Conference: 21 - 2016    Case: 1     -


Signalment:  

Nine-year-old castrated male Labrador retriever (Canis familiaris).


Gross Description:  

A right pelvic limb from the femoral head and distally was submitted. The stifle joint and muscles of the thigh were expanded by palpably viscous, coalescing nodules. The popliteal lymph node was bi-lobed and measured approximately 2.6 x 1.4 x 1 cm. On cut surface, was mottled dull yellow, red to red-brown, slightly bulging and contained multifocal to coalescing round to oval, 0.2-0.5cm, soft to firm cystic structures filled alternatively with small amounts of clear, colorless fluid to opaque, firm, off-white material. On cut surface, the stifle joint was expanded by a 5x6x5cm, mottled dull yellow, red to red-brown, slightly bulging mass of multifocal to coalescing round to oval, soft to firm cyst-like structures that were filled alternatively with small amounts of clear, colorless fluid to opaque, firm, off-white material. Large amounts of mucoid, gelatinous, dull, yellow-red material expanded fascial planes, lymphatic vessels, and subcutaneous tissues from the mid-femur distally, and most severely, along the proximal and mid-tibia. The stifle joint was expanded by approximately 40 ml of the same material. The synovium of the stifle joint was diffusely thickened with papillary and ovoid projections and cavitations as previously described in the popliteal lymph node. The joint capsule as variably friable to firm. The entire limb was sagittally sectioned and on cut surface a firm to soft mass composed of thousands of small, firm, semi-transparent, off-white nodules emanated from the plantar aspect of the level of the stifle joint. The mass com-pressed the normal structures of the region. Approximately 3-5 small (0.8x0.5cm), ovoid, firm, semi-translucent, off-white masses tracked along and were adhered the femoral vasculature adventitia, including approximately 1.0cm from the surgical margin.

The inguinal lymph node was also submitted and measured 6 x 3.5 x 1.8 cm and on cut surface is expanded by multilobulated, multicavitated nodules that vary in size from 0.9 cm to 1.3 cm in diameter. They are round to oval and contain variable amounts of mucoid, tenacious, clear, colorless fluid.


History:  

Right pelvic limb swelling noticed in July 2012. Treated with prednisone, diphenhydramine, cephalexin. Viscous fluid aspirate from limb 8/8/12. Presented to Internal Medicine 9/4/12 - chest x-rays unremarkable, right pelvic limb x-rays showed an aggressive lesion involving distal femur, with soft tissue swelling involving down to distal tibia. Aspiration cytology - probable sarcoma.

Abdominal ultrasound and pelvic CT scan showed a large cystic mass involving the right pelvic limb with bone invasion and presumed metastasis to the right inguinal and right medial iliac lymph node. Possible femoral vein thrombus. High coxofemoral disarticulation amputation performed. Clinical diagnosis: Sarcoma with lymph node metastasis.


Histopathologic Description:

Examined are two cross sections of joint capsule which are markedly thickened up to 0.9 cm by a poorly cellular, abundantly myxoid, multinodular, unencapsulated, expansile neoplastic mass that primarily occupies the subintimal space. Individual variably-sized nodules are separated by thin bands of fibrous connective tissue. The neoplastic nodules often merge and are comprised of abundant amounts of lacy, gelatinous, pale, amphophilic to basophilic matrix and widely spaced stellate to spindloid cells. The cells are cytologically bland, have ill-defined borders and small amounts of a finely granular, eosinophilic cytoplasm. Nuclei are oval, with granular chromatin and variable numbers of ill-defined nucleoli. Aniso-cytosis and anisokaryosis are mild. No mitotic figures are observed. Multifocally along the most superficial aspects of the subintima, deep to synoviocytes, there are moderate to large numbers of lymphocytes and fewer plasma cells. Rarely, pigment-laden cells (macrophages) admix with the lymphocytes and plasma cells. The intimal layer is multifocally hyperplastic and jumbled up to 10 layers. The fibrous capsule is expanded by abundant fibrovascular tissue, adipose, and multifocal aggregates of plasma cells, lymphocytes, and fewer mast cells.


