JPC SYSTEMIC PATHOLOGY

MUSCULOSKELETAL SYSTEM

April 2025

M-N07 (NP)

 

SIGNALMENT (JPC #3102342): 10-year-old male rottweiler, canine (Canis familiaris)

HISTORY: This dog presented with a 3-month history of painless swelling of the left pelvic limb that was treated empirically with corticosteroids but showed no improvement. The swelling involved the thigh, stifle, and crural region, but it was not associated with lameness and there was no history of trauma.

HISTOPATHOLOGIC DESCRIPTION: Joint capsule with attached muscle and tertiary lymphoid structure: Arising from the joint capsule, elevating the predominantly intact synovial lining, forming multifocal nodular projections into the joint space and adjacent tertiary lymphoid structure, and compressing the multifocally mildly atrophic skeletal muscle is an unencapsulated, paucicellular, multilobulated, well-demarcated, expansile neoplasm composed of poorly defined bundles of spindle to stellate cells that multifocally are embedded within and surround lakes of myxomatous. Neoplastic cells have distinct cell borders, a small amount of occasionally vacuolated eosinophilic cytoplasm, and an irregularly round, occasionally compressed and peripheralized nucleus with finely stippled chromatin and one variably distinct nucleolus. Anisocytosis and anisokaryosis are minimal and there is <1 mitosis per 2.37 mm squared. The synoviocytes lining the articular luminal surface and overlying the neoplasm are multifocally either attenuated or occasionally hyperplastic and hypertrophic, forming multiple layers up to five cells thick. There are scattered foamy macrophages throughout the neoplasm and percolating through the tertiary lymphoid structure that, along with the remaining synoviocytes, occasionally contain intracytoplasmic hemosiderin.

MORPHOLOGIC DIAGNOSIS: Joint: Synovial myxoma, Rottweiler, canine

GENERAL DISCUSSION:

• Second most common neoplasm occurring in the joints of dogs; also reported in cats
• Tumors can theoretically arise from either of the two synoviocyte populations:
  • Type A synoviocytes: Histiocytic origin; phagocytic; immunoreactive for CD18 and IBA-1
  • Type B synoviocytes: Termed “fibroblastic” synoviocytes; however, these cells produce the viscous glycosaminoglycan component of joint fluid, not collagen; currently there is no immunohistochemical marker for this population
• Synovial tumors of canines:
• Histiocytic sarcoma: Most common joint tumor in dogs; may arise from either type A synoviocytes or subintimal dendritic cells; immunoreactive for CD18; may also express other leukocyte markers (i.e. CD1, CD11c, MHC II), but this requires frozen tissue specimens
• Synovial myxoma: Second most common joint tumor in dogs; may arise from type B synoviocytes (not proven); previously often diagnosed as myxosarcoma or nodular synovial hyperplasia
  • A recent publication suggests that these neoplasms be diagnosed as synovial myxosarcoma because histologic features do not indicate which will metastasize to lymph nodes and therefore all should be treated as potentially malignant (Glahn, J Vet Diagn Invest, 2024)
• “Synovial cell sarcoma” and “synovial sarcoma” are terms that should not be used in veterinary medicine; these are human diagnoses that are not necessarily synovial in origin and do not translate well to the condition in animals

TYPICAL CLINICAL FINDINGS:

• Large-breed, middle-aged dogs are most commonly affected
• Breed predilection: Doberman pinscher, Labrador retriever
• Slow-growing tumors with long (months to years) history of clinical signs preceding diagnosis
• Prognosis is typically good with surgical excision even if neoplastic cells extend to surgical margins of amputation sites; however, can be locally invasive and therefore are considered by some to be a low-grade malignancy

TYPICAL GROSS FINDINGS:

• The neoplasm affects a single joint; stifle and digit > tarsus, elbow, carpus, vertebral facets
• Soft, white, translucent, gelatinous nodules and pockets of viscous fluid that often line the entire inner joint capsule and can fill the joint cavity; exudes abundant clear, viscous fluid on cut section
• +/- bone lysis on both sides of the affected joint, hindering differentiation from malignancies
• +/- grossly invasive growth along fascial planes outside of the joint capsule into adjacent bones and muscle

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Characteristic paucicellular round nodules composed of long spindle to stellate-shaped cells with small, hyperchromatic nuclei and rare mitoses suspended in abundant poorly vascular myxoid matrix
• Foamy macrophages are often scattered throughout the neoplasm and there may be cystic, fluid-filled spaces lined by synoviocytes or compressed mesenchymal cells
• Histologic features are not a good indication of which neoplasms are going to metastasize to local lymph nodes (Glahn, J Vet Diagn Invest, 2024)

ADDITIONAL DIAGNOSTICS:

• Histochemical stains:
  • Alcian blue: Large amount of Alcian blue positive (alcianophilic) mucopolysaccharide matrix (due to hyaluronic acid)
• Immunohistochemistry:
  • Lack specific IHC markers; however, tumors are immunoreactive for vimentin
  • Cytokeratin is an outdated recommendation and should not be used; stems from human synovial sarcomas which are of non-synoviocyte origin
• Cytology: Pleomorphic spindle shaped and occasionally epithelioid neoplastic cells with variable amounts of matrix; histology +/- IHC are required for definitive diagnosis

DIFFERENTIAL DIAGNOSIS:

Synovial and juxta-articular tumors in the dog:

