Case reports:
The first patient is a 14-year-old male with a history of kidney transplant one year prior, who presented with chest pain and shortness of breath and was found to have near-complete opacification of the left hemithorax with rightward mediastinal shift and moderate pleural effusion. Laboratory studies revealed an elevated uric acid, Lactate Dehydrogenase (LDH), and EBV DNA in peripheral blood. The flow cytometry analysis of pleural fluid confirmed a monoclonal B-cell population with high forward scatter, CD20 rarely dim+, CD45+, CD19+, CD2 dim+, and kappa light chain restriction. Concurrent cytological evaluation revealed a large B-cell neoplasm with plasmablastic morphology and high Ki67 proliferation rate, positive for LMP1, PAX5, BCL2, CD19, MUM1, CD38, kappa light chain, while negative for CD20, CD10, BCL6, HHV8, ALK1, and MYC. The cytogenetics identified a complex karyotype, while Fluorescence in situ hybridization (FISH) studies were negative forMYC , BCL6 and BCL2 rearrangements, positive for gains of BCL6 , MYC , BCL2 and IGH . These findings were consistent with an EBV positive monomorphic PTLD. The patient was initially treated with rituximab monotherapy but developed disease progression. He was switched to chemoimmunotherapy with bortezomib, cyclophosphamide, dexamethasone, and daratumumab. Repeat Positron emission tomography - computed tomography (PET/CT) scan showed near resolution of the pleural/pericardial effusions and lesions after two cycles of chemoimmunotherapy. He received an additional four cycles of this regimen but relapsed while on therapy with recurrence of his pericardial effusion and mediastinal disease as well as new intra-abdominal and skeletal disease. Interestingly, the relapsed lymphoma showed similar plasmablastic morphology with acquired expression of cytoplasmic CD3, which was not seen in the original diagnostic lymphoma. CD30 was positive on 2-3% of tumor cells. The morphology and immunophenotype are consistent with PT-PBL. Patient received six cycles of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) with rituximab and remains in remission two months after completion of therapy.
The second patient, a 9-year-old male who received heart transplant within the first year of life, presented with intestinal obstruction after a prolonged prodrome of feeding intolerance. A 4 cm mass in small bowel causing intussusception was surgically removed. The histology showed a large B-cell neoplasm with plasmablastic morphology and nearly 100% Ki67 proliferation rate, positive for variable PAX5, variable CD38, cytoplasmic CD3, and CD30; while negative for CD20, HHV8, ALK1, and EBER (Figure 1). The FISH was negative for MYC -rearrangement. Polymerase Chain Reaction (PCR) studies were positive for IgH clonal rearrangement while negative for T-cell receptor (TCR) clonal rearrangement. Concurrent flow cytometry identified a surface kappa light chain restricted B cell population, negative for CD19, CD20 and surface CD3. The findings were diagnostic for PT-PBL. Patient received chemotherapy with EPOCH and the addition of bortezomib. He achieved a partial response but eventually died of disease approximately 5 months after the PBL diagnosis.