Biopsy

Histopathologic evaluation is necessary for a definitive diagnosis of osteosarcoma. The sample may be obtained by closed, open, or excisional biopsy. A presumptive diagnosis is often made when the signalment, clinical history, physical examination, and radiographic findings (site and lesion) are consistent with a primary bone tumor. If the presentation of the case is typical of a primary bone tumor and the owner’s willingness to treat is not altered by the tumor type, the clinician may opt to omit this step and move forward with definitive therapy. This practice carries an inherent risk of misdiagnosis. However, the chance of this is exceedingly low with a solid presumptive diagnosis. This practice is not universal, and some clinicians will biopsy all bone lesions prior to the start of therapy. In each case, the advantages and disadvantages of bone biopsy should be considered. Biopsy should be considered in geographic areas where there is a high rate of endemic fungal disease, especially when the bone lesion is not in a typical site for a primary bone tumor, and biopsy or fine needle aspiration should be performed in all cases where the clinical picture is not completely consistent with a primary bone tumor.

Bone biopsy is performed using a Jamshidi needle or a Michele trephine and a closed technique in most cases.⁷⁶ The accuracy rate of bone biopsy is 80% to 90%.⁷⁶ Because of the larger size of the core sample removed (and therefore the larger defect in the bone), the risk of pathologic fracture is increased with a Michele trephine compared with a Jamshidi needle. For this reason, a single core is taken when a Michele trephine is used, compared with multiple cores with use of a Jamshidi needle. Core samples can be rolled onto a slide for cytologic evaluation. A portion of the sample should be reserved for bacterial and fungal culture.

Several important points should be considered before a bone biopsy is performed. Risks of biopsy include exacerbation of lameness after biopsy and risk of fracture at the time of biopsy or post biopsy. There is also the risk that a nondiagnostic sample will be obtained; this would require repeating the procedure or moving to an excisional biopsy. Selection of the biopsy site is important. Unlike soft tissue tumors, in which a biopsy is often taken from the periphery to avoid the necrotic tissue at the center, the center of the radiographic lesion is the desired site for biopsy in bone tumors. The reason for this is the periosteal reaction at the periphery of the lesion, which is often large, may consist of only reactive bone. Therefore, a histologic diagnosis of reactive bone is often based on a nonrepresentative sample instead of accurately confirming or excluding a diagnosis of osteosarcoma.

When planning the site of bone biopsy, it is important to take options for definitive therapy into consideration. The biopsy tract is considered contaminated with tumor cells and must be removed during definitive therapy. This is particularly important if limb-sparing surgery is an option. Only one small skin incision should be made in an area that is amenable to resection. A Jamshidi needle can be used to obtain multiple samples, but these should always be obtained through a single incision. Ideally, the skin incision is planned in an area of minimal soft tissue coverage over the bone. When obtaining the biopsy, care is taken to not penetrate the opposite cortex of the bone, as this may seed tumor cells that are not removed with local resection or may further weaken the bone. Tumors of the distal region of the radius should be biopsied from the cranial surface, slightly lateral or medial, depending on the preferred approach to the radius for limb-sparing surgery. If limb-sparing surgery is an option that the owner wishes to pursue, it is recommended that the case be discussed with the surgeon who will perform the limb-sparing procedure before the bone biopsy is performed. An emerging concern is that if stereotactic radiosurgery is a consideration for limb-sparing surgery, a bone biopsy may increase the risk of pathologic fracture at bone biopsy tract sites.^29a

An alternative to bone biopsy and histopathologic evaluation is cytologic evaluation of a sample obtained via a fine needle aspirate. The diagnostic accuracy of cytology was found to be 71% overall and was 92% when a neoplastic process was identified.⁸ This technique has been used in concert with ultrasound in an attempt to improve the diagnostic yield. Ultrasound can be used to identify a break in the cortex through which a 20 gauge hypodermic needle can be inserted. A diagnostic sample was obtained in a recent study in 32 of 36 cases, indicating that this technique may be a good alternative to surgical biopsy or reliance on a presumptive diagnosis.¹²

Staging

Staging is performed when osteosarcoma is suspected or has been confirmed, to determine whether there is gross metastasis of disease. Metastasis has occurred in nearly all patients by the time a diagnosis of osteosarcoma is made. However, this is micrometastatic disease in most cases, as gross metastasis is identified in ≈15% of patients at the time appendicular osteosarcoma is diagnosed.²¹ The two most common sites of metastasis are the lungs and another bone site. Three-view thoracic radiographs are an essential part of tumor staging, and lung lesions that are 7 to 9 mm in diameter should be visible on high-quality radiographs.⁶⁹ Less than 10% of patients with osteosarcoma will be positive for gross disease on thoracic radiography at the time of initial staging.²¹ Computed tomography (CT) scan is the modality of choice for identifying lung metastasis in human beings with osteosarcoma.^74,97 This test has been shown to be highly sensitive but not specific for diagnosing gross metastasis to the lung in human beings.^74,97 The threshold size of the lesion for diagnosis of pulmonary metastatic nodules in dogs in one study was 1 mm.⁶⁹

