Primary central nervous system posttransplant lymphoproliferative disorder

Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) represents a spectrum of diseases characterized by abnormal proliferation of lymphoid tissues encountered in patients who have received solid organ or bone marrow transplants. It can be thought of as one of the immunodeficiency-associated CNS lymphomas ³.

For a general discussion of systemic disease, please refer to PTLD article. 

Epidemiology

Although uncommon, PCNS-PTLD represents the third most common CNS disorder in patients who have transplants; cerebrovascular disease and infection are more common ¹. Autopsy-based series have identified PCNS-PTLD in 2-7% of patients. However, only a small subset of these patients would have had clinical evidence of disease ¹.

PCNS-PTLD was seen more commonly when azathioprine-based immunosuppression was widespread; with the introduction of newer agents (e.g. cyclosporine) the incidence of PCNS-PTLD has reduced ^1,2.

Clinical presentation

Clinical presentation is variable, and can occur over a wide range of time after transplantation; typically a few years, but the reported range is from 3 months to 11 years ¹. As the inclusion of the term ‘primary’ in the name suggests, CNS involvement in PTLD is usually isolated to the central nervous system without evidence of systemic disease ^1,2. 

Pathology

The vast majority of cases are monoclonal tumors of B-cell origin, and many are Epstein-Barr virus-positive, similar to PCNS lymphoma encountered in HIV-positive patients ¹. Polymorphic (P-PTLD) and plasmacytic hyperplasia, both seen with greater frequency in the periphery, are uncommon intracranially ¹. 

Radiographic features

MRI is the investigation of choice for assessing patients with suspected neurological disease in the setting of transplant. The appearance of PCNS-PTLD is variable but is generally recognized as a highly cellular tumor, with distribution throughout all parts of the brain, similar to non-transplant related lymphoma. In the majority of cases, patients will present with multiple masses, often with central necrosis, surrounded by vasogenic edema, which is similar to the pattern seen in PCNS lymphoma in patients who have immunodeficiency-associated CNS lymphomas ^1,2. 

CT

The masses tend to be hyperdense and are surrounded by low attenuation vasogenic edema. 

MRI

• T1: iso- to hypointense to cortex

• T1 C+ (Gd): vivid contrast enhancement

• T2

  • variable

  • majority are iso to hypointense

  • hyperintense is more common when necrosis is present

  • surrounding vasogenic edema

• DWI/ADC: low ADC values (due to high cellularity)

Treatment and prognosis

Reduction of immunosuppression is important along with a variety of agents (e.g. corticosteroids) and radiotherapy ¹. 

Although in some patients disease progression can be rapidly fatal, overall provided it is recognized in time and immunosuppression reduced, significantly longer survival can be expected compared to non-transplant related CNS lymphoma ¹. 

Differential diagnosis

On imaging PCNS-PTLD cannot readily be distinguished from non-transplant CNS lymphoma, especially in patients who are also immunocompromised, as they too tend to have multifocal disease and a greater propensity for central necrosis; both features are uncommon in non-immunocompromised patients with PCNS lymphoma ¹. 

The other main differential is that of cerebral abscesses.