Cutaneous Hemangiosarcoma in a Dog

A male golden retriever of unknown age presented with multiple cutaneous and subcutaneous masses from the left elbow to the digits. Histopathologically, multiple tumor foci had formed from the dermis to the subcutaneous tissue. Tumor foci consisted of a vascular structure, alveolar structure and solid proliferative area. The borders among these areas were not clear. Some neoplastic cells resembled a mature endothelium, while others were large pleomorphic cells. Immunohistochemically, the tumor cells were usually strongly positive for CD31 and often positive for PROX-1, the lymphatic endothelial cell marker. Based on these findings, the tumor was diagnosed as a hemangiosarcoma with lymphatic differentiation.     

Phenotypic characterization of normal and neoplastic canine endothelial cells by lectin histochemistry

Cell surface glycoconjugate expression of endothelial cells in canine cutaneous hemangiomas and hemangiosarcomas was compared to normal cutaneous endothelial cells using eight different lectins (with and without neuraminidase pretreatment) in an indirect immunoperoxidase technique. Direct comparison of lectin binding pattern of neoplastic endothelial cells with adjacent normal endothelial cells revealed minor changes in the binding intensity of several lectins (enhanced: Wheat germ agglutinin [WGA]; reduced: Griffonia simplicifolia-I [GS-I], Ricinus communis agglutinin-I [RCA-I], Soybean agglutinin after neuraminidase pretreatment [Neu-SBA], and Wheat germ agglutinin after neuraminidase treatment [Neu-WGA]). Neoplastic endothelial cells in some tumors exhibited varying binding of Ulex europaeus agglutinin-I (UEA-I; not binding to normal canine endothelial cells) and no Soybean agglutinin (SBA) binding (variably binding to normal endothelial cells in small cutaneous vessels). Lectin binding of neoplastic cells was rather heterogenous within one tumor compared to the uniform binding pattern of normal endothelial cells. These lectin binding studies demonstrate the phenotypic heterogeneity of neoplastic endothelial cells, indicating changes of cell surface glycosylation during neoplastic transformation.     

Soft tissue sarcomas in the African hedgehog (Atelerix albiventris): microscopic and immunohistologic study of three cases.

Three soft tissue tumors from 2 female hedgehogs were examined microscopically and immunohistochemically. Two tumors involved haired skin and the third one was vaginal. Microscopically, the cutaneous tumors had features of malignant peripheral nerve sheath tumor (MPNST), whereas the vaginal tumor was classified only as a spindle cell sarcoma. Immunohistochemically, all 3 tumors were strongly positive for vimentin and strongly to moderately positive for CD10 and neuron-specific enolase but did not stain with antibody to S100 protein, an antigen typically present in human MPNST The cutaneous tumor from hedgehog no. 1 was examined ultrastructurally and the neoplastic cells resembled fibroblasts. Hedgehog no. 1 was euthanized at the time of the biopsy. The outcome of the other hedgehog was unknown.     

Intramedullary hemangioblastoma in a dog

A 6-year-old male Pointer dog was presented with a 4-week history of progressive hind-limb stiffness. Magnetic resonance imaging demonstrated a focal intramedullary lesion at T1 level with a pattern of ring contrast enhancement. At necropsy, a circumscribed intramedullary reddish-gray tumor was observed. Microscopically, the tumor was composed of thin-walled capillaries lined by endothelial cells and separated by pleomorphic cells (stromal cells) with a moderate degree of anisokaryosis. Immunohistochemically, the endothelial cells were positive for factor VIII-related antigen and the stromal cells were positive for neuron-specific enolase and vimentin. GFAP-positive astrocytes were occasionally observed within the tumor. Both endothelial and stromal cells were negative for synaptophysin, S-100 protein, pankeratin, smooth muscle actin, CD34, CD68, alpha1-antichymotrypsin, and lysozyme. The tumor showed considerable morphologic and immunohistochemical similarities with human hemangioblastoma, and hence the inclusion of this tumor type within the primary neoplasms of the canine central nervous system is suggested.     

