Musculoskeletal neoplasia Flashcards
In a study by Nakano 2022 in JAVMA, what was the rate of distant metastasis following amputation for appendicular osteosarcoma in cats? What was the MST?
42% rate of distant metastatic disease following amputation (particularly high incidence with osteosarcoma of the humerus).
MST was 527 days.
In a study by Crooks 2021 in VRU, what was the detection rate of PET/CT in detecting metastatic or comorbid neoplasia in dogs with primary appendicular osteosarcoma? What agent was used for detection?
24% of dogs had metastatic disease on PET/CT, and 16% had comorbid conditions.
18F-FDG (or Fluorine-18-fluorodeoxyglucose was used as the agent for testing). Increased uptake indicates increased glucose metabolism in the selected tissue, most commonly secondary to neoplasia or inflammation.
In a study by Martin 2022 in VRU, what was the MST for dogs with appendicular osteosarcoma undergoing stereotactic radiation therapy with <40% or >40% of the bone affected?
<40%: 256 day survival (8.5 months)
>40%: 178 day survival (6 months)
Increased subchondral bone lysis was associated with an increased risk of pathologic fracture during treatment.
In a study by Brewer 2022 in JVIM, what side effect was noted in some dogs receiving zoledronate?
Progressive azotemia that was not associated with the cumulative dose.
What factors have been associated with an increased risk of osteosarcoma?
Increased height and weight, adolescent body weight, circumference of the distal radius and ulna.
Early neutering has also been shown to increase the risk of OSA in Rottweilers.
At what age is OSA most typically diagnosed?
Two peaks in age of diagnosis; one at 18-24 months, and a larger one at 10 years.
What are the most common location of OSA in dogs?
Distal radius (may be associated with a better prognosis) and proximal humerus (may be associated with a worse prognosis).
Other common sites include the distal and proximal tibia and distal femur.
What is the average surgical time of dogs with OSA undergoing aggressive local and systemic therapy?
10-12 months.
What are common radiologic signs of OSA?
Cortical lysis, periosteal reaction, extension of osteogenesis into adjacent soft tissue, loss of the fine trabecular pattern of the metaphysis, areas of fine punctuate lysis.
Is a distinct boundary between normal and abnormal bone common with OSA?
No - more indicative of a bone cyst or infection.
What are the types of OSA?
- Endosteal: most common.
- Periosteal.
- Parosteal: similar to periosteal except does not invade the underlying cortex.
What are some DDx for OSA?
Sarcomas (chondrosarcoma, fibrosarcoma, and hemangiosarcoma), which originate from the other mesenchymal cells present in bone, metastatic neoplasia, multiple myeloma, lymphoma, bacterial or fungal osteomyelitis, and bone cyst.
What are options for pre-operative definitive diagnosis of OSA?
- Bone biopsy: open, closed or excisional. Closed with a Jamshidi or Michelle trephine performed most commonly. Accuracy rate of 80-90%.
- FNA with an 18 gauge needle (overall accuracy of 71%, or 91% when neoplastic disease present). Can be ultrasound or CT guided. ALP staining may improve diagnostic accuracy.
What are some disadvantages of pre-operative bone biopsy collection for suspected OSA?
- Pathologic fracture (more likely with Michelle trephine than Jamshidi). May also increase the risk of subsequent pathologic fracture if stereotactic radiosurgery is performed.
- Seeding of neoplastic cells to the surrounding soft tissues or contralateral side of the bone if the opposite cortex is inadvertently penetrated.
When should preoperative biopsy be considered for suspected OSA?
- Region of endemic fungal disease.
- Bone lesion is not a typical site for a primary bone neoplasia.
- Clinical picture is not completely consistent with a primary bone neoplasia.
What are the most common sites of metastasis for OSA?
Lungs and other bone sites.
What percentage of patients with OSA have metastatic disease at the time of diagnosis?
Almost all cases, although often micrometastatic disease (<10% of cases diagnosed with gross metastatic disease at the time of initial staging).
Detection of pulmonary metastatic disease can be increased by using CT (nodules of 1mm detected compared to 7-9mm for radiography).
What staging tests should be performed in patients with suspected OSA?
- Orthopedic examination.
- Thoracic radiographs or CT.
- Scintigraphy +/- limb radiographs and/or CT.
- PET-CT (may be very useful but not widely available).
CBC/biochem/urinalysis also recommended to assess for evidence of renal disease (may impact chemotherapeutic options), and bone/total ALP.
Are long bone survey radiographs sensitive for the detection of bone metastasis with OSA?
