Primary central nervous system posttransplant lymphoproliferative disorder
Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) represents a spectrum of diseases characterised 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.
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. cyclosporin) the incidence of PCNS-PTLD has reduced 1,2.
Clinical presentation is variable, and can occur over a wide range of time after transplantation; typically a few years, but 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.
The vast majority of cases are monoclonal tumours 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.
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 recognisable as a highly cellular tumour, 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 oedema, which is similar to the pattern seen in PCNS lymphoma in patients who have immunodeficiency-associated CNS lymphomas 1,2.
The masses tend to be hyperdense and are surrounded by low attenuation vasogenic oedema.
- T1: iso- to hypointense to cortex
- T1 C+ (Gd): vivid contrast enhancement
- majority are iso to hypointense
- hyperintense is more common when necrosis is present
- surrounding vasogenic oedema
- 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 recognised in time and immunosuppression reduced, significantly longer survival can be expected compared to non-transplant related CNS lymphoma 1.
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.
- 1. Castellano-Sanchez AA, Li S, Qian J et-al. Primary central nervous system posttransplant lymphoproliferative disorders. Am. J. Clin. Pathol. 2004;121 (2): 246-53. doi:10.1309/N82C-TQ1J-0XEV-EFQB - Pubmed citation
- 2. Brennan KC, Lowe LH, Yeaney GA. Pediatric central nervous system posttransplant lymphoproliferative disorder. AJNR Am J Neuroradiol. 2005;26 (7): 1695-7. Pubmed citation
- 3. Louis DN, Ohgaki H, Wiestler OD et-al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114 (2): 97-109. Acta Neuropathol. (full text) - doi:10.1007/s00401-007-0243-4 - Free text at pubmed - Pubmed citation