Soft Tissue and Bone Tumors

Clinical Evaluation

Staging

Staging is an important part of the evaluation of the patient with a malignant tumor. Accurate staging helps provide prognostic value and guides treatment decision making. Additionally, having a validated and widely implemented staging system improves communication across treating specialties, improving patient care and research. Terminology for tumor grade and stage are sometimes inappropriately interchanged. The grade of a tumor is determined by the pathologist reviewing the tumor sample (whether biopsy or surgically resected specimen). Grade is an important part of staging systems and factored in along with the presence of metastasis, size, and location in the staging of sarcoma. Historically, the Enneking Musculoskeletal Tumor Society (MSTS) staging system ( Table 17-5 ) has been used by orthopaedic oncologists, which included histologic grade, compartmental involvement, and metastasis. The compartmental description was based on its utility in extent of disease and surgical planning. This concept and importance of the compartment may be less important with improved cross-sectional, high-resolution imaging that provides detailed anatomic extent. Additionally, the use of multimodal treatment has allowed for closer margins with acceptable oncologic outcomes, thereby decreasing the relevance of the entire compartment resection. The treatment of sarcoma is often multimodal, requiring multidisciplinary discussion and planning between surgeons, radiation oncologists, and medical oncologists. Treatment implementation therefore requires staging to be done by a unified system across specialties.

The American Joint Committee on Cancer (AJCC) system uses the familiar tumor size–lymph nodes–metastasis (TNM) nomenclature for staging of common cancers. The staging for bone and soft tissue sarcomas in the AJCC system utilizes three factors: histologic grade, size, and metastasis. With the updated 8th edition of the AJCC Cancer Staging Manual , the system switched away from considering depth for soft tissue sarcoma. Instead, the “T” (tumor size) was broken up into four categories: T1: < 5 cm, T2: 5 cm to 10 cm, T3: 10 cm to 15 cm, and T4: >15 cm. Additionally, in this current edition, lymph stage IV disease. Refer to the 8th edition of the AJCC Cancer Staging Manual for staging information about bone sarcoma of the appendicular skeleton and about extremity soft tissue sarcoma. Box 17-1 lists soft tissue sarcoma subtypes that are more associated with lymphatic spread.

The foot and ankle surgeon should be familiar with the tests that are utilized in the staging of the patient with a foot and ankle sarcoma. These are listed in Table 17-6 . Studies ordered should also be based on NCCN guidelines. Additionally, staging is repeated prior to surgery if neoadjuvant chemotherapy or radiation is given.

Biopsy

After history, physical, and imaging evaluations have been completed, the biopsy is a crucial step in the management of tumors of the foot and ankle. Effective treatment planning hinges on the accuracy of the diagnosis. The biopsy should be done in a manner that provides adequate tissue for diagnosis without compromising eventual definitive resection—especially in the setting of sarcoma. Many of the most common tumors of the foot ankle may not require a biopsy if the history, physical examination, and imaging are classic for common benign diagnosis. For instance, a ganglion emanating from a joint will wax and wane in size and transilluminates on examination. However, it is paramount that foot and ankle surgeons have a heightened awareness to avoid the inappropriate or unplanned excision. Due to the anatomical confines of the foot and ankle, an inappropriate excision of a sarcoma may result in a more difficult limb salvage with more complications and need for free flaps or even require an amputation. A sound principle is that a biopsy should be performed on any mass for which there is a chance of malignant diagnosis. Additionally, general guidelines state that any mass that has a history of rapid growth, is larger than 5 cm, and is deep should be considered malignant and a biopsy should be performed after MRI imaging has been obtained. Multiple studies have demonstrated that sarcoma treatment outcomes are optimized when treatment is at specialized sarcoma centers and an early referral should be considered, even prior to biopsy, in aggressive-appearing tumors.

Biopsy technique can be either needle or open. Needle biopsies are further broken down as fine needle aspirations (FNA) and core needle biopsies. Open biopsies can be described as incisional and excisional, and the advantages and disadvantages of each biopsy technique is summarized in Table 17-7 . Most needle biopsies can be done in either an office setting or under image guidance in radiologic or procedure suite. If the biopsy is being performed by a radiologist, this should be done in coordination and planning with the treating oncologic surgeon. With regards to open biopsy, the difference between an incisional and excisional biopsy is often misunderstood. Excisional biopsy refers to technique or approach in which the entire tumor is excised in either a marginal or wide (cuff of normal tissue surrounding) margin. This is best performed by an experienced tumor surgeon and in cases in which the tumor is small and superficial. Unfortunately, many surgeons term unplanned excisions as excisional biopsies. Unplanned or inappropriate excisions are done without appropriate imaging, biopsy, staging, multimodal treatment planning, or surgical technique. While these cases can be salvaged from an oncologic standpoint, these procedures complicate the definitive resection and result in more flaps and amputations.

