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.     

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.     

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.     

Well-differentiated biphasic synovial sarcoma in the atlanto-occipital joint of a Holstein cow

A 7-year-old Holstein cow developed a large cystic mass in the region between the atlantoaxis and larynx. The mass extended to the synovium in the atlanto-occipital joint. Many villous projections were present on the inner surface of the tumor tissue, and irregular clefts were formed in the inside. Two cell types, epithelioid-like synovioblasts and spindle cells, were present. Immunohistochemical analysis showed that the cells stained positively for cytokeratin (AE1/AE3) and vimentin. Both cells had similar fine structures ultra-structurally. Vacuoles present in the cytoplasm were full of an acid mucous substance. The tumor was diagnosed as a well-differentiated biphasic synovial sarcoma. This is the first report of a rare case of synovial sarcoma, from the viewpoint of its origin.     

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.     

The adrenergic receptor antagonists propranolol and carvedilol decrease bone sarcoma cell viability and sustained carvedilol reduces clonogenic survival and increases radiosensitivity in canine osteosarcoma cells

Adrenergic receptor (AR) expression has been demonstrated at several sites of primary and metastatic tumour growth and may influence proliferation, survival, metastasis and angiogenesis. AR antagonists like propranolol and carvedilol inhibit proliferation, induce apoptosis and synergize with chemotherapy agents in some cancers. Radiation resistance is mediated in many cells by upregulation of pro‐survival pathways, which may be influenced by ARs. Studies evaluating AR antagonists combined with radiation are limited. The purpose of this study was to determine the effect of propranolol and carvedilol on viability and radiosensitivity in sarcoma cell lines. The hypothesis was that propranolol and carvedilol would increase radiosensitivity in four primary bone sarcoma cell lines. Single agent propranolol or carvedilol inhibited cell viability in all cell lines in a concentration‐dependent manner. The mean inhibitory concentrations (IC₅₀) for carvedilol were approximately 4‐fold lower than propranolol and may be clinically relevant in vivo. Immunoblot analysis confirmed AR expression in both human and canine sarcoma cell lines; however, there was no correlation between baseline AR protein expression and radiosensitivity. Short duration treatment with carvedilol and propranolol did not significantly affect clonogenic survival. Prolonged exposure to propranolol and carvedilol significantly decreased the surviving fraction of canine osteosarcoma cells after 3Gy radiation. Based on our results and possible in vivo activity in dogs, further studies investigating the effects of carvedilol on sarcoma are warranted.     

Metastatic synovial cell sarcoma in two cats

Synovial cell sarcoma (SCS) with metastasis to the regional lymph node was diagnosed in two cats. Synovial cell sarcomas are rare in cats and metastatic SCS has not previously been reported. In both cases, treatment consisted of limb amputation and adjuvant doxorubicin. Local tumour recurrence and pulmonary metastases were diagnosed in one cat 316 days postoperatively. This cat died of chronic renal failure 444 days after limb amputation. The second cat died of an acute pulmonary thromboembolism 41 days postoperatively without evidence of local tumour recurrence or metastatic disease.     

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.     

A review of sentinel lymph node evaluation and the need for its incorporation into veterinary oncology

Being the first lymph node or nodes to which many primary tumours reliably drain, the disease status of the sentinel lymph node/s (SLN) is important in the prediction of survival. SLN identification and biopsy are critical in the staging of human cancers. The status of the SLN helps determine prognosis and shape treatment plans. SLN evaluation is currently not routinely performed in veterinary oncology, not even at specialty oncology practices. Given the prognostic importance of lymph node involvement in tumours such as mammary gland carcinoma, osteosarcoma, synovial cell sarcoma and mast cell tumours, SLN evaluation should be incorporated into routine clinical practice so as to improve our clinical assessment of veterinary oncologic patients.     

