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.