PMC4466218_01
Clinical history and pathology. (A) High power (500X) of peripheral blood smear showing circulating lymphocytes. (B) Total circulating lymphocytes (ALC) and B cell and T cell subsets from 3 months of age to present. Arrows mark key events (a = EBV infection; b=splenectomy; c= MTX started). (C) Micrographs of H&E stained sections from lymph node (top, 100X) and laparascopic splenectomy tissue (bottom, 40X) from a normal adult and the patient. (D) Low power (40X) CD4 (top) and CD8 (bottom)-stained lymph node biopsy taken during acute EBV infection. (E) CD4/CD8 ratio of peripheral T cells over time, with an arrow denoting the timing of an acute EBV infection. Shaded area represents normal range (1:1 - 4:1).
nihms691916f1.jpg
PMC4466218_01_nihms691916f1.jpg
F1
His clinical presentation initially resembled acute lymphoblastic leukemia, but his circulating lymphocytes appeared to be morphologically unremarkable with small resting lymphocytes (Figure 1A). Subsequently, his lymphocyte count continued to range from 50-80x103/mL, composed predominantly of CD19+/CD20+/CD5int/CD27- B cells with normal numbers of CD3+/CD5+/CD7+/TCRalphabeta+, CD4/CD8 segregated T cells (Figure 1B). Although the basic architecture of the patient's lymph nodes was preserved, an intense B cell infiltrate superimposed upon and obscured both follicular and parafollicular areas (Figure 1C and Supplemental Figure 1). A moderate number of T cells (Figure 1D) were present in the interfollicular zone and showed a predominance of CD8 over CD4 T cells as also seen in peripheral blood (Figure 1E). After the EBV infection his circulating lymphocyte count dropped to the 10 - 20 x 103/muL range, and his CD4:CD8 ratio, which had ranged from 2-8 and which had dropped precipitously to as low as 0.12 during the acute EBV infection, slowly recovered to a range of 0.8-1.7 (Figure 1D). The spleen was markedly enlarged (889 grams) but architecturally unremarkable compared to normal tissue from an older individual (Figure 1C). The patient's spleen showed follicular hyperplasia and red pulp expansion (Figure 1C) with increased polyclonal B lymphocytes in both follicles and splenic cords.