Chapter 5-13: Primary CNS Lymphoma (PCL)

TEXTBOOK PRESENTATION

Typically, PCL develops in patients with advanced AIDS. While patients may present with focal signs such as weakness, many patients present with altered mental status or seizures.

DISEASE HIGHLIGHTS

1. Biologically distinct from PCL in other immunocompromised states

2. Diffuse, high-grade, B cell, non-Hodgkin lymphoma arising and confined to the CNS (not due to CNS involvement by systemic lymphoma)

3. CD4TL usually < 50 cells/mcL

4. Consistently associated with EBV (early EBV RNA transcripts detected in 100% of biopsies)

5. Pathogenesis likely involves activation of latent EBV genes due to immunodeficiency. The relative immunologic sanctuary of the CNS from immune surveillance may facilitate growth of these tumors at this location.

6. Rapidly progressive with a short interval from symptoms to diagnosis (1.8 months)

7. Median survival without treatment is about 1 month.

8. Supratentorial location 3 times more common than infratentorial.

9. Most common cause of death in patients with PCL is other OI.

10. Marked reduction in PCL incidence (about 90%) from 1995 to 2000 because of the introduction of ART

EVIDENCE-BASED DIAGNOSIS

1. History and physical exam

   1. B symptoms (weight loss > 10% body weight, unexplained temperatures > 38.0°C, drenching sweats): present in 80%

   2. Focal neurologic deficits: 51%

   3. Mental status changes: 53%

   4. Seizures: 27%

2. Laboratory findings

   1. CSF EBV PCR:

      1. 87% sensitive, 98% specific

      2. LR+, 43; LR–, 0.13

   2. Positive CSF cytology only 15–23% sensitive. Special studies are required to distinguish monoclonal proliferations from reactive T cell populations.

3. Radiologic studies

   1. CT scanning

      1. 90% sensitive

      2. Usually reveals contrast enhancement (90%), characteristically diffuse rather than ring enhancement

      3. 48% single lesion, 52% multiple lesions

      4. Usually associated with mass effect (as in toxoplasmosis but not seen in PML)

   2. MRI more sensitive than CT scanning (see Figure 5-5)

   3. SPECT thallium imaging

      1. PCL usually demonstrates early uptake and retention (compared with decreased uptake in necrotic centers of toxoplasmosis).

         1. 86–100% sensitive, 77–100% specific (higher specificity if retention index measured).

         2. Increased uptake is noted in 15% of patients with TE not receiving ART but up to 50% of patients with TE receiving ART, making this test less useful when on ART.

4. Biopsy

   1. Positive CSF EBV PCR makes biopsy unnecessary if imaging is typical.

   2. Biopsy is useful when CSF EBV PCR is negative.

   3. Lympholytic effect of corticosteroids may render biopsy nondiagnostic.

Corticosteroids should generally not be administered before brain biopsy in patients with suspected PCL unless the patient is at an increased risk for herniation.