J. Comp. Path. 2014, Vol. 150, 204e207
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/jcpa
NEOPLASTIC DISEASE
A Non-joint Tissue Biphasic Synovial Sarcoma in a Dog N. Takimoto*, K. Suzuki†, T. Ogawa*, R. Segawa*, S. Hara*, M. Itahashi*,x, M. Kimura*,x, N. Iwasaki‡, K. Nishifuji‡ and M. Shibutani* *Laboratory of Veterinary Pathology, † Laboratory of Veterinary Toxicology, ‡ Laboratory of Veterinary Medicine, Tokyo University of Agriculture and Technology, Tokyo and x Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan
Summary A subcutaneous tumour was identified in the malar region of a 14-year-old neutered female mixed breed dog. The dog was humanely destroyed and necropsy examination was performed. The tumour did not invade neighbouring tissues and no metastasis was found. Microscopically, the tumour showed a range of features including the presence of multinucleated giant cells, chondrocyte differentiation and cystic or slit-like structures. All of these features are consistent with previously reported descriptions of synovial sarcomas in dogs. Mesenchymal cells accounted for the majority of the tumour, but cytokeratin-positive epithelioid components were also confirmed by immunohistochemistry. The tumour was diagnosed as a biphasic type of synovial sarcoma. Synovial sarcoma in man may develop in tissues unrelated to joints and this is the first report of a nonjoint synovial sarcoma in a dog. Ó 2013 Elsevier Ltd. All rights reserved. Keywords: biphasic tumour; dog; immunohistochemistry; synovial sarcoma
Synovial sarcomas arise in joints and have been reported in dogs, cats, cattle and ferrets (Tremblay et al., 2000; Oyamada et al., 2004). Canine synovial sarcomas occur mainly in the elbow or stifle and rarely involve the hip or jaw (Griffith et al., 1987; Karayannopoulou et al., 1992). Microscopically, synovial sarcomas are categorized into four subtypes: (1) spindle cell dominant, monophasic fibroblastic type, (2) epithelioid cell dominant, monophasic epithelioid type, (3) biphasic type and (4) poorly differentiated type. Of these subtypes, the fibroblastic type is predominant in animals (Fox et al., 2002). Although synovial sarcomas have several characteristic histological features, they are difficult to distinguish from other tumours such as malignant fibrous histiocytomas, fibrosarcomas, peripheral nerve sheath tumours, melanomas, chondrosarcomas
Correspondence to: K Suzuki (e-mail: [email protected]). 0021-9975/$ - see front matter http://dx.doi.org/10.1016/j.jcpa.2013.11.206
and giant cell tumours of the soft tissue (Loukopoulos et al., 2004). Despite the term ‘synovial’ sarcoma, the tissue of origin of these tumours remains controversial. In some reports, these tumours were derived from primitive mesenchymal precursor cells, which are located outside of the synovial membrane and have the ability to differentiate into epithelioid or fibroblastic cells (Mitchell and Hurov, 1979; Vail et al., 1994). In the present paper, we report a tumour of the jaw, unrelated to the joint, but with histological characters of a synovial sarcoma. A 14-year-old neutered female mixed breed dog was referred to a veterinary hospital for swelling of the left mandibular region. The swelling had enlarged markedly over a period of several months and the presence of the mass had prevented the dog from closing its left eye for the past 3 months. The clinical condition of the dog had worsened as the size of the tumour increased. Four months after the consultation, the dog was humanely destroyed. Post-mortem Ó 2013 Elsevier Ltd. All rights reserved.