Morphologic Diagnosis:  

Femorotibial (Stifle) Joint and associated skeletal muscle, Right Popliteal and Inguinal Lymph Nodes: Synovial myxoma with local invasion and multiple lymph node metastases.


Lab Results:  

Radiographic findings: There is marked soft tissue swelling surrounding the tibia and loss of the normal fascial plane distinction. There are lobular soft tissue densities at the medial aspect of the right stifle joint. There is permeative lysis of the distal femur, resulting in a coarse trabecular pattern and sclerosis with an indistinct transition zone between normal and abnormal bone. Periarticular osteo-phytes are present on the apex of the patella, the fabellae, the proximal tibia, and the distal femur. There is marked increased soft tissue opacity associated with the stifle joint.

Radiographic Impressions: Aggressive bone lesion affecting the distal right femur with adjacent lobular soft tissue opacities is concerning for a soft tissue neoplasm with extension to the bone such as a synovial cell sarcoma. Mild secondary joint disease. Marked edema of the right crus. An ultrasound examination of the right stifle is recommended if clinically indicated. Pulmonary osteomas. No radiographic evidence of pulmonary metastatic disease.

CT Scanning impressions: Large cystic right pelvic limb mass with associated sub-cutaneous edema and bone invasion. Filling defect of the right femoral vein may be secondary to tumor invasion or thrombus formation. Metastatic inguinal and sub-lumbar lymph nodes. The appearance of the right hypogastric and mesenteric lymph nodes may represent metastases or reactivity.

Cytology of stifle mass: Four moderately cellular coverslips are examined that have a medium pink stippled background and a mild amount of blood with erythrocytes frequently distributed in a prominent windrowing pattern. Nucleated cells are distributed individually and in variably sized loose aggregates. Thick pink fibrillar material is frequently seen associated with cell aggregates. Individual cells consist predominantly of macrophages / synoviocytes. Cells in clusters have a low to moderate amount of pale cytoplasm that frequently causes polar wisps giving the cells a spindloid shape. Nuclei are ovoid with coarsely stippled chromatin and small nucleoli. Low numbers of small mature lymphocytes are also noted.

Cytologic interpretation and comments: Probably sarcoma. The large aggregates of spindloid shape cells are consistent with a sarcoma, with considerations including spindle cell sarcoma, synovial sarcoma or even atypical chondrosarcoma, however, this is considered less likely.


Contributor Comment:  

Histiocytic sarcoma, synovial sarcoma, and synovial myxoma are three differentials for canine primary joint tumors.2,3 All can cross joints and cause bony lysis and proliferation. Synovial myxoma occurs uncommonly in dogs and is widely considered to be a benign, but infiltrative, tumor of the joint. Numerous cases of lymph node metastases, however, have been observed (Contributing Institution experience). The stifle and digital joints are most commonly affected. The three types of cells in synovial membranes are Type A synoviocytes (macro-phage/dendritic cell origin), type B (fibroblast-like), and type C (“transitional”, hematopoietic, or stem cell-like). Although a joint tumor, the cell of origin of synovial myxomas is unknown; this is reflected in the non-specific immunohistochemistry (IHC). They are vimentin positive. Approximately 20-40% of synovial myxoma cells are CD18 immunoreactive and are morphologically indistinguishable from CD18 negative joint cells. Synovial myxomas are cadherin 11 and HSP25 immunoreactive, much like synovial cell sarcomas and histiocytic sarcomas.3 The most striking histologic feature of synovial myxomas is the sparse, stellate to spindle cells that elaborate abundant, coalescing nodules of myxo-matous matrix.2,3,5 Again, although cytomorphologic features are generally bland, synovial myxomas can metastasize to lymph nodes and be highly locally invasive.2,3,5


AFIP Diagnosis:  

Joint, stifle (per contributor): Synovial myxoma, Labrador retriever, Canis familiaris.