• Histiocytic sarcoma: The most common joint tumor of dogs; dendritic cell origin; most commonly affects the stifle joint; multilobulated, infiltrative, less distinctly nodular than synovial myxoma; cells often have vacuolated cytoplasm and are round to polygonal to spindloid, often admixed with inflammation; CD18 immunoreactive; breed predilection in Bernese mountain dogs, Rottweilers, Bullmastiffs, Golden retrievers, Labrador retrievers, and Flat coated retrievers especially with a pre-existing joint issue (e.g. ruptured cranial cruciate ligament); joint histiocytic sarcoma has a more favorable outcome than histiocytic sarcoma of other locations
• Other sarcomas (fibrosarcoma, hemangiopericytoma, liposarcoma, peripheral nerve sheath tumors, and other soft tissue sarcomas) can arise within or adjacent to joints and can have myxoid variants; similar methods of differentiating soft tissue sarcomas should be used
• Rhabdomyosarcoma including embryonal rhabdomyosarcoma with myxoid stroma
• Osteosarcoma (M-N02)
• Multicentric lymphosarcoma
• Chondrosarcoma (M-N03): arising from cartilaginous metaplasia or rests of cartilage embedded within the synovium rather than mitotically inactive articular cartilage
• Periarticular fibroma: Uncommon; discrete, firm, nodular, white mass attached to the lateral or medial joint capsule or tendon sheath; most often affects the carpal joint; may represent focal fibrous scar tissue but are typically more spherical; some can have dissecting bands of myxomatous stroma

Non-neoplastic synovial lesions:

• Synovial chondromatosis/osteochondromatosis: firmer than synovial myxoma
• Synovial cysts: Grossly appear as fluctuant swellings most common in and around the elbows in geriatric cats or intraspinal and extradural in dogs; microscopically are periarticular and typically lined by suspected synoviocytes

COMPARATIVE PATHOLOGY:

Synovial tumors in other species:

• Cats: Most commonly occur adjacent to the elbow, often along the medial aspect, in aged cats with concurrent degenerative joint disease; lesions appear to represent a continuum of synovial cysts progressing towards synovial myxomas with no reports of metastasis (Craig, Vet Pathol, 2020)
• Birds:
• “Synovial sarcomas” have been occasionally reported in birds; composed of oviblastic (epithelioid) cells and fusiform cells with spaces and clefts; can be difficult to distinguish from air sac carcinoma of bone; can metastasize widely
• Chondromatosis affecting the synovium and peri-articular tissues is reported in raptors
• Reptiles: One case report of a unilateral synovial myxoma in the hip joint of a female central bearded dragon (Pogona vitticeps) (Rasper-Hössinger, J Vet Diagn Invest, 2025)

Non-synovial myxomas/myxosarcomas:

• Rabbits: Myxomatosis (I-V10), caused by the myxoma virus (Poxviridae family, Leporipoxvirus genus), results in exophytic, gelatinous skin tumors (myxomas) typically on the face and perineum in wild rabbits and hares; systemic disease in domestic rabbits
• Koalas: Few koalas reported with multiple intra-abdominal serosal myosarcomas; histologically similar to myxomatous mesothelioma, but lack cytokeratin immunopositivity
• Horses: Myxosarcoma is rare in horses, with metastasis only reported to lymph nodes except for a case report (Samuelson, 2018) of metastatic myxosarcoma in a Quarter Horse with large retroperitoneal gelatinous mass and similar nodules in the lungs, liver, mesentery, cecum, and caudal mesenteric artery

REFERENCES:

1. Barger AM. Chapter 14: Musculoskeletal System. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:494.
2. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016: 261-263.
3. Craig LE. Sarcomas of synovial origin in dogs: An updated review. Vet Pathol. 2025;62(1):13-19. 
4. Craig LE, Dittmer KE, Thompson KG. Bones and joints. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:159-163.
5. Craig LE, Krimer PM, O'Toole AD. Synovial Cysts and Myxomas in 16 Cats. Vet Pathol. 2020;57(4):554-558.
6. Delaney MA, Treuting PM, Rothenburger JL. Lagamorpha. In: Terio KA, McAloose D, St. Leger J. Pathology of Wildlife and Zoo Animals. London, England: Elsevier; 2018:487-489.
7. Glahn I, Donovan TA, Bertram CA. Synovial myxoma or myxosarcoma? Lymph node metastasis in 2 dogs. J Vet Diagn Invest. 2024;36(6):874-878.
8. Higgins D, Rose K, Spratt D. Monotremes and marsupials. In: Terio KA, McAloose D, St. Leger J. Pathology of Wildlife and Zoo Animals. London, England: Elsevier; 2018:464.
9. Kim R. Musculoskeletal System. In: Schmidt RE, Struthers JD, Phalen DN, eds. Pathology of Pet and Aviary Birds. 3rd ed. Ames, IA: John Wiley and Sons Inc; 2024:368.
10. Olson EJ, Dykstra JA, Armstrong AR, Carlson CS. Bones, Joints, Tendons, and Ligaments. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 1090-1091
11. Rasper-Hössinger M, Kunze PE, Schmid D, Dervas E. Synovial myxoma with cyst formation in the hip joint of a central bearded dragon. J Vet Diagn Invest. 2024;36(6):891-895.
12. Samuelson JP, Echeverria KO, Foreman JH, Frederickson RL, Sauberli D, Whiteley HE. Metastatic myxosarcoma in a Quarter Horse gelding. J Vet Diagn Invest. 2018;30(1):121-125.
13. Schmidt RE, Reavill DR, Phalen DN. Musculoskeletal system. In: Schmidt RE, Reavill DR, Phalen DN, ed. Pathology of Pet and Aviary Birds. 2^nd Ames, IA: Wiley Blackwell; 2015:218.

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