Biphasic Synovial Sarcoma in a Dog
examination revealed a multilobulated, pale white mass (15 12 11 cm) in the subcutaneous tissue of the left cheek, extending to the base of the left ear. The mass did not invade the mandibular joint. No metastasis was found in any other tissues. A small amount of serous fluid leaked from the tumour on gross sectioning. The mass was fixed in 10% neutral buffered formalin and embedded in paraffin wax. Sections were stained with haematoxylin and eosin (HE) and Masson’s trichrome stain. Immunohistochemistry (IHC) was performed using a VECTASTAINÒ Elite ABC Kit (Vector Laboratories Inc., Burlingame, California, USA). The primary antibodies used were: anti-cytokeratin AE1/AE3 (CK AE1/AE3; clones AE1/AE3, mouse monoclonal, 1 in 50 dilution; Dako, Glostrup, Denmark), anti-cytokeratin (clone MNF116, mouse monoclonal, 1 in 50 dilution; Dako), anti-vimentin (clone V9, mouse monoclonal, 1 in 50 dilution; Dako), anti-chromogranin A (CGA; rabbit polyclonal, 1 in 3,000 dilution; Yanaihara Institute Inc., Shizuoka, Japan), anti-S100 protein (rabbit polyclonal, 1 in 400 dilution; Dako), antineuron-specific enolase (NSE; clone BBS/NC/VIH14, mouse monoclonal, 1 in 100 dilution; Dako), anti-ionized calcium-binding adapter molecule-1 (Iba-1; rabbit polyclonal, 1 in 250 dilution; Wako Pure Chemical Co., Osaka, Japan), anti-glial fibrillary acidic protein (GFAP; clone 6F2, mouse monoclonal, 1 in 50 dilution; Dako), anti-a-smooth muscle actin (a-SMA; clone 1A4, mouse monoclonal, 1 in 100 dilution; Dako), anti-desmin (clone D33, mouse monoclonal, 1 in 2 dilution; Dako), anti-von Willebrand factor (vWF; rabbit polyclonal, 1 in 500 dilution; Dako), anti-melan-A (clone A103, mouse monoclonal, 1 in 25 dilution; Dako) and antiosteocalcin (clone OC4-30, mouse monoclonal, 1 in 100 dilution; GeneTex Inc., Los Angeles, California, USA). Antigen retrieval was performed by either microwaving in 10 mM citrate buffer (pH 6.0) at 90 C for 10 min (NSE, GFAP and vWF), autoclaving in 10 mM citrate buffer (pH 6.0) at 121 C for 10 min (CK AE1/AE3, CK MNF116, vimentin, Iba-1, aSMA and melan-A), incubating in a hot water bath in 10 mM citrate buffer (pH 6.0) at 60 C for 20 min (chromogranin A) or covering sections with Proteinase K and incubating for 10 min at 37 C (S100 and osteocalcin). No antigen retrieval methods were performed for the desmin IHC. Sections were treated with H2O2 0.3% in methanol for 30 min to block endogenous peroxidase activity. The sections were blocked with normal goat or horse serum at room temperature for 30 min. Each section was incubated with primary antibody at 4 C overnight and then with a secondary antibody against mouse or rabbit
205
immunoglobulin (Ig) G applied at room temperature for 30 min. The ABC reagent was applied at room temperature for 30 min. Antibody-binding was ‘visualized’ with 3, 30 -diaminobenzidine (DAB) chromogen and counterstaining with haematoxylin. Microscopically, the tumour was composed of round and spindle cells with an oval to round nucleus and eosinophilic cytoplasm with ill-defined borders. Mitotic figures were frequently observed (mitotic index 11.2 per 10 40 objective fields), particularly in cells that surrounded blood vessels or formed slitlike spaces (Fig. 1). A large area of necrosis was present. Between the neoplastic lobules, there was a large amount of collagen. Tumour cells with chondroid differentiation or multinucleated giant cells were also observed (Fig. 2). In some regions, there were cystic structures with neoplastic cells within the cystic space. The tumour cells near blood vessels and those forming slit-like structures were positive for CK AE1/AE3 and all other cell components expressed vimentin (Figs. 3 and 4). Iba-1-positive cells, consistent with macrophages, were scattered throughout the tumour. These cells were negative for all other antibodies. Cystic or slit-like structures and multinucleated giant cells are commonly documented in animal synovial sarcomas (Lipowitz et al., 1979; Silva-Krott et al., 1993; Slayter et al., 1994; Pool and Thompson, 2002; Yamate et al., 2006). In addition, the presence of chondroid differentiation has also been reported in the dog (Griffith et al., 1987). Similar findings were also observed in the present case, leading to a diagnosis of synovial sarcoma. The tumour was formed of both cytokeratin-positive epithelioid and vimentin-positive mesenchymal components, but was negative for the other antibodies tested. These
Fig. 1. Neoplastic cells proliferating around blood vessels or slitlike spaces (arrow). Necrotic areas (arrowhead) and cystic structures (asterisk) are also present. HE. 40.