No, low sensitivity. Bone lesions are not detectable until >30% bone loss and >2cm in size.
Scintigraphy using Technetium 99 has a much higher sensitivity but is not specific for disease.
How should metastatic bone disease in cases of OSA be confirmed following assessment with scintigraphy?
Evaluation with site specific radiographs or CT scan.
What is the relevance of bone and total ALP levels in dogs with OSA?
May be a prognostic factors, with increased levels associated with decreased prognosis.
Is metastasis to the regional lymph nodes common in dogs with OSA?
No, only 4%.
Presence of lymph node metastasis is a negative prognostic indicator (MST 59 days with, compared to 318 days without).
What options are available for staging the extent of disease with OSA?
- Radiographs.
- Scintigraphy.
- CT.
- MRI.
MRI might be the most accurate (least likely to underestimate the extent of disease, which is important when considering limb sparing procedures), but the ideal technique is still not determined.
CT might be the most practical and allows for excellent bony detail and concurrent evaluation of the thorax.
Radiographs are required for implant selection and planning.
What are the primary goals of amputation in the treatment of OSA?
Prevent further metastasis, achieve local control, and remove the source of pain.
What are the treatment options for pathologic fracture secondary to OSA?
- Amputation.
- Fracture repair if limb amputation is not an option, staging test results are negative for metastatic disease, fracture repair is technically feasible, and the owner plans to follow-up with adjuvant chemotherapy.
What is thought to be the cause of fracture associated OSA?
Chronic inflammation and infection, corrosion of the implant, delayed healing, decreased vascularity of bone after fracture.
Most frequently affects the diaphysis, and occurs in dogs with history of complicated fracture healing, implant loosening or infection.
Typically a lag period of 5 years.
Is the staging and treatment for fracture associated and spontaneous OSA different?
No, the biologic behaviour appears similar.
What types of scapulectomy can be performed for cases of scapula neoplasia (most frequently OSA or CSA)?
- Partial: preservation of the acromium, acromial head of the deltoid, and distal portions of the supraspinatous and infraspinatous muscles.
- Subtotal: removing most of the scapula (to the level of the scapula notch) with preservation of the glenoid and shoulder joint.
- Total.
Which patients are considered good candidates for scapulectomy?
- Proximal scapula affected.
- Neoplasia has not extended into the surrounding soft tissues.
- Scapula can be removed with a 2-3cm margin distal to the neoplasia and the shoulder joint preserved.
Does degree of scapulectomy influence limb use post-operatively?
No, although increasing body weight appears to decrease limb use.
Seroma is the most commonly reported complication.
What is the MST for dogs with OSA undergoing scapulectomy?
246 days (similar to other appendicular sites).
What are the categories of hemipelvectomy?
Subtotal or total.
Further categorization includes:
(1) total hemipelvectomy: entire hemipelvis from the pubic symphysis to the sacroiliac joint.
(2) mid to caudal hemipelvectomy (see image): hemipelvis from the pubic symphysis to the ilium just cranial to the acetabulum.
(3) mid to cranial hemipelvectomy: the sacroiliac joint to just caudal to the acetabulum.
(4) caudal hemipelvectomy: pubic symphysis to just caudal to the acetabulum and allows for limb preservation.
What are intraoperative and post-operative complications associated with hemipelvectomy?
Intra: hemorrhage, urethral transection.
Post: abdominal wall hernia, wound complications, urine retention, aspiration pneumonia.
What were the most common neoplasms in dogs and cats undergoing hemipelvectomy?
Dogs: STS, OSA, CSA.
Cats: FSA, OSA, CSA.
High incidence of fibrosarcoma in cats likely secondary to injection site sarcomas at this location.
What are options for closure of the abdominal wall defect following hemipelvectomy?
- Cranial sartorius muscle flap (secured to the remaining abdominal wall muscles, adductor muscle, and pelvic diaphragm). Can only be used if part of the cranial ilium can be preserved.
- Mesh (usually not necessary if the cranial sartorius is able to be preserved).
- Use of the medial muscles of the thigh (adductor, gracilis). Paramedian pubectomy must be performed in this instance to preserve the muscular origins. Can be used if the entire ilium requires resection (precluding preservation of the cranial sartorius).
Omentalization of the defect may also aid in more rapid peritonealization.
How much of the sacrum may be safely resected during hemipelvectomy if a neoplasm crosses the SI joint?
Up to one-third.
What type of hemipelvectomy is shown? What is the benefit of this technique?
Caudal hemipelvectomy. Preservation of limb function is possible in this instance.
What are indications for limb sparing surgery?