As CT scans become more commonplace for the staging of canine osteosarcoma, more information will become available on how to interpret positive lesions on CT scan. Currently, it is unknown how identification of lesions that are <3 mm diameter, which are not visible on radiographs but are seen on CT, will affect the prognosis of the canine patient, or if these smaller lesions will be responsive to chemotherapy. Intuitively, confirmation of metastasis by identification of lesions on CT scan would suggest a worse prognosis. However, one major difference in human patients with osteosarcoma compared with canine patients is that the presence of gross metastatic disease on CT scan does not preclude curative intent treatment. In human beings, larger lung lesions are removed surgically and smaller lesions are monitored during chemotherapy and can be used to gauge response to treatment. The stage creep, meaning diagnosis of a more advanced stage of disease by more advanced diagnostic techniques, that is created with CT scan in canine patients should be interpreted with caution until additional data become available.

Detection of metastasis to bone before definitive therapy is initiated is important not only for prognostic purposes but because it will preclude amputation in most cases and may make other treatment options more practical. The probability of diagnosing gross bone metastases at the time of diagnosis of osteosarcoma is similar to the probability of finding gross pulmonary metastases.⁴⁴ Detection of metastasis to other bones involves a complete orthopedic examination and long bone survey radiography or nuclear scintigraphy. A complete orthopedic examination, including palpation of the spine, is important in determining whether the dog is a good candidate for an amputation and in evaluating for possible metastatic disease. Focused radiographic evaluation should be performed on areas that are identified as being associated with a pain response. Radiography of all of the long bones and the pelvis can be performed to survey for evidence of metastatic disease.⁸⁸ If available, nuclear scintigraphy using technetium-99m is a more sensitive way to evaluate for metastatic disease. Technetium is administered by an intravenous injection and is incorporated into areas of bone with active metabolism. Relative uptake in different areas of the skeleton is then evaluated using a gamma camera. This is a sensitive but not specific method of evaluating for bone metastases because it does not discriminate between bone tumor, infection, fracture, and other orthopedic conditions. However, an experienced radiologist can generally determine the likelihood of metastatic disease when evaluating areas of increased uptake. Areas that appear abnormal on bone scan should be radiographed to determine the cause of increased uptake of radioisotope (Figure 72-3). Jankowski et al. evaluated 399 dogs with osteosarcoma that were staged with a bone scan and found that 7.8% of those dogs were highly suspected as having metastatic disease based on follow-up radiographs of suspicious areas.⁴⁴

The incidence of metastasis to regional lymph nodes is reported to be 4.4%.⁴³ Dogs with osteosarcoma treated with limb amputation and chemotherapy had a much shorter median survival time when evidence of lymph node metastasis was found (median survival time = 59 days) compared with dogs in which such evidence was not found (median survival time = 318 days).⁴³ The regional lymph nodes should be palpated and aspirated if enlarged. If the diagnosis of lymph node metastasis is not made before amputation, histologic examination of the regional lymph node removed during amputation may provide valuable prognostic information. Regional lymph nodes are considered to be the axillary and prescapular lymph nodes for front limb amputation and the popliteal and inguinal lymph nodes for hindlimb amputation.

Complete blood count (CBC), serum biochemistry, and urinalysis are important parts of the overall evaluation of the patient prior to surgery and treatment. Renal status should be determined before initiation of chemotherapy, as renal toxicity is a potential side effect of some chemotherapeutic agents. Total alkaline phosphatase (ALP) should be assessed preoperatively because bone alkaline phosphatase (BALP) is an isoenzyme of alkaline phosphatase. Although bone alkaline phosphatase is not routinely evaluated separately, an increase in both total alkaline phosphatase and bone alkaline phosphatase has been identified as an indicator of poor prognosis in dogs with osteosarcoma.²⁶ Failure of bone alkaline phosphatase activity to decrease after amputation was associated with a shorter survival and disease-free interval.²⁶