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Fig. 2. Chondroid cells (arrowhead) and multinucleated giant cells (arrows) are present in the tumour. HE. 200.
Fig. 4. Most of the neoplastic cells express vimentin. IHC. 200.
results suggest that the origin of the tumour cells was not neurological (NSE, GFAP and S100 protein negative) or related to neuroendocrine cells (CGA negative), smooth or striated muscles (a-SMA and desmin negative), melanocytic cells (melan-A negative) or osteoblastic cells (osteocalcin negative). A potential differential diagnosis for the tumour was sarcomatoid carcinoma; however, the tumour had no definite epithelial component and the majority of the neoplastic cells were vimentin-positive mesenchymal components. Moreover, the morphological features (i.e. multinucleated giant cells, chondroid differentiation and cystic or slit-like structures) were not consistent with sarcomatoid carcinoma. In contrast to human cases, which have a glandular proliferation pattern, synovial sarcomas in dogs do not have a definite epithelial component (Vail et al., 1994). In the present case, histologically recognizable
epithelioid cells were sparse, but epithelial components were confirmed by the presence of cytokeratin-positive neoplastic cells. Although use of the term ‘biphasic’ suggests that the tumour had both definitive epithelioid and fibroblastic cells, this tumour could be classified as ‘biphasic-type’ from the IHC results. Therefore, considering the immunohistochemical and histological characteristics, the tumour was diagnosed as a biphasic type of synovial sarcoma. The definition of synovial sarcoma differs between domestic animals and man (Rob, 2002). In veterinary pathology, information about synovial sarcomas has been extrapolated from the established definition in human medicine, which requires a joint-derived origin for diagnosis as a synovial sarcoma (Slayter et al., 1994; Pool and Thompson, 2002). Conversely, a variety of ‘synovial sarcomas’ reported in man have occurred in non-joint tissues such as the lung, heart and kidney (Koyama et al., 2001; Nuwal et al., 2012; Varma and Adegboyega, 2012). Because more than 90% of human synovial sarcomas have a unique chromosomal translocation between X and the 18th chromosome, leading to the formation of the SS18-SSX fusion gene, the presence of SS18-SSX transcripts is a reliable diagnostic molecular marker for synovial sarcomas regardless of tumour origin (Craig et al., 2002; Naka et al., 2010). Therefore, although the name ‘synovial sarcoma’ was given by pathologists who believed that this tumour had derived from the normal synovium, most synovial sarcomas in man do not arise from the synovium, but from mesenchymal precursor cells. In addition, the hypothesis that ‘synovial sarcomas’ are derived from mesenchymal precursor cells may support the morphological variation, such as the presence of multinucleated giant cells, chondroid differentiation
Fig. 3. Neoplastic cells close to blood vessels and slit-like structures express cytokeratin AE1/AE3. IHC. 200.
Biphasic Synovial Sarcoma in a Dog
and cystic or slit-like structures, observed in the present tumour. Synovial sarcomas occurring in nonjoint tissues have not been previously reported in animals, but we suggest that, as in humans, synovial sarcomas in animals can originate in tissues unrelated to the joints. Because a unique chromosomal translocation in synovial sarcomas has not been reported in animals, it is difficult to make a definitive diagnosis at present. Further investigation may be required to refine the notion of synovial sarcomas in animals and this case provides important information for that reconsideration.
Conflicts of Interest The authors declare no conflicts of interest.