While biopsies are considered relatively simple procedures, appropriate planning and meticulous surgical technique are necessary to avoid contamination of tissue planes while ensuring adequate sample for an accurate diagnosis. While core needle biopsies are the preferred biopsy method for most musculoskeletal neoplasms, there may be more indications for open incisional biopsies for foot and ankle tumors. Preoperative planning for a biopsy is important for targeting the solid enhancing portion of a mass based on contrast MRI. Additionally, biopsies should be performed in a manner that considers future treatment strategies to ensure incisions are placed in advantageous location for future surgeries while avoiding contaminating tissue planes or critical structures. Incisions should be placed in a longitudinal manner to facilitate excision of the biopsy track should it be necessary and still avoid complex soft tissue reconstruction. Additionally, if needed, drains should be placed in-line with the incision and large skin and soft tissue flaps should be avoided and meticulous hemostasis achieved. The surgeon should ensure all equipment is available including C-arm intensifier, trephine—or bone biopsy set for bone lesions. The surgeon should also ensure that a pathologist with bone and soft tissue expertise is available for frozen section analysis. Intraoperative frozen section analysis facilitates ensuring adequacy of sample to make a diagnosis as well as initial diagnostic impression. In some settings with experienced tumor surgeons and pathologists, definitive excision/treatment can be performed if an intraoperative frozen diagnosis can be rendered. In contrast, amputative and more morbid surgeries should not be performed on basis of a frozen section diagnosis. Another consideration is sample preparation for definitive diagnosis. While most musculoskeletal neoplasms are diagnosed from formalin-fixed specimens, in some tumor settings a fresh sample is also required for flow cytometry, cytogenetic studies, etc. Surgical principles of open biopsy are summarized in Box 17-2 .

Radiation for Foot and Ankle Tumors

While a detailed discussion of radiation therapy is beyond the scope of this chapter, the surgeon operating on foot and ankle tumors should be aware of what tumors may require neoadjuvant or adjuvant radiation treatment. Radiation treatment plays a key role in the treatment of high-grade soft tissue sarcoma of the extremities. Neoadjuvant (preoperative) and adjuvant (postoperative) radiation have distinct advantages and disadvantages. Per the randomized, controlled trial (referred to as the SR2 trial) preoperative radiation treatment resulted in significantly increased risk of wound complications. Some studies have also reported a survival benefit in favor or preoperative over postoperative radiation treatment. Postoperative radiation treatment is traditionally associated with a larger dose and over a larger field area (in order to cover entire surgical bed rather than just the tumor). It is also associated with higher rates of long-term complications including fibrosis, stiffness, and fracture. In the foot and ankle, radiation can be used with reasonable limb salvage outcomes. Even in children with sarcomas of the foot, the use of adjuvant or definitive (in the setting of rhabdomyosarcoma) radiation therapy may be preferred over ablative procedures.

Radiation is used less often in the management of bone sarcomas. Ewing sarcoma as compared to other bone sarcomas is radiosensitive, but definitive radiation treatment is infrequently used in the foot and ankle as definitive resection is often possible in this location. While radiation therapy may be used in other locations/tumors that would require an amputation, it is often not used in the foot and ankle as below knee amputations are regarded as quite functional and even sometimes selected over complex limb salvage options as discussed in later sections of this chapter.

Metastatic bone disease is often treated with palliative radiation therapy. Surgical intervention is often used for both impending and realized fractures. In some rare instances, an en bloc resection and endoprosthetic replacement may be used for oligometastatic disease and with histologies that are relatively radioresistant (i.e., renal clear cell carcinoma). The foot and ankle surgeon should coordinate treatment of metastatic bone disease with the treating medical and radiation oncologists. Similar to other locations, palliative radiation therapy is an important part of the treatment of osseous metastasis involving the foot.

Chemotherapy for Foot and Ankle Tumors

Bone sarcomas, specifically osteosarcoma and Ewing sarcoma, have known response rates to chemotherapy and specific first-line regimens are well established. For both osteosarcoma and Ewing sarcoma, chemotherapy is given neoadjuvant (preoperative), followed by additional adjuvant chemotherapy after resection. Chemotherapy is rarely given for chondrosarcoma.