Amputation

The goal of surgical treatment is complete resection of the primary tumor to prevent further metastasis, achieve local control, and remove the source of pain. Most commonly, this is achieved by amputation of the affected limb. In most cases, a significant reduction in weight bearing occurs in the affected limb before surgery, and the patient will adjust easily to walking on three legs postoperatively. A thorough orthopedic examination should be performed before amputation is completed. In most cases, dogs adjust well after amputation, even if osteoarthritis is evident in the remaining limbs. Postoperative physiotherapy should be considered after amputation in dogs that are overweight and in those with concurrent orthopedic disease. Forequarter amputation is recommended for treatment of osteosarcoma of the front limb, because removal of the scapula avoids the aesthetically displeasing appearance of atrophy of the scapular musculature post amputation. The level of amputation for osteosarcoma of the hindlimb is determined by tumor location and the surgeon’s preference. Amputation of the entire hindlimb with en bloc resection of the acetabulum is recommended for tumors of the proximal femur. Amputation by disarticulation of the hip joint is recommended for tumors of the mid or distal femur. Both disarticulation of the hip joint and proximal femoral shaft amputation typically allow complete resection of the primary tumor for patients with osteosarcoma of the tibia.

A small percentage of patients with appendicular osteosarcoma will present with a pathologic fracture (Figure 72-4). The pathologic nature of the fracture may or may not be apparent radiographically, and a high index of suspicion for a neoplastic process should be maintained in large- or giant-breed dogs that present for a fracture without a history of trauma. Appropriate radiographic evaluation and tumor staging are recommended if pathologic fracture is suspected.

Scapulectomy

Bone tumors that commonly affect the scapula include chondrosarcoma and osteosarcoma. Tumors of the scapula can be treated with forequarter amputation or, in some cases, with partial or subtotal scapulectomy and limb preservation. A partial scapulectomy involves the removal of a section of the proximal scapula, with preservation of the acromion, the acromial head of the deltoideus muscle, and the distal portion of the infraspinatus and supraspinatus muscles. This allows for greater stability of the shoulder joint compared with a subtotal scapulectomy.⁹⁵ A subtotal scapulectomy involves removing most of the scapula (as far distal as the scapular notch) while preserving the glenoid and the glenohumeral joint. This procedure is sometimes referred to as a total scapulectomy; however, the glenoid is preserved in all cases. Loss of muscular support that occurs with subtotal scapulectomy will result in a greater dorsoventral excursion during weight bearing.⁹⁵ The amount of scapula removed is dependent on the extent of disease. Advanced imaging of the scapula using MRI or CT is recommended prior to scapulectomy to aid with surgical planning. Candidates for scapulectomy include patients in which the proximal scapula is affected, the tumor has not extended into surrounding soft tissues, the scapula can be removed with a 2 to 3 cm tumor-free margin distal to the tumor, and the glenohumeral joint is preserved. If biopsy was performed, the biopsy tract must be removed with the scapula. The surgical technique is summarized in the following paragraph.⁹⁵

A skin incision is made that encompasses the biopsy tract. For primary bone tumors, the skin directly over the scapula is preserved. Muscle attachments of the omotransversarius, trapezius, and deltoideus muscles are identified and excised 2 to 3 cm from their attachment to the scapula to allow an adequate soft tissue margin. The lateral surface of the distal part of the scapula is exposed by separating the supraspinatus and infraspinatus muscles. The teres major muscle is identified on the caudal aspect of the scapula and is transected. The rhomboideus, serratus ventralis, and subscapularis muscles are identified on the medial aspect of the scapula and are transected. The teres minor muscle and the long head of the triceps brachii muscle are cut along the caudal edge of the scapula. An oscillating saw is used to transect the scapula at the appropriate level.⁹⁵ Depending on the level of the scapulectomy, holes can be drilled in the remaining scapula, and muscles can be sutured to their approximate origins or insertions using bone tunnels for suture placement. If a subtotal scapulectomy has been performed, the muscle edges are reapposed across the defect. A closed suction drain is placed to minimize dead space. Seroma formation is a commonly reported complication of scapulectomy.^70,95

In three case series reporting on scapulectomy, limb use was determined to be good to excellent in 6 of 6, 4 of 5, and 3 of 4 cases, based on postoperative clinical assessment.48,70,95

In the author’s opinion, limb use after partial and especially subtotal scapulectomy is not completely normal. However, pain-free ambulation with functional lameness is possible. Some dogs will use the limb for support, much like a crutch or a cane. More normal ambulation may be achieved in dogs with a partial scapulectomy than in those with a subtotal scapulectomy. In a cases series reporting four dogs that underwent scapulectomy, the three dogs that underwent a partial scapulectomy were found to have excellent limb function, whereas the one dog that underwent a total scapulectomy had fair limb function. That dog had mechanical lameness but was thought to be pain-free.⁴⁸