Conference Comment:  

We thank the contributor for their institution’s extensive work-up on this case and excellent quality gross images. Of the three differentials for canine joint neoplasms mentioned above, synovial myxoma is the second most common neoplasm occurring within the joints of dogs, behind histiocytic sarcoma and ahead of the rare synovial sarcoma  (if such a tumor truly exists.) 1,3,4 This neoplasm most commonly affects middle-aged large breed dogs. Doberman pinschers and Labrador retrievers, as in this case, are most often affected. It has also been rarely reported in cats.1,4 Synovial myxomas usually affect a single joint, with the stifle and digit the most commonly reported locations. These neoplasms are slow-growing and can persist for months to years and often present as chronic lameness with or without evidence of joint swelling.1,3,4

Although this is classified as a benign neoplasm, it can be locally infiltrative and cause lytic lesions in the bone with significant articular lesions and periarticular osteophyte formation. The conference moderator instructed that radiographically, synovial myxoma cannot be reliably differentiated from histiocytic sarcoma or synovial sarcoma.3,4 Despite this locally invasive behavior, the prognosis is typically good after complete surgical excision. Bony lysis and infiltration usually necessitate amputation; however, cases that lack bone lysis and extension outside of the joint capsule can be treated with a simple synovectomy, which is curative in about 90% of reported cases. In contrast, histiocytic sarcomas are associated with a poor prognosis, with an average survival of just 5.3 months.1,3,4 This significant difference in biological behavior and prognosis highlights the importance of histopathology of the mass prior to treatment. Interestingly, the conference moderator and highly regarded veterinary pathologist with expertise in bone and joint pathology, Dr. Linden Craig, remarked that this is the first example of a synovial myxoma she has seen with metastasis. Given the observation by the contributor’s intuition of multiple cases of lymph node metastasis for this neoplasm, Dr. Craig remarked that the biological behavior of this neoplasm may need further review.

Conference participants noted that once the tissue is identified as joint capsule with adjacent skeletal muscle, the diagnosis of synovial myxoma is relatively straight-forward. This neoplasm has a highly characteristic appearance of variably sized nodules of stellate to spindle cells with long cytoplasmic processes supported in a highly myxoid matrix and covered by a hyperplastic synovial lining.1,3,4 The conference moderator noted that the cell of origin of synovial myxoma is not yet known; although, it is thought that given the abundant myxoid matrix, the cell type is likely type B (fibroblastic) synoviocytes. Type B synoviocytes normally produce hya-luronan, a large linear glycosaminoglycan and major component of synovial fluid.1,3,4 Despite this uncertainty of cell origin, the diagnosis can usually be made without the aid of immuno-histochemical staining.


References:

  1. Craig LE, Ditmer KE, Thompson KG. Bones and joints. In Maxie, MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals, Vol I. 6th ed. Philadelphia, PA: Elsevier Ltd; 2016:159-162.
  2. Craig LE, Julian ME, Ferracone JD. The diagnosis and prognosis of synovial tumors in dogs: 35 cases. Vet Pathol. 2002; 39(1):66-7.
  3. Craig LE, Krimer PM, Cooley AJ. Canine synovial myxoma: 39 cases. Vet Pathol. 2010; 47(5):931-6.
  4. Craig LE, Thompson KG. Tumors of joints. In: Meuten DJ ed. Tumors in Domestic Animals. 5th ed. Ames, IA: John Wiley and Sons Inc; 2017:337-350.
  5. Izawa T, Tanaka M, Aoki M, Ohashi F, Yamate J, Kuwamura M. Incidental synovial myxoma with extensive intermuscular infiltration in a dog. J Vet Med Sci. 2012; 74(12):1631-3.

Conference: 21 - 2016 (Cases 1 - 4) write up  


Click the slide to view.



1.1. Stifle,dog.


1.2. Stifle,dog


1.3. Stifle,dog


1.4. Stifle,dog


1.5. Stifle,dog


1.6. Stifle,dog


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