Figure 3

Histopathology of tumors induced by Akv and derived splice site mutants. Representative examples are shown. (A to D) de novo diffuse large B-cell lymphoma. (A) Low magnification of a spleen infiltrated by a vaguely nodular lymphoid neoplasia (H&E staining). Magnification, ×25. (B) Higher magnification demonstrates that the neoplasia is composed of a monotonous population of large cells with blastic chromatin, one to three nucleoli and abundant eosinophilic cytoplasm characteristic of centroblasts (H&E staining). Magnification, ×640. (C) Anti-B220 highlights the large neoplastic cells, which are strongly positive (immunohistochemistry). Magnification, ×400. (D) Anti-CD3 shows that only few residual reactive T-cells are present (immunohistochemistry). Magnification, ×400. (E to H) Follicular lymphoma. (E) Low magnification of a spleen infiltrated by a clear nodular lymphoid proliferation (H&E staining). Magnification, ×25 (F) Higher magnification shows a combination of large centroblasts intermingled with small- to medium-sized lymphocytes or centrocytes (H&E staining). Magnification, ×640. (G) Anti-B220 highlights the expansion of the follicles, mainly of the germinal center lymphoid cells (light brown) (immunohistochemistry). Magnification, ×25. (H) Anti-CD3 reveals the presence of abundant reactive T-cells intermingled with the neoplastic B-cells (immunohistochemistry). Magnification, ×400. (I to L) Marginal zone cell lymphoma. (I) Low magnification of a spleen infiltrated by a marginal zone lymphoma. Note that the follicles (F) are small and the cells surrounding these follicles expand and infiltrate the red pulp in a marginal zone pattern (H&E staining). Magnification, ×100. (J) Higher magnification showing that the neoplasia is composed of a monotonous population of small- to medium-sized cells with open fine chromatin, inconspicuous nucleoli and abundant light eosinophilic cytoplasm (H&E staining). Magnification, ×400. (K) Anti-CD79a reveals that the tumor cells in the marginal zone area are strongly positive, whereas the cells in the germinal centers (F) are weakly positive. The opposite staining pattern is seen with anti-B220 (data not shown) (immunohistochemistry). Magnification, ×200. (L) Higher magnification with anti-CD79a shows a uniform membranous positivity of the tumor cells (immunohistochemistry). Magnification, ×400. (M to O) Histiocytic sarcoma. (M) Low magnification of a spleen diffusely infiltrated by a histiocytic sarcoma (H&E staining). Magnification, ×25. (N) Higher magnification shows the presence of large cells with abundant eosinophilic cytoplasm and bland nuclei characteristic of histiocytes (H&E staining). Magnification, ×400. (O) Anti-Mac 3 shows that all tumor cells are positive for this histiocytic marker, both in the cytoplasm and in the cell membrane (immunohistochemistry). Magnification, ×4 Histopathological and immunohistological analyses of tumor tissues.