Introduction
Primary musculoskeletal malignancies are uncommon and represent approximately 1% of the cancer burden in adults and 10% in children1–2. Malignant tumors involving the foot and ankle are even less common and probably less than 5% of all malignancies of bone and soft tissues affect the foot3. Due to their low rates of occurrence the true burden of disease is difficult to establish. Unlike bone tumors elsewhere, malignant neoplasms affecting the foot are more likely to be primary than metastatic.
In the foot malignant tumors can arise from any of the tissues, including soft tissue, bone, nerves, and blood vessels. An understanding of the basic principles of the management of bone and soft tissue malignancies is critical for any orthopedic surgeon.
The clinical features of a malignant tumor arising in the foot and ankle may be similar to those of a benign tumor. Patients commonly present with pain and may attribute this to an antecedent traumatic episode, which can be misleading. Patients with sarcomas of the foot and ankle are often misdiagnosed and initially treated for benign pathologies. Early recognition of foot and ankle malignancies remains the biggest challenge in the management of these tumors. Sound knowledge is essential to ensure prompt recognition and appropriate management.
The following chapter looks in detail at the more common types of malignant tumors affecting the foot and ankle. The principles of management are discussed in general toward the end of the chapter.
Soft Tissue Sarcoma
Soft tissue sarcomas arise from extraskeletal tissues including fat, muscle, ligaments, synovium, and neurovascular structures. Soft tissue sarcomas are rare. The annual incidence is approximately two to three cases per 100 000 people, which accounts for less than 1% of adult and 8% of pediatric malignancies4. They are typically classified histologically according to their tissue of origin or as tumors of uncertain differentiation: it may be impossible to characterize the lesion (undifferentiated/unclassified sarcomas).
Soft tissue sarcomas are particularly rare in the foot and ankle. Most patients complain of a swelling, which may or may not be painful. A long history does not exclude the diagnosis. A careful history and examination are essential. Soft tissue swellings that are large, rapidly growing, deep to the fascia, and painful are more likely to be malignant5.
There are over 50 subtypes of soft tissue sarcoma and cases involving the foot and ankle have been described for many of them, including synovial sarcoma, clear cell sarcoma, the condition previously described as malignant fibrous histiocytoma (now undifferentiated pleomorphic sarcoma), leiomyosarcoma, and fibrosarcoma6. However, in a review of 12 370 patients with soft tissue malignancies only 638 cases (5%) involved the foot and ankle6. Despite their infrequent occurrence, certain subtypes of soft tissue sarcoma seem to have a predilection for the foot and ankle. These are discussed below. The principles of management are discussed at the end of the chapter and can be applied to any malignant sarcoma involving the foot and ankle.
Synovial Sarcoma
Synovial sarcoma accounts for approximately 8 to 10% of all soft tissue sarcomas. Its peak incidence is in the third decade of life, with 30% arising in those aged under 20 years. Synovial sarcoma is slightly commoner in males and it is the commonest soft tissue sarcoma to arise in the foot and ankle, comprising 45 to 56% of all sarcomas in this region7. Typically the tumors arise in a periarticular position (Figure 18.1), although very rarely they occur within the joint. They are typically considered high-grade tumors with characteristically invasive features and a tendency to metastasize.
Figure 18.1 Synovial sarcoma in the left tarsal tunnel of a 42-year-old male. (a) Sagittal STIR MRI shows a large, homogeneous mass in the tarsal tunnel (*), inferior to the flexor digitorum longus tendon (arrows). (b) Axial PD MRI shows encasement of the posterior tibial artery (white arrow) and medial and lateral plantar nerves (black arrows). Below knee amputation was performed.
The name synovial sarcoma is a misnomer as these tumors do not originate from cells within the synovium. The exact cell of origin is unknown and in the WHO classification of tumors they are included among sarcomas of uncertain differentiation, lacking a precise, normal tissue counterpart1. Three main subtypes of synovial sarcoma exist:
biphasic – with epithelial and spindle cells in varying proportions
monophasic – consisting of sheets of spindle cells only
poorly differentiated – a more aggressive subtype with signs of necrosis, hemorrhage, and a high mitotic index.
