"Neoplastic Lesions

T-cell lymphoblastic lymphomas usually presented in mice 􏰀10

months old as a mediastinal mass with attendant respiratory distress and rapid

clinical decline when the en- larging mass compressed the thoracic inlet.

Non-lympho- blastic lymphomas occurred predominantly in animals 􏰁10

months of age and generally caused progressively increas- ing abdominal

distension due to marked and readily pal- pable splenomegaly with or without

mesenteric lymph node enlargement.

The clinical course of disease for non-lymphoblastic lymphomas

was less rapid than for lymphoblastic lympho- ma and the use of the

standardized classification criteria for assigning mice to necropsy was very

important in main- taining consistency of selection of mice for necropsy par-

ticularly when during the later stages of the study several different disease

processes occurred in the same mouse, such as unilateral hydronephrosis in addition

to lymphoma. In contrast, earlier during the study, the rapid decline of mice

having lymphoblastic lymphoma left the animal house staff with little doubt as

to whether necropsy was required and concurrent disease processes were

infrequent. The stan- dardized classification criteria were especially useful

in de- tecting mice with pituitary adenomas as some of these mice exhibited

mild chronic weight loss and nonspecific ill health and were sent to necropsy

as a result of the stan- dardized criteria having been applied prior to a later

stage when neurological signs may have developed.

Lymphoblastic lymphomas were composed of a mono- morphic

population of CD3-reactive lymphoblasts having round to ovoid nuclei sometimes

containing a prominent central nucleolus and possessing scant basophilic cyto-

plasm.

Non-lymphoblastic lymphomas caused splenic pallor due to

irregular and multifocal enlargement of the white matter with effacement of

much of the normal follicular pattern, invasion of the red pulp, compression of

adjoining splenic tissue, and frequently capsular invasion. Lymphomatous

mesenteric lymph nodes were common and often became 1–2 cm in diameter with

partial or complete loss of normal architecture. In contrast to the findings

reported by Re- pacholi et al. (1), enlargements of superficial lymph

nodes occurred infrequently in our study. The majority of non- lymphoblastic

lymphomas resembled follicular center cell type human lymphomas of B-cell

origin and were usually composed of a mixed population of large (centroblastic)

and small (centrocytic) cells with cleaved and noncleaved nuclei and a variable

mitotic rate.

A small number of splenic neoplasms were composed of large

histiocytic cells and multinucleated giant cells and resembled large cell

non-Hodgkin’s lymphoma of humans. Metastatic involvement of lungs, liver and

kidneys was common.

Excluding lymphomas, pituitary adenoma was found in 5% of mice

and was distributed evenly across the exposure groups. A small number of other

tumors included heman- giomas/malignant hemangioendotheliomas occurring main-

ly on the extremities and alveolar/bronchiolar adenomas. Only three pituitary

adenomas occurred before 18 months of exposure, and this may be the main reason

why they were not found in the study of Repacholi et al. (1), which terminated at 18 months.

The positive control proved satisfactory and demonstrat- ed a

dependence of tumor incidence on genotype with 56.6% of heterozygotes and 6.7%

of wild types developing lymphomas in our study compared with 60% lymphoma

incidence in heterozygotes and 5% in wild types reported by Repacholi et al. (1)

during the same exposure period."

E mu pim-1 mice, heterozygous, female

HAWC