Foot and Ankle Pain in the Oncologic Population
Michael Harbus
Amitabh Gulati
INTRODUCTION
The primary oncological processes that have commonly been associated with foot and ankle pain include sarcoma, melanoma, and bony metastasis.1,2,3 However, the vast majority of masses which occur in the foot and ankle are benign; therefore, distinguishing between benign and malignant growths is of great clinical significance. When a malignant tumor occurs in the foot and ankle, the aims of therapy are twofold: treating the tumor, which is usually done through chemotherapy, radiotherapy, or surgical excision, and managing pain, which can be done through a number of treatment modalities including analgesic pain medications, rehabilitation, and in the case of metastasis to the bone, bisphosphonates, denosumab, cementoplasty, and radiopharmaceuticals. Foot and ankle pain can also develop as a consequence of oncologic treatments. Among the treatment-associated causes of pain are chemotherapy-induced peripheral neuropathy (CIPN), radiation-induced peripheral neuropathy (RIPN), immunotherapy-induced joint pain, and aromatase inhibitor-induced arthralgias.4,5
When addressing foot and ankle pain in the oncologic population, special attention must be given to conditions that occur either with higher incidence or exclusively in patients with cancer. These conditions include lymphedema, deep vein thrombosis, and cancer-related fatigue and disuse syndrome. This chapter is intended to provide an overview of the most common causes of pain in the oncologic population and to outline a stepwise treatment approach for each pain-generating condition.
TUMORS OF THE FOOT AND ANKLE
Tumors and pseudotumors of the foot are relatively common; however, the vast majority of these are benign. Masses in the foot and ankle can be divided into those that affect the soft tissue and those that affect the bone. The most common benign masses that occur in the soft tissue of the foot are plantar fibromatosis, tenosynovial giant cell tumors, ganglion cysts, and lipomas.1,6,7 The most common malignant soft-tissue tumors are synovial cell carcinomas, clear cell carcinomas, fibrosarcomas, malignant fibrous histiocytoma, and melanoma. The most common benign bone tumors that affect the foot are enchondromas, osteoid osteomas, and chondroblastomas, while the most common malignant bone tumors that occur in the foot are chondrosarcoma, Ewing sarcoma, osteosarcoma, and bony metastasis.7 Clinically, when malignant tumors occur, they are more likely to occur in children or adolescents, are more commonly found in the heel, and are more likely to present with pain.1 This section will examine the presenting symptoms,
diagnostic workup, and treatment options for the most frequently occurring benign and malignant tumors of the foot and ankle.
diagnostic workup, and treatment options for the most frequently occurring benign and malignant tumors of the foot and ankle.
BENIGN SOFT-TISSUE PSEUDOTUMORS AND TUMORS
Plantar Fibromatosis
Plantar fibromatosis, or Ledderhose disease, is the most common soft-tissue pseudotumor of the foot, which presents as a slow-growing nodule located on the plantar aponeurosis. The nodule is due to the hyperproliferation of fibrous tissue and is analogous to Dupuytren contracture of the hand. As the nodule enlarges, it can cause pain exacerbated by direct pressure, prolonged standing, and barefoot walking.7,8 Comorbities that have been associated with plantar fibromatosis are epilepsy, diabetes, and liver disease.9
The diagnosis of plantar fibromatosis depends primarily on history and physical examination. Ultrasound and magnetic resonance imaging (MRI) can both be used to confirm the diagnosis of plantar fibromatosis, and if there is suspicion for malignancy, a biopsy can be performed. On MRI, the fibroma will have low to intermediate signal relative to muscle, and on ultrasound, the fibroma will be hypoechoic relative to the much brighter plantar fascia.8
Treatment options include nonoperative measures such as steroid injections, verapamil, radiation therapy, extracorporeal shockwave therapy, tamoxifen and collagenase, or surgical excision.8 It should be noted that after surgical excision there is a 60% recurrence rate and a 50% recurrence rate when surgical excision is paired with radiation.
