We are all aware of the fact that most lumps under the skin are benign. Usually they are fatty lumps called lipomas. Small lumps can be sebaceous cysts, and there are many other types, mostly harmless. So, what does it matter if an occasional malignant one slips through and takes a while to be diagnosed?

Well, it actually matters a lot; in fact, it’s probably a matter of life or death for the patient with a sarcoma. The fact is that for a sarcoma, the bigger the lump, the worse the outlook. The most aggressive types carry some risk of spreading to other parts of the body, even when they’re less than 5 cm (2") in size. This means that every delay waiting for a test, falsely reassuring the patient that it is "just a haematoma", "lymph gland", "lipoma" etc, means that it is simply getting larger all the while, becoming increasingly likely to spread to other parts of the body, e.g. the lungs, and hence, be incurable.

Where’s the proof that early diagnosis makes a difference?

Unfortunately, unlike with common cancers such as breast cancer, the evidence that removing sarcomas at an early stage improves outcome is somewhat hard to find, because it isn’t possible to do a clinical trial. However, every study that has ever looked at all the factors influencing outcome, has concluded that for each individual sarcoma subtype - and they do, of course, vary - tumor size and grade (the degree of aggressiveness) are the most important. Therefore, it seems inconceivable that earlier diagnosis and removal when the disease is smaller would not improve the outlook.

What harm is done if I take it out myself?

Sadly, one of the most common ways in which a doctor hears about the diagnosis of sarcoma is when the pathologist rings up to say that the "benign" lump he/she took out under local anaesthetic is actually a sarcoma, and it hasn’t been completely removed. In fact, if you take out a sarcoma and you can actually see it as you go along, then you’ve left some behind. They appear to "shell out" very easily but the so-called "pseudocapsule" is just that, a false capsule or margin; tumour cells extend beyond it. To remove a sarcoma properly, you have to plan the operation based on appropriate imaging and take it out with a good margin of normal tissue all around it. A poor initial operation contaminates the tissues and will sometimes put a scar in the wrong place, which compromises a definitive operation, and makes it more likely that the disease will come back locally.

Among the many horror stories I could relate are the following glaring examples: the first was a patient with sarcoma who was initially treated with antibiotics and then attacked with a scalpel in the mistaken belief that the lump was an abscess – it wasn’t, indeed it was rock hard; the second was a patient with a bleeding tendency who was repeatedly told that the enlarging lump in his thigh was a blood clot. By the time the diagnosis was made, the tumour had spread to the lungs. Clearly, in such cases, inappropriate intervention and delay in diagnosis proved very damaging. In the majority of cases where the tumour is small, a second operation can be performed to remove residual tumour cells without this having a major impact on survival. However, where the second operation reveals residual tumour, there is an increased risk of distant disease spread.

So how can I know if a lump is worrying without taking it out?

There are some very simply rules. These are the characteristics of a subcutaneous mass that should alert you. Remember that sarcomas can occur anywhere, but the most common site is the leg. A lump that has 2 or more of the following characteristics is potentially malignant and should be treated as such:

• Deep within the tissues (technically, deep to deep fascia, which means you can’t easily move it around)
• 5 cm or more in diameter
• Is growing

Some doctors would add "especially if it is painful," but this isn’t a very reliable sign, and lack of pain is not necessarily reassuring. So, if you find a lump with any of these characteristics, it should be imaged, (e.g. Magnetic Resonance Imaging, MRI scan) and you should send the patient/have yourself referred to a team that is experienced in the management of sarcomas.

Why refer to a multidisciplinary team in a cancer centre?

To diagnose and treat a sarcoma properly, you need to have specialists with the necessary experience in diagnostic radiology, histopathology, surgery, radiation oncology and medical oncology. A scan (usually MRI) is required to identify the size and extent of the disease. A biopsy needs to be done appropriately, and an experienced pathologist is then required to make the diagnosis - these are rare diseases. Surgery needs to be done in a planned way that will ensure complete removal of the tumour, hopefully preserving normal function. Depending on the size, grade, and completeness of resection, radiotherapy may be required. Sometimes this is employed pre-operatively. For some diseases, and in some clinical situations, it is appropriate to use chemotherapy either before or after the operation (or both).

Final Message

Sarcomas cannot be treated appropriately in the community. If there is doubt as to the nature of a lump, it should be referred to a specialist centre. Follow the simple rules: firm, deep lumps that are growing are rarely benign. Early diagnosis is the key to improving outcomes for patients with sarcoma.

Questions, Comments and Counterpoints

Suzie Siegel, who wrote an article for ESUN, Options and Follow-up Care for Women with Uterine Sarcoma, sent the following note to Ian Judson in response to the above editorial.

