Corneal hemangiosarcoma in a cat

A 10 year-old castrated male Domestic Short-hair cat with a history of chronic bilateral keratitis was referred for assessment of a red, elevated mass involving the left cornea. The rapid growth of the mass, over a month period in combination with pronounced vascularization and invasion of the corneal surface suggested an aggressive inflammatory or neoplastic process. Following keratectomy, the lesion was diagnosed histopathologically as a hemangiosarcoma. The tumor recurred locally within 3 weeks and enucleation was performed. Histopathologic examination of the globe confirmed the diagnosis and did not reveal infiltration of the limbus and conjunctiva. No signs of local recurrence or metastatic disease have been observed 18 months following enucleation. To the authors' knowledge this is the first case of primary corneal hemangiosarcoma described in the feline species.     

大鼠感染微小隐孢子虫后肝、脾和胰腺的病理学变化

60只SPF级SD大鼠随机分成地塞米松免疫抑制感染组和对照组（n=30）,免疫抑制感染组大鼠一次接种1×106个/L微小隐孢子虫卵囊液1mL,空白对照组接种1mL灭菌生理盐水。于试验结束后宰杀大鼠,立即解剖取肝脏、脾和胰腺,Bouin液固定,常规石蜡切片,HE染色,奥林巴斯显微摄影系统观察并显微摄影。结果显示：感染组大鼠肝脏组织肝小叶分界不明显,中央静脉淤血水肿,没有清晰的肝细胞索和肝血窦,呈空泡样病变;肝细胞广泛水泡变性和气球样变,肝血窦充血,肝小叶内有大的纤维性坏死灶。隐孢子虫感染可引起脾脏的脾小结体积变小,边缘区变薄,动脉周围淋巴鞘变薄,脾索变得狭窄、紧缩,脾窦内充血。试验组大鼠的胰腺组织胰岛缩小;内分泌细胞构成的卵圆形细胞团内毛细血管萎缩;胰岛细胞排列紊乱;腺泡细胞溶解变性。     

Spontaneous Mammary Adenocarcinoma in a Twelve-week-old Female Sprague-Dawley Rat

Spontaneous mammary adenocarcinoma was observed in a 12-week-old female SD rat. A movable mass in the right cervical region was found at 11 weeks of age, and the rat was sacrificed the following week. The mass was located in the vicinity of the right salivary gland and measured 38 mm × 26 mm × 16 mm in gross size. It was a firm whitish mass, with a cut surface that was also whitish in appearance. Histopathologically, neoplastic cells formed glandular structures that contained secreted eosinophilic material. Ultrastructurally, similar secreted material and lipid droplets were in the cytoplasm of the neoplastic cells. Immunohistochemically, the neoplastic cells were positive for cytokeratin 8, cytokeratin 18 and estrogen receptor α. Based on these findings, the tumor was diagnosed as a mammary gland adenocarcinoma, and we therefore conclude that this tumor type can occur spontaneously in female SD rats as young as 12 weeks of age.     

Malignant stromal cell tumor of the spleen in a WBN/Kob rat

Primary splenic stromal tumors have rarely been reported in rodents. We report the case of a 90-week-old male WBN/Kob rat with a nodular demarcated mass in the spleen, which was kept as a non-treated animal in a long-term animal study. Histopathology revealed round to short spindle-shaped tumor cells arranged in a solid growth pattern. Invasive growth, anisokaryosis, and high mitotic activity (46 per 10 high-power fields [2.37 mm²]) were observed to be multifocal, but most tumor cells showed mild nuclear pleomorphism. The pattern of silver impregnation corresponded to that of the marginal zone of the red pulp. Immunohistochemistry revealed that the tumor cells were double positive for fascin and desmin and focally positive for Iba-1 and OX-6 expression. These characteristics were similar to those observed in fibroblastic reticular cells and dendritic cells in the marginal zone of the red pulp. These findings suggest that the malignant stromal cell tumor of the spleen in this case had characteristics of both fibroblastic reticular cells and dendritic cells.     

