Keratoconus in a cynomolgus monkey

In a seven-year-old male cynomolgus monkey, erythema of the upper eyelid and forehead and corneal opacity, edema and conical protrusion in the eye were observed. At necropsy, ophthalmological and serological examinations revealed binocular corneal opacity and conical protrusion and a high IgE level, respectively. Thinning of the epithelium and stroma of the cornea were noted histopathologically. At the center of the corneal epithelium, the number of epithelial cells was reduced, their cytoplasm was poorer and the basal cells were flatter than at the periphery. Bowman's membrane was folded with partial loss or breakage. Collagen fibers were compacted or disarranged, and the keratocytes were increased in the stroma, with focal pyknosis or loss of the endothelium and folding of Descemet's membrane. Electron microscopical examination revealed atrophy of the corneal epithelial basal cells. This is the first report of a case of keratoconus in a cynomolgus monkey.     

Bilateral cataract in a cynomolgus monkey

Severe bilateral cataract was found in a 7 year-old naïve female cynomolgus monkey (Macaca fascicularis) 3 months before necropsy. During macroscopic examination, severe opacity and thinning of the lens were observed in both eyes. Histopathology revealed that the lens nuclei and majority of cortex lens fibers had disappeared and become excavated, while the lens fibers in the subcapsular area were swollen and distorted. Other observations included atrophy and vacuolation in the lens epithelial cells and proliferation of spindle cells and collagen fiber beneath the anterior capsule of the right eye. Immunohistochemical staining of these spindle cells revealed the presence of vimentin, cytokeratin and α-smooth muscle actin (α-SMA), which were considered to be derived from lens epithelial cells. This is a rare case of spontaneous, bilateral, hypermature cataract in a cynomolgus monkey.     

Ovarian mucinous cystadenoma with smooth muscle proliferation in a cynomolgus monkey (Macaca fascicularis)

An ovarian mucinous cystadenoma was found in a 5-year-old female cynomolgus monkey (Macaca fascicularis). The tumor was composed of various sizes of multilocular cystic glands lined by a single layer of mucin-filled epithelium. Each of these cystic glands was surrounded by a large amount of solid fibrous stroma resembling smooth muscle. The ovarian surface epithelium showed partial invagination into the ovarian cortex, and a transition was observed between the surface epithelium and the mucinous cyst-forming epithelium. Immunohistochemically, the stromal cells were positive for alpha-smooth muscle actin and proliferating cell nuclear antigen. Ultrastructurally, the glandular epithelium had numerous mucinous secretory granules and microvilli. The stromal cells had numerous parallel microfibrils with focal density. It is rare to encounter evidence of a transition from the surface epithelium to the mucinous tumor epithelium and to show stromal smooth muscle proliferation in a mucinous cystadenoma.     

Nodular thyroid hyperplasia in a cynomolgus monkey

Nodular thyroid hyperplasia was found in a 4-year-old male cynomolgus monkey (Macaca fascicularis). The monkey was clinically normal; however, necropsy revealed multiple variably sized nodules in both lobes of the thyroid gland. In contrast to the fairly uniform diameter of the lumen of follicles in the surrounding gland, the diameter of the follicular lumen within the hyperplastic nodules was highly variable and ranged from nonexistent to cystlike. Occasionally, in the larger follicles there were papillary infoldings of epithelium. The hyperplastic nodules were partially encapsulated by a fibrous capsule and showed little compression of the surrounding tissue. The follicular cells and colloid comprising the hyperplastic nodule were immunohistochemically positively stained with the antibody for thyroglobulin. Ultrastructurally, the cells forming follicles had numerous microvilli along the luminal surface, and lysosomal bodies and dilated rough endoplasmic reticulum in the cytoplasm. All these morphologic findings are consistent with nodular thyroid hyperplasia, which is rare in nonhuman primates.     

Non-gestational malignant placental site trophoblastic tumor of the ovary in a 4-year-old rhesus monkey

We report a case of ovarian malignant intermediate-type trophoblastic tumor in a clinically normal, nonpregnant 4-year-old rhesus monkey (Macaca mulatta). A large solid lobulated mass replaced the right ovary and filled the pelvis. Multiple metastases were observed within the lungs and the liver. The tumor was histologically identified as predominantly composed of intermediate trophoblastic cells, without prominent hemorrhages and the classic bilaminar pattern of cyto- and syncytiotrophoblastic cells characteristic of choriocarcinoma. Immunohistochemical analysis showed the presence of placental lactogen hormone in many tumor cells and chorionic gonadotropin in a few multinucleated cells consistent with syncytiotrophoblastic differentiation. No other germ cell differentiation was identified in the pelvis mass nor in the metastases. In the absence of previous and present pregnancy, this neoplasm has to be considered as a nongestational malignant placental site trophoblastic tumor of the ovary.     

