Published 8/1/2012

Talking About Musculoskeletal Tumors

What to do when you find a lump, bump, or other soft-tissue mass

Although some orthopaedic specialists may rarely encounter tumors, generalists and orthopaedists in private practice who do identify soft-tissue masses in patients may wonder about best practices. Recently, AAOS Now sponsored a roundtable discussion on the topic of musculoskeletal tumors with the following participants:

  • Valerae O. Lewis, MD, associate professor, department of orthopaedic oncology, and chief of orthopaedic oncology, division of surgery, at The University of Texas MD Anderson Cancer Center, who served as moderator
  • Joel Mayerson, MD, associate professor of orthopaedics and chief of the division of musculoskeletal oncology at the Ohio State Wexler Medical Center
  • R. Lor Randall, MD, FACS, the L.B. & Olive S. Young Endowed Chair for Cancer Research, professor of orthopaedic surgery, director of sarcoma services at the University of Utah’s Huntsman Cancer Institute and Primary Children’s Medical Center
  • Timothy A. Damron, MD, vice-chair and David G. Murray professor of orthopedics, SUNY Upstate Medical University, Syracuse, New York
  • Terrance D. Peabody, MD, Edwin Warner Ryerson Professor of Orthopaedic Surgery and chairman of the department of orthopaedic surgery at Northwestern University Feinberg School of Medicine
  • Kristy L. Weber, MD, professor of orthopaedics and chief of the division of orthopaedic oncology, Johns Hopkins departments of orthopaedics and oncology

Dr. Lewis: What does your initial workup of a soft-tissue mass entail?

Dr. Mayerson: All patients with soft-tissue masses should have a physical exam before any imaging is done. All soft-tissue masses above the fascia that are larger than 5 cm and all soft-tissue masses deep to the fascia need advanced imaging.

If the mass feels fluid filled, an ultrasound can be used to find any evidence of a solid component, and if there is any, magnetic resonance imaging (MRI) should be performed. The MRI should include gadolinium contrast if the physician is concerned that the mass is malignant.

If the nature of the mass cannot be determined on physical exam, start with an MRI.

Dr. Randall: After doing a careful history and physical, if I am concerned about a neoplastic process (one that is progressing or evolving), I order an MRI with gadolinium contrast. If the mass is suspicious for a soft-tissue sarcoma, I generally perform a core needle biopsy—in clinic for adults and in the operating room (OR) under anesthesia for children. I always obtain a few extra cores for advanced studies such as fluorescence in situ hybridization (FISH) and research purposes. We always try to snap freeze tissue as well. If I have a high index of suspicion, I will order chest imaging, usually a noncontrast chest computed tomography scan.

Every case is presented at our weekly interdisciplinary sarcoma conference. As an institutional and panel member of the National Comprehensive Cancer Network (NCCN), we contribute and adhere to their guidelines.

Dr. Damron: I base the initial work-up on a triage algorithm, considering the size and depth of the soft-tissue mass. Most small, superficial masses can be diagnosed clinically without imaging, because they will show the characteristic doughy feel of a lipoma or they will transilluminate if they are ganglion cysts in typical locations. However, for all masses that are larger than 5 cm, deep, or don’t fit the characteristic clinical findings of a lipoma or cyst, I will obtain imaging—both plain radiographs and MRIs.

Dr. Peabody: Because soft-tissue masses are most commonly related to nontumorous conditions, it is important to consider infection, degenerative, and traumatic causes first. If the history suggests that the mass gets bigger and smaller or is associated with an injection, insect bite, or a wound more distally on the extremity, the likelihood of its being a tumor is less.

The size and depth of the mass are important, as has been pointed out. Masses less than 5 cm and in a subcutaneous location can ordinarily be observed with serial exams. For masses larger than 5 cm or in a deep location, imaging should be considered. An MRI with contrast is the most valuable imaging test in the evaluation of a soft-tissue mass.

Dr. Weber: The history should focus on how long the mass has been present, how quickly it is growing, whether other masses are present, if there is a family history of masses. The physical exam should measure size, location, depth, tenderness, presence of lymphadenopathy. Based on these results, I will order imaging—usually an MRI with contrast, although for small subcutaneous lesions that might be cystic I might get an ultrasound.

Dr. Lewis: There’s been some discussion about where’s the best place to perform a biopsy—at the patient’s primary institution or at the referral institution. What do you advise, and why?

Dr. Randall: We strongly prefer to do the biopsy ourselves because this limits the time and energy consumed by obtaining the blocks and slides from the referring center. Patients travel a great distance to see us and we can often perform the biopsy on the same day and have a preliminary result and therefore a far more comprehensive discussion.

I always tell the referring surgeon that our preference to do the biopsy ourselves is not necessarily a reflection on the technical aspects of doing the biopsy but also how the tissue is processed. Handling the tissue appropriately can optimize the amount of molecular information available from a limited quantity of tissue. An open biopsy should be performed by the definitive surgical team as well. We also want to be able to provide tissues for cooperative groups’ correlative biology studies as well as our own.

