Canine synovial sarcoma: a retrospective assessment of described prognostic criteria in 16 cases (1994-1999)

Pertinent patient data and biopsied tissue from 16 cases of canine synovial sarcoma (SS) were reviewed. Histopathological grade, clinical stage, and tissue immunoreactivity to cytokeratin (broad stain, AE1/AE3 and cytokeratin 7) and vimentin were determined and correlated with survival. Effect of treatment on survival was similarly evaluated. Neither clinical stage nor histopathological grade significantly affected survival patterns. Tissues from all cases stained >30% positively with vimentin, whereas no tissue from any case exhibited cytokeratin immunoreactivity. Dogs receiving surgical tumor excision or amputation had a significantly higher survivability than those receiving no treatment (P<0.02). Treatment aggressiveness may be more appropriate than clinical staging or tumor grading in predicting survival. Reliability of diagnosing and prognosticating canine SS with current immunohistochemistry protocols should be questioned.     

A case of glomus tumor in a dog

A subcutaneous mass at the digit of the left-hind limb of a 12-year-old, male mongrel dog was examined. A white firm mass, approximately 1 x 2 cm in diameter, was excided surgically. Histopathologically, the mass formed multiple nodules consisting of mixed proliferation of round epithelioid cells arranged in cord or sheet-like structures and small spindle cells forming loose irregular bundles. The epithelioid cells often showed proliferation around the blood vessels. A few giant cells scattering in the neoplastic foci were observed. The neoplastic cells were positive for alpha-smooth muscle actin and vimentin, and were negative for cytokeratin (AE1/AE3), desmin, factor-VIII related antigen, S-100 protein, and neuron specific enolase. On the basis of these findings, this tumor was diagnosed as glomus tumor. Since the present neoplasm had neither recurrence nor distal metastasis during the 12 month after surgical resection, the biological natures of the present neoplasm are supposed to be benign.     

Synovial sarcoma in an Ayrshire heifer

An 8-month-old Ayrshire heifer had a rapidly growing mass in the axillary region of the left thoracic limb. The mass surrounded the distal humerus and entrapped nerves of the brachial plexus, causing an abnormal gait. Histologically, the mass was composed of clusters and cords of round to polygonal cells with scattered, spindle-shaped cells. The neoplastic cells stained positively for vimentin and cytokeratin. No staining was found with S-100 protein, kappa and lambda light chains, or T-cell markers by immunohistochemistry. On electron microscopic evaluation, the cytoplasm of the neoplastic cells contained few organelles, principally rough and smooth endoplasmic reticulum and mitochondria. This synovial sarcoma has histologic and ultrastructural features characteristic of the poorly differentiated subtype of synovial sarcoma in the human classification system.     

Pathological features of olfactory neuroblastoma in an axolotl (Ambystoma mexicanum)

A one-year-old, female Mexican axolotl (Ambystoma mexicanum) had a rough-surfaced, polypoid, pink tumor mass of approximately 10 mm in diameter in the oral cavity. Histologically, the tumor extended from the ethmoturbinate region and into the oral cavity and had replaced some of the maxillary bone tissue. The tumor mass was composed of a lobular architecture of small round-shaped tumor cells with occasional Flexner-Wintersteiner-like rosette formation. There were no metastatic lesions in the other organs. Immunohistochemically, the tumor cells were partly positive for several neural markers (class III beta-tubulin, S-100 protein, and doublecortin) and intensely positive for an epithelial marker (cytokeratin AE1/AE3). These results suggest that the present tumor originated from neuroectodermal tissue. Considering the location and histological and immunohistochemical features of the tumor, a diagnosis of olfactory neuroblastoma was made.     

Palliative radiation therapy in the treatment of canine appendicular synovial sarcoma

Synovial sarcoma is a rare tumor in dogs, occurring in approximately 27% of neoplasms involving joints, with the elbow representing a common site of occurrence. The recommended treatment of canine synovial sarcoma is amputation. The authors describe the use of palliative radiation therapy for the treatment of synovial sarcoma involving the elbow of a dog and conclude that this treatment modality may have use in some patients affected with synovial sarcoma.     

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.     