Alkaline phosphatase reaction of canine mammary mixed tumours: a light and electron microscopic study

Alkaline phosphatase (ALK-P) reactions at the light and electron microscopic levels were performed on eight canine mammary mixed tumours. In the morphologically normal gland next to the tumours, the myoepithelial cells and the stromal tissues near the acinar basement membranes both showed a positive ALK-P reaction by light microscopy. At the electron microscopic level, those parts of the myoepithelial cell membrane that were in contact with other cells--myoepithelial or lumenal epithelial--showed an ALK-P-positive reaction, as did the adjacent stromal tissue. The characteristic tumour cells, at sites of early proliferation, were ALK-P-positive, while in the mucoid and chondroid areas of the mixed tumours they were largely ALK-P-negative by light microscopy. By electron microscopy, those neoplastic cells which were in contact with other cells typically showed a positive ALK-P reaction, while those cells which were in contact with mucoid or chondroid matrix were largely negative. Although the cytoplasmic filaments of the neoplastic cells were 10 nm thick, and those of normal myoepithelial cells were 6 to 8 nm thick, the observations reported provide further evidence for the view that the essential cells of the canine mammary mixed tumour are derived from myoepithelial cells.     

The pagetoid variant of urothelial carcinoma in situ of urinary bladder in a cow

A case of urothelial carcinoma in situ of urinary bladder is reported in a 10-year-old cow naturally grazing on bracken-infested land. The cow suffered from enzootic hematuria for more than 5 years. The presence of bovine papillomavirus type 2 (BPV-2) DNA sequences was detected by polymerase chain reaction. The carcinoma in situ was characterized by the presence of anaplastic cells with amphophilic cytoplasm and pleomorphic nuclei containing granular, irregularly dispersed chromatin. Focal areas within the tumor contained large isolated and/or clustered cells. These cells had pale acidophilic cytoplasm, large nuclei with single or multiple nucleoli, and well-defined borders resembling Paget's cells. Immunohistochemically, all malignant cells were negative for vimentin and S-100 and positive for cytokeratins. In addition, normal and neoplastic cells expressed fragile histidine triad (FHIT) protein; surprisingly, some pagetoid cells did not. FHIT, the tumor suppressor gene at 3p14.2, encodes a protein of 147 amino acids (16.8 kd) with diadenosine triphosphate hydrolase activity and is a common target of deletions in human cancers of epithelial origin. Antibody to laminin detected a continuous epithelial basement membrane, thus clearly showing that neoplastic changes were limited to urothelial cells without invading stromal tissue. To our knowledge, this is the first report of an unusual pattern of spread of urothelial carcinoma in situ in a cow.     

Presumed primary ocular lymphangiosarcoma with metastasis in a miniature horse

A 7‐year‐old, 153.0‐kg American Miniature mare presented for evaluation of keratoconjunctivitis of the right eye (OD). A superior palpebral conjunctival mass and stromal keratitis were diagnosed. The incisional biopsy diagnosis was a presumptive corneal hemangiosarcoma. Transpalpebral enucleation was performed, and histopathologic evaluation confirmed angiosarcoma of the conjunctiva, cornea, and extraocular muscles. The horse developed progressive epistaxis and orbital swelling following surgery. A systemic workup was performed 3 months after enucleation, revealing regrowth within the orbit and marked cranial cervical lymphomegaly, suggestive of metastasis. Humane euthanasia was performed, and necropsy confirmed a locally invasive periorbital tumor with metastasis to the submandibular tissue, submandibular lymph node, and thoracic inlet. Histopathologic evaluation of necropsy specimens revealed polygonal to spindle neoplastic cells lining neoplastic vascular channels lacking erythrocytes. Immunohistochemically, the neoplastic cells labeled strongly positive for PROX‐1, vimentin, CD‐31, VEGF, weakly positive for factor VIII‐related antigen, and negative for collagen IV. Based on the clinical, histological, and immunohistochemical features of this tumor, a primary ocular lymphangiosarcoma with metastasis was diagnosed.     

Nasal tumor with widespread cutaneous metastases in a Golden Retriever

An intact, 8-year-old, male Golden Retriever dog was presented for evaluation of a nasal mass and approximately 30 firm, raised, variably ulcerated dermal and subcutaneous masses. Histopathology of both nasal and multiple skin masses revealed multiple nonencapsulated, infiltrative masses comprising clusters, anastomosing trabeculae, and packets of neoplastic, round to ovoid, hyperchromatic cells with marked nuclear molding. Surrounding the neoplastic cells was a marked stromal response in which many of the spindle-shaped cells expressed muscle-specific actin and had ultrastructural features consistent with myofibroblasts. A literature search indicates that this is the first report in a peer-reviewed journal of cutaneous metastasis of a nasal neuroendocrine tumor in any domestic animal species.     