Dr. Mayerson: All lesions that on imaging demonstrate characteristics of a possible malignancy should be evaluated and biopsied when necessary by a surgeon experienced in managing musculoskeletal tumors. Most often this will require referral to a tertiary care center.

This referral is vitally important in the care of these patients as placement of the biopsy incision can directly affect the amount of tissue that becomes contaminated and eventually needs to be removed. A poorly planned biopsy incision can lead to unnecessary resection of nearby tissues and even to unnecessary amputation.

Dr. Damron: For numerous reasons, I prefer that the decision making regarding biopsy be left to the orthopaedic oncologist at his or her own institution. Biopsies done elsewhere can lead to delays in patient care when the tissue needs to be retrieved and re-reviewed. Numerous choices regarding the biopsy must be made, and each can affect the patient’s ultimate outcome.

Dr. Lewis: What is the role of a biopsy in the diagnosis of a soft-tissue mass?

Dr. Weber: If you are part of a research program that relies on large pieces of pretreatment tumor tissue or if your institution does not have experienced musculoskeletal radiologists or pathologists who are comfortable working with small pieces of tissue, you might do an open biopsy. However, core biopsy—with or without fine needle aspiration (FNA)—has become the standard of care in many U.S. cancer centers. Its safety and efficacy are supported in the literature.

Dr. Randall: Strategic core needle biopsy performed by an experienced surgeon or interventionalist can yield as much, if not more, information than an open biopsy. Sampling can be more extensive with the core technique. It is also less expensive. Again, for children we often do the biopsy in the OR concurrent with line placement and possible bone marrow biopsies.

Dr. Peabody: A biopsy is important if imaging tests are ambiguous or worrisome that the mass is malignant and observation is not an option. Excisional biopsies, where the mass is excised and subsequently sent for pathologic examination, are appropriate for small masses (3 cm or less), nerve sheath tumors, or lipomatous tumors in which imaging suggests fat intensity. For large tumors, a trochar or core biopsy is preferable, while open incisional biopsies are done if the diagnosis remains in question.

Dr. Mayerson: The best type of biopsy to perform in a community setting is an open biopsy. This removes the most tissue and gives the pathologist, who likely does not often see soft-tissue lesions, a better opportunity to make a proper diagnosis.

Fig. 1 Synovial sarcomas. Axial T1-weighted (A) and T2-weighted (B) MRI scans of the wrist reveal a small soft-tissue mass associated with the flexor carpi radialis tendon sheath (arrow). It is indeterminate in appearance, and a biopsy revealed a synovial sarcoma. C, Histology of a biphasic synovial sarcoma showing the typical pattern of epithelial cells and fibrosarcoma-like spindle cells. D, Monophasic synovial sarcoma variant showing only spindle cells (would be keratin positive). Reproduced from: Weber K: Malignant Soft-Tissue Tumors, in Lieberman JR: AAOS Comprehensive Orthopaedic Review, Rosemont, Ill., American Academy of Orthopaedic Surgeons, 2009, pages 459–470.

In most tertiary care centers, core needle biopsy can be done with good diagnostic efficacy and safety. FNA biopsy should not be attempted in centers that do not have the appropriate cytologic expertise available.

Dr. Lewis: What is the role of an excisional biopsy?

Dr. Weber: In my opinion, the only time that an excisional biopsy is appropriate is when the surgeon knows what the tumor is without a biopsy or when a margin can be achieved around the tumor that is appropriate even if malignant.

Dr. Damron: There is a role, I believe, for excisional biopsy of small, superficial soft-tissue masses by a trained orthopaedic oncologist. When the purpose of the procedure is to excise a benign mass for which the diagnosis has already been established clinically or radiographically, such as a lipoma or cyst, a simple excision—shelling out the mass and achieving a marginal margin—is fine.

I don’t like a core needle biopsy for these small masses that could be sarcomas because of the fear that the needle will pass through the lesion and potentially contaminate deeper tissue. If this contamination is unrecognized, and the mass turns out to be a soft-tissue sarcoma, it may lead to failure to adequately excise the sarcoma and potential for local recurrence. If the excision of a small superficial mass leads to the diagnosis of a soft-tissue sarcoma, I will usually do a wider resection of the wound to improve local control.

Dr. Lewis: What is the role of adjuvant therapy in soft-tissue sarcomas? How do you use adjuvant therapies in your practice?

Dr. Peabody: Adjuvant radiation is very helpful in the treatment of many soft-tissue sarcomas. It can be used preoperatively, intraoperatively, or postoperatively. Many centers use it preoperatively to induce a rind around the tumor that may help preserve important neurovascular or osseous structures and to induce tumor necrosis. The radiation field is smaller, which may result in better function, but the treatment has an increased risk of wound healing problems.

The role of chemotherapy is controversial and likely should be considered investigational as an adjuvant therapy. It may have a role in young individuals with large high grade sarcomas or in the treatment of individuals with metastatic disease.

Dr. Mayerson: In areas where the neurovascular structures are adjacent to the malignant mass and limb salvage will be performed, preoperative radiation therapy should be considered. In most other situations, it is the surgeon’s preference whether to use preoperative or postoperative radiation. If there’s a very high likelihood of having close or microscopic positive margins (and the equipment is available), intraoperative radiation therapy should be considered.