Almost all synovial sarcomas demonstrate a reciprocal translocation t(X;18), which is not seen in other sarcomas. This fuses the SYT (SYnovial Tumor) gene from chromosome 18 with one of three SS (Synovial Sarcoma) genes (SSX 1, 2 and 4) from chromosome X. The resultant fusion gene produces a protein which is thought to underlie synovial sarcoma pathogenesis by deregulating gene expression8. The SYT/SSX 1 fusion gene is more commonly associated with biphasic synovial sarcoma.
There are no clinical features or examination findings that distinguish synovial sarcoma from other soft tissue tumors. One review of 14 patients with synovial sarcoma of the foot and ankle found that pain, tenderness, edema, and an enlarging mass were the commonest symptoms7. However, frequently the mass behaves indolently and is present for considerable periods of time, sometimes years. Such non-specific features make prompt diagnosis a challenge. Indeed, the same study reported that six out of 14 patients had been initially diagnosed with benign pathologies including ganglion cyst, plantar fasciitis, and non-specific synovitis (Figure 18.2). Ten patients also gave a history of trauma prior to the onset of symptoms7. Initial conservative management led to delays in definitive diagnosis and management with a median duration of symptoms of 14 months prior to presentation7. It is the commonest malignancy to be mistaken for a benign condition.
Figure 18.2 Synovial sarcoma in the plantar aspect of the left foot in a 21-year-old male. The mass had been present for 18 months with no significant growth and was thought to represent a benign synovial mass, possibly a ganglion – these relatively non-specific, non-aggressive clinical and imaging features are a significant pitfall in the management of this tumor. (a) Coronal T2 MRI and (b) sagittal T1 post-contrast MRI with fat saturation, showing a small, solid, enhancing mass (arrow) located dorsal to the knot of Henry.
Synovial sarcoma is an aggressive tumor, which commonly metastasizes. As with other soft tissue sarcomas, negative prognostic factors include high grade, large tumor size, and metastases at the time of presentation. Hajdu et al. reviewed 126 cases and concluded that patients with tumors smaller than 5 cm had better five-year survival rates (79%) than those with tumors larger than 5 cm (33%)9. A large population-based study of 1268 patients with synovial sarcoma demonstrated that adults tend to have a worse outcome than children10 with five-year survival rates estimated to be 83% for children and 62% for adults. The same study also showed more favorable outcomes for tumors involving the extremities. That said, of 14 cases involving the foot and ankle eight died of metastatic disease7.
Undifferentiated Pleomorphic Sarcoma (or Malignant Fibrous Histiocytoma)
Undifferentiated pleomorphic sarcoma (UPS) may arise in both soft tissues and bone. They are relatively common and account for 20 to 30% of all soft tissue sarcomas. The peak prevalence is in the fifth decade of life and males are more affected than females (M:F, 1.5:1). Most patients present with a slowly enlarging, painless mass. These tumors commonly affect the extremities and 50% involve the lower limb11. Approximately 7% of malignant tumors affecting the foot are of this type12.
Its true cell of origin is unknown and many feel that it represents the final common pathway of many different tumors, which become undifferentiated as they progress13. The WHO declassified malignant fibrous histiocytoma and renamed it as an undifferentiated pleomorphic sarcoma not otherwise specified, NOS1. Several subtypes have been described based on the predominant cellular features. These include storiform-pleomorphic, myxoid, giant cell, and angiomatoid. The storiform-pleomorphic subtype accounts for approximately 50 to 60% of these tumors and the remainder are usually of the myxoid type (25%)11.
