Osteosarcoma of the Tibia 6 Years After Tibial Plateau Leveling Osteotomy
A 7 yr old spayed female mastiff presented for examination of a left pelvic limb lameness of 3 mo duration. Six years previously, the dog had undergone tibial plateau leveling osteotomy (TPLO) surgery of the left pelvic limb for the treatment of cranial cruciate disease. On presentation, the dog had a painful and swollen proximal tibia. Following investigation, a diagnosis of osteosarcoma of the proximal left tibia at the site of the previous TPLO surgery was made. This is the first reported case of osteosarcoma following TPLO using an implant other than the Slocum plate.
Introduction
Cranial cruciate ligament disease is one of the most common causes of lameness in dogs.1 Numerous surgical techniques have been described to manage this condition, including extra- and intracapsular, tibial plateau leveling osteotomy (TPLO), and tibial tuberosity advancement (TTA) surgeries.2–4 There is little good scientific evidence that any one surgical procedure is better than any other, except for one study that found outcome following intracapsular stabilization was less favorable than both the TPLO and extracapsular stabilization surgeries.5
In 1978, Henderson and Milton observed and documented cranial tibial thrust in the canine cranial cruciate ligament deficient stifle.6 Afterward, Slocum developed the TPLO operation, which reduces the tibial plateau angle and neutralizes cranial tibial thrust.3,7,8
Reported complications associated with the TPLO surgery include osteomyelitis, tibial crest fractures, patella ligament desmitis, and malunion. The most common complications identified are infection (incidence of 2.5–12.5%), tibial tuberosity fracture (3–4%), and loose or broken implants (1–4%).9–11 One very rare complication of TPLO is neoplasia of the proximal tibia originating at the same location as the TPLO surgery. Cases of soft tissue and bone tumor formation following fractures and placement of orthopedic implants have previously been reported in both human and veterinary patients.12–15 The authors are aware of only three such cases following TPLO surgery in dogs: one case of osteosarcoma and two cases of histiocytic sarcoma.16–18 All of these cases of sarcoma following TPLO used the Slocum plate to stabilize the osteotomy. The case described herein did not have a Slocum TPLO plate and did not have a standard TPLO osteotomy. To the authors’ knowledge, this is the first report of an osteosarcoma following TPLO using a non Slocum plate.
Case Report
A 7 yr old spayed female mastiff presented for investigation of a 3 mo history of progressively deteriorating lameness affecting the left pelvic limb. The lameness had not responded to firocoxiba (227 mg per os q 24 hr) and tramadolb (100 mg per os q 12 hr). The dog's history included a diagnosis of bilateral cranial cruciate disease at 20 mo of age. As a result, the dog had TPLO surgery of the left tibia. The osteotomy had not been made using the custom-designed Slocum biradial saw blade. Instead, an arc was scribed on the medial aspect of the proximal tibia using a protractor, and the tibia was subsequently cut free-hand using an air-powered reciprocating saw. The osteotomy was rotated and stabilized with a 7-hole 3.5 mm TPLO platec and 3.5 mm cortical screwsd. Recovery from surgery was uncomplicated, and the dog had good functional use of the operated limb postsurgically. In addition, the dog was diagnosed with chylothorax at 4 yr of age (that was successfully managed surgically), and at 4.5 yr of age she underwent surgical decompression for Hansen type I intervertebral disc extrusion between the sixth and seventh cervical vertebrae. Finally, at 6 yr of age the dog underwent dorsal laminectomy of the second and third cervical vertebrae due to cervical spinal stenosis.
At the time of presentation, the dog was grade 8/10 lame in the left pelvic limb. The left stifle joint was grossly thickened, joint effusion and medial buttress were palpable, and joint range of motion was good. Pain was elicited on application of pressure to the proximal tibia. In addition, the dog's right carpus was thickened, painful, crepitant on manipulation, and had a decreased range of motion.
