Epididymal interstitial (Leydig) cell tumors in B6C3F1 mice

Six primary interstitial cell tumors of the epididymis were identified from 46,752 male B6C3F1 mice used in chronic toxicity and carcinogenicity studies. Five of the tumors occurred at the end of 2-year studies; none were attributed to treatment. None of the mice with epididymal tumors had a primary testicular tumor. Histologically, tumors were characterized by a nodular or diffuse proliferation of tumor cells in the epididymal interstitium. Most cells were polygonal with highly vacuolated cytoplasm (vacuolated cells) or eosinophilic cytoplasm (eosinophilic cells). Smaller hyperchromatic cells with scant basophilic cytoplasm (basophilic cells) and cells with yellow-brown pigment characteristic of lipofuscin (pigmented cells) were less common. In each tumor two or more cell types were present. Extension of these tumors through the capsule, invasion of the testis, or metastasis did not occur. By electron microscopy both eosinophilic and vacuolated cell types had a large round or oval nucleus with sparse heterochromatin, abundant mitochondria with tubulovesicular cristae, and frequent desmosome structures between cell membranes. Vacuolated cells contained numerous lipid droplets. Morphological features of the epididymal tumors are similar to those of the testicular interstitial (Leydig) cell tumor in mice and rats.     

Characterization of uterine granular cell tumors in B6C3F1 mice: a histomorphologic, immunohistochemical, and ultrastructural study

The granular cell tumor is most often a benign neoplasm of uncertain origin. Four uterine granular cell tumors in control and treated female B6C3F1 mice were identified in chronic studies at the National Toxicology Program. Two tumors occurred in untreated control animals and 2 in treated animals receiving different compounds. Tissue sections were evaluated histologically and stained with hematoxylin and eosin, periodic acid-Schiff with diastase resistance, Masson's trichrome, toluidine blue, phosphotungstic acid-hematoxylin, and stained immunohistochemically with a panel of antibodies to muscle (desmin, alpha smooth muscle actin), neural (S-100, neuron specific enolase), epithelial (wide-spectrum cytokeratin), and macrophage (F4/80) markers. The main histomorphologic feature of tumor cells was the presence of abundant cytoplasmic eosinophilic granules that stained positive for periodic acid-Schiff with diastase resistance. Tumors varied in appearance and were comprised of sheets and nests of round to polygonal cells with distinct borders. Nuclei were hyperchromatic, pleomorphic, and centrally to eccentrically located and often contained single nucleoli. Occasional multinucleated giant cells were observed. Tumors were pale pink and homogeneous with trichrome stain and negative with toluidine blue. Three tumors had positive to weakly positive immunoreactivity for desmin, and 1 was positive for alpha smooth muscle actin. Expression of S-100, wide-spectrum cytokeratin, and neuron-specific enolase was negative for all tumors. Ultrastructurally, prominent electron-dense cytoplasmic granules were abundant and contained secondary lysosomes with heterogeneous lysosomal contents. The characteristics of these uterine granular cell tumors were suggestive of a myogenic origin.     

Immunohistochemical characterization of hepatoblastomas in B6C3F1 mice treated with diethylnitrosamine and sodium phenobarbital.

Hepatoblastomas (HBs) were induced in B6C3F1 male mice by diethylnitrosamine (DEN) and sodium phenobarbital (PB). Six-week-old mice received a single intraperitoneal dose of DEN followed by a continuous treatment with PB in diet at a concentration of 0 (group 1) or 500 (group 2) ppm for 50 weeks. HBs were observed in 13 of 21 (62%) group 2 mice, with typical histologic features as reported previously, while no such tumors were observed in group 1. Seven of 13 (54%) HBs were found in and/or adjacent to hepatocellular adenomas (HCAs) or hepatocellular carcinomas (HCCs). Immunohistochemically, all HBs were positive for S-100 protein but negative for keratin, alpha-fetoprotein (AFP), albumin (ALB) and vimentin, while HCC cells occasionally reacted positively for AFP with a mosaic pattern. HCC and HCA cells were occasionally positive for ALB. Non-neoplastic hepatocytes and normal bile ducts were positively stained for ALB and keratin/S-100 protein, respectively. S-100 protein is known to be expressed in many mesenchymal tissues and neoplasms including neuroectodermal elements but negative in cells of the hepatic lineage. Thus, the present immunohistochemical results suggested that mesenchymal differentiation occurs in mouse HB cells as observed in human HBs, one of the most frequent infant liver tumors in humans. Although the susceptibility of mouse HBs to PB-promotion suggests a hepatocytic histogenesis, the present immunohistochemical results support the hypothesis that the mouse HB is derived from pluripotent endodermal stem-like cells.     

