognosis

  • The overall outcome for immunodeficiency-associated CNS lymphoma is poor.
  • SEER: median survival 2 months for the HIV- associated PCNSL.