Hemipelvectomy

Hemipelvectomy is a treatment option for some patients with primary bone tumors of the pelvis. Although a closed approach may not be possible for biopsy of a tumor of the pelvis, if a biopsy is performed, a minimal approach should be used, with care taken to biopsy at a location that can be removed easily with definitive resection. Hemipelvectomy was first reported in veterinary patients in 1992.⁹¹ In that case series of 13 dogs and 2 cats, the tumor types encountered included osteosarcoma (8), fibrosarcoma (3), and chondrosarcoma (2), with fibrosarcoma (1) and rhabdomyosarcoma (1) identified in the 2 cats.⁹¹ Vaccine-associated fibrosarcoma may now be a common diagnosis and indication for cats undergoing hemipelvectomy.⁸²

Hemipelvectomy can be divided into four categories: total hemipelvectomy, which includes the entire hemipelvis from the pubic symphysis to the sacroiliac joint; mid-to-caudal hemipelvectomy, which includes the hemipelvis from the pubic symphysis to mid-ilium, including the acetabulum (Figure 72-6); mid-to-cranial hemipelvectomy, which extends from the sacroiliac joint to just caudal to the acetabulum; and caudal hemipelvectomy, which includes the pubic symphysis to just caudal to the acetabulum.⁵⁰ Caudal hemipelvectomy allows limb preservation.⁵⁰ In general, the limb is resected with the acetabulum, but anecdotal reports have described preservation of the limb with a partial hemipelvectomy that involves the acetabulum. The amount of the hemipelvis that is removed is dependent on the degree of tumor involvement. Potential candidacy for a hemipelvectomy can be determined with the use of plain radiographs. However, CT scan is recommended for surgical planning. If an osteosarcoma has been definitively or presumptively diagnosed, scintigraphy is recommended for local and distant staging.

When the procedure is planned and performed, 2 to 3 cm margins should be achieved beyond the extent of the tumor. It is possible to extend the resection across the contralateral pubis, but this will complicate reconstruction of the caudal body wall. Usually the abdominal wall defect can be reconstructed using local tissue. However, in some cases, a prosthetic mesh is used for reconstruction. Although it is conventional to disarticulate the ilium at the sacroiliac joint, a partial sacrectomy may be necessary to achieve appropriate margins in tumors that cross the sacroiliac joint. Resection of up to one third of the sacrum can be performed with normal function in the remaining contralateral limb.^102a Significant blood loss is possible with hemipelvectomy, and preparations should be made so blood transfusion can be performed without delay if necessary.

Surgical preparation should involve the entire limb with a hanging limb preparation, and skin preparation should extend beyond the dorsal and ventral midline. The cranial extent of the skin preparation should be well in front of the wing of the ilium. The rectum should be packed with gauze so that it is easily identified in surgery, and a purse-string suture should be placed in the anus. A urinary catheter is placed to assist with identification of the urethra during surgery. Standard broad-spectrum perioperative antibiotic use should be in effect. A strategy for reconstruction of the region should be developed before the time of surgery. Tissues overlying the medial or lateral surface of the limb may serve as an invaluable source of skin and muscle to reconstruct the defect and can be preserved on the side of the limb that is opposite the tumor. For tumors that arise from the bone, skin excision is not necessary, except for the biopsy tract.

Although every hemipelvectomy will vary based on tumor type and the resection dictated by tumor extent, following is a description of a standard total hemipelvectomy. Muscles should be severed 2 to 3 cm from their attachments when they are involved in the tumor capsule. This technique must be modified according to the individual patient’s tumor characteristics. The patient is placed in 45 degrees of dorsolateral recumbency. A curved incision is made starting from just cranial to the iliac crest, passing over the lateral surface of the midthigh, and ending at the medial aspect of the ipsilateral ischiatic tuberosity. The insertion of the sacrospinalis muscle is cut. The sartorius and tensor fascia lata muscles are transected ventral to the iliac crest, with care taken to preserve the superficial branch of the circumflex iliac vessels. The insertion of the superficial gluteal muscle is transected and the muscle reflected dorsally, with care taken to avoid separating it from the overlying subcutaneous tissues. The sacrococcygeal origins of the superficial gluteal muscle are preserved, but its attachment to the sacrotuberous ligament is transected. The sacrotuberous ligament is transected just anterior to the origin of the piriformis muscle. The leg is reflected laterally, and a medial incision is made from the ends of the lateral incision around the limb, crossing the pectineus muscle. The femoral artery and vein are identified. The superficial circumflex iliac branch is preserved cranially if possible, but the more proximal and caudal deep femoral artery and vein are ligated and transected. The prepubic tendon and psoas (major and minor), iliacus, and quadratus lumborum muscles are transected. The pubic symphysis is cut with an osteotome or oscillating saw along the ventral midline. Care is taken to identify and protect the urethra and the rectum. The sciatic nerve is identified, infiltrated with local anesthetic, and cut at the level of the sacroiliac junction. Associated gluteal vessels are ligated and transected. The patient is repositioned to lateral recumbency, and an osteotome is used to separate the sacroiliac articulation by cutting from cranial to caudal. The hemipelvis now is free and can be removed.