Fibro-osseous proliferation in the sternums and femurs of female B6C3F1, C57black and CD-1 mice: a comparative study

Sternums and femurs from B6C3F1, C57black and CD-1 mice, used as controls in carcinogenicity studies, were microscopically examined for the presence of fibro-osseous proliferation (syn. hyperostosis, myelofibrosis, osteofibrosis). The uterus, vagina and ovaries of the same animals were microscopically examined, particularly for the morphological changes indicative of hyperestrogenism. The incidences of each finding in each strain were compared using a chi square test to detect any interstrain variations of statistical significance. Despite the markedly high incidence of endometrial cystic hyperplasia, vaginal epithelial cell hyperplasia and hyperkeratosis, which are morphological changes indicative of hyperestrogenism in all three strains of mice, the incidence of fibro-osseous proliferation in B6C3F1 mice was markedly higher than in the other two strains and statistically significant. This could be explained by a more sustained and higher level of endogenous estradiol in B6C3F1 mice, as brought into evidence by the markedly high, and stastically significant, incidence of follicular development/atresia, with cystic formation, in the ovaries of this strain. However, genetic factors that could determine the general predisposition to fibro-osseous proliferation in B6C3F1 mice cannot be ruled out.     

The utility of intraoperative impression smear cytology of intracranial granular cell tumors: Three cases

Two adult male dogs (a 7‐year‐old shorthaired Chihuahua and 14‐year‐old Shih Tzu) and one adult female dog (a 9‐year‐old Maltese) presented for evaluation of new‐onset seizure activity. Magnetic resonance imaging of the brain demonstrated a large, poorly marginated T2‐weighted hyperintense, and strong contrast enhancing extra‐axial mass in each case. A surgical biopsy for histopathologic evaluation was elected in all cases, and intraoperative impression smears were successfully obtained. Intraoperative cytology identified a homogenous population of round to polygonal cells with central to eccentric nuclei, coarse chromatin, and variably amphophilic to eosinophilic granular cytoplasm. Cytologic findings led to a suspected diagnosis of granular cell tumor (GCT) in all cases. Histopathologic review identified a densely cellular, unencapsulated neoplastic mass comprised of sheets of large round to polygonal cells with abundant eosinophilic cytoplasm containing numerous eosinophilic intracytoplasmic granules, confirming the diagnosis of GCT in all cases. The cases reported here are unique in that they reveal an accurate intraoperative cytologic diagnosis of a rare canine central nervous system neoplasm. Intraoperative cytology of the intracranial masses could provide clinicians with important and quick diagnostic and prognostic information; therefore, expediting decisions made intraoperatively. Further research is warranted to determine the diagnostic accuracy of intraoperative cytology for neoplasia in veterinary patients.     

Comparison of the effectiveness of high and low LET radiations for the proportion of survivals with liver tumors at every age in (C57BL/6N x C3H/HeN) F1 mice

To investigate the late effects of neutrons at the energy below 1 MeV on the liver carcinogenesis as a function of age, one-week old mice were exposed to 1.0 Gy monoenergetic neutrons (0.317, 0.525 and 1.026 MeV) or 137Cs gamma rays. Survival and carcinogenesis were examined by 18 months of age. Following radiation, tumor incidences in liver, Harderian gland, lung, ovary and pituitary gland were compared. The proportion of the lifespan with liver tumors exposed to neutrons to that exposed to gamma rays was calculated as a function of age. Survival rates among the three groups exposed to neutrons of different energies were not significantly different from one another but shorter than those treated with gamma rays for both sexes. With regard to liver tumor incidence evaluated at 18 months of age, the effectiveness of neutrons to gamma rays was 2.54 for females, and 2.08 for males by the factor. Levels of estrogen in the serum were similar between mice bearing liver tumors and those devoid of tumors. In conclusion, all three energies of neutrons induced similar effectiveness with respect to liver carcinogenicity. Proportions of the lifespan with liver tumors of neutron-exposed to gamma-exposed were shorter in females than males along with ages over 12 months. To obtain this factor at every age contributed for the evaluation of the biological effectiveness of radiations with the parameter of tumor incidence and latency simultaneously.     

Equine basal cell tumors: 6 cases (1985-1999)

Basal cell tumors are rare benign tumors in horses. Over a 15-year period, 6 horses were diagnosed with basal cell tumors. The tumors were well-circumscribed. freely moveable, firm, raised papules, nodules, or masses that ranged from 0.6 to 5 cm in diameter. Five of the 6 tumors were ulcerated. Based on gross appearance, the tumors were diagnosed as sarcoids, and 1 was diagnosed as a melanoma. The range of age of affected horses was 6-26 years. The tumors were identified clinically 1 week to 3 years before excision. In 4 horses for which information was available, complete surgical excision was curative with no recurrence 4 months to 2 years after removal.     

