Multilobular tumor of bone on the forehead of a guinea pig.

Multilobular tumor of bone (MLTB) is an infrequent, slow-growing, bone neoplasm formed predominantly on the head. These tumors can behave as malignant neoplasms clinically and pathologically and can metastasize occasionally. No cases of MLTB in rodents have been reported, to our knowledge. We describe a novel case of an MLTB in a guinea pig. An adult guinea pig had an exophytic mass fixed on the frontal bone, maxilla, and nasal bone. On radiography, the mass had a spherical contour and variable density and was formed on the surface of the cranial bones. The mass was excised surgically. The cut surface was light-yellow to milky-white and had a granular texture with fine fibrous septa. Histologically, the neoplasm had a multilobular pattern, which consisted of many islands of bone and/or cartilage matrix surrounded by small cells and separated by fibrous septa, which closely resembles the equivalent neoplasm in dogs.

Revised taxonomy and nomenclature of rodent Pasteurellaceae: Implications for monitoring.

Pasteurellosis is a well-recognized disease with similar pathology in all laboratory rodent species. Pasteurella pneumotropica is the most frequently mentioned member of the Pasteurellaceae isolated from mice and rats. Numerous other Pasteurellaceae taxa have been obtained from mice, rats, and other rodent species. Recently, rodent Pasteurellaceae have been submitted to comprehensive genetic and phenotypic (polyphasic) taxonomic studies. As a result they are now classed within six validly published new genera, namely Cricetibacter, Mesocricetibacter, Mannheimia, Muribacter, Necropsobacter, and Rodentibacter. All previously used names such as P. pneumotropica have become obsolete. The new classification forms a firm basis for the correct phenotypic identification of Pasteurellaceae from laboratory animals and for the selection of strains for pathogenicity studies. Consequences of taxonomic changes notably involve molecular methods used for the detection of Pasteurellaceae infection in laboratory animal colonies. Testing may be done using primer sets that detect all Pasteurellaceae taxa or sets developed to detect host-specific members of the family.

Primary neoplasms of bones in mice: retrospective study and review of literature.

To compare and summarize the mechanisms, frequencies of occurrence, and classification schemes of spontaneous, experimental, and genetically engineered mouse skeletal neoplasms, the literature was reviewed, and archived case material at The Jackson Laboratory was examined. The frequency of occurrence of spontaneous bone neoplasms was less than 1% for most strains, with the exceptions of osteomas in CF-1 (5.5% and 10% in two studies) and OF-1 outbred strains (35%), and osteosarcomas in NOD/ShiLtJ (11.5%) and NOD-derived (7.1%) mice. The frequency was 100% for osteochondromas induced by conditional inactivation of exostoses (multiple) 1 (Ext1) in chondrocytes, osteosarcomas induced by tibial intramedullary inoculation of Moloney murine sarcoma virus, and osteosarcomas induced by conditional inactivation of Trp53-with or without inactivation of Rb1-in osteoblast precursors. Spontaneous osteogenic neoplasms were more frequent than spontaneous cartilaginous and vascular types. Malignant neoplasms were more frequent than benign ones. The age of occurrence for spontaneous neoplasms ranged from 37 to 720 days (M = 316.35) for benign neoplasms and 35 to 990 (M = 299.28) days for malignant. In genetically engineered mice, the average age of occurrence ranged from 28 to 70 days for benign and from 35 to 690 days for malignant. Histologically, nonosteogenic neoplasms were similar across strains and mutant stocks; osteogenic neoplasms exhibited greater diversity. This comparison and summarization of mouse bone neoplasms provides valuable information for the selection of strains to create, compare, and validate models of bone neoplasms.

Proliferative and nonproliferative lesions of the rat and mouse hepatobiliary system.

The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally-accepted nomenclature for proliferative and non-proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and differential diagnosis for classifying microscopic lesions observed in the hepatobiliary system of laboratory rats and mice, with color microphotographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available for society members electronically on the internet (http://goreni.org). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for lesions of the hepatobiliary system in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.

Lymphomas and leukemias in mice.