Spontaneous cholangiofibrosis adjacent to a dilated common bile duct with intestinal metaplasia in a Royal College of Surgeons rat

A 130-week-old male Royal College of Surgeons rat kept as a non-treated animal in a long-term animal study presented with a mass in the hepatic portal region that adhered to a dilated common bile duct and the duodenum. Histopathologically, the solitary mass showed expansive growth with no apparent compression and continued to dilate the common bile duct, which had a hyperplastic epithelium with intestinal metaplasia. The mass mainly consisted of small to large dilated and/or tortuous ducts with abundant dense connective tissue and many inflammatory cells. The single-layer lining epithelium of the duct changed from cuboidal to columnar. Immunohistochemically, the lining cells were positive for cytokeratin 7, cytokeratin 19, and OV-6, which are bile duct markers. Based on the pathological characteristics, the rat was diagnosed as spontaneous cholangiofibrosis adjacent to a dilated common bile duct with intestinal metaplasia.     

Spontaneous well-differentiated pancreatic islet cell carcinoma with vascular invasion in a male F344 rat

This case report describes a case of spontaneous pancreatic islet cell carcinoma with vascular invasion in a 110-week-old male F344 rat. Histologically, a pancreatic nodule consisting of tumor cells and many blood-rich vessels, and covered with a fibrous capsule showed local invasion in the capsule and adjacent acinar tissues, encircling a large duct-like structure (DS). The tumor was composed of well-differentiated tumor cells resembling normal pancreatic islet cells, which had small round nuclei and eosinophilic cytoplasm. Mitotic figures were rare. Immunohistochemistry revealed that the tumor cells were positive for insulin. Although endothelial cells were not detected, the DS wall showed cells positive for α-smooth muscle actin and elastic fibers, suggesting that the DS is the pancreatic artery. This is a rare case of islet cell carcinoma consisting of well-differentiated tumor cells with invasion of the pancreatic artery in a rat.     

Splenic Hemangiosarcoma in a Young Sprague-Dawley Rat

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.     

Spontaneous thymoma in a 10-week-old sprague-dawley rat

Spontaneous thymoma was found in the left lobe of the thymus of a male 10-week-old Sprague-Dawley (SD) rat. Microscopically, the thymic mass showed a sheet of dark area with multiple pale foci. The dark area mainly consisted of densely compacted small lymphoid cells with sporadic large epithelioid cells and mitotic figures. The epithelioid cells and mitotic figures were more frequent than those of the normal thymic cortex in this animal. The multiple pale foci were similar to the normal thymic medulla and occasionally had Hassall's corpuscles; thus, they were regarded as medullary differentiation areas. Furthermore, some perivascular spaces recognized as characteristics of thymoma were present in the center of the mass. Immunohistochemically, the epithelioid cells in the dark area were positive for cytokeratin. Ultrastructurally, desmosomes and tonofilaments were observed in the epithelioid cells. Thus, this tumor was diagnosed as a thymoma. This is a rare case of thymoma occurring spontaneously in young adult SD rat.     

Dynamic left ventricular outflow tract obstruction secondary to hypovolemia in a German Shepard dog with splenic hemangiosarcoma

Dynamic left ventricular outflow tract obstruction (DLVOTO) is a common condition in cats and humans. In this case report, a dog is described with DLVOTO secondary to severe intra-abdominal hemorrhage caused by a hemangiosarcoma. The dog was a 9-year-old, 35.7-kg, spayed female German Shepard dog that presented with a history of tachypnea and collapse. A Levine II/VI systolic murmur was present at the heart base. Abdominal ultrasonography revealed a splenic mass and a large amount of ascites. Echocardiography showed a reduced left ventricular diameter and an increased aortic velocity caused by systolic anterior motion (SAM) of the mitral valve apparatus. The heart murmur and the SAM were resolved after treatment including a splenectomy and a blood transfusion.     