Acknowledgements The authors thank Mrs. S. Suzuki for technical assistance in preparing the histological specimens.
References Craig LE, Julian ME, Ferracone JD (2002) The diagnosis and prognosis of synovial tumors in dogs: 35 cases. Veterinary Pathology, 39, 66e73. Fox DB, Cook JL, Kreeger JM, Beissenherz M, Henry CJ (2002) Canine synovial sarcoma: a retrospective assessment of described prognostic criteria in 16 cases (1994e1999). Journal of the American Animal Hospital Association, 38, 347e355. Griffith JW, Frey RA, Sharkey FE (1987) Synovial sarcoma of the jaw in a dog. Journal of Comparative Pathology, 97, 361e364. Karayannopoulou M, Kaldrimidou E, Dessiris A (1992) Synovial sarcoma in a dog. Journal of Veterinary Medical Science, 39, 76e80. Koyama S, Morimitsu Y, Morokuma F, Hashimoto H (2001) Primary synovial sarcoma of the kidney: report of a case confirmed by molecular detection of the SYT-SSX2 fusion transcripts. Pathology International, 51, 385e391. Lipowitz AJ, Fetter AW, Walker MA (1979) Synovial sarcoma of the dog. Journal of the American Veterinary Medical Association, 174, 76e81. Loukopoulos P, Heng HG, Arshad H (2004) Canine biphasic synovial sarcoma: case report and immunohistochemical characterization. Journal of Veterinary Science, 5, 173e180.
207
Mitchell M, Hurov LI (1979) Synovial sarcoma in a dog. Journal of the American Veterinary Medical Association, 173, 53e55. Naka N, Takenaka S, Araki N, Miwa T, Hashimoto N et al. (2010) Synovial sarcoma is a stem cell malignancy. Stem Cells, 28, 1119e1131. Nuwal P, Dixit R, Shah NS, Samaria A (2012) Primary monophasic synovial sarcoma lung with brain metastasis diagnosed on transthoracic FNAC: report of a case with literature review. Lung India, 29, 384e387. Oyamada T, Otsuka H, Kohiruimaki M, Ohta J, Yoshikawa H (2004) Well-differentiated biphasic synovial sarcoma in the atlanto-occipital joint of a Holstein cow. Veterinary Pathology, 41, 687e691. Pool RR, Thompson KG (2002) Tumors of joints. In: Tumors in Domestic Animals, 4th edit., DJ Meuten, Ed., Iowa State University Press, Ames, pp. 199e244. Rob F (2002) Letter to the Editor. Veterinary Pathology, 39, 413e414. Silva-Krott IU, Tucker RL, Meeks JC (1993) Synovial sarcoma in a cat. Journal of the American Veterinary Medical Association, 203, 1430e1431. Slayter MV, Boosinger TR, Inskeep W, Pool RR, D€ ammrich K et al. (1994) Synovial sarcoma. Histological Classification of Bone and Joint Tumors of Domestic Animals: World Health Organization International Histological Classification of Tumors of Domestic Animals, Armed Forces Institute of Pathology, Washington DC, p. 15. Tremblay C, Girard C, Dubreuil P, Desrochers A, Lanevschi A (2000) Synovial sarcoma in an Ayrshire heifer. Veterinary Pathology, 37, 357e359. Vail DM, Powers BE, Getzy DM, Morrison WB, McEntee MC et al. (1994) Evaluation of prognostic factors for dogs with synovial sarcoma: 36 cases (1986e1991). Journal of the American Veterinary Medical Association, 205, 1300e1307. Varma T, Adegboyega P (2012) Primary cardiac synovial sarcoma. Archives of Pathology and Laboratory Medicine, 136, 454e458. Yamate J, Aota M, Kuwamura M, Kotani T, Shimada T (2006) Synovial sarcoma of the tendon and tendon sheath in a dog. Journal of Veterinary Medical Science, 68, 983e986.