Extensive cutaneous metastases in a dog with duodenal adenocarcinoma

Abstract: A 6-year-old Rottweiler was presented to the North Carolina State University College of Veterinary Medicine for evaluation of multiple cutaneous nodules. The dog had a history of anorexia, vomiting, and hind-limb paraplegia. Results of cytologic examination of the cutaneous nodules were consistent with a round cell tumor. At necropsy, primary tumors were found coalescing in the duodenum and the pancreas and extending into the associated mesentery. Numerous masses also were found throughout the skin, abdominal and thoracic viscera, and lumbar spinal cord. Histologically, the duodenal tumor had variable morphology, with some areas resembling adenocarcinoma and others resembling anaplastic round cell neoplasia; the skin and other metastatic lesions resembled round cell neoplasia. Immunohistochemistry of the cutaneous, duodenal, and pancreatic masses showed the neoplastic cells were positive for pancytokeratin, supporting an epithelial origin. In addition, low numbers of neoplastic cells were positive for periodic acid-Schiff and Alcian blue, consistent with acid mucin production by duodenal epithelium. These findings confirmed that the cutaneous nodules were metastatic lesions originating from the duodenal adenocarcinoma. Cutaneous metastasis of intestinal carcinoma is rare in domestic animals. This case demonstrates the potential difficulty in diagnosing metastatic lesions based on cytologic and histologic morphology alone, because the cutaneous metastases may not resemble the primary neoplasm morphologically.     

Identification of matrix metalloproteinases in canine neoplastic tissue

OBJECTIVE: To identify matrix metalloproteinases (MMP) 2 and 9 in canine tumor tissue and to compare the amount of activity to that in unaffected stromal tissue. ANIMALS: 30 dogs with spontaneously developing, high-grade osteosarcoma. PROCEDURE: Tumor and nearby stromal tissue (muscle) were obtained at the time of surgery. Specimens were homogenized, and supernatants were assayed, using gelatin zymography. Human derived standards were run concurrently. Densitometry was done to obtain a semiquantitative arbitrary unit value for each specimen. The amount of activity in tumor tissue was compared with the amount in stromal tissue. RESULTS: Gelatinolytic bands were observed from the analysis of all tumor tissues and in most stromal tissues. These bands migrated in the same molecular weight area as the human MMP 2 and 9 standards. Gelatinolytic activity could be quenched by the addition of 50 mM EDTA and 1 microg of synthetic tissue inhibitor of metalloproteinase (TIMP) 2 per 100 ml. There was significantly more gelatinolytic activity in tumor tissue than in stromal tissue. CONCLUSIONS AND CLINICAL RELEVANCE: MMP 2 and 9 are detectable in canine neoplastic tissue. Matrix metalloproteinases activity in tumor tissue is higher than in unaffected stromal tissue, indicating that canine MMP may be involved in the pathogenesis of tumor growth and metastasis.     

Extramedullary plasmacytoma in a horse with ptyalism and dysphagia.

A Clydesdale mare was examined for weight loss, inappetence, ptyalism, and dysphagia. The main abnormality revealed by serum biochemistry was a marked hyperglobulinemia, and protein electrophoresis revealed a monoclonal gammopathy in the gamma region. The urine was positive for Bence Jones proteins. These findings suggested a plasma cell tumor. The neoplasm could not be located with extensive antemortem examination. At postmortem, neoplastic cells morphologically compatible with plasma cells and positive for equine IgG with imunoperoxidase staining infiltrated the pericardium, mediastinal stromal tissues, adrenal glands, meninges, atrioventricular valves, aorta, abdominal and thoracic fat, and nerves, including the trigeminal nerve. The neoplastic cells invading the cranial nerves were responsible for many of the presenting signs.     