Identification of drug‐resistant subpopulations in canine hemangiosarcoma

Canine hemangiosarcoma is a rapidly progressive disease that is poorly responsive to conventional chemotherapy. Despite numerous attempts to advance treatment options and improve outcomes, drug resistance remains a hurdle to successful therapy. To address this problem, we used recently characterized progenitor cell populations derived from canine hemangiosarcoma cell lines and grown as non‐adherent spheres to identify potential drug resistance mechanisms as well as drug‐resistant cell populations. Cells from sphere‐forming cultures displayed enhanced resistance to chemotherapy drugs, expansion of dye‐excluding side populations and altered ATP‐binding cassette (ABC) transporter expression. Invasion studies demonstrated variability between cell lines as well as between sphere and monolayer cell populations. Collectively, our results suggest that sphere cell populations contain distinct subpopulations of drug‐resistant cells that utilize multiple mechanisms to evade cytotoxic drugs. Our approach represents a new tool for the study of drug resistance in hemangiosarcoma, which could alter approaches for treating this disease.     

Spontaneous Pulmonary Hemangiosarcoma in a Norway Rat (Rattus norvegicus)

A second parity, 1-year-old female Norway rat (Rattus norvegicus) presented for veterinary evaluation 5 weeks postpartum with a progressively decreased appetite, weight loss, lethargy, and labored breathing. On physical examination, the animal was in fair body condition, dyspneic, and dehydrated. Owing to a poor prognosis, the owner opted for palliative care for the animal, declined further diagnostic testing, and requested for the rat to be discharged from the hospital. The following day the animal was found dead in its cage, and the body was submitted for necropsy. Gross observations included numerous, variably sized, soft, dark red pulmonary nodules concurrent with hemothorax and hemopericardium. Microscopically, the pulmonary architecture was effaced by nodules of variably sized, irregular, vascular channels lined with neoplastic endothelial cells. The cytoplasm of neoplastic cells in the lung was immunohistochemically positive for von Willebrand factor (i.e., factor VIII–related antigen) and was more intensively and more often positive for vascular endothelial growth factor as compared with nonneoplastic cells. Ultrastructurally, vascular channels were formed by spindloid neoplastic cells with elongated, fused, and interdigitated processes. Based on these findings, a diagnosis of spontaneous pulmonary hemangiosarcoma was made in this Norway rat.     

Comparison of doxorubicin–cyclophosphamide with doxorubicin–dacarbazine for the adjuvant treatment of canine hemangiosarcoma

Canine hemangiosarcoma (HSA) is a neoplasm of vascular endothelial origin that has an aggressive biological behaviour, with less than 10% of dogs alive at 12‐months postdiagnosis. Treatment of choice consists of surgery followed by adjuvant doxorubicin‐based chemotherapy. We prospectively compared adjuvant doxorubicin and dacarbazine (ADTIC) to a traditional doxorubicin and cyclophosphamide (AC) treatment, aiming at determining safety and assessing whether this regimen prolongs survival and time to metastasis (TTM). Twenty‐seven dogs were enrolled; following staging work‐up, 18 were treated with AC and 9 with ADTIC. Median TTM and survival time were longer for dogs treated with ADTIC compared with those receiving AC (>550 versus 112 days, P = 0.021 and >550 versus 142 days, P = 0.011, respectively). Both protocols were well tolerated, without need for dose reduction or increased interval between treatments. A protocol consisting of combined doxorubicin and dacarbazine is safe in dogs with HSA and prolongs TTM and survival time.     

Diagnosis of a large splenic tumor in a dog: computed tomography versus magnetic resonance imaging

This study demonstrated magnetic resonance imaging (MRI) and computed tomography for large-sized splenic hemangiosarcoma. Radiography and ultrasonography revealed the presence of a large-sized soft-tissue mass in the cranial abdomen. Computed tomography showed hypoattenuating mass. The mass was located in contact with liver, spleen and stomach, and the origin of the mass remained ambiguous. The mass was T2-hyperintense and T1-hypointense with mild contrast enhancement. MRI allowed a differentiation between large-sized tumor and neighboring normal structure, and the mass was consequently identified as arising from spleen. These results suggested that MRI might be a useful tool to visualize large-sized splenic tumors and improve the accuracy of diagnosis.     