Dr. Judson replied:

Introduction

Sarcomas are rare cancers that arise within connective tissues such as bone, muscle, cartilage, nerves and fat. Annually, they represent about 1% of newly diagnosed cancers. Because these tumors are exceedingly rare when compared with visceral cancers (carcinomas), awareness among health care providers and the population at large is limited. This leads to many unfortunate problems for patients with sarcoma. Among the most worrisome of these is the unplanned excision. This occurs when a lesion is felt to be "probably benign" and is removed with inadequate preoperative diagnostic evaluation (i.e. MRI, staging studies and biopsy) and without a well-planned attempt at securing clean margins. Only after removal of the mass is the diagnosis of sarcoma made, and inevitably the resection is incomplete. Care of the sarcoma is ultimately compromised and the risk of tumor recurrence and metastatic spread is potentially increased. Such an error may obviate the possibility of limb-sparing surgery and may even endanger the life of the patient.

The main culprit leading to an unplanned excision of a malignant tumor is lack of awareness. Surgeons who do not have experience with sarcomas may simply not consider it in their differential diagnosis for a given lesion. Fortunately, sarcomas are quite rare, and in the grand scheme, this error is made infrequently. However, when a subtotal sarcoma excision does occur accidentally, it is devastating for the patient and may significantly compromise his/her subsequent oncologic care. Physicians, nurses and practice extenders (nurse practitioners and physician’s assistants) must be better educated in an effort to diminish the number of unplanned excisions performed.

Clinical Evaluation and Staging

After an unplanned excision of sarcoma has occurred, the patient is typically referred to a center specializing in the care of sarcoma (occasionally, the patient may need to seek out such a center to prevent any undue delay in appropriate care). At that time, a thorough history and physical examination is performed. It is critical for the clinician to obtain information regarding the mass (i.e. how long it was present, if it was growing), any symptoms it may have caused, and any other symptoms the patient may be experiencing.

A complete physical examination should be performed. Evaluation of the primary site is, of course, critical. Of particular interest is the incision site and notation of any bruising or swelling. These can be clues as to where residual tumor cells may exist. The principle is that anywhere a red blood cell can track, so too can a tumor cell. Any area of ecchymosis (bruising) should be addressed in the treatment plan if cure is to be achieved. Also of great importance is the status of the individual’s lungs and lymph nodes. The vast majority of sarcomas spread to the lungs primarily. Rarely, nodal metastasis may occur. This is more common in epithelioid sarcoma, synovial sarcoma, clear cell sarcoma and rhabdomyosarcoma.

Staging studies are also critical in the evaluation of any person with a diagnosis of sarcoma. MRI with gadolinium contrast is the imaging modality of choice for the primary site (Figure 1). Interpretation of MRI after incomplete excision can be difficult due to post-surgical changes in the surrounding tissues and the fact that often what tumor remains is microscopic and undetectable by currently available imaging techniques. Review of any imaging showing the tumor prior to excision is of tremendous value, but is usually unavailable due to the lack of suspicion of malignancy initially.

Another key piece of the staging process is computed tomography (CT or CAT scan) of the lungs (and sometimes of the abdomen and pelvis). The presence of detectable metastasis on these studies may have profound prognostic and treatment implications. Occasionally, special tests such as a PET scan (Positron Emission Tomography) may be ordered. This is used most frequently for sarcomas with unusual patterns of spread (e.g., lymph nodes or visceral organs), particularly epithelioid sarcoma, synovial sarcoma, rhabdomyosarcoma and clear cell sarcoma, for instance.

Normally, biopsy is the final piece of the staging puzzle. In the case of unplanned excision, a tissue diagnosis has been already rendered. The incomplete resection, though crude and suboptimal for the reasons previously discussed, serves, in essence, as an excisional biopsy (normally not done for diagnostic purposes in cases of suspected sarcoma). Since most of these "biopsies" are done in non-tertiary centers (i.e., centers not specializing in sarcoma care), a review of the material by an experienced bone and soft tissue pathologist is necessary. Randall et al (2004) reported that upon re-review of material sent from non-specialty centers, 37% of the histological diagnoses actually changed, and 82% of the reviewed cases had positive margins (incomplete resection). These data reinforce the point that sarcoma care is best rendered in sarcoma specialty centers by professionals with training specific to the management of these rare tumors.

Treatment

Once the staging process is complete, a treatment plan is formulated. Typically this follows detailed discussion by a multidisciplinary team involving a radiation oncologist (radiation therapy), a medical oncologist (chemotherapy), a radiologist (image interpretation), a pathologist (review of diagnostic material) and a musculoskeletal oncologic surgeon.

Local treatment for incomplete sarcoma excision involves re-excision with or without radiation therapy (RT) (Figure 2). Radiation, when given, is used to kill microscopic tumor cells left behind by the initial procedure in order to aid with local control, since surgery in this instance may often be less than exact. The decision whether or not to include systemic chemotherapy depends on many factors, including the tumor type, the initial tumor size, presence of metastatic disease on staging studies, and the histologic grade of the lesion, as well as the overall health of the patient.

