Splenic marginal zone B-cell and thymic T-cell lymphomas in p53-deficient mice

The molecular pathology and histogenesis of lymphomas in 56 retired breeder male and 14 12-week-old male homozygous p53-deficient (p53(-/-)) mice (C57 BL/6TacfBR-[KO]p53 N4) were evaluated. Lymphomas were assessed by serial mo rphologic techniques, immunohistochemistry, flow cytometry, and analysis of T cell receptor (TCR) or immunoglobulin heavy chain (IgH) gene rearrangeme nts. We found two common types of lymphomas. T-cell lymphomas arose in the thymus through a sequence of lymphocyte depletion, medullary hyperplasia, a nd unilateral lymphoma. Tumor cells were CD3(+), CD90(+), and usually TCR a lpha/beta(+) and possessed clonal TCR beta gene rearrangements. Thymic lymp hoblastic lymphomas (LL) were highly malignant and quickly metastasized to the splenic white pulp and liver, even when the thymus was only slightly in creased in weight. In the spleen, a novel lymphoma was found. Marginal zone hyperplasia led to marginal zone lymphoma (MZL), a well-differentiated lym phoma that usually expressed CD45R (B220) and CD5 at low levels and that ha d clonal IgH gene rearrangements. IgH gene rearrangements were also seen in spleens with marginal zone hyperplasias only. Hyperplastic and neoplastic marginal zone B cells expressed IgM at low to normal levels, as seen by FAG S analysis and immunohistochemistry. These tumors only metastasized to the liver at a later stage, as they became less differentiated. Several mice ha d both types of tumors present in the spleen. Two B-cell lymphoblastic lymp homas of uncertain origin were also found. In this article, we discuss the possible mechanisms responsible for development of the lymphomas seen in th ese p53-deficient mice.