Malignant synovial and perisynovial tumor in the stifle joint of a juvenile cat: histopathological and immunohistochemical findings

Abstract

Case summary

A 1-year-old domestic cat was presented with lameness and progressive swelling of the right stifle joint. The condition had been present for 1 month; during the consultation, it was evident that the cat was not bearing weight on the limb, which also exhibited muscle atrophy and tremors, as well as signs of pain upon manipulation. After sedation, crepitus was noted at the femorotibial-patellar joint. Radiographic examination showed osteolysis, and during clinical exploration, tumor cells destroying the joint were confirmed by cytology. Surgical excision was performed via limb amputation, and the mass was found to measure 3 × 5 × 3 cm. Histopathological analysis showed a biphasic neoplasm composed of spindle-shaped mesenchymal-like cells and large epithelial-like cells. Normal joint structures, including the capsule and articular cartilage, were completely effaced by neoplastic infiltration, including similar neoplastic changes in distal femur and proximal tibia epiphyses, metaphyses and diaphyses. Tumor cells were immunopositive for either vimentin or cytokeratin. Based on the 2020 World Health Organization (WHO) classification, the tumor was diagnosed as a malignant synovial and perisynovial neoplasm. The cat died 3 months after surgery; at the owner’s request, no post-mortem examination was conducted.

Relevance and novel information

 To the authors’ knowledge, this is the first reported case of malignant synovial and perisynovial neoplasia diagnosed in a juvenile cat in accordance with the 2020 WHO classification. This case provides new insights into the histopathological findings of this rare tumor type in feline patients.

Plain language summary

Rare joint cancer in a young cat

A 1-year-old domestic cat was examined because of lameness and progressive swelling of the right stifle joint that had been present for about 1 month. The cat was unable to bear weight on the limb and showed muscle loss, tremors and pain when the joint was moved. Imaging showed bone destruction around the joint. Examination of cells collected from the joint indicated the presence of a tumor. The affected limb was surgically removed, and the mass measured 3 × 5 × 3 cm. Microscopic examination showed an invasive cancer made up of two different types of tumor cells that had destroyed the normal structures of the joint and extended into the surrounding bones. Additional tests confirmed that the tumor was a malignant synovial and perisynovial neoplasm, according to the 2020 World Health Organization classification. The cat died 3 months after surgery. To the authors’ knowledge, this is the first reported case of this type of joint cancer in a young cat diagnosed using the current classification system.

Introduction

Malignant tumors arising around the joints in cats are rare, with reported types including osteosarcoma, chondrosarcoma, fibrosarcoma, histiocytic sarcoma, plasma cell tumors and synovial cell sarcoma.^{1 –5} In humans, the pathogenesis of joint malignancies is complex. ⁶ Tumors originating in the joint capsule can arise from various cell types within the capsule or periarticular tissues, and several have been associated with specific gene translocations, making genetic testing a valuable diagnostic tool.^{6 –9}

In animals, the World Health Organization (WHO) classification previously used the term ‘synovial sarcoma’ until 2015. ¹⁰ The revised 2020 classification replaced this with the term ‘malignant synovial and perisynovial tumor’. ¹¹ In cats, synovial sarcomas are typically reported in individuals aged 6–10 years, although a case has been described in a 2.5-year-old cat. ¹²

This report describes the histopathological and immunohistochemical (IHC) findings of a malignant synovial and perisynovial tumor in the stifle joint of a 1-year-old growing cat.

Case description

A 1-year-old, male mixed-breed cat was presented to the Department of Clinics & Veterinary Hospital, Faculty of Veterinary, Universidad de la República (Udelar, Montevideo, Uruguay) with right hindlimb lameness. Clinical examination revealed difficulty ambulating and muscle atrophy of the affected limb. Radiographs of the right stifle joint showed severe osteolytic lesions and cortical bone destruction of the distal femur and proximal tibia, with no evidence of proliferative bone formation (Figure 1). The normal joint outline was absent, and the patella presented severe osteolysis, making visualization difficult. Thoracic radiographs obtained at the time of the initial consultation showed no abnormalities (Figure 2). The open growth plates of the shoulders were visible, confirming that the bone was still growing (Figure 3). Treatment with meloxicam was initiated as 0.2 mg/kg PO on day 1 and then continued at 0.1 mg/kg PO q24h. Ranitidine was administered at 2 mg/kg PO q12h. After a fine-needle puncture, diagnostic cytology revealed pleomorphic tumor cell proliferation, characterized by a moderate number of osteoclasts, some fibroblast-like cells and a few macrophages, with a moderate number of epithelial-like cell plaques with anisocytosis, anisokaryosis, macrokaryosis, evident nucleoli and nuclear molding. These atypical morphological characteristics suggested high-grade malignancy neoplasia. Amputation of the right hindlimb was performed. The cat remained stable for 3 months postoperatively, until it came back to the hospital with severe dyspnea. To avoid further respiratory distress and because of suspicion of thoracic effusion, thoracic ultrasound was performed in sternal recumbency instead of radiography. Ultrasound revealed a moderate amount of anechoic pleural effusion, hepatization of caudal pulmonary lobes with irregular borders and heterogeneous pulmonary parenchyma. In addition, the remaining lobes showed irregular pleuropulmonary borders, multiple B-lines and irregular, rounded hypoechoic areas of different sizes (Figure 4). These findings were suggestive of a pulmonary nodular process, possibly metastatic in nature. The cat was euthanized because of respiratory distress. Necropsy was declined.

