Polymorphous post - transplant lymphoproliferative disorder, EBV positive (PTLD, WHO)
Post-transplantation lymphoproliferative disorders (PTLD) are rare but very serious complications that occur primarily after solid organ transplantation1. Most cases are driven and linked to the Epstein-Barr virus (EBV) and occurs as a consequence of an impaired immune surveillance. PTLD has a predilection for extranodal sites or the transplanted organ. Certain features are associated with a worse prognosis: age > 55 at PTLD diagnosis, late-onset after the transplant, elevated LDH and serum creatinine levels, widespread PTLD, CNS localization, T-cell lymphoma and monomorphous histology. The polymorphous subtypes, usually can be managed clinically with a reduction of the immunosuppression, as opposed to the monomorphic types, that require systemic chemotherapy1. The incidence of PTLD also varies in concordance to the subtype of transplantation and intensity of the immune suppression: its lowest incidence occurs in kidney (1%) and the highest in bowel transplants (20%)2.
The occurrence of PTLD in the brain is very rare (less than a total of 90 cases reported worldwide) and was described in 1970. It is more frequently associated with renal transplants. However, other types of solid transplant in association with CNS-PTLD like liver, heart, lung, pancreas and bone marrow have been reported3-5. The disease has a multifocal distribution involving the cerebral hemispheres and usually in the subcortical white matter or basal ganglia2. Rarely, leptomeningeal involvement can be seen6. Imaging studies reveal that all lesions show contrast enhancement homogeneously or with a ring-enhancing pattern7. Cytology and flow cytometry are usually of low yield as tend to be negative in most cases2.
Histologically, monomorphous PTLD is classified based on histological resemblance with lymphomas arising in immunocompetent patients. Typically, these lymphomas show the morphologic features of diffuse large B-cell lymphomas in the CNS system. Classically, there are sheets of large cells with a perivascular distribution, frequent mitoses and areas of necrosis. Polymorphous PTLD show a full spectrum of B-cells from small to intermediate-sized lymphocytes to immunoblasts and mature plasma cells8. A third subtype of PTLD with classical Hodgkin lymphoma-like appearance has not been described in the brain. In a small pediatric series of CNS-PTLD half of cases were monomorphous and the other half polymorphous. Evens et al found a monomorphic histology in 83% of cases3. They found that upon 42 months of follow-up, the progression free survival and overall survival was 32% and 43%, respectively.
The differential diagnosis is broad and includes primary CNS lymphomas, infections, hemorrhage and other brain tumors. Intraparenchymal hemorrhages, a very uncommon phenomenon in primary CNS lymphomas, are relatively common in CNS-PTLD4. The clinical history of transplant, and very frequent association with EBER, usually makes the distinction between PTLD and primary CNS lymphoma easy. Interestingly, Martinez described a very large series of neuropathologic findings in autopsies of transplant recipients and found that hematologic-vascular complications were very frequent followed by infections. CNS-PTLD occur in 6% of liver, 7% of heart, 5% of the lung and 4% of kidney allografts5.
Ours represents one of the few cases of coexistent monomorphous and polymorphous PTLD with nodal and extranodal presentation.
Contributed by Alejandro A Gru, MD, Norman L Lehman, MD, PhD, Jose Otero, MD, PhD