As with other soft tissue sarcomas, patients with larger and more deeply invested tumors tend to have a worse prognosis. Patients under 60 years of age with a small, low-grade myxoid type tumor typically have a better prognosis. Local recurrence is common and occurs in up to 50% of patients treated with radical, complete excision.
Clear Cell Sarcoma of Soft Tissue
Clear cell sarcoma of the soft tissue is a rare malignant tumor, which was first described by Enzinger in 196514. Due to the presence of differentiated melanocytes this tumor has also been referred to as “malignant melanoma of soft parts”; however, it is recognized as being distinct from malignant melanoma.
The extremities are the principal site of involvement, with approximately 40% of these tumors arising in the foot and ankle15. It mainly affects young adults (mean 22 years)16 but as it is so rare the exact incidence is unknown. They usually arise deep in the soft tissues and are commonly fixed to surrounding tendons or aponeuroses. Approximately 8% of soft tissue malignancies affecting the foot and ankle are clear cell sarcomas6.
Patients usually present with a slow-growing mass, which is painful or tender in 50% of cases15.
The prognosis is poor for patients with this tumor. Five-year survival rate has been estimated at 67%, which declines to 33% and 10% at 10 and 20 years respectively17. Patients succumb to widespread metastases, which can develop many years after complete surgical excision. Tumor size and necrosis are poor prognostic indicators17.
Bone Tumors
Bone sarcomas involving the foot and ankle are rare. However, unlike elsewhere in the skeletal system, malignancies arising in this region are more likely to be primary tumors than metastases.
Patients rarely present with systemic symptoms18 and the commonest complaint is pain. Often patients are initially treated for benign pathologies and delays in diagnosis are common.
Ewing’s Sarcoma
The commonest primary malignant bone tumor to arise in the foot and ankle is Ewing’s sarcoma. Out of a series of 8452 bone tumors only 54 were found to be malignant lesions arising in the foot19. Of these 54 cases 20 were Ewing’s sarcomas (37%)19.
Ewing’s sarcoma typically occurs during childhood or adolescence, with the vast majority of cases arising before the age of 25. It can arise in any bone but is most frequently found in the diaphyses of the long bones of the lower limb, and flat bones such as the pelvis. It is the second most common primary malignant bone tumor to occur in children after osteosarcoma.
In a review of 16 patients with Ewing’s sarcoma of the foot the mean age of the patients was 17 years (range 10–42)18. The tumor involved the metatarsals (Figure 18.3) or phalanges in 10 of the 16 patients, with the remainder arising in the calcaneus, navicular, and talus18. All the patients presented with pain and swelling in the foot, and fever was present in four cases18. As with other malignant tumors the diagnosis of Ewing’s sarcoma in the foot is often delayed. The diagnosis took an average of 14 months, with many patients initially being treated for benign conditions18. Delays in diagnosis put patients at risk of developing advanced disease and in this case series 7 out of 16 patients had metastases at diagnosis18.
Figure 18.3 Ewing’s sarcoma in the first metatarsal of a 25-year-old male. (a) Dorsoplantar radiograph showing permeative bone destruction (*) and extra-osseous mass (arrow). (b) T1-weighted coronal and (c) T2-weighted axial MRI showing infiltration of the first metatarsal (*) and surrounding mass (arrow).
Ewing’s sarcoma shows variable neural differentiation and is morphologically similar and genetically identical to primitive neuroectodermal tumor (PNET). They are part of a spectrum of tumors collectively termed the Ewing’s sarcoma family. The cell of origin for Ewing’s sarcoma is not known but it is thought to arise from mesenchymal stem cells. It has a typical histological appearance consisting of small round cells that stain blue with hematoxylin and eosin (H&E).
In most cases, a genetic translocation occurs between the EWS gene on chromosome 22 and the FLI-1 gene on chromosome 1120. The resultant fusion protein regulates the expression of other genes leading to the development of the cancer.