Histiocytic sarcoma in the tarsus of a cat

A 12-year-old Persian cat was examined for a firm swelling of the right tarsal region and enlargement of the corresponding right popliteal lymph node. Cytologic evaluation demonstrated a population of malignant cells consistent with large cell lymphoma. Necropsy revealed a multi-lobulated subcutaneous mass involving the tarsus with some extension into adjacent deep muscular tissue. Histologically, the mass was composed of round cells with eosinophilic cytoplasm and pleomorphic anisokaryotic nuclei. Evidence of articular and nodal infiltration by these cells was observed. Differential diagnoses included synovial sarcoma and histiocytic sarcoma. Neoplastic cells were negative for cytokeratin, CD79a, and CD3 and positive for CD18, vimentin, lysozyme, and alpha-1-antitrypsin, most consistent with a diagnosis of histiocytic sarcoma. This is the first report of a histiocytic sarcoma involving a joint of a cat. The final diagnosis was based on the light microscopic appearance in combination with the immunohistochemical stains.     

Chemotherapy of synovial cell sarcoma in a dog

A synovial cell sarcoma of the tarsus in a 6-year-old dog was treated with doxorubicin HCl and cyclophosphamide. The tumor regressed after treatment. There was no recurrence 3 years after initiation of treatment. Previously, synovial cell sarcoma has not been reported to be responsive to chemotherapeutic agents, and the treatment of choice has been amputation.     

Ovarian epithelioid trophoblastic tumor in a cynomolgus monkey

Epithelioid trophoblastic tumor (ETT) is an unusual type of trophoblastic tumor, with features resembling carcinoma. In this study, we describe a 4-year-old cynomolgus monkey (Macaca fascicularis) showing, at necropsy, a lobulated mass replacing the left ovary and several nodular lesions within the lungs. Histologically, the mass in the ovary and lung metastases were characterized by nests of epithelioid cells, with intermingled, occasional, multinucleate tumor cells consistent with syncytiotrophoblasts and moderate amount of eosinophilic, hyaline-like material. Immunohistochemically, the tumor cells were diffusely positive for cytokeratins (AE1/AE3) and inhibin-alpha, but only focal immunoreactivity was observed for human chorionic gonadotropin, whereas placental alkaline phosphatase was always negative. On the basis of morphology and immunohistochemical reactivity, tumor cells were identified as intermediate trophoblast.     

Orbital adenocarcinoma of lacrimal gland origin in a dog.

A 13-year-old intact female mixed-breed dog was presented for a progressive enlargement of the right eye, which had been treated previously for conjunctivitis. A round, firm mass, approximately 4 cm in diameter, was protruding from the superotemporal aspect of the right orbit, displacing the eyeball anteriorly and ventromedially. The mass was encapsulated, distinct from the eyeball, and not associated with the eyelids. On cut surface, there was a pale multilobulated periphery, with a dark red, soft, and depressed core. Histologically, tumor cells formed cords and tubules, which were stained with mouse anti-human cytokeratin antibody AE1/AE3. Residual glands were serous, and the majority of tumor cells were negative for mucin. The supraorbital location, encapsulation, and residual serous glands suggest that this mass was a low-grade adenocarcinoma of the lacrimal gland.     

Granular variant of a histiocytic tumor on the toe of a cat: Case report and literature review

A 16-year-old female spayed domestic shorthaired cat was examined for lameness and a mass on the fourth digit of the right hindlimb. Cytologic examination of an aspirate of the mass revealed large discrete cells admixed with low numbers of well-granulated mast cells. The discrete cells contained single to many variably sized light pink to purple granules in their cytoplasm and had pleomorphic nuclei, with intranuclear cytoplasmic inclusions. Karyomegalic, binucleated and multinucleated cells were seen. Histologic examination of formalin-fixed sections of the excised mass showed a mildly infiltrative, unencapsulated, multinodular dermal mass that extended into the subcutis and consisted of similar discrete cells. On immunohistochemical staining, the tumor cells expressed ionized calcium-binding adapter molecule 1 (Iba1) and CD18. The tumor cells did not express CD3, CD20, CD117, pancytokeratin (AE1/AE3), melanoma antigen (Melan-A), multiple myeloma oncogene-1 (MUM1), melanoma-associated antigen (PNL-2), and S-100. Low numbers of tumor cells expressed CD204 and protein gene product 9.5 (PGP9.5). Granules were variably positive for Periodic-acid Schiff (PAS) and Alcian blue. On transmission electron microscopy, the cells contained filopodia, abundant endoplasmic reticulum, and moderate numbers of low-density membrane-bound granules. This case documents a previously undescribed granular variant of a histiocytic tumor in a cat.     