Closure is performed by suturing the cranial edge of the sartorius muscle to the cut edge of the abdominal muscles, prepubic tendon, and inner aspect of the pubic symphysis. Holes are drilled in the pubic bone to anchor the suture. The proximal end of the sartorius and the tensor fascia lata muscles are anchored to the ventral aspect of the sacrum. Holes can be drilled in the ventral sacrum to anchor sutures. The distal end of the sartorius muscle is sutured to the levator ani muscle. The dorsal edge of the tensor fascia lata is sutured to the remnant of the sacrotuberous ligament and the coccygeus muscle. The distal end of the superficial gluteal muscle is sutured to the outer edge of the pubic symphysis via bone tunnels. The remaining skin flap is trimmed to an appropriate length, and the rest of the closure is routine.

Postoperative pain management is an essential part of this procedure. A closed suction drain or a pain diffusion (soaker) catheter, or both, can be employed postoperatively to limit dead space and manage pain, respectively. This procedure lends itself to preemptive analgesia with an epidural,⁷¹ and an indwelling epidural catheter can be placed for postoperative management. A multimodal approach to analgesia should be used, with opioids, NSAIDs, and other analgesics administered as needed. The urinary catheter can remain in place for the first 8 to 24 hours to limit ambulation in the immediate postoperative period. The surgical procedure and recovery are more complicated for patients undergoing hemipelvectomy than for patients undergoing amputation by disarticulation or at the mid-femur level. However, for all intents and purposes, patients treated by hemipelvectomy are very similar functionally and cosmetically to other hindlimb amputees.

Limb-Sparing Surgery

The primary indication for limb-sparing surgery is when it is anticipated that the patient will not ambulate well if the limb is amputated. This may be due to concurrent orthopedic or neurologic disease, the dog’s size in the case of giant breeds, or previous amputation of another limb. A vast majority of dogs do well with an amputation, even if some degree of orthopedic disease is present in another limb. Further, the complication rate after an amputation is very low compared with limb-sparing surgery. Dogs with osteosarcoma of the distal radius are the most amenable to limb sparing.

Many limb-sparing techniques are currently used by surgical oncologists to treat canine distal radial osteosarcoma. These include cortical allograft, pasteurized autograft, intraoperative radiation (autograft), endoprosthesis, vascularized ulnar transposition, stereotactic radiosurgery, and bone transport osteogenesis. With the exception of intraoperative radiation and stereotactic radiosurgery, these techniques involve resection of the distal part of the radius with appropriate margins and replacement of the defect that is created with autograft, allograft, prosthesis, or regenerated bone. As with many surgical procedures in which multiple techniques are available, there is not one perfect technique that is without its own set of complications. Currently, the endoprosthesis technique appears to be used most commonly by surgical oncologists.⁹⁸

Limb-sparing surgery is most commonly performed to treat osteosarcoma of the distal radius. However, procedures to treat tumors involving other sites are continually being developed. Full staging should be performed before limb-sparing surgery to ensure that gross disease at another site is not evident. For distal radial sites, ideal candidates are dogs that do not have a large amount of soft tissue involvement or evidence of pathologic fracture. Either of these situations greatly increases the probability of local recurrence. The tumor should involve less than 50% of the radial length to facilitate implant placement and decrease the risk of implant failure.²⁰

Limb-sparing surgery is a costly procedure with a high complication rate in patients with disease that will be fatal in most cases. Owners must be somewhat resilient and must have the time and resources needed to manage potential complications. Extensive client education is critical before one embarks on a limb-sparing procedure.

Cortical Allograft

Limb-sparing surgery with a cortical allograft (Figure 72-7) was first reported in dogs in 1989.⁵² This technique initially involved preoperative radiation to downstage the tumor. Preoperative radiation is not currently administered prior to limb-sparing surgery because of the high complication rate associated with this technique. Because this was the first limb-sparing technique developed in dogs, it is often referred to as traditional limb-sparing surgery.