Contributed by Matthew Smith, MD and Fiona Craig, MD
The patient is a previously healthy 54-year-old woman with a 12 year history of anemia and recent (3 months) onset of pancytopenia of unknown etiology (leukocytes 2.5 x 109 /L, hemoglobin 7.8 gm/dL, platelets 30 x 109 /L). Her past medical history was unremarkable. The physical examination revealed moderate splenomegaly and was otherwise unremarkable. An abdominal computed tomography scan revealed splenomegaly. Additional laboratory examinations revealed a negative Coombs test, slightly elevated lactate dehydrogenase, and slightly increased haptoglobin. The spleen was removed and her pancytopenia resolved.
Grossly, the spleen was 37.0 x 23.0 x 7.0 cm and 3286 grams. It demonstrated a smooth capsule without adhesions (Figure 1). The cut surface revealed deep red to purple, soft, parenchyma with a subtle micronodular appearance (Figure 2).
Histologically, the spleen demonstrated a subtle, nodular, perisinusoidal infiltrate extending into the red and white pulp. The infiltrate consisted of large cells with vesicular chromatin, occasional multinucleation, and prominent nucleoli (Figures 3 and 4). There were scattered residual nodules of normal tissue. Erythrophagocytosis was also identified.
Immunohistochemical studies revealed the large cells to be CD20 positive, CD3 negative (Figures 5 and 6). A CD8 stain highlighted the splenic architecture and helped to demonstrate involvement of both red and white pulp compartments (Figure 7a and 7b). The Ki67 stain showed positivity within some of the larger cells (Figure 8).
Flow cytometric immunophenotypic studies reveled the abnormal population of cells to be CD19 positive and lambda light chain restricted, while negative for CD5 and CD10 (Figures 9, 10 and 11).
Conventional cytogenetic analysis demonstrated multiple abnormalities (52~59,XX,+X,+i(1)(q10),+5,add(6)(q21),+7,del(8)(p11.2),+9,psu dic(10;3)(q26;p12),+11,t(11;14)(q13;q32),+12,+13,del(13)(q14q22),der(14)t(11;14)(q13;q32),-16,add(16)(q24),+17,+21,+1-2mar1[cp8]/46,XX), most notably an extra X chromosome; and a translocation between the long arms of chromosomes 11 and 14. Fluorescence in situ hybridization (FISH) was positive for the IGH gene rearrangement but negative for the CCND1 rearrangement.