Phase II evaluation of doxorubicin for treatment of various canine neoplasms

One hundred eighty-five dogs with histologically confirmed, measurable malignant tumors were used in a prospective study to determine the response to 2 doses of the anthracycline antitumor antibiotic, doxorubicin. Eighty-three dogs had been refractory to one or more previous treatment modalities (surgery, n = 54; chemotherapy, n = 22; radiation, n = 10; hyperthermia, n = 1; biological response modifier, n = 1). The extent of neoplastic disease was determined immediately prior to and 3 weeks after 2 doses of doxorubicin were administered (30 mg/m2 of body surface area, iv) 21 days apart. Eighty-four percent (n = 157) of the dogs received 2 doses of doxorubicin and were evaluated. Of the 28 dogs ruled ineligible, 4 had serious side effects to the first dose of doxorubicin, and 24 others acquired complications resulting from their malignant tumors. A partial or complete remission was obtained in 41% (64/157) of all evaluable dogs: 26% (11/43) of the dogs with carcinoma, 67% (42/63) of the dogs with lymphoma, and 22% (11/51) of the dogs with sarcoma. Tumors in which there was at least a 50% volume reduction (partial or complete remission) included malignant lymphoma (42/63), fibrosarcoma (1/14), solid follicular thyroid carcinoma (3/13), mammary adenocarcinoma (2/8), hemangiosarcoma (2/8), osteosarcoma (1/6), circumanal carcinoma (3/5), synovial cell sarcoma (2/3), undifferentiated sarcoma (2/3), nasal adenocarcinoma (1/2), liposarcoma (1/2), infiltrating lipoma (1/1), malignant melanoma (1/1), sclerosing mesothelioma (1/1), and neurofibrosarcoma (1/2).(ABSTRACT TRUNCATED AT 250 WORDS)     

USE OF [123I]-2-IODO-l-PHENYLALANINE AS A TUMOR IMAGING AGENT IN TWO DOGS WITH SYNOVIAL CELL SARCOMA

[123I]-iodo-L-phenylalanine was successfully evaluated for gamma camera imaging in vivo in tumor-bearing athymic mice and in humans with brain tumors. Here, we report the use of this tracer in two dogs with synovial cell sarcoma of the tarsus. [123I]-iodo-L-phenylalanine was quantitatively prepared as a kit formulation using the Cu(1+) +-assisted nucleophilic exchange. Rapid [123I]-2-iodo-L-phenylalanine tumor accumulation was observed with good tumor to background contrast and rapid clearance in these two dogs. This radiopharmaceutical is a promising alternative tumor tracer to overcome the known limitations of 18F-fluorodeoxyglucose and, when labelled with radioiodine-131, has the potential to be used for therapeutic purposes.     

Synovial sarcoma in a dog.

A 6.5-year-old, female Saint Bernard had a slowly growing tumor of the right tibiotarsal joint. Radiographically, bone surrounding the tumor was not involved. Subtotal surgical resection was undertaken. The tumor was classified histologically as a synovioma. Within 6 months, the tumor recurred locally and invaded the soft tissue proximal to the tibiotarsal joint. Eighteen months after initial examination, there was widespread right tibial invasion and pulmonary metastasis. The dog was euthanatized. The final histopathologic diagnosis was synovial sarcoma.     

Anti‐tumour activity of oncolytic reovirus against canine histiocytic sarcoma cells

Canine histiocytic sarcoma is an aggressive, fatal neoplastic disease with a poor prognosis. Lomustine is generally accepted as the first‐line systemic therapy, although this compound does not provide complete regression. Therefore, research into a novel approach against canine histiocytic sarcoma is needed. However, anti‐tumour effects of oncolytic therapy using reovirus against histiocytic sarcoma are unknown. Here, we showed that reovirus has oncolytic activity in canine histiocytic sarcoma cell lines in vitro and in vivo. We found that reovirus can replicate and induce caspase‐dependent apoptosis in canine histiocytic sarcoma cell lines. A single intra‐tumoural injection of reovirus completely suppressed the growth of subcutaneously grafted tumours in NOD/SCID mice. Additionally, we demonstrated that susceptibility to reovirus‐induced cell death was attributable to the extent of expression of type I interferons induced by reovirus infection in vitro. In conclusion, oncolytic reovirus appears to be an effective treatment option for histiocytic sarcoma, and therefore warrants further investigation in early clinical trials.     

Idiopathic gonitis in heifers: 34 cases (1976-1986)

Acute suppurative arthritis of the stifle joint was diagnosed in 34 Holstein heifers between 1976 and 1986. Only 1 stifle joint was affected in each heifer; however, 1 heifer also had involvement of the contralateral radiocarpal joint. In each heifer, there was marked lameness and synovitis characterized by an effusion with high synovial fluid nucleated cell counts and total protein concentration. Seventy-four percent (25/34) of the heifers had radiographic evidence of an osteolytic lesion involving the lateral tibial plateau. Bacteriologic cultures of synovial fluid, synovial membrane, and bone yielded no growth. Eighteen of 23 (78%) affected heifers for which follow-up data was obtained became productive herd members after treatment.     