Figure 1

Mediolateral radiographic image of the right knee joint of a 1-year-old cat diagnosed with synovial sarcoma at initial consultation. Radiographic findings show osteolytic changes in the distal femur and proximal tibia, and the normal structure of the knee joint disappears (arrow)

Figure 2

(a) Right lateral and (b) ventrodorsal thoracic radiographs of a 1-year-old cat diagnosed with synovial sarcoma at the initial consultation, showing no radiographic abnormalities

Figure 3

Detail of a laterolateral thoracic radiographic image of a 1-year-old cat diagnosed with synovial sarcoma at initial consultation. The open growth plate of the left shoulder is visible (arrow), confirming that the bone is still growing

Figure 4

(a,b) Transverse intercostal ultrasound images of a 1-year-old cat diagnosed with synovial sarcoma. (a) Hypoechoic area (between calipers) measuring 0.69 × 0.48 cm on pulmonary lobe border. (b) Anechoic pleural effusion (asterisks) and hepatization (white arrowheads) of the right caudal pulmonary lobe, with irregular borders and heterogeneous parenchymal echotexture. The overall findings are suggestive of a pulmonary infiltrative process, possibly metastatic in nature

Immediately after surgery, the entire excised limb was submitted for histopathological evaluation. On macroscopic examination, a 3 × 5 × 3 cm white to gray, firm mass was observed, centered on the stifle joint. The tumor infiltrated the epiphysis of the proximal tibia and distal femur, with greater involvement of the tibia. Tumor extension into the bone marrow cavities of both bones was noted, and the normal joint architecture was entirely effaced. The patella could not be identified.

Histopathological examination was performed on the resected joint tissue. Samples were fixed in 10% neutral-buffered formalin, decalcified with 3% nitric acid, embedded in paraffin, sectioned at 4 μm, and stained with hematoxylin and eosin. Masson’s trichrome stain was used for connective tissue evaluation. After histopathological results, IHC studies were performed on paraffin-embedded sections using mouse monoclonal antibodies specific for pan-cytokeratin (AE1/AE3, dilution 1:200; Biocare Medical) and for vimentin (dilution 1:600; Biocare Medical), applied overnight at 4°C, followed by the MACH 4 Universal HRP-polymer detection system (Biocare Medical). Positive antigen-antibody reactions were observed by incubation with 3.3’-diaminobenzidine-tetrahidrochloride (DAB). All samples were counterstained with Mayer’s hematoxylin. All slides were reviewed by four veterinary pathologists. For negative control, primary antibody was replaced with phosphate-buffered saline and positive control followed the manufacturer’s instructions (Figure 5).

Figure 5

(a) Cat, skin. Immunohistochemical (IHC) negative control for cytokeratin antigen, showing immunonegative epithelial cells of the epidermis and dermal ducts (arrowheads). Scale = 100 μm. (b) Cat, skin. IHC positive control for cytokeratin antigen, showing immunopositive tumoral epithelial cells in a case of feline basocellular carcinoma (arrowheads); immunonegative spindle cells are bundles of fibroblasts. Scale = 100 μm. (c) Cat, skin. IHC negative control for vimentin antigen, showing immunonegative bundles of fibroblasts in another case of feline basocellular carcinoma (arrowheads). Scale = 100 μm. (d) Cat, palpebral skin. IHC positive control for vimentin antigen, showing overexpression of immunopositive tumoral cells in a case of palpebral melanoma (arrowheads). Scale = 100 μm

Tumor cells proliferated predominantly in the joint capsule, infiltrating the articular cartilage, epiphysis, metaphysis and surrounding soft tissues (Figure 6). At the tibial epiphysis, tumor cells destroyed the cartilage and invaded the bone marrow cavity, replacing much of the marrow with neoplastic tissue. Extensive necrosis was observed. Remnants of trabecular bone and articular cartilage were surrounded by tumor cells. Neoplastic infiltration extended to the diaphyseal region and into surrounding muscle and connective tissue, with concurrent inflammation and necrosis. Vascular invasion by neoplastic epithelial-like cells was also noted (Figure 7).