Tenosynovial Giant Cell Tumor
The tenosynovial giant cell tumor, also called pigmented villonodular synovitis, is the most commonly found soft-tissue tumor of the foot and ankle.9,10,11 Behind the flexor tendons of the hands, the foot and ankle represent the most common site of tenosynovial giant cell tumors.12,13 Within the foot and ankle, tenosynovial giant cell tumors can be either inter-articular or extra-articular with the tibiotalar joint, representing the most common intra-articular site of occurrence, and the dorsum of the forefoot, adjacent to the metatarsal heads representing the most common extra-articular site of occurrence. The clinical presentation of tenosynovial giant cell tumors differs based on whether the tumor is diffuse or localized.10 For diffuse tenosynovial giant cell tumors, pain is the most common presenting complaint followed by swelling.14 Localized tenosynovial giant cell tumors usually present as a painless, slow-growing mass or nodule, which can cause pain during weight-bearing.15
MRI is the preferred imaging modality for diagnosing tenosynovial giant cell tumors. MRI findings consistent with synovial proliferation, joint effusion, and osteochondral erosion are suggestive of tenosynovial giant cell tumors. An area of hypointensity within the tumor mass, known as “blooming artifact,” and may be pathognomonic for tenosynovial giant cell tumors.10,16,17 However, the diagnosis is most often only confirmed histologically after the tumor has been surgically excised.
The gold-standard treatment for tenosynovial giant cell tumors is surgical excision. Surgical excisions are either a local excision, which is primarily used for localized tenosynovial giant cell tumors, or an open synovectomy primarily used for diffuse tenosynovial giant cell tumors.10 Arthrodesis can be performed if there is extensive osteochondral damage, and amputation has been reported in cases in which tenosynovial giant cell tumors affect the interphalangeal joints.18,19 External beam radiation has been used as an adjunctive therapy in patients with tenosynovial giant cell tumors and has been shown to decrease the risk of tumor recurrence.20 Additionally, novel targeted therapies that act to block colony-stimulating factor-mediated recruitment of macrophages and monocytes to the tumor site are being used in conjunction with tyrosine kinase inhibitors in the treatment of either locally advanced or recalcitrant tenosynovial giant cell tumors.10
Ganglion Cyst
Ganglion cysts are benign, tumor-like masses that originate from connective tissue in areas that experience frequent physical stress like the joint capsule and tendon sheaths.21,22 Ganglion
cysts present as firm subcutaneous lumps that can be painful.21 Ganglion cysts appear as round to oval, monoloculated or multiloculated anechogenic lesions, with posterior acoustic enhancement on ultrasound examination and produce a thick gel-like fluid when aspiration.21,23 Treatment for ganglion cysts is usually conservative and includes careful neglect, manual rupture, or aspiration; however, for recurrent ganglion cysts, surgical excision is warranted.24
cysts present as firm subcutaneous lumps that can be painful.21 Ganglion cysts appear as round to oval, monoloculated or multiloculated anechogenic lesions, with posterior acoustic enhancement on ultrasound examination and produce a thick gel-like fluid when aspiration.21,23 Treatment for ganglion cysts is usually conservative and includes careful neglect, manual rupture, or aspiration; however, for recurrent ganglion cysts, surgical excision is warranted.24
Lipoma
Lipomas are benign tumors made up of well-encapsulated nodules of fat and are rarely found in the foot. They present as a soft, circumscribed, movable nodule, which may be either asymptomatic or painful.25,26 On radiographs, large lipomas may appear as areas of radiolucency, but they are better characterized by MRI. MRI is unable to distinguish between lipoma and liposarcoma. This can only be done with biopsy. Treatment for lipomas consists of surgical excision.26
MALIGNANT SOFT-TISSUE TUMORS
Synovial Cell Sarcoma
Synovial cell sarcomas occur most often in patients between the ages of 15 and 40 years and are found more frequently in women. Synovial cell carcinoma presents as pain on the plantar aspect of the foot, exacerbated by walking.27,28 Synovial cell sarcoma is slow-growing and typically located in a juxta-articular rather than intra-articular location.29The treatment of choice for synovial cell carcinoma is surgical resection. Smaller tumors located in the midfoot or forefoot can be treated with wide margin surgical resection, while larger tumors should be treated with more aggressive surgical procedures or below the knee amputations.29
Clear Cell Sarcoma