Porencephaly in a cynomolgus monkey ( macaca fascicularis )

Porencephaly was observed in a female cynomolgus monkey (Macaca fascicularis) aged 5 years and 7 months. The cerebral hemisphere exhibited diffuse brownish excavation with partial defects of the full thickness of the hemispheric wall, and it constituted open channels between the lateral ventricular system and arachnoid space. In addition, the bilateral occipital lobe was slightly atrophied. Histopathologically, fibrous gliosis was spread out around the excavation area and its periphery. In the roof tissue over the cavity, small round cells were arranged in the laminae. They seemed to be neural or glial precursor cells because they were positive for Musashi 1 and negative for NeuN and GFAP. In the area of fibrous gliosis, hemosiderin or lipofuscin were deposited in the macrophages, and activated astroglias were observed extensively around the excavation area.     

An unusual case of generalized ceroid-lipofuscinosis in a cynomolgus monkey

Histologic, histochemical, and electron microscopic studies of generalized ceroid-lipofuscinosis in a cynomolgus monkey are presented. Histologically, a wide variety of tissue cells contained numerous bright eosinophilic intracytoplasmic granules that varied in size from 0.5 micron to 4.0 microns in diameter. Histochemically, the granules gave a weakly positive reaction with periodic acid-Schiff and for lipids. They were weakly acid fast and capable of emitting autofluorescence. Ultrastructurally, the granules were single unit membrane-bound, and contained dense osmiophilic material with frequent concentric or fingerprint-type lamellar formation. The granules were different than hemofuscin, iron, and bilirubin. Tinctorially the granules were unique--they were bright red with hematoxylin and eosin and, thus, differed from typical age-related lipofuscin pigment.     

Choriocarcinoma and teratoma in the ovary of a cynomolgus monkey

An ovarian choriocarcinoma was found in a 13-year-old cynomolgus monkey (Macaca fascicularis). The tumor was accompanied by a mature teratoma in the contralateral ovary. Histologically, the choriocarcinoma was characterized by nests of cells where cytotrophoblasts occupied the periphery with syncytiotrophoblasts at the center. Immunohistochemical staining for anti-human chorionic gonadotropin was positive in the syncytiotrophoblasts. The teratoma consisted of well-differentiated epidermal cells, sebaceous glands, hair follicles, cartilage, bone, and teeth. Choriocarcinoma metastases were in multiple organs. The concomitant development of choriocarcinoma and teratoma in the ovary is a consistent finding with the human counterparts of these lesions.     

Congenital cystic adenomatoid-like malformation in a cynomolgus monkey (Macaca fascicularis)

Congenital cystic adenomatoid malformation (CCAM) is a developmental lung abnormality characterized by abnormal proliferation of mesenchymal elements and failure of bronchiolar structures to mature, ultimately resulting in the compression of normal pulmonary tissue and mediastinal shift with rapid expansion of cysts. Although various clinical and pathologic studies of CCAM in humans exist, CCAM has yet to be reported in animals, even in nonhuman primates. In the present study, histopathologic analyses of a neonatal cynomolgus monkey that died 17 days after birth revealed that normal lung architecture was replaced by disorganized overgrowths of cysts lined with simple cuboidal epithelium. The epithelium projected a few ciliates into the air spaces and produced mucus. To our knowledge, this is the first case study describing CCAM or a CCAM-like lesion in nonhuman primates.     

Measles in the cynomolgus monkey (Macaca fascicularis)

The measles virus is known to infect several species of monkeys. A group of 87 cynomolgus monkeys (Macaca fascicularis) was screened to observe whether there was an association between measles and the cold symptoms seen in most of the animals. Another 23 monkeys were vaccinated with attenuated measles vaccine and their antibody titres monitored to ascertain whether the vaccine would protect them against measles.     