The utilization of chemotherapy in soft tissue sarcoma is less well defined. Some trials and meta-analyses have demonstrated some improvement even if only modest while others have shown no benefit with standard chemotherapy regimens. Thus, its implementation in soft tissue sarcoma has remained a point of controversary and in general it is recommended that the treatment planning be done at a sarcoma center with a multidisciplinary panel. In addition to systemic chemotherapy, isolated limb perfusion has been used to deliver high dose chemotherapy to the involved limb. This has been utilized in cases in which limb salvage surgery with typical treatment modalities is not possible due to locally advanced disease or in the setting of complex recurrence. This technique allows for dosing isolated to the affected limb as the dose is too toxic for systemic administration. It has remained relatively uncommon in the US, but it has been used in Europe and Asia for the treatment of advanced soft tissue sarcoma and melanoma of the foot and ankle.

General Principles of Surgical Treatment for Soft Tissue and Bone Tumors

Foot and ankle tumor surgery is much different than other foot and ankle surgeries as the surgeon needs to balance prevention of tumor recurrence while also maintaining or restoring function. Maximizing both aims requires expertise in the particular tumor histology as well as in surgery about the foot and ankle. For benign disease, the surgeon must always remember to ensure that the surgical outcomes are not worse than the original tumor/disease. Local recurrence is impacted by both the biology of a particular tumor as well as to the treatment rendered, including surgical technique. Dr. Enneking provided a straightforward approach to defining the type of surgical resection performed ( Table 17-8 ). He defined resections as intralesional, marginal, wide, and radical ( Fig. 17-1 ). These are defined by the relationship of the surgical resection plane and the tumor margins. For instance, an intralesional resection entails cutting through the substance of the tumor itself, as would be done with a curettage. A wide excision just means that the dissection was done in such a manner the plane of dissection was carried out through cuff of normal tissue around the tumor, which would result in a “negative” margin on microscopic pathology. The Enneking definitions of resection are still widely used for conceptual and didactic purposes, but the residual “R” disease classification is used more frequently in the reporting of margins and in the literature (see Table 17-8 ). In this system, the margins are defined by the microscopic margin result on histopathology. Use of this system helps consolidate the reporting of margins into more reproducible and widely understood format.

The surgical treatment of the heterogenous group of tumors that occur in the foot and ankle must be determined in a patient and tumor specific manner. The treatment for individual histologic tumor types will be discussed in subsequent sections of this chapter, but some general principles will be discussed here. All preoperative imaging should be reviewed for anatomic location, nearby structures, and for the extent of disease. Disease staging should be completed prior to surgical treatment, so as to render a multidisciplinary treatment plan based on the stage and accepted guidelines. All special equipment or implants need to be ensured to be available as well as any other required surgical specialty consultants. Incisions should be planned in longitudinal manner such that a biopsy can be excised with specimen if required with subsequent surgery. Incisions should also be placed in a thoughtful manner that considers requirement for extensile approaches and possible future surgical procedures for recurrence or revisions surgery. When using a tourniquet, Esmarch exsanguination is not used and rather exsanguination is achieved via elevation. Forceps and sharp retractors should not inadvertently come in direct contact with the tumor tissue in order to prevent contamination. Additionally, to further prevent cross-contamination of separate surgical sites and soft tissue and bone graft harvest sites, separate instrument sets and regloving should be performed. Specimens should also be sent for routine pathology and results followed up by the surgeon. The specimen should be oriented for the pathologist with long and short silk sutures, such as short superior and long lateral. Additionally, the surgeon should review the gross specimen with pathologist for further orientation, such as deep margins or margins along critical structures, that is, where neurovascular structures were adjacent to the mass. Culture should also be performed in cases where infection is in the differential diagnosis. If there is a chance that the post-resection pathology may require adjuvant radiation treatment, surgical clips should be placed throughout the tumor bed so that the radiation oncologist has some guide for targeting. Closure of the wound should be without undue tension given the nature of limited soft tissue coverage of the foot and especially in the setting of radiation or chemotherapy. Additionally, the surgeon should anticipate preoperatively resections that may require flap reconstruction. Finally, there is not necessarily a prescribed tumor size or location that requires a drain, but in general, they should be considered whenever there is a large dead space after resection.

Benign Soft Tissue Tumors

The majority of soft tissue tumors and Tumor-Like masses are benign about the foot and ankle. The true incidence is often difficult to define because many people with small, indolent, and stable masses rarely ever seek treatment and often don’t seek treatment at specialized tumor/sarcoma centers and thus previous studies have inherent referral bias for larger, more aggressive tumors. In a large, consecutive series (83 cases) of foot soft tissue tumors seen at the Hospital for Joint Disease in NY, 87% of the lesions were benign, and the most common diagnoses were ganglion cysts and plantar fibromatosis. Another series from a tertiary referral orthopaedic oncology center consisted of 153 cases, of which 80 were soft tissue tumors of which tenosynovial giant cell tumor (previously referred to as pigmented villonodular synovitis [PVNS] and giant cell tumor of tendon sheath [GCTTS]) was the most common. Table 17-9 summarizes the most common benign soft tissue tumors of the foot and ankle and their relative recurrence risk after excision.

