Splenic Hemangiosarcoma in a Young Sprague-Dawley Rat

Abstract

The present report describes a rare case of spontaneous hemangiosarcoma in a nine-week-old male Sprague-Dawley rat. At necropsy, multiple white nodules of various sizes were observed on and within the enlarged spleen and liver and were histopathologically determined to be composed of spindle- to oval-shaped cells that showed invasive growth without encapsulation and were arranged solidly but partially in whorls or faint alveolar patterns with vascular-like spaces containing small clefts or erythrocytes in the tumor mass. Immunohistochemical analysis revealed that most of the tumor cells were strongly positive for vimentin, von Willebrand factor (vWF) and CD34 but negative for podoplanin. In addition, electron microscopic examination revealed the presence of Weibel-Palade bodies in the cytoplasm of the tumor cells. Based on these findings, this case was diagnosed as a hemangiosarcoma. The splenic masses were larger than the hepatic ones, with tumor cells mainly observed at periportal regions with tumor embolism in the liver, suggesting that primary hemangiosarcoma initially developed in the spleen before metastasizing.

Unexpected Toxicology Findings in Rats Dosed With an Antihuman IL-13 Monoclonal Antibody

“…Therefore, the early occurrence of these vascular neoplasms in rats is somewhat unusual although a few isolated incidences of spontaneous angiosarcomas have been reported in rats younger than 10 months of age. 23,24 A number of hypothesis have been proposed for the mechanisms underlying the drug-induced increases in hemangiosarcomas reported for mice. 25 For nongenotoxic agents, these include hypoxia, dysregulated angiogenesis and/or erythropoiesis, macrophage activation, increased angiogenic growth factors, and increased endothelial cell proliferation.…”

Metastatic hemangiosarcoma of the liver in a young rat

“…Narrow spaces contained erythrocytes that were thought to be part of an incomplete blood vessel structure. Reticular fibers that formed in the tumor cells, as documented in another case report of hemangiosarcoma 9 , 10 , could have possibly been a basal membrane formed by vascular endothelia. These findings suggest that the tumor cells had the characteristics of blood endothelial cells, which are the key features of a diagnosis of hemangiosarcoma.…”

“…Spontaneous hemangiosarcoma is a rare tumor, and its incidence in Sprague-Dawley rats is reported to range from 0.3% (female) to 0.4% (male) 7 . There are only a few case reports 8 , 9 on young rats. Although the spleen is reported to be the most frequent site of the primary lesion in rats 7 , the tongue 8 , pancreas 10 , lung 11 , and mesenteric lymph node 12 have also been reported as sites of primary lesions.…”

“…Although the spleen is reported to be the most frequent site of the primary lesion in rats 7 , the tongue 8 , pancreas 10 , lung 11 , and mesenteric lymph node 12 have also been reported as sites of primary lesions. Metastasis is often present 1 , and cases of distant metastasis have also been reported 8 , 9 . In this paper, we report a spontaneous case of metastatic hemangiosarcoma in a young rat and describe histopathological and immunohistochemical features of the tumor.…”

“…Moreover, the foci were all small and multicentrically located mainly in the perilobular region, indicating that the liver lesion was likely formed by hematogenic metastasis. In a case report of metastatic hemangiosarcoma 9 , which developed primarily in the spleen, tumor embolism was mainly observed in periportal regions in the liver. The above report implies the pathogenesis of the liver lesion was hematogenic metastasis.…”