Spontaneous hemangiosarcoma in the spleen and liver of a young rat

Spontaneous hemangiosarcoma in young rats is rare. In this report, we describe a case of a spontaneous hemangiosarcoma in the spleen and liver of young rats. At necropsy, multiple pale red masses were observed in the spleen. Histopathologically, solid growth and haphazardly arranged neoplastic cells were observed, although no characteristic growth pattern was observed. In contrast, irregularly sized small slit-shaped spaces containing erythrocytes were found among the neoplastic cells. Reticular fibers incompletely surrounding the neoplastic cells were observed by silver staining. Immunohistochemistry revealed that the neoplastic cells were positive for vWF and CD34. Electron microscopic examination revealed that the neoplastic cells had erythrocytes in the lumen and Weibel-Palade bodies in the cytoplasm and were arranged along a discontinuous basal lamina. These features indicate that the tumor originated from vascular endothelial cells. Based on these results, the tumor was diagnosed as a hemangiosarcoma in the spleen and liver.     

Cutaneous melanoma in a red-footed tortoise (Chelonoidis carbonaria)

There are few clinical reports of melanomas in reptiles. A 10-year-old male red-footed tortoise (Chelonoidis carbonaria) was referred to the Veterinary Hospital presenting with an ulcerated mass in the lateral aspect of the left pelvic limb. Radiographs demonstrated swelling and increased soft tissue density overlying the femur, tibia, and fibula, without bone involvement. Fine-needle aspiration cytology revealed innumerable round cells, with a defined cytoplasm filled with fine brown-black granules (melanin), which were considered well-differentiated melanocytes, suggesting a case of cutaneous melanoma. The mass was surgically removed. It was encapsulated and had an abundant blood supply. Histopathological examination revealed a well demarcated and encapsulated neoplastic proliferation of mesenchymal cells, with high cellularity and moderate fibrous stroma. Lymphangiectasia in the dermis adjacent to the tumor was also observed. Immunohistochemistry confirmed the diagnosis, with cells staining positive for Melan-A antibody being observed in neoplastic proliferation, adjacent dermis, inside lymphatic vessels, and invading the delimiting tumor's capsule. There was no evidence of local or systemic recurrence of the neoplasm over 500 days after removal. Chelonians can be affected by cutaneous melanomas. Surgical removal in this case was curative.     

Morphologic characteristics of a transplantable tumor derived from a spontaneous malignant fibrous histiocytoma in the rat

Malignant fibrous histiocytoma (MFH) developed spontaneously in subcutaneous tissue of the head of a 15-month-old male Fischer 344 rat. The tumor was serially transplanted into syngeneic rats up to the 45th generation and was designated MFH-MT. Light and electron microscopic examinations revealed that the original and serially transplanted tumors were composed of an admixture of fibroblast-like and histiocyte-like cells arranged in a storiform pattern. Neoplastic cells gave positive reactions for acid phosphatase, alkaline phosphatase, nonspecific esterase, alpha-1 antitrypsin and lysozyme. The tumors transplanted into the lungs and cutaneous tissue of the tail had a mixed histologic appearance of storiform, pleomorphic, myxoid and giant cell types. Moreover sclerosing hemangioma-like and osteosarcoma-like structures were also found. MFH-MT grew well in athymic nude mice showing neoplastic proliferation of pleomorphic cells strongly positive for alpha-1 antitrypsin. Development of MFH-MT was significantly retarded by the two antitumor drugs tested. The retarded tumors consisted predominantly of fibroblast-like cells and abundant collagenic fibers, whereas histiocytic cells decreased in number.     

Histological and immunohistochemical features of cutaneous mast cell tumor in six captive four-toed hedgehogs (Atelerix albiventris)

This report described the histopathological and immunohistochemical features of cutaneous mast cell tumor (MCT) in six hedgehogs. The hedgehogs presented single cutaneous mass with ulcer and crusting. Histologically, the neoplastic lesions were characterized by the proliferation of well-differentiated mast cells (3 cases), and atypical mast cells (3 cases) with one atypical histiocytic morphology. Immunohistochemically, tumor cells were positive for KIT and mast cell tryptase, and were negative for Iba-1. In well-differentiated MCT, all patients were clinically improved and survived more than 365 days after surgical excision, whereas an atypical histiocytic MCT showed aggressive behavior with re-recurrence, and the animal died 115 days after surgery. These findings suggest that, compatible with other animals, well-differentiated MCT has a better prognosis in hedgehogs.     

