Yuko Yamaguchi

Highly Metastatic Ovarian Yolk Sac Carcinoma in a Rat

We investigated a highly metastatic ovarian yolk sac carcinoma in a 52-week-old female Crl:CD(SD) rat. Macroscopically, the present case had severe ascites, bilateral ovarian masses and numerous nodules in the abdominal and thoracic cavities. Histopathologically, these masses and nodules were generally composed of two types of cells mimicking a parietal and visceral yolk sac. The parietal cells were round to polygonal, contained eosinophilic droplets and were arranged in nests and cords in the eosinophilic matrix. Both the intracytoplasmic droplets and the matrix were stained positively with PAS. The visceral cells were cylindriform, and proliferated in papillary and tubular patterns and occasionally formed Shiller-Duval body-like structures. In the dissemination sites, the neoplastic cells proliferated on the surface of the various tissues and often infiltrated into deeper parts of the tissues. Immunohistochemically, both neoplastic cells were positive for α-fetoprotein and keratin, and the eosinophilic matrix was positive for laminin. Ultrastructurally, the parietal cells had dilated rough endoplasmic reticulums, which were filled with electron-lucent laminated structures. The visceral cells had poorly to moderately developed intracytoplasmic organelles and were interconnected with desmosomes. Taken together, the present tumor was diagnosed as yolk sac carcinoma arising from the ovary and was characterized by not only high metastasis but also invasive infiltration with biphasic proliferation of the parietal and visceral cells.

Spontaneous Malignant T-cell Lymphoma in a Young Adult Crl:CD (SD) Rat

We investigated a case of spontaneous malignant T-cell lymphoma observed in a 19-week-old male Crl:CD (SD) rat. The rat showed paralysis beginning 1 week before euthanasia. Hematological examination revealed marked lymphocytosis without distinct atypia. Macroscopically, hepatosplenomegaly and partial atrophy of the thoracic spinal cord were observed. Microscopically, neoplastic cells infiltrated into the liver, splenic red pulp, bone marrow and epidural space of the thoracic spinal cord, while no neoplastic cells were observed in the thymus and lymph nodes. Moreover, the spinal cord showed focal degeneration due to compression by marked infiltration of neoplastic cells in the subdural space. The neoplastic cells were generally small-sized round cells that had a round nucleus with/without a single nucleolus and scanty cytoplasm. Immunohistochemically, the neoplastic cells were positive for CD3 and CD8 and negative for CD79α. Judging from these results, the present tumor in this young adult rat was diagnosed as malignant T-cell lymphoma.

Renal Tubular Cyst Formation in Newborn Rats Treated with p-Cumylphenol.

In this study, we investigated the sequential changes in the development of renal tubular cysts in newborn rats treated with p-cumylphenol (PCP). Fifteen animals per sex were treated orally with 300 mg/kg/day of PCP for up to 18 days from postnatal day (PND) 4 and were sacrificed on PNDs 8, 12, 19 and 22 and after a 7 day recovery period. On PNDs 8 and 12, slight dilatation of the collecting ducts was frequently observed in the medulla and slight papillary necrosis was also noted in some cases. These dilated collecting ducts were lined with slightly hyperplastic epithelial cells. On PNDs 19 and 22, multiple large cystic changes arising from the collecting ducts in the outer medulla were seen. These cystically dilated ducts were also lined with hyperplastic epithelial cells. During the dosing period, the labeling index of proliferating cell nuclear antigen in the collecting duct epithelium was higher in the PCP-treated group than in the control group at all time points. After a 7 day recovery period, the cystic change still remained, although the cell density was decreased and the epithelial cells became flattened. On the other hand, basophilic tubules with peritubular lymphoid cell infiltration were multifocally observed in the cortex. In conclusion, PCP induced multiple renal cysts that developed in the collecting ducts of the outer medulla in neonatal rats, and it is suggested that epithelial cell proliferation may play some roles in the induction of cystic lesions.

