Gross and Microscopic Changes in the Lymphoreticular System During Genesis of Malignant Lymphoma Induced by a Single Injection of Methylnitrosourea in Adult Mice2

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Abstract
The weights and histological changes in the thymus and spleen, histological changes in the mesenteric lymph node, and total and differential white blood cell counts were determined at various intervals after treatment with a single lymphoma-inducing dose of methylnitrosourea (MNUA). The changes observed could be divided into 3 stages, viz., cell depletion, regeneration, and neoplasia. Although the thymus was the site of origin of malignant lymphomas, the bone marrow, spleen, and lymph nodes were also affected during the genesis of malignant lymphoma. The evolution of the neoplastic changes in the thymus was described in detail, and at least in some instances, malignant lymphoma involving the thymus arose by confluence of more than one focus of neoplasia. The evidence suggested that the involvement of other lymphoid organs occurred by metastasis from the thymic lymphoma. Most malignant lymphomas were lymphoblastic and many had a starry-sky pattern due to the presence of large periodic acid-Schiff-positive cells, around which the tumor cells showed mitotic activity. Lymphoid follicles formed in the medulla of the thymus during the genesis of malignant lymphoma. The possibilities that a virus may be implicated in the genesis of MNUA-induced lymphoma and that immunological reactions may be part of the development are discussed.

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