Malignant schwannoma of the intracranial trigeminal nerve in a 19-week-old female sprague-dawley rat.

Yoshizawa, Katsuhiko; Oishi, Yuji; Makino, Natsuyo; Suzuki, Junya; Matsumoto, Masahiro; Yamauchi, Kenji; Fujihira, Shiro; Fujii, Toshiyuki

doi:10.1293/tox.9.107

Cited by 8 publications

(5 citation statements)

References 15 publications

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“…The incidence of spontaneous intracranial tumors is very low in rats, with the exception of pituitary neoplasms 1 , 2 . Spontaneous tumors of the pituitary gland are one of the most common neoplasms in aging Sprague-Dawley (SD) rats, with most pituitary tumors arising from the pars distalis.…”

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A spontaneously occurring malignant pituicytoma in a male sprague dawley rat

et al. 2015

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Pituicytoma is an extremely rare neoplasm derived from pituicytes, which are glial cells in the posterior lobe of the pituitary gland. A malignant pituicytoma was found in the intracranial cavity of a 55-week-old male Sprague-Dawley rat. Macroscopically, the tumor was located on the sphenoid bone and involved the pituitary gland. The tumor was composed of sheets of fusiform cells with spindle- or pleomorphic-shaped nuclei and abundant eosinophilic cytoplasms. The cells were arranged in a whirling or irregular growth pattern. Some tumor cells were bizarre multinucleated giant cells with cytoplasmic eosinophilic hyaline droplets. Many tumor cells were strongly positive for vimentin and glial fibrillary acidic protein, and some cells were positive for ED-1 and S-100. These findings closely resembled those of a giant cell glioblastoma derived from the pituitary gland, suggesting anaplastic pituicytoma. From our review of the literature, we believe this is the first report of a spontaneous malignant pituicytoma in a rodent.

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A spontaneously occurring malignant pituicytoma in a male sprague dawley rat

et al. 2015

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“…Sequential sections of nodules were stained with periodic acid Schiff (PAS). Immunohistochemistry was performed with antibodies to proliferating cell nuclear antigen (PCNA) to detect the proliferative activity 14 , pancytokeratin (CK) as an epithelial cell marker, vimentin as a mesenchymal cell marker 15 , the common acute lymphoblastic leukemia antigen 10 (CD10) as a uterine interstitial cell marker 16 , α-smooth muscle actin (SMA) and desmin as muscular cell markers 15 , S-100 as a Schwann cell and adipocyte marker 17 , and estrogen receptor α (ER) and progesterone receptor (PgR) to detect steroid hormone receptors 18 . Detailed staining protocols for all antibodies are listed in Table 1…”

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Histopathological and Immunohistochemical Characterization of Spontaneously Occurring Uterine Deciduomas in Young Adult Rats

et al. 2013

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Uterine deciduomas were found in two female virgin rats, a 15-week-old Lewis rat and a 7-week-old Sprague-Dawley rat. The firm white nodules were located at the base of unilateral uterine horns and were approximately 6 mm and 4 mm in diameter. Histopathologically, the nodules were composed of three areas, each with a distinct type of proliferating cells: large epithelioid decidual cells with round nuclei, prominent nucleoli and abundant eosinophilic cytoplasm (antimesometrial region); compact spindle-shaped cells with oval nuclei and vacuolar cytoplasm (transitional region); and pleomorphic and spiny cells with round to oval nuclei and compact eosinophilic cytoplasm (mesometrial region). These cells proliferated in sheet-like arrangements and transformed into the other types of cells located in surrounding regions. Immunohistochemically, proliferating cells in all regions were strongly positive for proliferating cell nuclear antigen. The proliferating cells were positive for vimentin, and large decidual cells were positive for common acute lymphoblastic leukemia antigen 10, a marker of uterine interstitial cells. Large decidual cells were positive for α-smooth muscle actin and desmin, suggesting differentiation into muscular cells. Progesterone receptor was expressed in all cell types; however, estrogen receptor α was not expressed in the antimesometrial region. These extremely rare tumor-like nodules represent nonneoplastic lesions referred as decidual reactions of endometrial interstitial cells, and their biological behavior is that of a space-occupying benign tumor in young rats. Our cases might provide information as a historical control in toxicity and pharmacological studies in rats.

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“…There were no incidences of schwannoma in similarly aged historical control rats at the test facility. However, based on reports of schwannoma in younger rats 27,28 and the single occurrence in the 6-month study, this finding was considered incidental.…”

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Regulatory Experience Assessing the Carcinogenic Potential of a Monoclonal Antibody Inhibiting PCSK9, Bococizumab, Including a 2-Year Carcinogenicity Study in Rats

et al. 2022

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Bococizumab is an anti-PCSK9 monoclonal antibody that was intended for the treatment of hypercholesterolemia. After reviewing the 6-month rat toxicity study data, in which there was a low spontaneous tumor incidence, unrelated to bococizumab administration, the U.S. FDA granted a carcinogenicity waiver request based on a weight-of-evidence assessment of low carcinogenic risk. Subsequently, after reviewing 6-month rat toxicity study data from another anti-PCSK9 antibody, RN317, with a similar low tumor incidence (unrelated to RN317), the U.S. FDA rescinded the bococizumab carcinogenicity study waiver and requested a full 2-year rat carcinogenicity study be conducted. The resulting 2-year carcinogenicity study demonstrated no bococizumab-related increase in tumors, confirming the weight-of-evidence evaluation and alleviating concerns regarding the carcinogenic potential. Here we report the scientific and regulatory background that led to the request for a rat carcinogenicity study, the feedback on the design of the carcinogenicity study, and the results from this study which affirmed the original weight-of-evidence assessment of low carcinogenic risk.

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Malignant schwannoma of the intracranial trigeminal nerve in a 19-week-old female sprague-dawley rat.

Abstract: Light microscopic, histochemical and ultrastructural observations were conducted to examine a

Cited by 8 publications

References 15 publications

A spontaneously occurring malignant pituicytoma in a male sprague dawley rat

A spontaneously occurring malignant pituicytoma in a male sprague dawley rat

Histopathological and Immunohistochemical Characterization of Spontaneously Occurring Uterine Deciduomas in Young Adult Rats

Regulatory Experience Assessing the Carcinogenic Potential of a Monoclonal Antibody Inhibiting PCSK9, Bococizumab, Including a 2-Year Carcinogenicity Study in Rats

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