Use of hyperthermia and radiotherapy in treatment of a large mast cell sarcoma in a dog

A large infiltrating mast cell sarcoma in a dog, which had been refractory before surgical excision, was controlled 2 months after completion of a combined radiotherapy and hyperthermia regimen. Treatment resulted in rapid tumor necrosis and resultant ulceration of adjacent skin. Ulceration was transient, resolving concurrently with tumor control. Radiation was administered as 3.5-Gy fractions 3 times/week, resulting in a total dose of 45.5 Gy in 13 treatments. Hyperthermia (44 C for 30 minutes) was given 4 to 5 hours after radiotherapy, once a week during the first 3 weeks of treatment.     

Synovial myxoma: magnetic resonance imaging in the assessment of an unusual canine soft tissue tumour

Magnetic resonance imaging (MRI) of the hindlimb of a 10-year-old Labrador retriever was performed preoperatively to define the limits and invasive nature of a synovial myxoma. This unusual tumour in dogs has also only rarely been reported in humans, although the use of advanced imaging techniques has been more widely reported in the assessment of soft tissue tumours in people. MRI was an invaluable aid in the delineation of the extensive pathological changes associated with this tumour and consequently its surgical treatment. Amputation was performed and the dog remained disease-free 18 months after surgery.     

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.     

Use of alkaline phosphatase staining to differentiate canine osteosarcoma from other vimentin-positive tumors

Aspiration of lytic bone lesions is an excellent diagnostic test in the initial evaluation of primary bone neoplasia. However, cytologically, it can be difficult to differentiate osteosarcoma (OSA) from other bone neoplasms, including fibrosarcoma, chondrosarcoma, synovial cell sarcoma, and plasma cell myeloma. The purpose of this study is to determine the sensitivity and specificity of alkaline phosphatase (ALP) staining to differentiate OSA from other tumors that express vimentin by immunocytochemistry or immunohistochemistry. ALP is a hydrolytic enzyme present in multiple tissues including liver, kidney, intestine, placenta, and bone. Hypothetically, neoplasms actively producing bone should be specifically positive for ALP staining. Unstained, cytologic specimens were incubated for 8-10 minutes with nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate toluidine salt-phosphatase substrate. A positive reaction stains the membrane of the cells gray to black. Samples were counterstained with a Romanowsky's stain to determine whether the sample was of representative cellularity. A total of 61 vimentin-positive neoplasms have been evaluated and confirmed histopathologically. Tumors that expressed vimentin and were positive for ALP included 33 OSAs, one multi-lobular tumor of bone, one amelanotic melanoma, and one chondrosarcoma. Tumors that expressed vimentin and were negative for ALP included chondrosarcomas (three of four), multiple fibrosarcomas, and multiple synovial cell sarcomas. The sensitivity is 100%, and the specificity is 89%. In conclusion, ALP appears to be a highly sensitive and fairly specific marker in the diagnosis of OSA.     

Effect of intrathecal amikacin administration and repeated centesis on digital flexor tendon sheath synovial fluid in horses

OBJECTIVE: To determine the effect of intrathecal amikacin administration and repeated tenovaginocentesis on the total nucleated cell count (TNCC), total protein (TP) concentration and cytologic characteristics of synovial fluid of the equine digital flexor tendon sheath (DFTS). STUDY DESIGN: Randomized, cross-over experimental design. ANIMALS: Adult horses (n=8). METHODS: Synovial fluid was aseptically collected from the DFTS and either 1 mL amikacin sulfate (250 mg/mL) or lactated Ringer's solution (LRS) was injected into the DFTS. Serial synovial fluid samples were obtained at 0, 12, 24, 48, and 72 hours. The opposite treatment was administered to the contralateral DFTS after a washout period of 2 weeks. RESULTS: Treatment increased TP concentration, TNCC, percentage of neutrophils, and neutrophil counts from baseline levels. There was no difference between treatment of the DFTS with amikacin or LRS. Values peaked at 12-24 hours after the initial centesis and then declined toward baseline levels. CONCLUSIONS: Injection and repeat centesis of the normal DFTS with 250 mg amikacin or an equivalent volume of LRS resulted in mild increases in synovial fluid analytes from baseline. Synovial inflammation in this study was not accompanied by lameness at the walk and measured analytes returned toward baseline levels within 12-24 hours of first injection. CLINICAL RELEVANCE: The effect of tenovaginocentesis and intrathecal administration of amikacin or LRS on DFTS synovial fluid values are modest in most horses; however, some horses can develop marked increases in synovial fluid values that may be interpreted as sepsis.