Epidemiology of hepatitis E virus in indoor-captive cynomolgus monkey colony

A serological survey of hepatitis E virus (HEV) antibody was conducted using 202 adult captive cynomolgus monkeys, who did not show any clinical signs of acute hepatitis. Out of these, 44 monkeys were sero-positive for anti-HEV IgG and all monkeys were negative for anti-HEV IgM. All positive monkeys came from either Vietnam or China, but none from the Philippines, Indonesia, or our facility. Selected 12 monkeys out of positive monkeys from Vietnam, including 9 positive and 3 negative, revealed mostly within the reference ranges for alanine aminotransferase (ALT) and asparatate aminotransferase (AST) by serum biochemistries. Their titers of anti-HEV IgG did not correlate with the concentrations of ALT and AST. Moreover, HEV-RNA could not be detected from any fecal specimens of the 12 monkeys. Thus, monkeys with anti-HEV IgG sero-positive did not seem to be source of the HEV-pollution, because 1) sero-positive monkeys did not excrete HEV-RNA from their feces, and 2) monkeys from the Philippines and Indonesia have remained to be sero-negative for anti-HEV IgG, even if the monkeys were kept in same animal room of our facility. From these results, it could be inferred that primary infection of HEV occurred in the exported countries, but not in our colony. The contamination of HEV in indoor-captive monkeys could be prevented by precise quarantine tests, including ELISA for detecting anti-HEV and RT-PCR for HEV RNA.     

Polycystic ovary syndrome with endometrial hyperplasia in a cynomolgus monkey (Macaca fascicularis)

A 13-year-old, obese, female cynomolgus monkey (Macaca fascicularis) was observed in a 5-year neurobehavioral study and was humanely euthanatized for experimental purposes. During this observational study, the monkey was noted to ovulate only rarely (0-3 times a year), with a prolonged menstrual cycle length (up to 161 days), hyperandrogenism (androstenedione area under the curve in response to adrenocorticotropic hormone up to 27.64 ng/ml), and hyperinsulinemia (fasting insulin up to 65.85 microIU/ml). This animal's body mass index was 65.46 kg/m(2), with central obesity. On postmortem examination, the uterus was moderately enlarged, with an eccentric lumen and a broad-based endometrial polyp that consisted of complex glandular hyperplasia with atypia. Both ovaries contained many 2- to 3-mm follicles, without any corpora lutea. A diagnosis of polycystic ovary syndrome was made based on the clinical history, endocrinology, and gross and histopathologic findings.     

Goblet cell hyperplasia and muscular layer thickening in the small intestine of a cynomolgus monkey

We report here the interesting case of a 5-year-old male cynomolgus monkey with goblet cell hyperplasia and thickening of the muscular layer throughout the small intestine without exhibiting any clinical symptoms. Necropsy examination showed diffuse thickening of the intestinal wall from the jejunum to the ileum, with an appearance likened to a rubber tube. Histopathologically, marked thickening was observed in both the mucosal and muscular layers in the jejunum and ileum, and slight thickening was observed in the duodenum. Goblet cell hyperplasia with extension of the circular folds and villi was prominently observed. The mucosal surface was covered with a thick mucus layer containing desquamated mucosal epithelial cells, and both the inner and outer muscular layers were markedly thickened due to smooth muscle hypertrophy. Neither macroscopic nor histopathological examination identified any causative factors, such as infection, enteritis and intestinal stenosis, or obstruction that may have caused development of this lesion. Given these observations, this case may simply be considered of spontaneous goblet cell hyperplasia and muscular layer thickening in the small intestine of a cynomolgus monkey.     

Icterus and amaurosis caused by lead poisoning in a cynomolgus monkey (Macaca fascicularis)

The diagnosis and treatment of a case of lead poisoning in a cynomolgus monkey (Macaca fascicularis) are described. The clinical signs were jaundice and amaurosis. Clinicopathological findings suggested cholestasis. A tentative diagnosis of lead poisoning was made when basophilic stippling of erythrocytes was observed in a peripheral blood smear. The diagnosis was confirmed by finding a lead concentration of 2280 micrograms/litre in a venous blood sample. Cage bars painted with red lead appeared to be the source of the poison. The lead was chelated by the intramuscular administration of 2,3 dimercapto-1-propanol (BAL) and calcium disodium edetate for seven days, followed by oral D-penicillamine for five weeks. The encephalopathy was treated with dexamethasone sodium phosphate. Recovery from the blindness was noted after 10 days and marked improvement of the general well being of the animal was observed after one month.