Lymphomas are among the most common tumors in many strains and stocks of mice, especially those used in safety assessment. CD-1, C57BL/6, B6C3F1 and B6;129 mice develop 10-50% incidences of lymphomas in aging mice. Most of the tumors are B-cell lymphomas of the follicular type, arising in spleen, mesenteric lymph node and/or Peyer's patches. Lymphomas and leukemias may be induced by chemicals, retroviruses and irradiation. Genetics also play a major role in mouse lymphomagenesis and leukemogenesis. The most potent chemical carcinogens require only a single injection in young mice to induce a high incidence of lymphomas, often thymic T-cell lymphoblastic lymphomas. Several genetically engineered mouse lines have high incidences of these tumors. In 2-year carcinogenesis bioassays, increases of incidences of B-cell lymphomas (which occur naturally in controls) are indicative of less potent carcinogens. Classifications of the lymphomas and leukemias have evolved over the years. The practical WHO toxicologic pathology lymphoma and leukemia classification was developed by collaboration between the US STP, RITA, BSTP and JSTP. A more recent mouse lymphoma and leukemia classification was published by a committee of the US NCI Mouse Models of Human Cancers Consortium. This classification follows closely the more detailed human WHO classification and can be used for mouse models of lymphoma and leukemia.

Survey on wild rodents for endoparasites in Iwate Prefecture, Japan.

Wild rodents (58 Apodemus speciosus, 29 A. argenteus and 7 Microtus montebelli) were surveyed for endoparasites in Iwate Prefecture, Japan, from October to December 1995 and from April to October 1996. Two trematodes (Echinostoma macrorchis, Plagiorchis muris), 4 or more cestodes (Hymenolepis diminuta, Raillietina coreensis, Cladothyridium spp., Cysticercus fasciolaris), 12 nematodes (Carolinensis minutus, Eucoleus sp., Heligmosomoides kurilensis, H. protobullosus, H. speciosus, Heterakis spumosa, Rhabditis (Pelodera) orbitalis, Rictularia cristata, Syphacia emileromani, S. frederici, S. montana, Trichuris sp.) and 3 protozoans (Giardia sp., Trichomonas sp., Trypanosoma sp.) were identified. The two species of Apodemus were similar to each other, but they were extremely different from M. montebelli in parasite fauna.

Ecotoxicological risks associated with land treatment of petrochemical wastes. I. Residual soil contamination and bioaccumulation by cotton rats (Sigmodon hispidus).

Petrochemical waste contains both organic and inorganic contaminants that can pollute soil and may pose significant ecological risks to wildlife. Petrochemical waste typically is disposed of in land treatment units, which are widespread throughout Oklahoma and the United States. Few studies have been conducted evaluating possible toxicity risks to terrestrial organisms residing on these units. In this study, the extent of soil contamination with fluoride (F), metals, and organic hydrocarbons, the bioaccumulation of F and metals in cotton rats (Sigmodon hispidus), the relationship between contaminants in soil and in tissues of cotton rats, and the level of potentially toxic polycyclic aromatic hydrocarbons (PAHs) in soil were determined on land treatment units. Over a 2-yr period, cotton rats and soils were collected and analyzed from 5 land treatment and matched reference units. The number of land treatment units with soil metal contamination (in parentheses) included: Cr, Cu, Pb (5). Al, As, Ni, Sr, Zn (4). Ba (3). and Cd, V (2). The number of land treatment units with soil PAH contamination (in parentheses) were naphthalene, phenanthrene, benzo[g,h,i]perylene (3). acenaphthene, anthracene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[a]pyrene, indeno[1,2,3-c,d]pyrene, dibenz[a,h]anthracene (2). and acenaphthylene, fluorene, fluoranthene, benzo[k]fluoranthene (1). Total PAH and total petroleum hydrocarbons (TPH) were elevated at all five land treatment units. Mean sums of benzo[a]pyrene (BaP) equivalents (BaPequiv ) were not affected on

Granular cell lesions in the distal female reproductive tract of aged Sprague-Dawley rats.

During the review of a rat carcinogenicity study, a spectrum of granular cell lesions was recognized in the distal female reproductive tract. To verify the diagnoses, cell populations of nine granular cell alterations of the cervix or vagina were characterized immunohistochemically and four were evaluated ultrastructurally. Immunoreactivity was demonstrated in 8/9 cases with S100 protein, 6/9 cases with neuron-specific enolase, and 7/9 cases with Leu-7. Granular cells were negative for smooth muscle-specific actin and calretinin. The immunohistochemical profile of these lesions was similar to that previously reported in other species, including humans. Ultrastructurally, as expected many lysosomal bodies were present in the cytoplasm of granular cells in all specimens evaluated. Based on the detailed evaluation of a series of lesions, we adopted the following diagnostic criteria and nomenclature for the granular cell changes of the female reproductive tract of rats. Granular cell aggregates were non-space-occupying lesions composed of clusters of typical granular cells. Benign granular cell tumors were space occupying lesions that typically contained prominent interstitial collagen and were either discrete masses or were difficult to discern from the surrounding tissues. Some benign tumors also contained foci of spindle cells with decreased granularity. Malignant tumors exhibited pleomorphism and an increased nucleus: cytoplasm ratio morphologically but had the same biologic behavior as the benign tumors. We applied these diagnostic criteria during the review of controls from 9 carcinogenicity studies. Up to 23% of control females in those carcinogenicity studies had granular cell lesions that could be classified into one of the three categories. Granular cell lesions appear to be common in the cervix/vagina of the Sprague-Dawley rat, and tumors may develop from granular cell aggregates.

