Testicular and epididymal appendages in the cynomolgus macaque (Macaca fascicularis).

BACKGROUND: Vestigial remnants of the mesonephric duct and paramesonephric duct are well-known developmental abnormalities of the human testis and epididymis. METHODS AND RESULTS: During routine macroscopic and histological examination of four cynomolgus macaques, three different forms of testicular and epididymal appendages were observed, namely a unilateral appendix testis, a bilateral appendix epididymidis, and several vasa aberrantia. By histological and immunohistochemical examinations it could be demonstrated that both the appendix testis and the appendix epididymidis consisted of a central fibromuscular core and a pseudostratified columnar epithelium at the outer surface. The vasa aberrantia were attached to the connective tissue sheaths of the epididymis/testis and were represented by small duct-like or cystic structures internally lined with a simple cuboidal to columnar, partly ciliated epithelium. CONCLUSION: Awareness of these rudimental tissues in non-human primates is necessary to determine actual incidence rates in non-human primate species used in toxicological research and avoids misdiagnosing during routine necropsy and histological examinations.

Spontaneous neoplasms observed in cynomolgus monkeys (Macaca fascicularis) during a 15-year period.

A total of 33 tumors were observed during a time period of 15 years (1992-2006) in cynomolgus monkeys. The great majority of neoplasms was benign (23 benign neoplasms versus 10 malignant tumors). Fourteen appeared in males and 19 in females. The age of tumor-bearing animals ranged between 2 years 2 months and 13 years 9 months. Most of the tumors (22) in the cynomolgus monkeys were seen in endocrine organs (adrenal cortical adenoma, adrenal hemangioma, C-cell carcinoma, follicular adenoma), respiratory system (nasal cavity adenoma, pulmonary squamous cell carcinoma, bronchio-alveolar carcinoma, bronchiolar papilloma, chondromatous hamartoma) and female genital system (uterine polyp, uterine adenoma, uterine leiomyoma and teratoma of the ovary). Four animals revealed malignant lymphoma infiltrating multiple organs.

Background pathology of the common marmoset (Callithrix jacchus) in toxicological studies.

Two hundred common marmosets (Callithrix jacchus) from control groups (100 males, 100 females) of toxicological studies were examined histopathologically to evaluate the spectrum of spontaneous lesions in this species. Frequent findings were extramedullary hematopoiesis affecting adrenal glands, liver, kidney and spleen, cystic Brunner's glands in the duodenum, acute or subacute inflammation in the large intestine and gall bladder, renal mineralization and pigmentation, hepatic Ito-cell vacuolation, microgranuloma and glycogen storage, pituitary cysts, C-cell hyperplasia and lymphocytic foci of the thyroid gland, luteal hyperplasia of the ovary and inflammatory cell foci in various organs.

Spontaneous epithelial plaques in the uterus of a non-pregnant cynomolgus monkey (Macaca fascicularis).

Two epithelial plaques were observed in the uterus of a 4 years 8 month old non-pregnant cynomolgus monkey. Normally, epithelial plaques occur near the implantation site of primates during early pregnancy but can also be induced by various procedures. Both plaques consisted of clusters and nest of cells with large nuclei and a faintly basophilic cytoplasm. Marked cellular pleomorphism was seen, including cells with giant nuclei and binucleated cells. Further histological features were vacuolation, mitosis and PAS-positive granules in several cells and polymorphonuclear infiltration in the periphery of the plaque. This is the second description of a spontaneous epithelial plaque in a primate and the first in a cynomolgus monkey.

Spontaneous squamous cysts and squamous epithelial plaques in the heart of cynomolgus monkeys (Macaca fascicularis).

Squamous cysts and squamous epithelial plaques were observed in a total of seventeen cynomolgus monkeys. Eleven monkeys had squamous cysts, three of them also revealed squamous plaques and six revealed squamous plaques exclusively. At necropsy, cysts were recognized as yellow-white nodules with a smooth surface, that were located superficially along the interventricular septum, on the surface of the left ventricle or the apex of the heart. Microscopically, cysts were lined by a flattened epithelium and filled with keratin. Occasionally the epithelium was multi-layered or replaced by a rim of foreign body-type multinucleated giant cells. All animals with squamous cysts came from Mauritius, while those with squamous plaques came from Mauritius, China and Vietnam. As discussed in man, squamous cysts and plaques in cynomolgus monkeys are considered to represent displaced foregut epithelium, that was sequestered in the dorsal mesocardium prior to closure of the pleuropericardial fold during early embryologic development.