Figure 6

Histopathological findings in the bone marrow cavity of the epiphysial region of one of the bones forming the femorotibiopatellar joint. Tumor cells (asterisks) proliferate with destruction of the articular cartilage at the femorotibiopatellar joint in a 1-year-old cat. Hematoxylin and eosin staining. Scale = 70 μm

Figure 7

Histopathological findings in the epiphysis of one of the bones forming the femorotibiopatellar joint in a 1-year-old cat. Tumor epithelial-like cell thrombi invading blood vessels (asterisks). An artifactual eosinophilic deposit is evident (a). Hematoxylin and eosin staining. Scale = 100 μm

The tumor had a biphasic pattern with spindle-shaped mesenchymal-like cells and large epithelial-like cells (Figure 8). Spindle cells exhibited oval-to-round atypical nuclei and abundant cytoplasm arranged in interwoven bundles, resembling fibrosarcoma. These cells stained positively with Masson’s trichrome (Figure 9). Epithelial-like cells exhibited marked nuclear atypia with prominent nucleoli, eight mitoses within an area of 2.37 mm², four multinucleated cells per high power field, anisocytosis, anisokaryosis and cytokeratin immunopositivity (Figure 10). Spindle cells were immunopositive for vimentin (Figure 11).

Figure 8

Histopathological findings in the connective tissue around the joint of a 1-year-old cat. Epithelial-like tumor cells proliferate mainly in this region. Cellular atypia is evident (arrows), with associated inflammatory infiltrate (asterisk). Hematoxylin and eosin staining. Scale = 30 μm

Figure 9

Histopathological findings in the connective tissue around the joint of a 1-year-old cat. Spindle-shaped tumor cells proliferate, producing dense bundles of collagen fibers (asterisks), together with epithelial-like tumor cells. Masson’s trichrome staining. Scale = 100 μm

Figure 10

Immunohistochemical findings in the joint of a 1-year-old cat. Some tumor cells in the epithelial component are positive for cytokeratin antigen. Scale = 100 μm. Top right: Inset showing detail of immunopositive rounded epithelial-like tumor cells. Scale = 50 μm

Figure 11

Immunohistochemical findings in the joint of a 1-year-old cat. Some tumor cells in the mesenchymal component are positive for the antigen vimentin. Immunohistochemistry. Scale = 100 μm. Top right: Inset showing detail of immunopositive spindle-shaped tumor cells. Scale = 50 μm

Discussion

Malignant periarticular tumors in cats are uncommon.^{1 –5} Although it is stated that malignant tumors in the stifle joint and surrounding tissues are rare in dogs, several reports exist.^{13 –19} Although genetic diagnosis plays an important role in humans, its application in veterinary medicine is still emerging.^{6 –9} In the near future, TLE1 could became an interesting diagnostic IHC tool to explore as biomarker for synovial sarcoma in companion animals. Diagnostic terminology has also evolved; the term ‘synovial sarcoma’ used in the 2015 WHO classification ¹⁰ was replaced by ‘malignant synovial and perisynovial tumor’ in the 2020 edition. ¹¹ Furthermore, the diagnostic term ‘synovial sarcoma’ was used in dogs until recently. ¹³

In the present case, histopathological evaluation revealed a biphasic tumor with both mesenchymal and epithelial components. Spindle cells showed deposition on Masson’s trichrome and positive vimentin expression, while epithelial-like cells were cytokeratin-positive. Histiocytic sarcoma, which may resemble epithelial tumors, was excluded based on morphology. In addition, tumor cells in histiocytic sarcoma are negative for cytokeratin. ⁵ Similarly, a reported case of synovial cell sarcoma arising in the tarsocrural joint was immunoreactive for vimentin, and only the larger polygonal cells were positive for cytokeratin. ¹² It has been reported that the differential diagnosis of synovial cell sarcoma requires IHC examination for at least vimentin and cytokeratin. ¹³ In the present case, synovial cell sarcoma was excluded based on the observed histopathological changes. Histiocytic sarcoma was also ruled out based on IHC findings. Although the tumor closely resembled previously reported cases of synovial cell sarcoma in cats,^{3,12,20 –22} the resultant diagnosis was aligned with the 2020 WHO classification as a malignant synovial and perisynovial tumor. Synovial tumors have been typically reported in older cats (aged 6–10 years).^{20 –22} The persistence of an epiphyseal cartilage plate in this case indicated the patient was still skeletally immature. Thus, to the authors’ knowledge, this is the first report of such a tumor in a juvenile cat.

The cat’s death 3 months after surgery may have been due to metastasis, as vascular invasion was confirmed histologically. Previous reports have described pulmonary metastasis after amputation for synovial cell sarcoma. ²¹ In the present case, a necropsy was not permitted by the owner, preventing diagnosis of metastatic lung disease or the identification of any other metastatic sites of this neoplasia.

Conclusions

Based on the histopathological features of this biphasic neoplasm composed of mesenchymal and epithelial-like tumor cells, together with the IHC positivity for vimentin and cytokeratin, and in accordance with the 2020 WHO classification, a diagnosis of malignant synovial and perisynovial tumor of the stifle joint was established in this juvenile cat.