Spontaneous unilateral renal dysplasia in a clinically healthy cynomolgus monkey (Macaca fascicularis).

Renal dysplasia is a congenital renal malformation characterized by disruption of normal renal development with asynchronous differentiation of nephrons, collecting ducts, and parenchyma and abnormal patterning of cortical and medullary tissues. The present article describes unilateral renal dysplasia discovered in a cynomolgus monkey from a routine toxicology study. The affected kidney was small and characterized by extensive interstitial fibrosis with the formation of fibromuscular collars around glomeruli and tubules, immature nephrons, and persistent mesenchyme encompassing few collecting ducts. The present case is remarkable in that there is a paucity of reports describing histopathologic findings of spontaneously occurring renal dysplasia in preclinical test species for use in large animal toxicity studies.

Proceedings of the 2011 National Toxicology Program Satellite Symposium.

The 2011 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was held in Denver, Colorado in advance of the Society of Toxicologic Pathology's 30th Annual Meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting or discussion. Some lesions and topics covered during the symposium include: proliferative lesions from various fish species including ameloblastoma, gas gland hyperplasia, nodular regenerative hepatocellular hyperplasia, and malignant granulosa cell tumor; spontaneous cystic hyperplasia in the stomach of CD1 mice and histiocytic aggregates in the duodenal villous tips of treated mice; an olfactory neuroblastoma in a cynomolgus monkey; various rodent skin lesions, including follicular parakeratotic hyperkeratosis, adnexal degeneration, and epithelial intracytoplasmic accumulations; oligodendroglioma and microgliomas in rats; a diagnostically challenging microcytic, hypochromic, responsive anemia in rats; a review of microcytes and microcytosis; nasal lesions associated with green tea extract and Ginkgo biloba in rats; corneal dystrophy in Dutch belted rabbits; valvulopathy in rats; and lymphoproliferative disease in a cynomolgus monkey.

Spontaneous complex polysaccharide inclusions in the skeletal muscle of purpose-bred beagle dogs.

Amylase-resistant, periodic acid-Schiff (PAS)-positive inclusions were identified in the skeletal muscle of four of twenty-four purpose-bred beagle dogs from a routine toxicology study. Affected myofibers contained amorphous material filling up to 20% of the sarcoplasm that stained lightly basophilic with hematoxylin and eosin and was strongly PAS-positive with amylase resistance. Transmission electron micrographic examination of the inclusions revealed granular, non-membrane-bound, electron-dense material, consistent with polysaccharide. Although skeletal muscle inclusions with similar features have been reported in dogs in conjunction with systemic metabolic disorders and less often in muscle adjacent to nonmyogenic sarcomas, all four of these dogs lacked clinical or pathological findings diagnostic of a concurrent systemic metabolic or localized skeletal muscle disorder. Furthermore, these skeletal muscle inclusions were present in both vehicle- and test article-treated dogs and were considered an incidental finding that may occur spontaneously in clinically normal beagle dogs; as such, their presence in drug-treated animals should be interpreted with caution.

Immunohistochemical localization of phosphodiesterase 2A in multiple mammalian species.

Phosphodiesterases (PDEs) comprise a family of enzymes that regulate the levels of cyclic nucleotides, key second messengers that mediate a diverse array of functions. PDE2A is an evolutionarily conserved cGMP-stimulated cAMP and cGMP PDE. In the present study, the regional and cellular distribution of PDE2A in tissues of rats, mice, cynomolgus monkeys, dogs, and humans was evaluated by immunohistochemistry. A polyclonal antibody directed to the C-terminal portion of PDE2A specifically detected PDE2A by Western blotting and by immunohistochemistry. The pattern of PDE2A immunoreactivity (ir) was consistent across all species. Western blot analysis demonstrated that PDE2A was most abundant in the brain relative to peripheral tissues. PDE2A ir was heterogeneously distributed within brain and was selectively expressed in particular peripheral tissues. In the brain, prominent immunoreactivity was apparent in components of the limbic system, including the isocortex, hippocampus, amygdala, habenula, basal ganglia, and interpeduncular nucleus. Cytoplasmic PDE2A staining was prominent in several peripheral tissues, including the adrenal zona glomerulosa, neurons of enteric ganglia, endothelial cells in all organs, lymphocytes of spleen and lymph nodes, and pituitary. These studies suggest that PDE2A is evolutionarily conserved across mammalian species and support the hypothesis that the enzyme plays a fundamental role in signal transduction.

An atypical equine gastrointestinal stromal tumor.

A 17-year-old, gelded Quarter Horse cross was found to have a large, intra-abdominal mass. Clinical signs included infrequent mild colic, weight loss, and chronic anemia. Surgery revealed a very large, discrete, hemorrhagic, multilobular mass with vascular attachments to the transverse colon, mesocolon, jejunal mesentery, and omentum; the site of origin was the transverse colon. Histologic examination demonstrated dense sheets, fascicles, palisades, and interconnecting streams of neoplastic spindle cells with lesser numbers of admixed multinucleated giant cells. Based on morphology alone, this neoplasm might have been misdiagnosed as a peripheral nerve sheath tumor because many of the morphologic features were suggestive of neural differentiation. Neoplastic cells expressed cluster of differentiation (CD)117 (c-kit), vimentin, desmin, smooth muscle actin, neuron-specific enolase, and S-100 protein and did not express cytokeratin. Based predominantly on the immunohistochemical profile, especially the CD117 positivity, this neoplasm was diagnosed as a gastrointestinal stromal tumor with both myogenic and neurogenic differentiation. The morphology and immunohistochemical profile of this neoplasm were different from published cases of equine gastrointestinal stromal tumors. Unusual aspects included the large size of this neoplasm, the neuroid rather than myxomatous morphology, the presence of multinucleated giant cells, and the expression of desmin.

Cystic nasal adenocarcinoma in a cat treated with piroxicam and chemoembolization.

A 13-year-old, castrated male Siamese cat was presented with a 4-month history of recurrent seizures and bilateral conjunctivitis and rhinitis. Computed tomography of the brain and nose revealed a cystic lesion in the cranial cavity that compressed the brain and invaded the nose. Nasal biopsy revealed a nasal adenocarcinoma. The cat was treated with intermittent antibiotics, phenobarbital, piroxicam, and chemoembolization; it survived for 2 years after diagnosis.