Ultrastructure of canine urinary bladder carcinoma

Luminal and intraepithelial asymmetric unit membrane plaques were found in the urinary bladder urothelium of normal dogs. Tight junctions were found only at the apical poles of the luminal cells. In four dogs with spontaneous urinary bladder carcinomas the asymmetric unit membrane plaques were replaced by symmetric unit membrane. In the neoplastic luminal cells the tight junctions were partially attenuated. Invasive and metastatic neoplastic cells had some tight junction at the stromal interface. Some gap junctions were seen in the normal urothelium but not in the neoplastic cells. The amount of desmosomes in the neoplastic cells varied according to their direction of differentiation (transitional, squamous or glandular).     

A case of canine apocrine sweat gland adenoma, clear cell variant

A cutaneous mass at the base of the retroauricular region of a 4-year-old, female Golden Retriever was examined pathologically. Histologically, the mass formed multiple nodules consisting of a proliferation of large clear cells with abundant cytoplasm. Mitotic figures among the neoplastic cells were very sparse. The large clear cells were intensely positive for cytokeratins (AE1/AE4, cytokeratin 8 and 18) and moderately positive for lysozyme and contained periodic acid-Schiff-positive granules in the cytoplasm. In addition, small flat cells lined the islands of neoplastic large clear cells, and these were strongly positive for alpha-smooth muscle actin and vimentin, and some were positive for cytokeratin (AE1/AE4), suggesting they were myoepithelial cells. No local recurrence or metastasis has been recognized during the 18 months since surgical excision. On the basis of these findings, the present tumor was diagnosed as apocrine sweat gland adenoma, clear cell variant. There have been few previous reports of canine apocrine adenomas showing a clear cell morphology.     

Glomus tumor of the liver in a cow

An 11-year-old Holstein-Friesian cow exhibited anorexia and jaundice. A large mass was found in the liver during necropsy. Macroscopically, the mass was composed of dark red multilobular tissue and a centrally located abscess, which was connected to the hepatic duct. Histologically, the mass consisted of proliferation of small neoplastic cells and was demarcated from the hepatic parenchyma by a thick region of granulation tissue. The neoplastic cells were predominantly arranged in solid sheets, but they also formed blood-filled cancellous structures, and proliferating foci were seen around blood vessels. Periodic acid-Schiff reaction demonstrated that a fine basement membrane-like structure surrounded the neoplastic cells. Immunohistochemically, the neoplastic cells were positive for vimentin and alpha smooth muscle actin and negative for cytokeratin, factor VIII-related antigen, chromogranin and desmin. Based on its histopathological features, the hepatic neoplasm was diagnosed as a primary glomus tumor. This is the first report about a primary glomus tumor of the liver in a cow.     

Cutaneous lymphoplasmacytic lymphoma with systemic metastasis in a cat

A lymphoplasmacytic lymphoma was diagnosed in a 12- year-old domestic cat that had a primary cutaneous mass involving the stomach, liver, kidneys, heart, abdominal wall, diaphragm, bone marrow and several lymph nodes. Histopathologically, the most characteristic feature of this tumor was the heterogeneity of cell components, such as small lymphocytes, well-differentiated plasma cells and plasmacytoid transformed lymphocytes. Amyloid was deposited in the skin, stomach, and several lymph nodes. Immunohistochemically, neoplastic small lymphocytes were positive for CD20, and well-differentiated plasma cells and plasmacytoid transformed lymphocytes were positive for λ-Ig light chains and MUM1/IRF-4. These results emphasize the importance of lymphoplasmacytic lymphoma as a differential diagnosis of extramedullary cutaneous plasmacytoma in cats.     

A canine peripheral nerve sheath tumor including peripheral nerve fibers

Peripheral nerve sheath tumor was found in a 7-year-old male mongrel dog. The tumors were located in the right cheek subcutis and oral submucosa. Histologically, neoplastic cells were arranged in streaming bundles, occasionally interlacing bundles or whorls of elongated and spindle cells. Cellular atypia was poor and mitotic figures were rarely observed. Ultrastructurally, neoplastic cells had basement membrane, typical of Schwann cells. One bundle of normal peripheral nerve fibers and some myelinated axons were seen within the tumor tissues. Immunohistochemically, neoplastic cells reacted to vimentin, glial fibrillary acidic protein, S-100 protein and neuron specific enolase. In addition to the above immunoreactions, the included nerve fibers were positive for myelin basic protein and neurofilament protein. This paper also discusses immunohistochemical findings on differential diagnosis in comparison with those of canine hemangiopericytomas reported hitherto.