Primary epididymis squamous cell carcinoma in a CB6F1-Tg rasH2 mouse

In a 26-week carcinogenicity study in rasH2-Tg mice, squamous cell carcinoma on the epididymis was observed in a male mouse in the positive control group treated with N-methyl-N-nitrosourea. A 29-week-old male rasH2-Tg mouse that was euthanized 21 weeks after the administration of N-methyl-N-nitrosourea had a white-grayish mass on the left caput epididymis. The mass was nodular and consisted of pleomorphic tumor cells forming alveolar, sheeted, and trabecular structures suggesting epithelial tumor growth. These cells presented a cobblestone-like arrangement and formed intercellular bridges. Keratinization was infrequently observed. Periodic acid-methenamine-silver staining revealed argyrophilic fibrous structures around the alveolar structure of the tumor cells. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3 and cytokeratin 14 and negative for cytokeratin 5, p63, uroplakin III, vimentin, desmin, and αSMA. These immunohistochemical results suggested the tumor cells originated from the epididymal ducts. Metastatic lesions were observed in the mesenteric, inguinal, and pancreaticoduodenal lymph nodes. Based on these results, this tumor was diagnosed to be a primary squamous cell carcinoma of the epididymis. This is the first report of primary squamous cell carcinoma of the epididymis in a rasH2-Tg mouse.     

The diagnosis and prognosis of synovial tumors in dogs: 35 cases

Although synovial cell sarcoma is reported to be the most common neoplasm of the canine synovium, this retrospective study of 35 canine synovial tumors found that the majority were of histiocytic origin. Five (14.3%) synovial cell sarcomas were identified by positive immunohistochemical staining with antibodies to cytokeratin. Eighteen (51.4%) histiocytic sarcomas were identified by cell morphology and immunohistochemical staining with antibodies to CD18. Six (17.1%) synovial myxomas were identified by histologic pattern. The remaining six (17.1%) synovial tumors represented a variety of sarcomas, including two malignant fibrous histiocytomas (actin positive), one fibrosarcoma, one chondrosarcoma, and two undifferentiated sarcomas. Rottweilers were overrepresented in the histiocytic sarcoma category and Doberman Pinschers were overrepresented in the synovial myxoma category. The average survival time was 31.8 months for dogs with synovial cell sarcoma, 5.3 months for dogs with histiocytic sarcoma, 30.7 months for dogs with synovial myxoma, and 3.5 months for dogs with other sarcomas. Among the dogs with follow-up information available, metastatic disease was detected in 25% of dogs with synovial cell sarcoma, in 91% of dogs with histiocytic sarcoma, in none of the dogs with synovial myxoma, and in 100% of dogs with other sarcomas. Immunohistochemical staining for cytokeratin, CD18, and smooth muscle actin is recommended to make the diagnosis and thereby predict the behavior of synovial tumors in dogs.     

Establishment and biological characterization of canine histiocytic sarcoma cell lines

Seven novel cell lines from canine histiocytic sarcoma (HS), three of which were disseminated cutaneous HS and four of which were synovial HS, were established. All of the established cell lines had the same morphological (by light and electron microscopic findings), cytochemical (alpha-naphthyl butyrate esterase-positive), and immunohistochemical (vimentin- and lysozyme-positive, and cyto-keratin-negative) characteristics as the original HS tumor cells. All of the established cell lines injected into nude mice subcutaneously produced solid tumors. Because the established cell lines also showed phagocytic and processing activities, the HS tumor cells appear to originate from the mononuclear phagocytic system cells, despite their differences in locations or organs.     

Synovial sarcoma of the tendon and tendon sheath in a dog

A 19.5-year-old male mongrel dog developed a progressive lameness and swelling around the right carpus. A tumor (6 x 3 x 3 cm) was found in the caudal of distal antebrachium of the right forelimb, including tendons of the superficial digital flexor muscle and deep digital flexor muscle. No joint destruction was observed. The tumor consisted of round and spindle cells arranged in a compact sheet. There were occasional slit-like spaces or lumina, and areas rich in collagen fibers giving an appearance of tendon tissues. Neoplastic cells gave a positive immunoreaction to vimentin, but negative reactions to antibodies against S-100 protein, cytokeratin and myoglobin. Based on these findings, this tumor was diagnosed as a synovial sarcoma generating from the tendon and tendon sheath, which is very uncommon in dogs.     

