Gross pathology and histopathology of transgenic mice. (A) Low power hematoxylin and eosin (H&E) stain of a spleen from a 2-month-old wild-type mouse. (B) Low power H&E stain of a spleen from a 2-month-old mouse derived from founder line 33. Note the prominent mantle zones and germinal centers in follicles. (C) Spleens from a healthy nontransgenic mouse (top) and a clinically ill transgenic mouse (bottom) from founder line 33 at the time of autopsy. Note massive enlargement of the transgenic spleen. (D) Wright’s-stained peripheral blood smear from a clinically ill mouse. At the time of autopsy, the mouse had massive hepatosplenomegaly and mesenteric lymphadenopathy. The white blood cell count at death was 156,600/μL, the hemoglobin level was 7.8 g/dL, the hematocrit was 17.7%, and the platelet count was 140,000/μL. Note the appearance of intermediate-sized, abnormal lymphocytes in the peripheral blood; ≥95% of peripheral blood cells had this appearance. (E) Low-power view of an H&E-stained section of a spleen from a mouse from founder line 33 dying with massive hepatosplenomegaly. Note the uniform appearance of large cleaved lymphocytes replacing the structure of the spleen. (F) Low-power view of a spleen from a mouse from founder line 37 dying with massive hepatosplenomegaly. Note that the tumor does not completely replace the spleen, in contrast to the spleen shown in (E). (G) High-power view of lymphocytes from a splenic tumor. Note the large cells with irregular cleaved nuclei and eosinophilic nucleoli. (H) Cell line 37.4. Note the appearance of large lymphocytes with multiple azurophilic granules, vacuolization, and large irregular nuclei. All cell lines had similar morphologic features.