Hematology showed a mild lymphopenia (0.78×109 lymphocytes/L; reference range, 1–4.8×109/L). Serum biochemistry revealed a mild elevation of urea (11.2 mmol/L; reference range, 3–9.1 mmol/L), a mild hyperkalemia (6.1 mmol/L; reference range, 4.1–5.3 mmol/L), a mild increase in serum amylase (1,367 U/L; reference range, 176–1,245 U/L), and a mild increase in serum lipase (1,527 U/L; reference range, 72–1,115 U/L). Alkaline phosphatase was normal (149 U/L; reference range, 19–285 U/L).
Radiographs of the left stifle (Figure 1) showed marked joint effusion and periarticular osteophytes associated with degenerative joint disease. The bone of the proximal tibia was markedly abnormal due to the presence of a poorly defined but broad area of permeative lysis of the proximal tibial diaphysis, metaphysis, and epiphysis, as well as cortical bone destruction. Production of new bone and a long but poorly defined transition zone was observed. These radiographic abnormalities of a highly destructive pathologic process of the proximal tibia suggested an aggressive bone lesion, most likely neoplastic. The lesion was located adjacent to the TPLO plate and apparently centered on the region of the previous osteotomy.
Citation: Journal of the American Animal Hospital Association 48, 3; 10.5326/JAAHA-MS-5730
Radiographs of the thorax taken during inspiration showed no significant abnormalities other than metallic opacities over the sternum consistent with the orthopedic wire used to close the previous thoracotomy. There was no radiographic evidence of pulmonary metastatic disease. Radiographs of the right carpus showed enthesiophytes at the origin of the medial collateral ligament.
Multiple fine-needle aspirate biopsies of the proximal tibia were obtained and submitted for cytology. Sections stained with a modified Wright-Giemsa stain showed a finely granular pink to magenta background containing few erythrocytes, rare neutrophils, lymphocytes, and low to moderate numbers of plump spindle to round cells. These latter cells displayed moderate and occasionally marked anisocytosis and anisokaryosis with a moderate amount of deeply basophilic and occasionally wispy cytoplasm. Moderate and high nuclear to cytoplasmic ratios were seen. The nuclei were round to oval in shape, contained prominent nucleoli that were variable in size and number, and displayed stippled to coarse chromatin. Other atypical features included occasionally bi- and multinucleate cells, moderate to marked anisokaryosis within the same cell, and rare macrocytosis and macrokaryosis. A few multinucleate osteoclasts were also present. These findings were interpreted as being consistent with a malignant mesenchymal neoplasia, most likely osteosarcoma (Figure 2).
Citation: Journal of the American Animal Hospital Association 48, 3; 10.5326/JAAHA-MS-5730
Multiple Jamshidie needle biopsies of the proximal tibia were obtained and submitted for histology. These showed sections of bone composed of trabeculae interspersed with sheets of pleomorphic spindle cells. These cells had sparse, pale, and faintly fibrillar cytoplasms and anisokaryotic nuclei. These nuclei were hyperchromatic or coarsely granular and most contained medium-sized dense nucleoli. An average of three mitoses per high-power field were noted, and bizarre forms of mitotic figures were present. Irregular seams of osteoid extended between the tumor cells in some sections. Moderate to marked bone remodeling was noted in other locations. On the basis of these findings, a diagnosis of osteosarcoma was made (Figure 3).
Citation: Journal of the American Animal Hospital Association 48, 3; 10.5326/JAAHA-MS-5730
Chemotherapy and amputation were offered, but the owners declined. Instead, the owners elected to treat the dog palliatively. The tramadol and firocoxib were therefore continued, and an IV infusion of 1 mg/kg bisphosphonate pamidronatef (diluted in 250 mL of 0.9% sodium chloride) was administered over 2 hr. The bisphosphonate pamidronate infusion was scheduled to be repeated 1 mo following the first treatment, but this was not given because the dog's owners declined further treatment. The dog presented for re-evaluation 8 wk following the initial presentation. She was recumbent and painful. Examination showed increased stifle swelling and tibial pain. Repeat radiographs of the left stifle and proximal tibia showed worsening of the tibial lysis, lengthening of the zone of transition and periosteal new bone formation. Thoracic radiographs showed no significant abnormalities. The dog was euthanized 1 wk later, and a postmortem examination was not performed.