Clear cell sarcomas are uncommon, making up less than 1% of soft-tissue tumors; however, when they do occur, they affect the foot and ankle most often.30 The tumor typically presents as a painful, slow-growing, palpable mass, which is usually less than 5 cm, and located in the deep soft tissue, next to tendon, fascia, or aponeurosis and is found more commonly on the heel.28,30 Radiographs may show a soft-tissue mass with diffuse calcification or even bone formation. Computed tomography (CT) and MRI will typically show a well-defined, homogenous mass.30 The mainstay of treatment for clear cell carcinoma is surgical resection. When metastatic disease is present, chemotherapy can be employed.30
Fibrosarcoma
Fibrosarcoma is a rare tumor that more frequently affects men between the ages of 30 and 60 years and that presents as a painless, slow-growing mass most often affecting the sole of the foot or the digits.27,28 Pain can, however, occur due to compression of adjacent structures.31 Radiographs will show a soft-tissue mass that may be calcified. In most cases, treatment consists of either a wide-margin surgical resection or an amputation and adjunctive radiation.28
Malignant Fibrous Histiocytoma
Malignant fibrous histiocytoma is a relatively common soft-tissue sarcoma of the foot that usually presents in older males as a slow-growing and painless mass. Radiographs show a soft-tissue mass and may also show bone involvement. Treatment often entails a wide-margin surgical resection or an amputation and adjunctive radiation or chemotherapy.28
Melanoma
Melanoma affecting the soles of the feet, also known as acral melanoma, makes up approximately 15% of all melanomas.28,32 It is the most common subtype of melanoma seen in patients of Asian or African descent. On presentation, the acral melanoma appears as a variegated, blue-black lesion with irregular borders. These lesions can be misattributed to other conditions like traumas, or diabetic foot ulcers, which can delay diagnosis, and they can go unnoticed, only receiving attention when associated symptoms like pain, itching, and bleeding begin to
appear. On microscopic examination, there is a classical “parallel ridge pattern.” To confirm the diagnosis of acral melanoma, an excisional biopsy must be performed. After confirmation of acral melanoma, the treatment of choice is surgical excision, but if surgery cannot be performed, then nonoperative treatments like radiation therapy, immunotherapy, and cryotherapy may be employed.32
appear. On microscopic examination, there is a classical “parallel ridge pattern.” To confirm the diagnosis of acral melanoma, an excisional biopsy must be performed. After confirmation of acral melanoma, the treatment of choice is surgical excision, but if surgery cannot be performed, then nonoperative treatments like radiation therapy, immunotherapy, and cryotherapy may be employed.32
BENIGN BONE TUMORS
Enchondroma
Enchondromas are among the most common benign osseous tumors that affect the foot.7,33 Enchondromas preferentially affect the medullary cavities of the bones of the appendicular skeleton, with a particular affinity for the phalanges.33 Enchondromas can occur in isolation, in conjunction with other enchondromas, which is known as multiple enchondromatosis or Ollier disease, or in conjunction with other enchondromas and soft-tissue hemangiomas in Maffucci disease.33
At presentation, enchondromas are most often asymptomatic but can cause pain if they compress adjacent structures or cause a pathologic fracture.33,34 The pain caused by enchondromas is due to expansion of the lesion such that the bone cortex is deformed.33,34 Diagnosis of enchondromas hinges on imaging with CT and MRI. Treatment consists of curettage of the tumor, followed by bone grafting.33
Osteoid Osteoma
Osteoid osteomas are vascularized, osteogenic, benign bone tumors that can be found in the foot, and which occur most frequently in the talus and the calcaneus.35 They preferentially affect males younger than 25 years and are categorized as either intracortical, cancellous, or subperiosteal depending on their location.36 Patients will present with swelling, tenderness, and pain. Pain seen in patients with osteoid osteomas is typically worse at night and responds to nonsteroidal anti-inflammatory drugs (NSAIDs). The response of osteoid osteomas to NSAIDs is thought to be due to the high level of prostaglandin production that is seen with osteoid osteomas.35,36
Osteoid osteomas are difficult to diagnose, resulting in a mean interval between presentation and diagnosis of 22 months.36 Diagnosis of osteoid osteomas includes plain radiographs, MRI, and CT. Among these imaging modalities, CT is the most effective, as MRIs have been reported to miss 34% of cases.36 The traditional treatment of osteoid osteoma is surgical excision, but thermal destruction with either laser photocoagulation of radiofrequency ablation has recently become a popular form of treatment.36
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