Occurrence of Spontaneous Tumors in the Central Nervous System (CNS) of F344 and SD Rats

In order to accurately assess the carcinogenicity of chemicals with regard to rare tumors such as rat CNS tumors, sufficient information about spontaneous tumors are very important. This paper presents the data on the type, incidence and detected age of CNS tumors in F344/DuCrlCrlj (a total of 1363 males and 1363 females) and Crl:CD(SD) rats (a total of 1650 males and 1705 females) collected from in-house background data-collection studies and control groups of carcinogenicity studies at our laboratory, together with those previously reported in F344 and SD rats. The present data on F344/DuCrlCrlj rats (F344 rats) and Crl:CD(SD) rats (SD rats) clarified the following. (1) The incidences of all CNS tumors observed in F344 rats were less than 1%. (2) The incidences of malignant astrocytoma and granular cell tumor were higher in male SD rats than in female SD rats. (3) The incidences of astrocytoma and granular cell tumor were higher in SD rats than in F344 rats. (4) Among astrocytoma, oligodendroglioma and granular cell tumor, oligodendroglioma was detected at the youngest age, followed by astrocytoma, and ultimately, granular cell tumor developed in both strains. The incidences observed in our study were almost consistent with those previously reported in F344 and SD rats.

An Occurrence of Multiple Carcinomas in Both Kidneys of a 5-year-old Female Cynomolgus Monkey (Macaca fascicularis)

An occurrence of multiple carcinoma in both kidneys of a 5-year-old female cynomolgus monkey is described in the present paper. Macroscopically, the kidneys were enlarged with multiple solid and grayish-white masses and cysts mainly in the cortex and outer medulla. Light microscopically, carcinomas showed either tubulopapillary or tubulosolid growth patterns. Carcinoma cells were pleomorphic cuboidal to columnar cells. Cytoplasm was abundant and either granular and eosinophilic or clear, and nuclei were large and vesicular with prominent nucleoli. Electron microscopy revealed the existence of a brush border-like structure on the cell surface of carcinoma cells, suggesting that carcinoma cells arose from proximal tubular epithelial cells. Small foci of tubular epithelial cell hyperplasia and adenomas were also observed independently of carcinomas. There was no evidence of transition from adenoma to carcinoma, and no metastases were detected.

Spontaneously Occurring Formation of Intranuclear and Cytoplasmic Inclusions in Renal Proximal Epithelium Due to Accumulation of d-Amino Acid Oxidase in Wistar Hannover Rats

Intranuclear and cytoplasmic inclusions in the renal proximal tubular epithelium were observed in nontreated male and female Wistar Hannover rats in a 26-week study (32 weeks of age) and a 104-week study (110 weeks of age). The incidence rates were less than 5% in these two studies. In affected animals, the inclusions were observed in more than 60% of proximal tubular epithelium as various sized (approximately 1–8 μm in diameter) round and eosinophilic materials, but not in distal tubules, Henle’s loop, or collecting ducts. Ultrastructurally, inclusions appeared finely granular, homogenous with middle-electron density, and without a limiting membrane. These inclusions were determined to be protein histochemically stained by Azan-Mallory and immunoreactive with an antibody against d-amino acid oxidase (DAO). There was no abnormality in in-life observations or in clinical test values suggestive of renal dysfunction. There were no associated degenerative or inflammatory changes in the kidneys, and no similar inclusions were observed in the other organs. These inclusions are very similar to propiverine hydrochloride (propiverine) and norepinephreine/serotonin reuptake inhibitor–induced inclusions. This is the first report of accumulation of DAO and formation of inclusions occurring spontaneously in rat kidneys. The data are important for toxicological studies using Wistar Hannover rats.

Spontaneous extraskeletal osteosarcoma in the duodenum of a Crlj:CD1 (ICR) mouse

Extraskeletal osteosarcoma is a very rare tumor in humans and animals. This paper describes a case of extraskeletal osteosarcoma observed in the duodenum of a male ICR mouse. Grossly, a solid mass pushing up the tunica serosa was observed in the duodenal wall. Histologically, the tumor was located in the lamina propria mucosae and tela mucosa. Neoplastic cells densely proliferated in these areas, and replaced of the normal tissue components. A small amount of osteoid and a small clump of bone tissue were observed in the area of neoplastic cell proliferation, especially in the lamina propria mucosae. Neoplastic cells consisted of atypical polygonal cells and pleomorphic spindle-shaped cells, and the former were predominant. Mitotic figures were occasionally observed. Neither invasion of vessels in the duodenum nor metastasis to distant organs was observed. There were no skeletal tumors in the body. Immunohistochemically, the neoplastic cells were positive for anti-osteocalcin, osteonectin, vimentin, and S-100 protein. Judging from these results, the present tumor was diagnosed as extraskeletal osteosarcoma. This is the first report of spontaneous extraskeletal osteosarcoma arising from the duodenum of a mouse.