At the age of four, patient was doing well and screening bone marrow
biopsy showed mildly hypocellular marrow without PTLD (Figure
3 ). Despite the persistent EBV viremia by serum PCR, EBV was negative
by EBER in situ hybridization. Molecular testing did not identify
a clonal population. However, cytogenetics revealed one cell with an
abnormal female karyotype with trisomy 3, similar to that previously
observed in this patient 47,XX,+3[1]/46,XX[19]. Although one
abnormal cell is considered non-clonal, due to the similar trisomy 3
finding in the previous bone marrow this finding was communicated to the
clinical team to alert them for the possibility of the residual PTLD.
Figure 3 . Patient 1: Bone marrow is negative for involvement by
PTLD. Bone marrow biopsy shows mildly hypocellular marrow for age
multilineage hematopoiesis (A. 100X and B. 400X). There is no
morphologic support for involvement by PTLD.
At the age of 11 and 14 years imaging studies identified multiple new
mesenteric FDG-avid mesenteric lymph nodes; however, tissue biopsy did
not confirm recurrence of PTLD. Screening biopsies of the intestine did
not demonstrate recurrence of the PTLD. Over the course of her disease,
patient’s EBV viremia was addressed by the immunosuppression reduction,
Ganciclovir, and Rituximab. Currently patient is doing well and does not
show signs of acute rejection or recurrent PTLD.
Case 2 . The patient is a 9-year-old female born full term with
a Hemoglobin (Hgb)C trait. At five weeks of age she started having
cyanotic episodes and was diagnosed with left ventricular non-compaction
dilated cardiomyopathy. Patient required an orthotopic heart transplant
at the three months of age. Immunosuppression was mediated by the
mycophenolate mofetil and tacrolimus (CellCept). Shortly after the
cardiac allograft patient developed cytomegalovirus (CMV) infection. CMV
viremia was successfully treated with Ganciclovir, with subsequent
negative serology. At the eight months her mother noticed that she
developed difficulty crawling and holding her head. At that time
hydrocephalus was diagnosed and a ventriculoperitoneal shunt placed.
Over the course of her clinical course patient was noted to have a
marked neutropenia and reticulocytopenia refractory to the granulocyte
colony stimulating growth factor Neupogen. By age four, patient required
transfusion.
At age five, patient developed cervical lymphadenopathy. Although EBV
viremia was noted, lymph node biopsy did not reveal PTLD. At age six,
patient developed diffuse lymphadenopathy with multiple FDG-avid lymph
nodes. At that time, an inguinal lymph node biopsy revealed near-total
nodal effacement by a diffuse proliferation of mixed atypical
lymphocytes, large transformed lymphocytes or immunoblasts, and numerous
plasma cells, consistent with the involvement by polymorphous PTLD.
Immunostains highlighted mixed lymphoplasmacytic cells with increased
numbers of immunoblasts and polytypic plasma cells. Proliferation index
was at 40%, and EBV-EBER was positive by in-situ hybridization.
Concurrent flow cytometry did not detect any monotypic B-cells or pan
T-cell aberrancy.