Patient is anticipated not to ambulate well with amputation (concurrent orthopedic or neurologic disease, giant breed, previous amputation of another limb).
In patients with OSA of the distal radius, for limb sparing to be feasible the extent of neoplasia should not affect more than what percentage of the bone?
50%
ideally should also not extend significantly into the surrounding soft tissues, and pathologic fracture should not be present.
What are surgical options for limb sparing surgery?
- Cortical allograft.
- Endoprosthesis.
- Pasteurized autograft.
- Vascularized ulna transposition.
- Bone transport osteogenesis.
- Irradiated autograft.
- Stereotactic radiosurgery.
What are the disadvantages associated with use of a cortical allograft for limb sparing surgery?
High rate of infection (50%), the allograft is large and does not become incorporated into the host bone within the patient’s life span (results in development of a sequestrum that is prone to infection). Implant failure and loosening can occur in long term survivors.
Filling of cortical allografts with what material at the time of implantation has been shown to increase strength of the construct and decrease screw pull-out?
Antimicrobial impregnated PMMA.
What implant for limb sparing surgery is shown in the image?
Endoprosthesis
What are the available endoprosthesis implants for limb sparing surgery?
- Original Charles Kuntz design (98 and 122mm). Consists of a bar and limb-sparing plate (2.7/3.5 mm screws distally, 3.5/4.5 mm screws proximally).
- Tantalum design (Biomedtrix). This is a trabecular metal which is highly fatigue resistant and porous, which is designed to facilitate bone ingrowth. Limited clinical reports of use.
- Fitzpatrick referrals implant.
Are complications reduced with the use of an endoprosthesis over cortical allograft for limb sparing surgery?
No. There was no difference in infection rate, infection severity, median time to infection, surgical time, limb use, implant failure rate, or oncologic outcome between the two methods.
Primary advantages of the endoprosthesis are ready availability and ease of use.
How many screws proximal and distal to the osteotomy are recommended when placing an endoprosthesis?
Three screws proximal and 4 screws distal are recommended. Ideally the plate should span at least 50% of the length of the metacarpal bone.
How is a pasteurized autograft prepared for implantation?
Placement in sterile saline at 65 degrees for 40 minutes (autograft is the section of radius resected for tumour removal).
The autograft is not filled with bone cement at the time of re-implantation.
What are the advantages/disadvantages of pasteurized autograft use of limb sparing surgery?
Advantages: perfectly fits the radial defect and mitigates the need for a bone bank. The autograft will eventually heal to the osteotomy site and may allow for eventual removal of the implant.
Disadvantages: similar complications as reported for cortical allografts (local recurrence, infection, implant failure). Risk of failure might be increased due to use of diseased bone.
What are the disadvantages/advantages of vascularized ulna transposition?
Advantages: vascularized graft that may be more resistant to infection, likely becomes stronger over time and allows for potential healing of the graft.
Disadvantages: some degree of limb shortening, only possible if the distal ulna is not involved in the neoplastic process, biomechanically weaker than cortical allograft when initially implanted (requires strict activity restriction).
Lateral manus translation is a modification of this technique (only reported in 8 dogs).
What vessels must be preserved during vascularized ulna transposition?
Caudal interosseous artery and vein.
If the distal ulna is involved in the neoplastic process, what alternative technique may be used for vascularized ulna transposition?
Microvascular transfer of the ipsilateral ulna. The interosseous vessels are anastomosed to the radial artery and vein, or the median artery and cephalic vein.
What are the disadvantages/advantages of bone transport osteogenesis?
Advantages: strong, vascularized bone that is resistant to infection.
Disadvantages: labor intensive, time (mean time to ESF removal 205 days), additional cost to the owner.
Note: Transverse bone transport osteogenesis has also been reported experimentally.
Why is intraoperative irradiation of an autograft no longer recommended?
Stereotactic radiosurgery can deliver high doses of radiation to the affected area while sparing the surrounding soft tissues without the need for surgical isolation.
What complications are reported with use of intraoperative irradiation of an autograft?
Infection, recurrence, implant failure, and collapse of the articular cartilage and subchondral bone of the distal radius (secondary to weakening of the bone from neoplasia and radiation).
What is stereotactic radiosurgery?
Delivery of an accurate, single, high dose of radiation to a bone neoplasm (3000 Gy), with a steep gradient of radiation between the neoplasia and the surrounding soft tissues.
Requires the use of a contrast enhanced CT for planning.
What are complications associated with the use of stereotactic radiosurgery for treatment of bony neoplasia?