Ewing’s sarcoma is an aggressive tumor with poor survival. The five-year survival for patients with non-metastatic disease is 50 to 70%21–22. Positive prognostic indicators include non-pelvic tumors and younger age groups22. Survival is significantly reduced if metastases are present at the time of diagnosis (five-year survival 10–15%). In the case series mentioned above the overall five-year survival for tumors affecting the foot was 53%18. Those patients with metastases at presentation had an overall five-year survival of only 14%18.
Osteosarcoma
Osteosarcoma is the commonest primary sarcoma of bone. It typically arises in patients in their second decade of life with a second peak occurring in the elderly population with preexisting Paget’s disease. Approximately half of all osteosarcomas arise around the knee. Involvement of the foot is rare. Only 0.2 to 2% of all primary osteosarcomas occur in the foot23.
The mean age of patients with osteosarcoma affecting the foot is estimated to be approximately 35 years24. This is over a decade older than expected for patients with osteosarcoma. The calcaneus is the most commonly affected bone and as in other tumors of the foot and ankle, pain is the most common presenting complaint24. Diagnosis is frequently delayed and has been reported to take up to two years24. Once again patients are frequently misdiagnosed with other conditions including osteoblastoma, chondroblastoma, osteomyelitis, and chondrosarcoma25.
The exact cause of osteosarcoma is unknown. Patients who survive the inherited form of retinoblastoma are at an increased risk of developing osteosarcoma later in life as a result of a shared chromosomal abnormality involving the Rb1 gene on chromosome 1326. However, this genetic defect only accounts for a small number of osteosarcomas. Previous radiation therapy and preexisting conditions such as Paget’s disease, hereditary multiple exostosis, and fibrous dysplasia are all linked to the development of osteosarcoma.
Various types of osteosarcoma have been described including intramedullary (conventional) osteosarcoma, parosteal osteosarcoma, and periosteal osteosarcoma. The microscopic appearance of intramedullary osteosarcoma varies according to the subtype:
osteoblastic osteosarcoma: predominately osteoid/bony matrix
chondroblastic osteosarcoma: predominately chondroid matrix
fibroblastic osteosarcoma: predominately spindle cell matrix with little osteoid.
In a case series of 52 osteosarcomas24 affecting the foot all were found to be intramedullary osteosarcomas with variations in subtype: osteoblastic osteosarcoma (46%), chondroblastic osteosarcoma (25%), fibroblastic osteosarcoma (29%). The tumor was high grade in over 80% of cases. Only one patient had an osteosarcoma arise from previously Pagetoid bone.
Osteosarcoma is an aggressive malignancy, which traditionally has had very poor outcomes. Advances in neo-adjuvant chemotherapy in conjunction with surgical resection have improved patient outcomes with overall five-year survival reaching 65%27. Outcomes for disease affecting the foot and ankle are hard to define as the published literature relies on case reports and case series. One series of 14 patients with osteosarcomas involving the foot reported 9 patients dying after a mean of 2½ years24.
Chondrosarcoma
Chondrosarcomas are malignant cartilage-forming tumors that can arise in any bone but are commoner in the proximal femur, pelvis, and ribs. They tend to occur in older age groups (40–75 years). They are not commonly found in the foot and ankle, and most examples cited in the literature are case reports or case series. The Scottish Bone Tumour Registry reported that 3% of 403 chondrosarcomas arose in the bones of the foot with a mean age at presentation of 52 years (range 17–83)28. Chondrosarcomas arising in the foot are commoner in males (M:F, 9:2), compared to elsewhere in the body where the incidence is nearly equal28.
Chondrosarcomas are described as either primary or secondary, based on whether the tumor has arisen de novo (primary) or from a preexisting benign lesion, such as an enchondroma (secondary). They are also described as central or peripheral. Central chondrosarcomas develop in the medullary cavity (Figure 18.4) and represent around 90% of chondrosarcomas, whereas peripheral tumors are rarer and tend to arise in the cartilage cap of a preexisting osteochondroma.