Discussion
Osteosarcoma is the most frequently diagnosed primary bone neoplasm in the dog, accounting for 85% of reported skeletal malignancies.19 The tumor behaves in a locally aggressive manner and has a high propensity to metastasize, and the lungs are the most common site for secondary lesions.19 Ninety percent of dogs die of metastatic disease within 1 yr following diagnosis if treated with amputation alone.19 The primary tumor can cause bone destruction, production, or a combination of both, which is usually associated with disruption and inflammation of the overlying soft tissues. The lesions are painful because of microfractures and periosteal disruption. Osteosarcoma is most frequently seen in large-breed dogs with a median age of 7 yr at the time of presentation.17 Osteosarcoma typically develops in the metaphysis of long bones, of which the proximal humerus and distal radius are the most common sites.20 Spontaneous osteosarcoma affecting the tibia and fibula is thought to account for ∼9% of all osteosarcoma cases.21
The initiating cause of osteosarcoma is unknown, but different mechanisms have been proposed. Osteosarcoma has been reported secondary to ionizing radiation.19 Genetic alterations in the tumor-suppressor genes Rb and p53 have been documented in dogs with osteosarcoma.22 It is also postulated that fatigue microdamage of the metaphyseal regions in large dogs may lead to the formation of malignant cells.19,22 Chronic inflammatory processes may lead to neoplastic transformation, and osteosarcomas could potentially form as a sequel to altered cellular activity of osteoblasts and osteoclasts associated with fractures and/or metallic implants.14,19 This latter hypothesis could be a result of chronic inflammation, which may be exacerbated by delayed healing as a result of fracture instability or the presence of infection. Bone infarcts have also been associated with osteosarcoma. For example, one case documented sarcoma development after infarct formation following total hip arthroplasty.23
Neoplasia of the surgical site is very uncommon following TPLO surgery. The authors of this report are aware of only three published case reports in the literature.14–16 Further, three large retrospective studies reviewing complications following TPLO surgery in 1,286 veterinary patients did not identify any cases of neoplasia; however, the longest follow-up interval was 4 yr, which is arguably too short to capture subsequent cases of neoplasia.9–11 A personal communication reporting a survey of 136 veterinarians and 37,082 standard TPLO procedures reported 28 cases of neoplasia.24 Most cases occurred in large-breed dogs, and only 5 of 28 cases occurred within 1 yr of surgery. When cases with <1 yr follow-up were excluded, 23 tumors from 30,636 TPLO surgeries were diagnosed, which equates to a tumor prevalence of 0.075%.24 In a large study of 394,061 insured Swedish dogs, there were 66 reported cases of primary bone tumors affecting the proximal tibia and fibula, which makes the prevalence 0.017%. It should be noted that all malignant bone tumors affecting the tibia/fibula were considered, not just osteosarcoma.21 In other words, the prevalence of TPLO-related tumor formation rate appears to be 4.4 times higher than that of spontaneously developing malignant bone tumors affecting the tibia and fibula. This suggests that a TPLO surgery-related factor is causative for the increased incidence, possibly by inducing chronic inflammation or fracture/implant-associated sarcoma as considered earlier.
One previous case study of a sarcoma affecting the stifle joint following TPLO surgery reported the presence of intra- and extracellular debris in histologic sections. Further analysis showed these particles were metallic. It was assumed, but not proven, that these metallic particles were a sequel to implant corrosion and that these particles may have contributed to neoplastic transformation.17 In the present case, neither metallic particles nor foreign material was observed within the histologic sections examined, but as the samples were obtained using a Jamshedi needle biopsy and only selected samples were examined, it is possible that such metallic particles could have been missed.