Occurrence of Spontaneous Tumors in the Central Nervous System (CNS) of F344 and SD Rats

In order to accurately assess the carcinogenicity of chemicals with regard to rare tumors such as rat CNS tumors, sufficient information about spontaneous tumors are very important. This paper presents the data on the type, incidence and detected age of CNS tumors in F344/DuCrlCrlj (a total of 1363 males and 1363 females) and Crl:CD(SD) rats (a total of 1650 males and 1705 females) collected from in-house background data-collection studies and control groups of carcinogenicity studies at our laboratory, together with those previously reported in F344 and SD rats. The present data on F344/DuCrlCrlj rats (F344 rats) and Crl:CD(SD) rats (SD rats) clarified the following. (1) The incidences of all CNS tumors observed in F344 rats were less than 1%. (2) The incidences of malignant astrocytoma and granular cell tumor were higher in male SD rats than in female SD rats. (3) The incidences of astrocytoma and granular cell tumor were higher in SD rats than in F344 rats. (4) Among astrocytoma, oligodendroglioma and granular cell tumor, oligodendroglioma was detected at the youngest age, followed by astrocytoma, and ultimately, granular cell tumor developed in both strains. The incidences observed in our study were almost consistent with those previously reported in F344 and SD rats.     

Canine conjunctival hemangioma and hemangiosarcoma: a retrospective evaluation of 108 cases (1989-2004)

Canine conjunctival tumors of vascular endothelial origin are common, although under-reported. The purpose of this study was to evaluate the epidemiology of and potential risk factors for these tumors. This study evaluated 108 cases (70 hemangiomas, 38 hemangiosarcomas) from 8300 canine submissions between 1989 and 2004. Signalment, location, pigmentation, size, duration, diagnosis, margins, ancillary therapy, and geographic location were recorded. Follow-up information was available for 49 cases. Each case was matched with two unaffected controls and compared using logistic regression analysis. Average age upon presentation was 8.6 years; there was no sex predilection. Risk of conjunctival tumors was statistically different among breed groups (P = 0.0010), demonstrating a propensity to occur in groups likely to have increased outdoor activity. Primary involvement occurred within nonpigmented epithelium along the leading edge of the nictitating membrane (41/108) and temporal bulbar conjunctiva (33/108). The etiology remains unknown; however, the strong site predilection, involvement of nonpigmented epithelium, and development within specific breed classes strongly suggest ultraviolet (UV) light as a significant risk factor. In a full-logistic model including breed, gender, age, and UV exposure, UV was not a statistically significant variable (P = 0.1215). In a reduced-model including UV only, significance was approached (P = 0.0696) and posthoc contrast demonstrated a significant linear trend with increasing UV exposure (P = 0.0147). In separate analysis of risks associated with hemangiosarcoma, compared with hemangioma, breed was not significant while increasing UV exposure was significant (P = 0.0381). Early surgical therapy is recommended and may be curative; however, recurrence is possible and more likely with hemangiosarcomas (11/20).     

Feline conjunctival hemangioma and hemangiosarcoma: a retrospective evaluation of eight cases (1993-2004)

The purpose of this retrospective study was to evaluate feline primary conjunctival vascular tumors of endothelial origin. Eight cases (six hemangiomas, two hemangiosarcomas) from a collection of 3460 feline submissions between 1993 and 2004 were evaluated using routine hematoxylin and eosin (H&E). Signalment, location, size, duration, epithelial pigmentation, margins, adjuvant therapy, outdoor activity, and geographic location, comparing ultraviolet (UV) radiation levels by state, were recorded. Follow-up information was available for five cases. In this study, the average age was 10.6 years, with neutered males over-represented. The Domestic Short-haired cat was most commonly affected. The most common anatomic site was the nictitating membrane, with the left eye preferentially affected. The average size and duration, prior to presentation, was 7.5 mm and 4.4 months, respectively. Seven of eight cases were devoid of epithelial pigmentation in nonaffected areas and the majority of cases were from states with high annual UV-light exposure. Only cases of hemangiosarcoma underwent surgical re-excisions following incomplete excision; however, no further recurrences were reported. No cases evaluated had evidence of metastatic disease at the time of excision. Surgical excision alone may be curative. However, recurrence is possible. These tumors demonstrate similar predilection sites and involvement of nonpigmented epithelium, as is true in canine cases, which may relate to risk factors as well.     