August 5th, 2013 ½ Received, Accepted, November 21st, 2013
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/jcpa
NEOPLASTIC DISEASE
A Non-joint Tissue Biphasic Synovial Sarcoma in a Dog N. Takimoto*, K. Suzuki†, T. Ogawa*, R. Segawa*, S. Hara*, M. Itahashi*,x, M. Kimura*,x, N. Iwasaki‡, K. Nishifuji‡ and M. Shibutani* *Laboratory of Veterinary Pathology, † Laboratory of Veterinary Toxicology, ‡ Laboratory of Veterinary Medicine, Tokyo University of Agriculture and Technology, Tokyo and x Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan
Summary A subcutaneous tumour was identified in the malar region of a 14-year-old neutered female mixed breed dog. The dog was humanely destroyed and necropsy examination was performed. The tumour did not invade neighbouring tissues and no metastasis was found. Microscopically, the tumour showed a range of features including the presence of multinucleated giant cells, chondrocyte differentiation and cystic or slit-like structures. All of these features are consistent with previously reported descriptions of synovial sarcomas in dogs. Mesenchymal cells accounted for the majority of the tumour, but cytokeratin-positive epithelioid components were also confirmed by immunohistochemistry. The tumour was diagnosed as a biphasic type of synovial sarcoma. Synovial sarcoma in man may develop in tissues unrelated to joints and this is the first report of a nonjoint synovial sarcoma in a dog. Ó 2013 Elsevier Ltd. All rights reserved. Keywords: biphasic tumour; dog; immunohistochemistry; synovial sarcoma
Synovial sarcomas arise in joints and have been reported in dogs, cats, cattle and ferrets (Tremblay et al., 2000; Oyamada et al., 2004). Canine synovial sarcomas occur mainly in the elbow or stifle and rarely involve the hip or jaw (Griffith et al., 1987; Karayannopoulou et al., 1992). Microscopically, synovial sarcomas are categorized into four subtypes: (1) spindle cell dominant, monophasic fibroblastic type, (2) epithelioid cell dominant, monophasic epithelioid type, (3) biphasic type and (4) poorly differentiated type. Of these subtypes, the fibroblastic type is predominant in animals (Fox et al., 2002). Although synovial sarcomas have several characteristic histological features, they are difficult to distinguish from other tumours such as malignant fibrous histiocytomas, fibrosarcomas, peripheral nerve sheath tumours, melanomas, chondrosarcomas
Correspondence to: K Suzuki (e-mail: [email protected]). 0021-9975/$ - see front matter http://dx.doi.org/10.1016/j.jcpa.2013.11.206
and giant cell tumours of the soft tissue (Loukopoulos et al., 2004). Despite the term ‘synovial’ sarcoma, the tissue of origin of these tumours remains controversial. In some reports, these tumours were derived from primitive mesenchymal precursor cells, which are located outside of the synovial membrane and have the ability to differentiate into epithelioid or fibroblastic cells (Mitchell and Hurov, 1979; Vail et al., 1994). In the present paper, we report a tumour of the jaw, unrelated to the joint, but with histological characters of a synovial sarcoma. A 14-year-old neutered female mixed breed dog was referred to a veterinary hospital for swelling of the left mandibular region. The swelling had enlarged markedly over a period of several months and the presence of the mass had prevented the dog from closing its left eye for the past 3 months. The clinical condition of the dog had worsened as the size of the tumour increased. Four months after the consultation, the dog was humanely destroyed. Post-mortem Ó 2013 Elsevier Ltd. All rights reserved.