An orthotopic model of ductal adenocarcinoma of the pancreas in severe combined immunodeficient mice representing all steps of the metastatic cascade.

INTRODUCTION: Clinically relevant animal models are needed to evaluate new therapeutic strategies against pancreatic adenocarcinoma, which is almost incurable by established treatment. AIMS: To establish and characterize a metastatic orthotopic transplant model for pancreatic ductal adenocarcinoma in severe combined immunodeficient (SCID) mice. METHODOLOGY: Human pancreatic ductal carcinoma cells, PancTu 1, were implanted either subcutaneously or orthotopically into the pancreas. RESULTS: After 4 weeks, orthotopic transplantation resulted in an extensive local tumor growth of an undifferentiated ductal adenocarcinoma with slight to moderate desmoplastic reaction. The tumor growth and spread resembled the situation in humans, including invasion into adjacent organs causing biliary and stomach obstruction. In addition, tumor metastases to regional lymph nodes of the pancreas, lung, liver, mesentery, and diaphragm, and attached to the kidneys, spleen, and reproductive organs were observed. In contrast, no invasion or metastases could be demonstrated by subcutaneous implanted PancTu I cells. Using immunohistochemical analysis, even single human tumor cells could be detected in blood vessels and metastatic organs, providing evidence that the orthotopic transplant model appropriately reflects the entire process of the metastatic cascade. CONCLUSION: This cancer model in SCID mice appears to be a powerful tool to investigate the identity of metastasis-associated genes and to evaluate preclinically the potency of novel antimetastatic agents in ductal adenocarcinoma of the pancreas.

Spontaneous pulmonary neoplasms in cynomolgus monkeys (Macaca fascicularis)--a report of two cases.

The first lung tumour-bearing animal was a 7 years and 3 months old cynomolgus monkey. Microscopic examination revealed a neoplastic mass under the pleura that consisted of squamous islands with little keratinization, multifocal mineralization of the keratin, inflammatory cell and foreign body-type giant cell infiltration. It was classified as pulmonary squamous cell carcinoma. In a second cynomolgus monkey (2 years and 10 months old) a lung mass was observed at necropsy. Microscopically the tumour consisted of numerous islands of cartilage with glandular structures lined by a cuboidal epithelium between them. The neoplasm was classified as cartilaginous hamartoma.

Spontaneous neoplastic lesions in Harlan Sprague-Dawley rats.

In a 24-months study, the spontaneous tumour spectrum of the Hsd:Sprague-Dawley stock was examined. Pituitary gland tumours were found in 20% of the males and 39% of the females. This relatively low incidence, compared to other SPRD stocks, had little effect on the survival of females (50%), due to the high incidence (76%) of mammary gland tumours (predominantly fibroadenomas) that resulted in unscheduled sacrifices of many females. Other common neoplasms in Hsd:Sprague-Dawley rats were benign medullary tumours (27% in males, 11% in females), C-cell adenomas (23% in males, 28% in females), and endometrial stromal polyps (22% in females).

Spontaneous neoplasms of the nasal cavity in rats.

The histomorphological features of two adenocarcinomas and two adenomas of the nasal cavity observed in two female Wistar rats and a male Sprague-Dawley rat are described. In one of the Wistar rats, a second tumour, classified as an adenoma, occurred in the posterior part of the nasal cavity.

Spontaneous cystic keratinizing epithelioma in the lung of a Sprague-Dawley rat.

