Nonproliferative and Proliferative Lesions of the Rat and Mouse Endocrine System

Abstract

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative among the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the endocrine organs (pituitary gland, pineal gland, thyroid gland, parathyroid glands, adrenal glands and pancreatic islets) of laboratory rats and mice, with color photomicrographs illustrating examples of the lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.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 endocrine lesions 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.

Pituitary Hyperplasia, Hormonal Changes and Prolactinoma Development in Males Exposed to Estrogens—An Insight From Translational Studies

“…When we tested how pituitary-thyroid-periphery signaling responds to orchidectomy in our middle-aged rat model, unchanged serum l-thyroxine (T 4 ) and TSH were detected [127]. On the other hand, liver Dio 1 and pituitary Dio 2 enzyme activities were decreased, which indicated a local hypothyroid state, in line with altered cytomorphology of thyrotropic cells, which appeared enlarged and vacuolated, as in hypothyroid states [122]. In addition to this, most recently, specific cell-type transcriptomic analysis showed that 100% of sex-dominant genes in TSH cells were male-dominant [16].…”

“…Sex steroids affect the feedback response of TSH cells to free thyroid hormone concentrations in blood diversely in male and female rodents [121,122]. Male rats have higher TSH values and are more prone to develop thyroid diseases (or even thyroid carcinoma) in response to goitrogenic agents compared with females [121,122]. In humans, sex-related differences in TSH values are not as clearly visible as in rodents, but women are more prone to thyroid dysfunctions in comparison with men.…”

A craniopharyngioma in a Wistar rat most likely originated in a Rathke’s cleft cyst

“…Within the cystic cavities, there was also a multifocal accumulation of cholesterol clefts and clusters of foamy macrophages ( The atypical and highly proliferative epithelium were characteristic of epithelial neoplasia. Given its location, the compression of the brain, and the presence of papillary projections lined by squamous epithelium with hyperkeratosis, the diagnosis was compatible with a craniopharyngioma (CP) 1 .…”

“…CPs and RCCs both originate in Rathke's pouch, and therefore arise from a common epithelial lining: cuboidal, ciliated epithelium, often containing mucus and goblet cells 1,19 . Histopathology is one of the most reliable tools for differential diagnosis; however, differentiating among RCCs and CPs can be challenging as some of the histological features overlap 8 .…”

“…The atypical and highly proliferative epithelium were characteristic of epithelial neoplasia. Given its location, the compression of the brain, and the presence of papillary projections lined by squamous epithelium with hyperkeratosis, the diagnosis was compatible with a craniopharyngioma (CP) 1 . Additional features such as the spongy squamous epithelium and the presence of cholesterol are frequently observed in CPs in humans 2 .…”