Chemotherapy should be considered for intermediate grade sarcomas of more than 8 cm and high grade sarcomas of more than 5 cm—either on a neoadjuvant or adjuvant basis. The advantage of neoadjuvant treatment is that response to treatment can be followed and the chemotherapy can be tailored or stopped if it is not working well or continued if it appears to induce a favorable treatment response.

My practice is to give neoadjuvant chemotherapy to all patients younger than age 70 who are medically able to tolerate the treatment regimen and who agree after appropriate informed consent.

Dr. Randall: I used to recommend neoadjuvant chemotherapy for stage III (high grade, > 5 cm) soft-tissue sarcomas for anyone who could tolerate it. But the data do not support this across all tumor subtypes. We now reserve systemic chemotherapy for patients with metastatic disease and/or young patients with somewhat more favorable histologies such as synovial sarcoma.

Preoperative radiation therapy enables a more strategic resection and minimizes long-term problems, although it can increase postoperative wound complications.

For stage I and stage II sarcomas, depending on anatomic considerations, I generally attempt to resect the sarcoma and selectively use postoperative radiation therapy as a function of final grade and margins status.

Dr. Weber: I generally recommend preoperative radiation, followed by surgical resection 3 to 4 weeks after the completion of the radiation therapy. I will recommend chemotherapy when the patient’s age, health, and interest warrant taking the risk of side effects.

Dr. Damron: I will involve radiation oncology in the decision-making process for any soft-tissue sarcoma that is larger than 5 cm, regardless of grade. I am most inclined to recommend preoperative radiotherapy for stage III tumors. For younger, healthier patients with stage III tumors who can tolerate chemotherapy, I involve our medical oncologists preoperatively as well. For stage IV tumors, I involve medical oncology right away.

Dr. Lewis: Do you see any new therapies on the horizon that are in development and/or clinically relevant?

Dr. Damron: I recently reviewed an interesting article evaluating the use of ultrasound guidance in image-guided core biopsies of soft-tissue masses. This technique is the same one that has become widely used for breast biopsies. The authors report improved diagnostic accuracy that is comparable to open biopsy in a comparative study. Although this technique has numerous theoretical advantages, I think that ultimately its role will probably be similar to that of other image-guided techniques. It will be interesting to watch how this develops over time.

Dr. Mayerson: New methods using biologic probes to determine margin status while the wound is open in the OR are being developed. Free tissue transfer flaps that have been designed as a carrier for specific chemotherapeutic targets are also being studied at my institution. Many centers are using mouse models to identify specific target sites for novel chemotherapeutic agents.

Several tyrosine kinase inhibitors have been shown to have efficacy against some soft-tissue sarcomas in both preclinical trials and early clinical trials. These newer agents, when used in combination with more standard chemotherapeutic agents, are being used to slow progression in patients with advanced disease. As evidence-based data become more available for positron emission tomography scanning, it likely will be increasingly used to monitor treatment with neoadjuvant chemotherapy and to differentiate responders from nonresponders based on imaging rather than on histology.

Dr. Peabody: Some interesting new drugs that affect the vascularity and growth potential of tumors by targeting molecular receptors have proven valuable in other forms of cancer. In addition, clinical trials involving vaccines against surface markers are ongoing. Last, there may be radiosensitive factors capable of causing tumor death. Currently, these are all investigational. For most malignant soft-tissue tumors, surgery with wide margins and radiation remain the standard of therapy for both the primary tumor and metastatic sites.

Dr. Randall: There will be no single magic biobullet. Monoclonal therapies directed against tyrosine kinases and other growth factors have tremendous potential but will probably still need backbone cytotoxic therapy. The same can be said of the small molecule inhibitors. Viral therapies may prove to be another mechanism by which to restrain cancers. In my mind, this is the most exciting aspect of the future of sarcomatology and helping our patients defeat their disease.

Disclosure information: Dr. Lewis—Hindawi Publishing Corporation; Western Orthopaedic Association; Dr. Mayerson—Millenium Pharmaceuticals; Journal of Surgical Oncology; Conference Papers in Oncology; National Comprehensive Cancer Network; Musculoskeletal Tumor Society(MSTS); Dr. Randall—Musculoskeletal Transplant Foundation (MTF); Annals of Surgical Oncology; Journal of Surgical Oncology; Peer Case; World Journal of Orthopaedics; American Society of Clinical Oncology; Children’s Oncology Group; Connective Tissue Oncology Society; MTF; MSTS; NCCN; The MHE Research Foundation; Dr. Damron— Wright Medical Technology, Inc.; Genentech, Inc.; Orthovita, Inc.; Lippincott, Williams, and Wilkins; Wolters Kluwer Health; Journal of Surgical Oncology eMedicine; MSTS; Dr. Peabody— Journal of Bone and Joint Surgery–American; Dr. Weber—Wolters Kluwer Health - Lippincott Williams & Wilkins; MSTS.