Biphasic Synovial Sarcoma in a Dog
examination revealed a multilobulated, pale white mass (15 12 11 cm) in the subcutaneous tissue of the left cheek, extending to the base of the left ear. The mass did not invade the mandibular joint. No metastasis was found in any other tissues. A small amount of serous fluid leaked from the tumour on gross sectioning. The mass was fixed in 10% neutral buffered formalin and embedded in paraffin wax. Sections were stained with haematoxylin and eosin (HE) and Masson’s trichrome stain. Immunohistochemistry (IHC) was performed using a VECTASTAINÒ Elite ABC Kit (Vector Laboratories Inc., Burlingame, California, USA). The primary antibodies used were: anti-cytokeratin AE1/AE3 (CK AE1/AE3; clones AE1/AE3, mouse monoclonal, 1 in 50 dilution; Dako, Glostrup, Denmark), anti-cytokeratin (clone MNF116, mouse monoclonal, 1 in 50 dilution; Dako), anti-vimentin (clone V9, mouse monoclonal, 1 in 50 dilution; Dako), anti-chromogranin A (CGA; rabbit polyclonal, 1 in 3,000 dilution; Yanaihara Institute Inc., Shizuoka, Japan), anti-S100 protein (rabbit polyclonal, 1 in 400 dilution; Dako), antineuron-specific enolase (NSE; clone BBS/NC/VIH14, mouse monoclonal, 1 in 100 dilution; Dako), anti-ionized calcium-binding adapter molecule-1 (Iba-1; rabbit polyclonal, 1 in 250 dilution; Wako Pure Chemical Co., Osaka, Japan), anti-glial fibrillary acidic protein (GFAP; clone 6F2, mouse monoclonal, 1 in 50 dilution; Dako), anti-a-smooth muscle actin (a-SMA; clone 1A4, mouse monoclonal, 1 in 100 dilution; Dako), anti-desmin (clone D33, mouse monoclonal, 1 in 2 dilution; Dako), anti-von Willebrand factor (vWF; rabbit polyclonal, 1 in 500 dilution; Dako), anti-melan-A (clone A103, mouse monoclonal, 1 in 25 dilution; Dako) and antiosteocalcin (clone OC4-30, mouse monoclonal, 1 in 100 dilution; GeneTex Inc., Los Angeles, California, USA). Antigen retrieval was performed by either microwaving in 10 mM citrate buffer (pH 6.0) at 90 C for 10 min (NSE, GFAP and vWF), autoclaving in 10 mM citrate buffer (pH 6.0) at 121 C for 10 min (CK AE1/AE3, CK MNF116, vimentin, Iba-1, aSMA and melan-A), incubating in a hot water bath in 10 mM citrate buffer (pH 6.0) at 60 C for 20 min (chromogranin A) or covering sections with Proteinase K and incubating for 10 min at 37 C (S100 and osteocalcin). No antigen retrieval methods were performed for the desmin IHC. Sections were treated with H2O2 0.3% in methanol for 30 min to block endogenous peroxidase activity. The sections were blocked with normal goat or horse serum at room temperature for 30 min. Each section was incubated with primary antibody at 4 C overnight and then with a secondary antibody against mouse or rabbit
205
immunoglobulin (Ig) G applied at room temperature for 30 min. The ABC reagent was applied at room temperature for 30 min. Antibody-binding was ‘visualized’ with 3, 30 -diaminobenzidine (DAB) chromogen and counterstaining with haematoxylin. Microscopically, the tumour was composed of round and spindle cells with an oval to round nucleus and eosinophilic cytoplasm with ill-defined borders. Mitotic figures were frequently observed (mitotic index 11.2 per 10 40 objective fields), particularly in cells that surrounded blood vessels or formed slitlike spaces (Fig. 1). A large area of necrosis was present. Between the neoplastic lobules, there was a large amount of collagen. Tumour cells with chondroid differentiation or multinucleated giant cells were also observed (Fig. 2). In some regions, there were cystic structures with neoplastic cells within the cystic space. The tumour cells near blood vessels and those forming slit-like structures were positive for CK AE1/AE3 and all other cell components expressed vimentin (Figs. 3 and 4). Iba-1-positive cells, consistent with macrophages, were scattered throughout the tumour. These cells were negative for all other antibodies. Cystic or slit-like structures and multinucleated giant cells are commonly documented in animal synovial sarcomas (Lipowitz et al., 1979; Silva-Krott et al., 1993; Slayter et al., 1994; Pool and Thompson, 2002; Yamate et al., 2006). In addition, the presence of chondroid differentiation has also been reported in the dog (Griffith et al., 1987). Similar findings were also observed in the present case, leading to a diagnosis of synovial sarcoma. The tumour was formed of both cytokeratin-positive epithelioid and vimentin-positive mesenchymal components, but was negative for the other antibodies tested. These
Fig. 1. Neoplastic cells proliferating around blood vessels or slitlike spaces (arrow). Necrotic areas (arrowhead) and cystic structures (asterisk) are also present. HE. 40.