Primary tumours of the thymus in the rat.

The features of 192 primary thymic tumours occurring in the rat are described. Of these neoplasms, 170 were classified as benign thymomas, one as a benign fibrous histiocytoma, 20 as various types of malignant thymoma, 3 lympho-epithelioma-like carcinomas, one mixed small cell undifferentiated-squamous cell carcinoma, one sarcoma-like carcinoma, 4 undifferentiated carcinomas, 11 squamous cell carcinomas and the one remaining tumour as a carcinoid. A mouse, anti-epithelial, monoclonal antibody, lu-5, was used to confirm the epithelial nature of the malignant thymomas, and neuron-specific enolase to confirm the diagnosis of carcinoid. The tumours showed many features in common with those reported in man.

Proliferative lesions in the male reproductive system of F344 rats and B6C3F1 mice: incidence and classification.

The incidences of all primary neoplasms in the testes and accessory reproductive organs of 51,230 male Fischer 344 (F344) rats and 46,752 male B6C3F1 mice were obtained from the pathology data base of more than 300 long-term toxicity/carcinogenicity studies performed for the National Toxicology Program. The overall incidence of reproductive system neoplasms in male F344 rats was 81.5%. The most common neoplasms were interstitial cell adenoma of the testis (76.6%), adenoma/carcinoma of the preputial glands (2.9%), mesothelioma of the tunica vaginalis (1.5%), and adenoma of the prostate gland (0.3%). The combined incidence (0.1%) of 59 other rare neoplasms consisted of 18 different types that occurred with a frequency of 4 or less. In contrast to the rats, male B6C3F1 mice had a low overall incidence (0.6%) of neoplasms in reproductive organs. The most common neoplasm was the interstitial cell adenoma (0.4%). Thirty additional types of neoplasms were identified. Each of these uncommon neoplasms occurred at a frequency of 12 or less with an overall combined incidence of 0.2%. Morphological features are described for neoplasms in the rat and mouse, and criteria are presented for differentiation of testicular interstitial cell adenoma, prostatic adenoma, and mesothelioma from hyperplastic changes.

Morphology and classification of 96 primary cardiac neoplasms in Fischer 344 rats.

Ninety-six primary cardiac neoplasms were identified from 79,971 Fischer 344 (F344) rats used in chronic toxicity and carcinogenicity studies by the National Toxicology Program (NTP) and National Cancer Institute (NCI), for an overall incidence of 0.1%. Neoplasms were classified as: 60 endocardial schwannomas, 23 intramural schwannomas, eight atriocaval mesotheliomas, three paragangliomas, one pericardial mesothelioma, and one hemangioma. Metastases occurred in four rats with endocardial schwannoma. Histological appearance of the endocardial and intramural schwannomas was consistent with origin from nerve sheath. Two of six endocardial schwannomas available for immunohistochemical staining were weakly positive for S-100 antigen. The atriocaval mesotheliomas, while morphologically resembling adenocarcinoma, were positive for vimentin and keratin, indicating mesothelial origin. Seventy of the 96 cardiac neoplasms occurred in rats 2 years of age or older at time of death. There were no sex or treatment-related differences in the incidence of these neoplasms, with the exception of atriocaval mesothelioma, which was more common in males.

Morphological classification and incidence of thyroid tumors in untreated aged mice.

The authors reviewed a total of 83 thyroid neoplasms in several strains of untreated mice. The 83 thyroid neoplasms consisted of 76 adenomas and 7 carcinomas. The adenomas and carcinomas were divided into the following three morphological types: papillary, follicular, and solid. The papillary adenoma was the most common type. The tumors were more common in female than male mice. The incidence ranged from 0.13% in BALB/c females to 8.6% in C3H-MTV females.