Vascular Tumors and Malformations

Hemangioma

Hemangiomas are benign vascular neoplasms that typically arise in children, but they rarely occur in the foot. They are composed of neoplastic formed blood vessels. In a retrospective series of 41 patients, excision of angiodysplastic lesions of the extremities, simple excision under tourniquet, resulted in a 48% recurrence rate. When these tumors are superficial, the lesion will be seen with a bluish hue ( Fig. 17-2 ). On exam the mass is described as soft and doughy. More extensive lesions can demonstrate associated gigantism of the involved/adjacent soft tissue and bone. Radiographs may show small calcified phleboliths. MR imaging will demonstrate characteristic “cluster of grapes” as well as interwoven fat between planes. Structurally hemangiomas can be cavernous, capillary, or mixed. Initial treatment of hemangiomas is most often conservative and includes compression and medical management.

Some patients will continue to have symptoms and require further treatment. Due to infiltrative pattern sometimes associated with hemangiomas, surgical treatment can be complicated and associated with recurrences. Therefore, other less invasive options have been used including sclerotherapy, and this may be preferred in most cases. Surgical treatment can also be performed for symptomatic hemangiomas that have failed conservative management. Marginal or even intralesional excision can be performed in these benign lesions. A retrospective series of 110 patients with average age of 22 years demonstrated that 76% of patients managed initially without surgery remained surgery free at 2 years. For patients treated with surgery, 86% of patients were recurrence free at 2 years. Margins at the time of excision were predictive of recurrence. Ninety-three percent of patients with either marginal or wide excisions were recurrence free at 5 years as compared to 65% with intralesional margins with no gross remaining tumor.

Arteriovenous Malformations

Arteriovenous malformations (AVMs) are frequently found in the head and neck and can be associated with congenital syndromes. They are rarely found in the foot and ankle but can be symptomatic. Proteus syndrome and Klippel-Trénaunay syndrome may present with extensive vascular malformation and associated gigantism of the leg and foot. Klippel-Trénaunay syndrome represents a triad of congenital anomalies including vascular nevus, varicose veins, and hypertrophy of the soft tissue and bone. Proteus syndrome is characterized by local overgrowth, subcutaneous tumors, and vascular anomalies. Different from Klippel-Trénaunay syndrome though, the vascular anomalies can be distributed at random sites throughout the body rather than confined to the hypertrophic limb. AVMs that are high flow can be treated with ethanol embolotherapy. In a retrospective review of 29 patients with AVMs of the foot, 17/29 (59%) of patients experienced improvement. However, major complications occurred in 7/29 (24%) and skin necrosis occurred in 10/29 (35%). This was deemed to be similar in effectiveness and safety as other anatomical locations.

Treatment of vascular malformations depends on whether they are high or slow flow. Venous malformations, which are slow flow vascular lesions, with minimal symptoms can be treated with observation and conservative management with compression garments. Medical management includes aspirin and low-molecular-weight heparin. These lesions can also be treated with sclerotherapy. The physician should be aware of muscle contracture in these patients and NSAIDs and physical therapy should be implemented.

Glomus Tumor

Glomus tumors, also called glomangiomas, are benign vascular tumors with a peak incidence in the 3rd to 5th decades of life. They arise from the cutaneous arteriovenous connection with sympathetic innervations. They are found most commonly in the distal extremities and often involve the nail beds. They are symptomatic and present with pain, tenderness, and temperature sensitivity. Subungual glomus tumors demonstrate female prevalence of 3:1. There are rare case reports of the hindfoot. When they occur in the typical subungual location, they are associated with bright red to bluish discoloration under the nail bed. Radiographs will demonstrate a well-marginated osteolytic lesion of the dorsal aspect of the distal phalanx. Surgical excision can be curative and patients experience significant symptomatic relief with excision. A case series for the treatment of subungual tumors described technique of subperiosteal elevation of skin, nail, and nail matrix in a full-thickness flap. The tumor is then excised from within the flap. The authors reported complete symptom resolution and recurrence free results. The foot and ankle surgeon is reminded to exercise caution in any lesion deep to the nail bed as the diagnosis of malignant melanoma should also be considered.