206
N. Takimoto et al.
Fig. 2. Chondroid cells (arrowhead) and multinucleated giant cells (arrows) are present in the tumour. HE. 200.
Fig. 4. Most of the neoplastic cells express vimentin. IHC. 200.
results suggest that the origin of the tumour cells was not neurological (NSE, GFAP and S100 protein negative) or related to neuroendocrine cells (CGA negative), smooth or striated muscles (a-SMA and desmin negative), melanocytic cells (melan-A negative) or osteoblastic cells (osteocalcin negative). A potential differential diagnosis for the tumour was sarcomatoid carcinoma; however, the tumour had no definite epithelial component and the majority of the neoplastic cells were vimentin-positive mesenchymal components. Moreover, the morphological features (i.e. multinucleated giant cells, chondroid differentiation and cystic or slit-like structures) were not consistent with sarcomatoid carcinoma. In contrast to human cases, which have a glandular proliferation pattern, synovial sarcomas in dogs do not have a definite epithelial component (Vail et al., 1994). In the present case, histologically recognizable
epithelioid cells were sparse, but epithelial components were confirmed by the presence of cytokeratin-positive neoplastic cells. Although use of the term ‘biphasic’ suggests that the tumour had both definitive epithelioid and fibroblastic cells, this tumour could be classified as ‘biphasic-type’ from the IHC results. Therefore, considering the immunohistochemical and histological characteristics, the tumour was diagnosed as a biphasic type of synovial sarcoma. The definition of synovial sarcoma differs between domestic animals and man (Rob, 2002). In veterinary pathology, information about synovial sarcomas has been extrapolated from the established definition in human medicine, which requires a joint-derived origin for diagnosis as a synovial sarcoma (Slayter et al., 1994; Pool and Thompson, 2002). Conversely, a variety of ‘synovial sarcomas’ reported in man have occurred in non-joint tissues such as the lung, heart and kidney (Koyama et al., 2001; Nuwal et al., 2012; Varma and Adegboyega, 2012). Because more than 90% of human synovial sarcomas have a unique chromosomal translocation between X and the 18th chromosome, leading to the formation of the SS18-SSX fusion gene, the presence of SS18-SSX transcripts is a reliable diagnostic molecular marker for synovial sarcomas regardless of tumour origin (Craig et al., 2002; Naka et al., 2010). Therefore, although the name ‘synovial sarcoma’ was given by pathologists who believed that this tumour had derived from the normal synovium, most synovial sarcomas in man do not arise from the synovium, but from mesenchymal precursor cells. In addition, the hypothesis that ‘synovial sarcomas’ are derived from mesenchymal precursor cells may support the morphological variation, such as the presence of multinucleated giant cells, chondroid differentiation
Fig. 3. Neoplastic cells close to blood vessels and slit-like structures express cytokeratin AE1/AE3. IHC. 200.
Biphasic Synovial Sarcoma in a Dog
and cystic or slit-like structures, observed in the present tumour. Synovial sarcomas occurring in nonjoint tissues have not been previously reported in animals, but we suggest that, as in humans, synovial sarcomas in animals can originate in tissues unrelated to the joints. Because a unique chromosomal translocation in synovial sarcomas has not been reported in animals, it is difficult to make a definitive diagnosis at present. Further investigation may be required to refine the notion of synovial sarcomas in animals and this case provides important information for that reconsideration.
Conflicts of Interest The authors declare no conflicts of interest.