Immunohistochemical study of autophagy associated molecules and cell adhesion molecules in canine intracranial granular cell tumors

Granular cell tumors (GCTs) are characterized by abundant eosinophilic cytoplasmic granules. Based on the hypothesis that canine intracranial GCT is a subtype of meningioma and its cytoplasmic granules are formed through autophagy processes, histopathological and immunohistochemical examination were performed on biopsy samples from 7 cases of canine intracranial GCTs and 15 cases of conventional meningiomas. Histopathologically, 7/7 cases of GCTs involved the meninges; foci of meningothelial-like cells were observed in 3/7 cases; brain invasion was observed in 2/7 cases. Immunohistochemically, neoplastic cells of GCTs were positive for E-cadherin and negative for S100, cytokeratin, CD204, and β-catenin in 7/7 cases. Neoplastic cells of 15/15 cases of meningiomas were positive for E-cadherin, and negative for S100 and CD204. Immunoreactivity of meningiomas for cytokeratin and β-catenin was observed in 6/15 cases and 8/15 cases, respectively. Cytoplasmic granules of GCTs were positive for ubiquitin (5/7), p62 (5/7), and LC3 (7/7). Compared to GCTs, the ratios of ubiquitin (6/15) and p62 (3/15) positive cases were lower in meningiomas, and 15/15 cases were negative for LC3. These findings indicate that the biological natures of GCTs including anatomical location, histopathological features and immunoreactivity for E-cadherin are almost in conformity with those of meningiomas. The immunoreactivity for autophagy associated molecules may suggest the possible involvement of autophagy in cytoplasmic granule formation of canine intracranial GCTs.     

Canine eyelid granular cell tumor: a report of eight cases

To describe a previously unreported neoplasm of the medial canthus and eyelid in dogs. Clinical and pathologic features of granular cell tumors in the dog were reviewed. Granular cell tumors, arising from the medial canthal eyelid of eight dogs, were identified from the archives of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). The affected dogs ranged in age from 5 to 12 years (mean of 9.25 years). Follow‐up information was available for seven of the eight cases. The clinical presentation included swollen hyperemic lids (4/8), ulcerated skin overlying the mass (2/8), and red conjunctiva (7/8). All eight of the cases had firm masses extending from the palpebral conjunctiva to the eyelid margin at the medial canthus. Histologically, the tissue was composed of a highly collagenous neoplastic growth. The neoplastic cells were oval to strap‐like cells with an oval bland appearing nucleus and abundant amounts of granular cytoplasm with very distinct cell boundaries. These granular cells were embedded in a dense collagen matrix. A PAS stain faintly highlighted the granular appearance of the neoplastic cells, which is a defining characteristic of this tumor. There was no recurrence in the seven cases available for follow‐up. Canine granular cell tumors of the medial canthus present clinically and histologically as a benign neoplasm. Granular cell tumors have a characteristic histological appearance. Granular cell tumors should be on the differential list for nodules of the medial canthus in dogs.     

An epizootic of parainfluenza virus type 1 in a group of C57B16 mice

An epizootic of respiratory troubles was noticed in a group of C57B16 mice used to study their response following inoculations of different thymic extracts. The infection was characterized by a high level of mortalities. Macroscopically, the lungs of affected animals showed red consolidated areas on the lobes. Microscopically, an acute bronchopneumonia with eosinophilic intracytoplasmic inclusion bodies in the epithelial cells of the bronchi were seen. Those lesions suggest a parainfluenza virus type 1 infection.

The presence of viral particles, morphologically similar to members of the Paramyxoviridae family in lung homogenates observed under electron microscopy and the elevated serum complement fixation and hemagglutination inhibition antibody titers to parainfluenza virus type 1 confirm the diagnosis. The source of the infection is unknown but four hypothesis are proposed.

Healthy animals free of demonstrable antibodies specific to parainfluenza virus type 1 were obtained and the experiment was repeated. No mortalities were observed and the animals remained free of demonstrable complement fixation and hemagglutination inhibition antibodies throughout the experiment.

     

Spleen cell population changes and hemolytic anemia in F344 rats with large granular lymphocyte leukemia

A spontaneous large granular lymphocyte leukemia from a F344 rat was transplanted to 36 syngeneic recipients to study the interactions among leukemia, T lymphocytes, and the development of immunemediated hemolytic anemia. Six rats were euthanatized at biweekly intervals, and spleen weight, total spleen cellularity, and differential spleen cell counts were correlated with hemograms and osmotic fragility. Sequential changes in splenic architecture were correlated with hematologic parameters. Monoclonal antibodies defining all T lymphocytes (W3/13), T helper-inducer cells (W3/25), and T suppressor cells (OX-8) were used to identify T cells in immunocytochemical techniques on spleen sections, as well as in fluorescence activated cell sorter analysis of spleen cell suspensions. The onset of hemolytic anemic at 7 weeks after transplantation coincided with the first detection of tumor cells in the spleen and peripheral blood. Tumor cells first accumulated in the marginal zones, and then they infiltrated the red pulp sinusoids. Although the leukemia caused dispersion of the splenic lymphoid tissue, there was no significant lymphopenia, and the relative number of helper (W3/25+) and suppressor (OX-8+) lymphocytes did not change. Because the induction of anemia was a relatively early event in splenic involvement, we concluded that anemia was unrelated to disruption of lymphoid architecture; furthermore, it does not appear to be caused by changes in the numbers of regulatory T lymphocytes.