The three previously reported cases of neoplasia following TPLO surgery all had a Slocum TPLO plate placed during surgery. Doubts have been raised regarding the metallurgic composition of the Slocum TPLO plate, and two studies have investigated crevice corrosion of the Slocum plate.17,25,26 One study found that the Slocum TPLO plates had evidence of corrosion and further speculated that this may lead to the generation of a number of chemical compounds that could have the potential to cause disease.25 However, another study found no evidence of corrosion of the Slocum TPLO plate, but did find evidence of biofilm formation on the plate-tissue interface. Biofilm is not a product of corrosion but could possibly be confused with corrosion without advanced investigative techniques.26 Biofilm is the result of the adhesion of bacteria to surfaces and the subsequent production of an exopolysaccharide material and is seen following placement of many types of medical implants within the body.27
The bone plate used in this current case was different from the Slocum TPLO plate in two ways. First, the bone plate used in the dog described in this report was manufactured from 316LVM surgical steel that meets all of the current standards for surgical implant manufacture in the UK (BS 3531 and ISO 5835).28 In contrast, the Slocum TPLO plate has some variations from the standard recommended chemical composition of metallic implants.17 Second, the TPLO plate used in this case was wrought as opposed to the Slocum TPLO plate that is cast.
Fracture-associated sarcomas of dogs tend to present with a median lag phase of 6 yr following initial fracture, and the original fracture usually occurs between 1 yr and 3 yr of age.29 Fracture-associated sarcomas are usually diaphyseal and may have an increased component of inflammatory cells. Inciting factors for fracture-associated sarcomas are thought to include local tissues reacting to implants, corrosion products from the metal implants, chronic infection, delayed bone healing, and impaired vascularity to the fractured bone.23 This case reported exhibits some of the features associated with fracture (osteotomy)-associated sarcomas, including the following: the dog was 18 mo old at the time of bone insult, there was a lag phase of 6 yr to tumor formation, and the location was the site of the previous bone trauma. Previous fracture-associated sarcomas have also featured an inflammatory cell component, but this was not noted in either the present case or in a case of osteosarcoma that occurred after triple pelvic osteotomy.30
As previously indicated, a number of different etiologic mechanisms may be responsible for tumor formation following TPLO surgery in the dog. Currently the precise etiology is unknown. This case report is the second confirmed case of osteosarcoma following TPLO surgery and is the first to demonstrate that neoplastic transformation following TPLO surgery is not a complication unique to the Slocum TPLO plate. Dogs presenting with cranial cruciate ligament ligament instability that are potential candidates for TPLO surgery are usually similar breed groups to those at higher risk of developing spontaneous primary bone tumours i.e. typically larger breeds. In these dogs demonstrating a causal relationship between osteotomy, implant placement and subsequent tumour formation is therefore challenging. 19 Such a causal relationship is suspected given that the prevalence of TPLO-related neoplasia is 4.4 times higher than all bone tumors of the tibia. Due to the recent rapid increase in the number of procedures involving elective osteotomy and implant placement for cranial cruciate disease (e.g., TPLO and TTA), a corresponding increase in the occurrence of osteotomy/implant-associated neoplasms reported would be expected if such a relationship exists. Similarly, TTA surgery has recently become more popular. At the time of writing this report, the authors were unaware of a TTA-related case of tibial neoplasia, but if either the osteotomy or implant is an inciting cause, then TTA-related tibial neoplasia cases will also doubtlessly occur. The same argument applies to other corrective osteotomies such as those performed for angular limb deformities. Given that osteotomies for angular limb deformities are performed less frequently than those for cruciate disease, it is likely to be even more challenging to prove a cause and effect relationship in that instance. Nonetheless, ongoing vigilance and recording of the prevalence and incidence of neoplasia after such surgical procedures should be encouraged.
Conclusion
This report describes a case of osteosarcoma of the proximal tibia that occurred 6 yr after TPLO during surgery in a dog that underwent an osteotomy, in which the Slocum TPLO plate was not used.
Lateral radiograph of the proximal tibia. Note the “moth eaten” proximal metaphysis and new bone formation.
Fine-needle aspirate of the proximal tibia. Note the population of plump spindle to round cells with multiple cytologic criteria of malignancy. Modified Wright-Giemsa stain, original magnification ×400.
Biopsy of the proximal tibia obtained using a Jamshedi needle. Note the irregular seams of osteoid between the sheets of pleomorphic spindle cells. Hematoxylin and eosin stain, original magnification ×400.
Contributor Notes
M. Atherton's current affiliation is Small Animal Hospital, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