A spontaneous cystic keratinizing epithelioma in the lung of a 704-day-old female Hsd:Sprague-Dawley rat is described. The rat had a white subpleural discoloration on 1 diaphragmatic lobe at necropsy. Microscopically, a central keratin mass, surrounded by a multilayered squamous epithelium of varying thickness, was found. In the periphery of the tumor, epithelial nests projected multifocally into the adjacent alveolar spaces. Immunohistochemical labeling of nuclei by PCNA (proliferating cell nuclear antigen) revealed proliferative activity in 1 or 2 peripheral cell layers in most locations. To the best of the authors' knowledge, this is the first report dealing with the morphological and immunohistochemical features of a spontaneous cystic keratinizing epithelioma in a rat.

Incidence and spectrum of spontaneous neoplasms in Han:NMRI mice of both sexes.

Two hundred Han:NMRI mice of both sexes were kept for their natural life-span to obtain information about the spontaneous tumour spectrum of this strain. Neoplasms were seen in 72% of the males and 64% of the females. Lung tumours, Harderian gland tumours, liver and adrenal gland neoplasms were common in males, while ovary tumours and lung tumours were the most frequent neoplasms in females.

Blood coagulation studies in guineapigs (Cavia porcellus).

Blood coagulation studies were performed on 45 healthy, adult guinea pigs. Additionally thrombelastograms of 30 animals were recorded. Guineapigs revealed short partial thromboplastin times and euglobulin lysis times, but long prothrombin times and thrombin times. Fibrinogen values were within the range of human normal values. Biphasic ADP-induced aggregation of platelets, as occurs in man, was found in 29% of the animals. Short r (reaction time until the beginning of clot formation) and k times (time from the beginning of clot formation until an amplitude of 20 mm) of their thrombelastograms indicate, that whole blood clotting is enhanced in guineapigs. Higher maximum amplitudes in this species suggest a stronger clot stability than in man.

An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to Pasteurella pneumotropica in murine colonies.

An ELISA for the detection of class specific IgG antibodies to Pasteurella pneumotropica was developed for the serological diagnosis of infections in mouse colonies. Heat inactivated whole cell preparations of an isolate of P. pneumotropica biotype Heyl (strain P 166) served as antigen for the ELISA procedure and for immune serum production in germ-free Han:NMRI mice. Cross reactions with the autochthonous flora of Han:NMRI SPF-mice were not observed, but were evident when a P. pneumotropica antiserum was tested against other antigens of the Pasteurella-Actinobacillus group. According to the reclassification of this bacterial group proposed by Mutters et al. (1), strains of the following species were tested: P. anatis, P. canis, P. dagmatis, P. langaa, Pl multocida sub. multocida, P. pneumotropica biotype Jawetz, P. stomatis, Actinobacillus equuli and A. lignieresii. Clear cross reactions could be shown with P. pneumotropica biotype Jawetz and A. equuli and to a lesser extent with P. anatis. Antibody formation profiles after nasal infection of Han:NMRI mice exhibited a primary rise of IgG-type antibody titer between 17 to 21 days post infection. Investigations of different mouse colonies free and infected with P. pneumotropica revealed good correlations between serological and bacteriological findings.

Endometrial carcinoma in BD II/Han rats: model of a spontaneous hormone-dependent tumor.

The incidence of endometrial carcinomas as well as the life-spans of 5 groups of female BD II/Han inbred rats were compared. Groups compared were control (CON), ovariectomized (OV), retired breeder (RB), germfree rats (GF), and rats fed a purified diet (PD). Carcinomas, for the most part adenocarcinomas, occurred in 90% of the CON and PD rats and approximately 60% of the RB and GF rats. Carcinomas did not develop in OV rats. The mean life-span of the CON and PD rats was 22 months. The RB and GF rats reached, respectively, 32 and 30 months; and the OV rats, 39 months. An essential influence of ovarian hormones on tumorigenesis was shown. Alimentary carcinogens and phytoestrogens, as well as chronic irritations of the endometrium due to bacteriologic inflammations, could be excluded as tumor initiators. Hormonal dysregulation in the aging BD II/Han rats was discussed as a possible cause of an inappropriate stimulation of the endometrium, promoting a previously transformed tumor cell or initiating an autonomous tumor growth. Such evidence supports the use of the BD II/Han rat as a suitable model for the study of hormonal effects on the tumorigenesis of endometrial carcinomas in women.