Synovial tumours in dogs

The morphological characteristics, breed predispositions, site predilections and behaviour of three of the most common types of synovial tumours were discussed. Synovial histiocytic sarcoma represents 50% of synovial tumours, occurring in breeds predisposed to histiocytic sarcoma, and has a poor prognosis. Their histological appearance is similar to histiocytic sarcomas occurring elsewhere. The stifle is the most common site; dogs with ruptured cranial cruciate ligament are predisposed. Synovial cell sarcoma represents 15% of synovial tumours in dogs. They have non-specific spindle cell morphology, and can only be distinguished using cytokeratin immunohistochemistry, which will label a small percentage of the spindle cells. Amputation is often curative, but metastases can occur. Synovial myxoma represents 20% of synovial tumours in dogs. They have a characteristic morphology of myxomatous nodules filling the joint cavity and sometimes extending into the surrounding tissues, including bone. Labrador Retrievers and Doberman Pinschers are predisposed, and the stifle and digit are the most common sites. Prognosis is good; even with incomplete excision some dogs survive years without progression or metastasis. Histopathological examination of synovial tumours is essential to determine the course of treatment, and prognosis.     

Mixed apocrine sweat gland tumor of the tail in a cow

A 4-year-old native-breed cow had a mass with wide areas of ulceration and hemorrhage at the base of the tail at the same level as the vulva. The tumor was 19 X 13 X 11 cm, appeared red-brown, and was firm to hard, with gritty areas apparent on cut surface. Histologically, the tumor mass was composed of multilayered epithelial cells forming glandular structures with occasional apical blebs and rare solidly packed cells in nests. The stroma included fibrous connective tissue, scattered or periglandular sheets of spindle-shaped cells resembling myoepithelium, several cartilaginous formations, and numerous irregular islands of mineralized osteoid, well-formed bone trabeculae lined by osteoblasts, and many osteoclast-like multinucleated giant cells among or near the neoplastic epithelium. Immunohistochemically, the neoplastic epithelium was positive for pan-cytokeratin (AE1/AE2) and cytokeratin 19 but was negative for cytokeratin 18. Spindle-shaped cells were stained with alpha smooth muscle actin (alphaSMA) and to a lesser extent vimentin antibodies. The cells of osteogenic lineage and spindle cells closely associated with the osteoid showed strong immunostaining for vimentin but not for alphaSMA. Immunostaining for neuron-specific enolase and S100 protein was not observed in any component of the tumor mass. These findings suggested that the origin of bone formation was undifferentiated mesenchymal cells with osteogenic potential.     

Immunohistochemical characterization of a hepatic neuroendocrine carcinoma in a cat.

A hepatic mass was identified in a 5-year-old, female mixed-breed cat that died spontaneously after a clinical history of progressive emaciation, ptyalism, and persistent coryza. At necropsy, a 7-cm-diameter, yellow-brown, firm, multilobulated tumor was identified in the liver. Microscopically, the mass consisted of neoplastic cells arranged in small, closely packed nests within a thin fibrovascular stroma. These cells were of medium sized and polygonal, with fine argyrophilic cytoplasmic granules. Nuclei were predominantly round with finely stippled chromatin and indistinct nucleoli. Mitotic figures were numerous. Immunohistochemically, most of the neoplastic cells were immunoreactive for chromogranin A, neuron-specific enolase (NSE), and cytokeratin AE1/AE3 and weakly labeled for synaptophysin. The tumor was negative for glial fibrillary acidic protein (GFAP), vimentin, and cytokeratins 5, 6, 8, and 17. Vascular emboli and intrahepatic micrometastasis were also identified with chromogranin A. All these features were consistent with a hepatic neuroendocrine carcinoma and emphasized the importance of using a panel of antibodies to diagnose such rare tumors.     

Amyloid-producing odontogenic tumor and its immunohistochemical characterization in a Shih Tzu dog

A 10-year-old, male, Shih-Tzu dog presented with swelling of the right lower jaw caused by a mass arising from the right mandibular gingiva. Radiographic examination revealed bone lysis of the right wing of the mandible. Histopathologically, the growth was characterized by indistinctly lobulated nests, islands, and strands of proliferating odontogenic and squamous epithelial cells, intermingled in close association with large numbers of irregular extracellular deposits of amyloid and amorphous calcified substance. Immunohistochemically, both epithelial components stained strongly positive for cytokeratin (AE1/AE3); the squamous epithelial cells also reacted strongly with neuron-specific enolase (NSE) and S-100 protein, whereas the odontogenic epithelial cells displayed weak immunoreactivity to NSE and partial reactivity to S-100 protein. The amyloid deposits were AE1/AE3-negative. The growth was diagnosed as an amyloid-producing odontogenic tumor.