Another factor that comes into consideration when planning the operative care of any sarcoma patient, particularly after radiation, is management of the surgical wound. Incisions in irradiated beds may have significantly impaired healing potential compared with other types of surgical incisions. Sometimes a transfer of healthy tissue into the area (a flap) with or without a skin graft is necessary for appropriate healing to occur. This may be done at the time of re-excision or after a period of attempted primary wound healing. Dialogue regarding soft tissue management and the potential need for tissue transfer is an important aspect of the preoperative discussion between the patient and his/her surgeon.

Follow-Up

Once the course of treatment has been completed, a necessary schedule of follow-up begins. Usually, this means visits with various members of the sarcoma care team. Physical examination, imaging (local MRI, chest CT, x-rays) and sometimes other ancillary testing (cardiac testing, laboratory exams, etc.) are performed every 3 months for 2-3 years, every 4-6 months until 5 years after treatment, then annually for at least 5 years after this. Many permutations of the follow up schedule exist, and may be varied for particular individuals. This may predicated on many potential factors, most frequently the type and grade of tumor, and the presence of metastasis. As opposed to certain other types of cancer, there is really no time when "cure" is felt to have been definitively achieved. Sarcoma is a lifelong diagnosis, and should be treated as such.

Having said this, most recurrences or metastases will be discovered within the first two to five years of the diagnosis and treatment. The longer a given person can go without evidence of systemic disease, the less likely it is that such disease will be detected. Still, late recurrences and metastases do occur, and therefore some type of follow-up is usually recommended for the rest of the patient’s life.

As with many entities in medicine, prevention of unplanned excision is the best method of intervention. Unfortunately, they continue to occur on a regular basis. The problem usually is a lack of consideration of sarcoma in the initial differential diagnosis of a given mass. Only through improved awareness of these rare tumors among health care providers and the population-at-large, will the frequency of unplanned sarcoma resections diminish.

The operative margin matters. Surgical resection remains the common and central modality in the care of the sarcoma patient. Whether the tumor responds to chemotherapy, radiotherapy or newly devised bio-targeting, the primary tumor, and often metastatic sites, must be resected in order to achieve a cure. It is also known that local recurrence of a sarcoma often is a function of the quality and quantity of the margin of normal tissue removed around the cancer. Furthermore, patients that do experience a local recurrence are at increased risk of dying from their disease.

Determining the optimal margin to maintain as much function as possible while still achieving the goal of complete tumor removal is a decision that is made intra-operatively after very careful and strategic preoperative planning. Accordingly, surgical experience matters. Surgeons that do not regularly remove these rare and deadly cancers are therefore more likely to execute a well-intended, but less than optimal, cancer operation. In such circumstances, local recurrence is more likely. This risk is further compounded when sarcoma surgery is performed outside recognized sarcoma centers by a surgical team that is not familiar with tissue handling protocols necessary to perform the latest molecular tests on the removed tumor. Furthermore, an inexperienced pathologist may also have a very difficult time establishing the correct diagnosis and margin status.

As has been emphasized previously in these editorials, patients and families must be made aware of the differences advantaged and disadvantaged by where they initiate their sarcoma care. While surgery may be only one but critical component of the treatment plan in some cases, it must be integrated into the overall care of the sarcoma patient. Appropriate surgical management not only affects the quality but the quantity of life for the patient afflicted with sarcoma. The margin of error, like the surgical margin, must be optimized. Someone’s life depends upon it.

In follow-up to CTOS President Ian Judson’s editorial in the last issue of ESUN emphasizing the importance of sarcoma patients being treated at centers with dedicated sarcoma teams, I wanted to take the opportunity to emphasize that while sarcomas are a surgical disease, every type of scalpel — from the stainless steel to the molecular — must be used to extirpate this deadly array of cancers. Yes, local control, or removal of the main tumor, is of paramount importance but often it is not the site of the original cancer that threatens a patient’s life. Rather, it is the systemic disease, or those cancer cells that break away, metastasizing to the lungs and other organs, that take away a beloved family member. Surgically resecting these metastatic foci may prolong or even save the lives of a few, but the bio-targeted agents, the "molecular scalpels" being brought into trials now hold the most promise for those sarcoma patients with advanced disease that has spread to other sites.

As such, it is critical that surgeons, who are often the first entry portal for sarcoma patients, be aware of the issues, provide adequate surveillance and have a working understanding of the protocols and latest modalities available to sarcoma patients. Patients should ask their surgeons about ongoing research at their centers, about institutional and (inter)national cooperative trials, and in general about the future of sarcoma care. While the sarcoma surgeon must be a technical master of the highly complex craft of sarcoma resection and reconstruction, he or she must also serve as chaperone for the patient as they embark on a phase in their life with many uncertainties and insecurities. The surgeon must be assiduous in facilitating, if not wielding, the molecular scalpel when his or her patient needs such assistance.

Therefore, in resonating with Dr. Judson’s editorial, sarcoma patients should seek their care at comprehensive centers where all modalities of therapy are readily available.