Mast cell and plasma cell collision tumor in the spleen of a dog

A 9‐year‐old spayed female English Mastiff was referred for outpatient ultrasound due to a 3‐week history of weight loss, vomiting, and decreased appetite. Abdominal ultrasound showed multiple splenic masses of varying sizes and serum chemistry panel showed hyperglobulinemia. Cytologic examination of fine‐needle aspirates of the splenic masses indicated a mast cell and plasma cell collision tumor. Results of serum and urine protein electrophoresis and immunofixation indicated the plasma cell neoplasia was producing IgA immunoglobulins.     

Spontaneous adenolipoma of the mammary gland in the male F344 rat

A 110-week-old male F344 rat from the high-dose group of a 104-week carcinogenicity study, exhibited a spontaneously occurring subcutaneous mass in the left axilla extending to the chest. Histologically, the mass was well-demarcated from the adjacent mammary tissue and slightly encapsulated without evidence of infiltration into the surrounding tissues. The mass contained both epithelial and adipose components. The epithelial component consisted of ductal structures of various sizes lined by a single layer of flattened to cuboidal epithelial cells with relatively clear or vacuolated cytoplasm. These ductal structures were well-intermingled with an adipose component that consisted of a uniform monomorphic cell population of mature adipocytes. Both cell types were well-differentiated and did not exhibit cellular atypia. Within the mass, fibrous connective tissue was found in the stroma with infiltration of numerous mast cells. Based on these findings, the mass was diagnosed as an adenolipoma of the mammary gland.     

A case of spontaneous rete testis adenoma in a Sprague–Dawley rat

A 104-week-old male CD (SD) rat exhibited enlargement of the left testis. Microscopically, this mass was demarcated from the testis by fibrous connective tissue and characterized by cystic dilatation with single-layered columnar cells and papillary proliferation connected to the solid growth area without clear boundaries. In the solid growth area, cells were dissected into irregular alveolar nests by scant fibrous tissue with small blood vessels. The nuclei of proliferating cells were variable in size and round- to oval-shaped, and their cytoplasm was pale or eosinophilic and sometimes contained vacuoles or eosinophilic granules. Immunohistochemically, the tumor cells were positive for vimentin and cytokeratin (CK) 7. Since CK7 was exclusively positive in the rete testis epithelium of the naïve rat, it was valuable to diagnose this tumor as rete testis-originated. Based on these results and the lack of apparent pleomorphism, mitotic figures, and metastasis, the present case was diagnosed as rete testis adenoma.     

A spontaneously occurring malignant ovarian Sertoli cell tumor in a young Sprague Dawley rat

Primary ovarian tumors are generally uncommon in rats used in toxicologic studies. A malignant Sertoli cell tumor was present in the ovary of a 19-week-old female Sprague Dawley rat. Macroscopically, the mass was white and firm, 10 × 13 × 17 mm in size, and located in the right ovary. Histopathologically, the mass was composed of nests of pleomorphic cells, which formed seminiferous-like tubules separated by a thin fibrovascular stroma. The tubules were lined by tumor cells, which had basally located nuclei and abundant eosinophilic and vacuolated cytoplasm. In some areas, the tumor cells were arranged in a retiform growth pattern, mimicking a rete testis/ovarii. Disseminated metastases to the surfaces of the mesentery, spleen and liver were also present. Immunohistochemically, many tumor cells were strongly positive for vimentin, estrogen receptor α and Ki 67. Some tumor cells were positive for pancytokeratin and inhibin α. These findings closely resemble those of an ovarian-derived human malignant Sertoli cell tumor. From our review of the literature, we believe this is the first report of a spontaneous malignant Sertoli cell tumor in the ovary of a young laboratory rat. This case might provide useful historical control information for rat toxicity studies.