Acknowledgements The authors thank Mrs. S. Suzuki for technical assistance in preparing the histological specimens.
References Craig LE, Julian ME, Ferracone JD (2002) The diagnosis and prognosis of synovial tumors in dogs: 35 cases. Veterinary Pathology, 39, 66e73. Fox DB, Cook JL, Kreeger JM, Beissenherz M, Henry CJ (2002) Canine synovial sarcoma: a retrospective assessment of described prognostic criteria in 16 cases (1994e1999). Journal of the American Animal Hospital Association, 38, 347e355. Griffith JW, Frey RA, Sharkey FE (1987) Synovial sarcoma of the jaw in a dog. Journal of Comparative Pathology, 97, 361e364. Karayannopoulou M, Kaldrimidou E, Dessiris A (1992) Synovial sarcoma in a dog. Journal of Veterinary Medical Science, 39, 76e80. Koyama S, Morimitsu Y, Morokuma F, Hashimoto H (2001) Primary synovial sarcoma of the kidney: report of a case confirmed by molecular detection of the SYT-SSX2 fusion transcripts. Pathology International, 51, 385e391. Lipowitz AJ, Fetter AW, Walker MA (1979) Synovial sarcoma of the dog. Journal of the American Veterinary Medical Association, 174, 76e81. Loukopoulos P, Heng HG, Arshad H (2004) Canine biphasic synovial sarcoma: case report and immunohistochemical characterization. Journal of Veterinary Science, 5, 173e180.
207
Mitchell M, Hurov LI (1979) Synovial sarcoma in a dog. Journal of the American Veterinary Medical Association, 173, 53e55. Naka N, Takenaka S, Araki N, Miwa T, Hashimoto N et al. (2010) Synovial sarcoma is a stem cell malignancy. Stem Cells, 28, 1119e1131. Nuwal P, Dixit R, Shah NS, Samaria A (2012) Primary monophasic synovial sarcoma lung with brain metastasis diagnosed on transthoracic FNAC: report of a case with literature review. Lung India, 29, 384e387. Oyamada T, Otsuka H, Kohiruimaki M, Ohta J, Yoshikawa H (2004) Well-differentiated biphasic synovial sarcoma in the atlanto-occipital joint of a Holstein cow. Veterinary Pathology, 41, 687e691. Pool RR, Thompson KG (2002) Tumors of joints. In: Tumors in Domestic Animals, 4th edit., DJ Meuten, Ed., Iowa State University Press, Ames, pp. 199e244. Rob F (2002) Letter to the Editor. Veterinary Pathology, 39, 413e414. Silva-Krott IU, Tucker RL, Meeks JC (1993) Synovial sarcoma in a cat. Journal of the American Veterinary Medical Association, 203, 1430e1431. Slayter MV, Boosinger TR, Inskeep W, Pool RR, D€ ammrich K et al. (1994) Synovial sarcoma. Histological Classification of Bone and Joint Tumors of Domestic Animals: World Health Organization International Histological Classification of Tumors of Domestic Animals, Armed Forces Institute of Pathology, Washington DC, p. 15. Tremblay C, Girard C, Dubreuil P, Desrochers A, Lanevschi A (2000) Synovial sarcoma in an Ayrshire heifer. Veterinary Pathology, 37, 357e359. Vail DM, Powers BE, Getzy DM, Morrison WB, McEntee MC et al. (1994) Evaluation of prognostic factors for dogs with synovial sarcoma: 36 cases (1986e1991). Journal of the American Veterinary Medical Association, 205, 1300e1307. Varma T, Adegboyega P (2012) Primary cardiac synovial sarcoma. Archives of Pathology and Laboratory Medicine, 136, 454e458. Yamate J, Aota M, Kuwamura M, Kotani T, Shimada T (2006) Synovial sarcoma of the tendon and tendon sheath in a dog. Journal of Veterinary Medical Science, 68, 983e986.
August 5th, 2013 ½ Received, Accepted, November 21st, 2013