Pathologic fracture, local recurrence. May be most useful for small bone tumours with limited bone destruction.
What might increase the risk of bone fracture following stereotactic radiosurgery for the treatment of bony neoplasia?
Bone biopsy
Is prophylactic plating recommended for patients at risk of pathologic fracture following the treatment of bony neoplasia?
No, associated with a high complication rate (infection most common).
Conversion to amputation during limb sparing surgery should be performed if examination of the distal radius reveals what?
Fracture or breakthrough of the neoplasm.
When is removal of the articular cartilage of the carpus recommended during limb sparing surgery?
When more biologic methods of limb sparing surgery are performed, in which autograft healing and implant removal may be possible.
Otherwise, removal of the articular cartilage does not appear to affect outcome (likely due to short survival times).
What are some complications associated with limb sparing surgery?
Infection (40-75%), local recurrence (25%), implant failure (40%).
How are infections managed following implant sparing surgery?
- Antimicrobials (single course for mild infections, or lifelong for moderate to severe infections) +/- placement of antimicrobial impregnated beads.
- Revision using bone distraction osteogenesis.
- Amputation (in instances of plate exposure).
What is the impact of infection or implant failure on survival following limb sparing surgery?
May prolong survival.
How is local recurrence managed following limb sparing surgery?
- Amputation.
- Analgesics, bisphosphonates, local and/or systemic chemotherapy, palliative radiation.
What is intercalary limb sparing surgery?
Reserved for treatment of OSA of the diaphyseal region of bone. The affected bone is removed and replaced with cortical allograft, pasteurized autograft, or irradiated autograft while sparing the proximal and distal joints.
May have a lower rate of complications as compared to limb sparing surgery of the distal radius.
How can limb sparing surgery be performed on neoplasms confined to the ulna?
- Intercalary limb sparing surgery.
- Ulnectomy without replacement of the ulna (must reconstruct the lateral collateral ligament).
Is limb sparing surgery for neoplasia of the proximal portion of the humerus recommended?
No. High rate of complications. Stereotactic radiation therapy may be more appropriate.
What limb sparing technique may be appropriate for neoplasms of the distal limb?
Partial amputation and endoprosthesis.
Does chemotherapy impact survival times in dogs with OSA?
Yes, significantly.
MST without chemo: 19 weeks.
MST with chemo: 52 weeks (doxorubicin) to 425 days (carboplatin).
Cisplatin not frequently used due to requirement for diuresis and potential for renal toxicosis.
Carboplatin tends to have fewer side effects than doxorubicin.
What are the advantages/disadvantages for use of palliative radiation therapy in the treatment of OSA?
Palliative radiation is administered in 2-4 doses of 8Gy coarse, fractionated radiation.
Advantages: less expensive than stereotactic radiotherapy, option for patients unable to undergo amputation or with metastatic disease.
Disadvantages: risk of pathologic fracture, not all dogs will respond to therapy (50-90% have a reported response). Short MST (122-313 days).
What is the median duration of pain relief for patients undergoing palliative radiation therapy for OSA?
53 days.
Why is full course, fractionated, curative intent radiation not recommended for treatment of OSA?
Significant side effects, duration of required radiation course, lack of survival benefit.
What are palliative treatment options for the management of OSA?
- Radiation +/- chemotherapy.
- NSAIDs, opioids, adjunctive analgesics.
- Biphosphonates (pamidronate, zoledronate).
What is the MOA of biphosphonates?
Osteoclast inhibitors (decrease the rate of osteolysis).
Due to decreased malignant and nonmalignant bone resorption they increase the bone mineral density, decrease pain, and decrease surrogate markers of bone turnover.
What are the differences between pamidronate and zoledronate?
Zoledronate has a much longer half life in bone which allows less frequent administration (every 3 months compared to every 1 month).
What is the MST for dogs with appendicular chondrosarcoma?
Grade dependent.
Grade 1: 6 years (pulmonary metastatic rate 0%).
Grade 2: 2.7 years (31%).
Grade 3: 0.9 years (50%).
When is chemotherapy considered for patients with appendicular CSA?
When there is a metastatic rate of >50% (grade III tumours). Unknown if ultimately beneficial.
Is OSA of the axial or appendicular skeleton more common in cats?
Appendicular (65%), axial (35%).
Axial carries a worse prognosis due to difficulty in achieving complete excision.
What is the metastatic rate of OSA in cats at the time of presentation?
10%
What is the MST for cats with appendicular osteosarcoma treated with amputation or excision?
17-64 months.
Adjunctive chemotherapy is not recommended.
