Pathogenesis of a Virus-Induced Rhabdomyosarcoma in Mice

Abstract

The pathogenesis of Moloney's sarcoma virus isolate was studied in a total of 374 newborn BALB/c and C57BL mice. Intact animals and newborn mice that received normal muscle extract served as respective control groups. The response of mice to 2 virus dose levels administered by 2 different routes, i.e., subcutaneous-intramuscular (inguinal area) and intrathymic, was studied. The latent period ranged from 6–16 days among the mice in the experimental groups. No significant differences were found between the sexes and strains employed or among the mouse groups receiving the 2 different levels of virus. The induced neoplasm arose and progressed rapidly in the muscle tissue. The tumor was often extensive and weighed up to 10% of the total body weight. The tumors occurring in the mice inoculated intrathymically arose from surrounding muscle tissue, attaching to or on the surface of the thymus with only minor involvements of the organ. These sarcomas grew to the neck, head, diaphragm, and foreleg muscles and occasionally were in the hind leg and psoas muscles. In some animals spleen and lung metastases were noted. Histologically the tumor was composed of elongated cells resembling young muscle cells, often with centrally located and frequently multiple large nuclei possessing several distinct nucleoli. In some of these cells distinct cross striations were noted. These cells were stained slightly red with Mallory azan and, when stained with periodic acid-Schiff, exhibited purplish-red cytoplasmic granules. From all these characteristics this tumor may be classified as a rhabdomyosarcoma. Further evidence for this classification is presented and discussed. In addition, undifferentiated small, round spindle and giant cells were found. The relation between the neoplastic cells is discussed. In the virus-treated animals spleen weights increased (without marked histologic changes), hematocrits decreased, and a decrease of red blood cell osmotic resistance was noted.