Fundamentals of Musculoskeletal Tumors

Musculoskeletal tumors represent a wide array of benign and malignant conditions. By far, benign conditions predominate at a rate of 200 to 1. Malignant tumors that arise from mesenchymal tissue are termed sarcomas and have an overall incidence of 9000 cases in the United States. Sarcomas can be highly aggressive with an estimated 50% mortality rate and tend to affect the elderly with 40% of cases arising in populations older that 55.

The mechanisms of formation are currently under investigation but they all represent a corruption of the normal cell cycle. In some instances this involves alterations in suppressor genes; which normally prevent progression of cell mitosis in the presence of an aberration. In others, oncogenes are the culprit as they allow or promote unchecked progression through mitosis. Production of these mutations occurs through many processes including translocations, deletions, amplifications, and point mutations among others. A list of translocations can be found in Figure #1.

Figure #1

Tumor	Translocation
Ewings Sarcoma	t(11;22)
Synovial Sarcoma	t(X;18)
Rhabdomyosarcoma	t(2;13)
Clear Cell Sarcoma	t(12;22)
Liposarcoma	t(12;16)

Initial evaluations should begin with a thorough history and physical. Key elements of the history include a description of associated pain and location, weight loss, history of trauma, malignancy or exposure. Of these, the characterization of the associated pain can be telling. A patient with a history of rapidly progressing pain preceding the formation of a mass could be consistent with an aggressive sarcoma, while less aggressive tumors may have a slower onset. Pain at night that awakens the patient from sleep is another classic presentation. However, pain with weight bearing could signal something more ominous such as eventual cortical failure of bone from a destructive process. A thorough exam should be performed with an emphasis on the lesion as well as sites of possible metastases including lungs and the lymphatic system. Sarcomas that are known to spread through the lymphatics include: rhabdomyosarcoma, synovial sarcoma, clear cell sarcoma, and epidermoid sarcoma. A complete set of labs that include a CBC, BMP, LFTs with alkaline phosphatase, SPEP/UPEP, ESR and CRP should be ordered and can provide clues as to the source of the tumor. For example, SPEP/UPEP can establish a diagnosis of multiple myeloma while an elevated WBC count, ESR and CRP can be a non-specific indicator of infection.

Plain radiographs should be taken of all suspected tumors to include orthogonal views of the involved extremity. Often this will help establish the diagnosis as certain tumors have characteristic locations. Tumors that arise within the epiphysis of long bones are classically benign and most often include giant cell tumors (adults) or chondroblastoma (pediatrics). Diaphyseal-based tumors classically include Ewing’s sarcoma, multiple myeloma and lymphomas. Finally, most malignant tumors are metaphyseal-based tumors. Another method of describing lesions deals with the effect of the lesion on the bone. Permeative or “moth-eaten” is a term used to describe a destructive lesion with poorly defined and indistinct borders that infiltrates native bone. It is classically used to describe the small round blue cell family of tumors (lymphoma and Ewing’s Sarcoma). Inflammatory processes, such as osteomyelitis, histiocytosis X, and metastatic lesions can fall under this category. Geographic bone destruction describes central loss of bone with a distinct and often sclerotic margin. This term is usually reserved for enchondroma descriptions. In general, classic appearing benign lesion on plain film radiographs do not warrant further work-up. Further diagnostics are required in cases where the diagnosis is uncertain or malignant.

This should begin with a MRI to define the extent of the lesion and degree to which surrounding structures are involved. Often this will help determine the amount of resection required, possibility of limb salvage, and surgical approach. Small, cortically-based lesions (such as osteoid osteoma) are usually not well visualized with MRI and CT scan is still the imaging of choice for this situation. Heavily calcified masses are often not well delineated by MRI. In the workup of a bone lesion, CT scan is often employed to visualize the chest, abdomen and pelvis to look for primary sources, metastases, and location of tumor spread. All soft tissue tumors and most bone lesions require a MRI scan.

Bone scans are best utilized to determine the extent and possible spread of metastatic disease. Usually a technetium-99 scan is utilized and is highly sensitive for bone lesions, but not specific. Technetium is utilized to tag the phosphate moiety and thus reflects bone formation with the formation of calcium phosphate. Many benign lesions will not show uptake on bone scan; on the other hand, some conditions, like infection, will be hot. Most malignant lesions of bone will be hot on bone scan with the important exception of multiple myeloma, which will show no uptake.

Biopsy is the final step in the work-up before treatment. Several types of biopsy are utilized. For many years the incisional biopsy was the gold standard. In this procedure a longitudinal incision is made in the location of the proposed incision should resection be required and a biopsy of the tumor is taken. Most tumors will have soft tissue extension through the bone and this is the area that should be sampled without violating the cortex. Outer portions of tumor are often more rewarding as deeper areas will have outgrown their blood supply and will appear more necrotic. If deeper portions of bone are required a round or elliptical hole should be made to avoid producing a stress riser that could weaken bone and produce a pathologic fracture. Sarcomas are infamous for their ability to recur locally. It is thought this is due to microscopic shedding of the tumor with resection as cells are dragged through the incision. Longitudinal biopsy incisions are utilized because they are easier to ellipse out with future resection and remove any possible seeding. Tumor resection incisions are always longitudinal to follow lymphatic channels where local involvement might occur. Involvement with an orthopedic oncologist is required to help determine the site of biopsy because involvement of uncontaminated vital structures, such as nerves or vessels, could necessitate amputation in circumstances where well-placed incisions might spare the limb. Finally, the biopsy is done following all imaging as the biopsy can distort the local imaging and examination of involved structures. In addition, most biopsies require a general anesthetic, which can distort chest CT scans used for staging and mimic metastatic disease. More recently, clinicians have been utilizing needle biopsy. It can be difficult to get a good sample in heterogeneous tissue such as sarcoma, but it is far less invasive and often runs less risk of contaminating surrounding compartments. All needle tracks need to be excised in the case of future excision and careful placement of the biopsy site is imperative. All samples must be cultured to ensure that infection is not mimicking a neoplastic process.

Once the above measures are complete, the patient can be appropriately staged and a plan for treatment can be devised. Anxiety will undoubtedly follow a malignant diagnosis but completion of the work-up is far more important than a hasty progression to treatment. The current method of staging is based on the Enneking system. The first part describes the biologic appearance of the tumor and its likelihood of metastasizing. Stage I describes a low-grade sarcoma and less than 25% chance of metastasizing. Stage II describes a high-grade lesion with more than 25% chance of metastasizing. Finally, stage III lesions are any grade lesions with metastases to distant sites such as lung or lymph nodes. The Enneking system further describes containment as either A (intracompartmental) or B (extracompartmental). Compartments are described as a single structure such as muscle belly or a bone that has intact cortex surrounding the lesion. Staging is the most accurate means of determining survival.

Perhaps on of the most important factors in dealing with bone lesions lies in the detection and prevention of pathologic fracture. In many malignant tumors, a realized pathologic fracture will lead to amputation where limb salvage may have been possible. Decisions on the use of prophylactic fixation can be made by consulting a system developed by Mirels in 1989 (Figure 2, below). By adding the points from each of the four categories the risk can be stratified. Less than or equal to 7 points is not at risk. A score of 8 and 9 has 15% and 33% chance of fracture, respectively. At or above 9 points is considered a solid indication for prophylactic fixation.

Figure #2

Variable	1	2	3
Site	upper limb	lower limb	peritrochanteric
Pain	Mild	moderate	severe
Lesion Quality	Blastic	mixed	lytic
Size (fraction of diameter)	<1/3	1/3-2/3	>2/3