JPC SYSTEMIC PATHOLOGY
MUSCULOSKELETAL SYSTEM
APRIL 2022
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 extensions into the joint space and the 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 surround lakes of paucicellular myxomatous matrix and are embedded within an abundant myxomatous matrix.  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 prominent nucleolus. Anisocytosis and anisokaryosis are minimal and mitotic figures average 0-1 per 2.37 sq mm.  The synoviocytes lining the articular luminal surface and overlying the neoplasm are multifocally either attenuated or occasionally hyperplastic and hypertrophic, forming multiple layers of plump, cuboidal synoviocytes up to five cells thick.  There are also 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:

• Primary synovial tumors are uncommon in dogs and very rare in other species
• 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
• “Synovial cell sarcoma:” Should not be diagnosed according to one primary reference; in humans, synovial cell sarcomas are characterized by a specific chromosomal translocation, are not of synovial origin, and are not restricted to the joints; neoplasms previously diagnosed as “synovial cell sarcomas” likely represent soft tissue sarcomas such as peripheral nerve sheath tumors, perivascular wall tumors, and fibrosarcomas

 

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
• May show bone lysis on both sides of the affected joint, hindering differentiation from malignancies
• May have 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

 

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 vimentin immunopositive

 

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; described as being typically composed of mucin-containing and fusiform cells but may contain an epithelial cell type as well; can be difficult to distinguish from air sac carcinoma of bone
• Chondromatosis affecting the synovium and peri-articular tissues is reported in raptors

 

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
• Dog: A case report (Choi, J Vet Diagn Invest. 2017) of a laryngeal myxosarcoma that histologically contained eosinophilic crystals identified most likely as hemoglobin crystals and not Charcot-Leyden crystals; this report suggests that Charcot-Leyden crystals are human-specific
• 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, J Vet Diagn Invest. 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. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016: 261-263.
2. Choi E, Miller AD, Devenish E, Asakawa M, McConkey M, Peters-Kennedy J. Charcot-Leyden crystals: do they exist in veterinary species? A case report and literature review.  J Vet Diag Invest.  2017;29(6):904-909.
3. 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.
4. Craig LE, Krimer PM, O'Toole AD. Synovial Cysts and Myxomas in 16 Cats. Vet Pathol. 2020;57(4):554-558.
5. Delaney MA, Treuting PM, Rothenburger JL.   In:  Terio KA, McAloose D, St. Leger J.  Pathology of Wildlife and Zoo Animals.  London, England: Elsevier; 2018:487-489.
6. 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.
7. Olson EJ, Carlson CS. Bones, joints, tendons and ligaments. In:  McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017: 1004-1005.
8. 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.
9. 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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