What are potential neoplasms that might arise from the synovium?
Synovial cell sarcoma, histiocytic sarcoma, synovial myxoma, other sarcomas.
Previously all termed synovial cell sarcomas and require IHC for differentiation.
IHC staining for what protein is diagnostic for synovial cell sarcoma?
Cytokeratin (although negative cytokeratin staining does not rule out synovial cell sarcoma).
What joints were most commonly affected by synovial cell sarcoma?
Elbow and stifle joints. Golden retrievers overrepresented.
What are potential risk factors for development of histiocytic sarcoma of the synovium?
Previous joint disease (5 x as likely). Rottweilers and Bernese mountain dogs at increased risk. This suggests both an environmental and genetic component to the disease.
Stifle joint was commonly affected.
What is the MST for neoplasms of the joint?
Histiocytic sarcoma: 5 months.
Synovial myxoma: 30 months.
Treatment is via amputation if staging is negative for metastatic disease.
Metastasis of histiocytic sarcoma is most commonly to the lungs, lymph nodes and liver.
What is the recommended treatment for rhabdomyosarcoma (neoplasm of striated muscle cells)?
Same management as for other soft tissue sarcomas.
Does intramuscular or subcutaneous hemangiosarcoma have a worse prognosis?
Intramuscular (270 day MST, compared to 1190 days for subcutaneous).
Wide or radical incision is recommended. Adjunctive chemotherapy is recommended.
What are the three types of neoplasm of the adipose tissue?
- Benign lipoma.
- Infiltrative lipoma.
- Liposarcoma.
What is the most common complication following intermuscular lipoma removal?
Seroma.
How can infiltrative lipomas and benign lipomas be differentiated?
- Histology if adjacent muscle demonstrating invasion is included.
- CT scan (infiltrative lipomas show an invasive pattern, do not enhance on contrast, and have a lower fat opacity).
What is the recurrence rate following aggressive resection of infiltrative lipomas?
36%.
If aggressive surgery is not possible, cytoreductive surgery with adjunctive radiation should be performed.
What is the MST for infiltrative lipoma?
40 months
How is liposarcoma differentiated from benign lipoma?
- Appearance on imaging (more heterogenous, with a soft tissue rather than fat opacity).
- Incisional biopsy.
What is the MST for patients with liposasrcoma?
MST 1188 days with wide excision, 649 with marginal excision.
Have an excellent long term prognosis if local control can be achieved.
Are the majority of digital neoplasms in the dog benign or malignant?
Malignant (61%).
20% are benign, and 26% are inflammatory.
What are the most common digital neoplasms of the digit in the dog?
SCC followed by melanoma.
Does subungual SCC carry a better or worse prognosis than for SSC of other locations of the digit in the dog?
Better (95% 1 year survival, compared to 60% from other locations of the digit).
What dogs are most likely to be affected by SCC of the digit?
Large-breed, black coated dogs (labradors and standard poodles).
What percentage of dogs with digital SCC had pulmonary metastasis at the time of diagnosis?
8-29%
What is the MST for dogs with digital melanoma?
1 year.
Scottish terriers are overrepresented.
What is the most common location of metastasis for malignant melanoma of the digit in dogs?
Draining lymph node.
What is the clinical approach to the work-up of digital masses in dogs?
- Radiographs to assess the extent of bony involvement (SCC normally have more bony lysis).
- Three view thoracic radiographs.
- Evaluation of regional lymph nodes.
- Incisional or excisional biopsy of the mass.
If the third and fourth digits require removal during partial foot amputation, what can be performed to move the outside digits centrally?
Centralization by osteotomy of the middiaphysis of the metacarpal or metatarsal bones and movement of the second and fifth metacarpal/tarsal bones under the 3rd and 4th with securing using a bone plate.
What might be associated with persistence of lameness in dogs undergoing partial foot amputation for digital neoplasia?
Increased weight (>25 kg).
Are the majority of digital neoplasms in the cat benign or malignant?
Malignant (71%), benign (4%), inflammatory (26%).
What digital neoplasms have been described in cats?
Squamous cell carcinoma (23.8%), fibrosarcoma (22%), adenocarcinoma (20.6%), osteosarcoma (7.9%), and hemangiosarcoma (7.9%).
The majority of adenocarcinomas are thought to originate as metastatic disease from pulmonary adenocarcinoma (lung digit syndrome).
Which part of the digit is most likely to be affected by lung digit syndrome in cats?
P3. Multiple digits affected in 32% of cases.
What is the MST for cats with lung digit syndrome?
67 days.
