Micrograph of Rhabdomyosarcoma (RMS)

The aggressive rhabdomyosarcoma (or RMS) develops from skeletal muscle cells that have failed to fully differentiate. It usually impacts people under age 18. 

If you were asked to name a type of cancer, how many could you list? Five? Perhaps 10? Maybe even the color of ribbon that represents at least a few? 

Now, what if you were asked to name a type of sarcoma? 

Never heard of it? You’re not alone.

The general term for a broad group of cancers that begin in the bones and in the soft connective tissues, sarcomas represent upward of 100 subtypes of cancer, but less than 1 percent of all newly diagnosed cancers. 

Equally confounding is that some of the more common risk factors for other forms of cancer — smoking, poor diet or lax exercise habits — don’t factor into sarcomas, according to the American Cancer Society. While radiation for past diseases, genetic disorders and mutations, damage to the lymph system and exposure to certain chemicals have gotten some attention as potential elements, most sarcomas simply develop in people with no known risk factors. More common in children — sarcomas account for nearly 20 percent of all childhood cancers — they are also among the top five causes of cancer deaths for Americans under the age of 20. 

Sarcoma specialist Dr. John Charlson, MD, Associate Professor of Medicine at the Medical College of Wisconsin, Division of Hematology and Oncology, shares insight into these uncommon cancers, their treatments and prognoses. 


Dr. John Charlson, MD, Associate Professor of Medicine at the Medical College of Wisconsin, Division of Hematology and Oncology

MKE Lifestyle: How rare is “rare” in the case of sarcoma?

Dr. Charlson: There are maybe 15,000 or so cases of soft tissue sarcoma per year in the United States. Within the sarcoma world, there’s soft tissue sarcomas and bone sarcomas. As a contrast, there are some 230,000 diagnosed breast cancers a year in the U.S. So it’s really relatively quite rare. By the World Health Organization categorization, there are maybe 100 subtypes of sarcoma. So it’s a diverse disease and it’s overall rare, but then each little subtype is even more rare.

These diseases can mimic a host of other ailments, making them a challenge to diagnose. How do some of the more common present themselves?

We think of sarcomas as arising from what we call connective tissues — blood vessels, muscle, fat, cartilage, bone — and those are all over your body. So they really can arise anywhere. But the most common location is the extremities — the lower extremities being more common than the upper extremities. Maybe 8-10 percent of them arise in the head and neck region, and 18-20 percent arise in the deep abdomen or the back of the abdomen.

Along with that, their presentations are different. The typical way that one of these will make itself known is a mass or a lump that’s getting bigger as time goes by. Classically, they’re located deep in the tissue, rather than superficially under the skin, so a deep mass that’s causing a swelling in the muscle of an extremity might be a typical presentation — sometimes painful, but a lot of times not really painful.

Soft tissue sarcomas are more common. But there are bone sarcomas, and they’ll generally present with pain. The disruption of the bone structure hurts. Ones that arise in the deep abdomen can’t be felt sometimes, so that’s a tricky one. I’ll see a case where [the patient’s] abdomen is getting a little more distended and they just think they’re gaining weight, but sometimes it’s a tumor. That’s a pretty uncommon presentation. But not all of them are apparent with a lump or a bump that you can see. 

When is it time to call the doctor?

If you have a lump somewhere that’s a good size — five centimeters or bigger [think an average lime] — or if it’s getting bigger with time, bring that to the attention of your doctor. If someone has a concerning lump, the right response is to work it up with imaging such as an MRI and take a look at it.

That said, it’s hard for a primary care doc to know what to do with these because people have lumps and bumps and the vast majority of those are going to be benign things, not cancer. So it’s hard to sort through what are the ones that are concerning and the ones that aren’t. But things that are big and getting bigger and things that are causing pain should be looked at a little more cautiously.

Is there a common pathway for your patients to come to you and the rest of the sarcoma team? 

These are found all sorts of ways, but a pretty typical pathway might be the patient sees a lump or a bump somewhere that’s new, or it’s getting bigger, and they show their doc and their doctor says, “We should have you go see one of the orthopedic oncologists — orthopedic surgeons that deal with cancer —and have them take a look at it.” They’ll order the imaging once they see the orthopedic surgeon here, and if it’s a concerning-looking mass in the soft tissue, then we’ll generally order a needle biopsy to be done so we can figure out exactly what it is. And then based on that is when you can start forming a treatment plan and figuring out what to do about it. 

Getting a little piece of the tissue that a pathologist can look at under a microscope is really the key to understanding exactly what it is.

When diagnosing these cancers, how important is a tumor board and having many expert voices at the table?

A tumor board consists of different specialists that would be involved in treating a certain type of cancer. On a sarcoma tumor board, you have orthopedic oncologists who are the orthopedic surgeons that deal with cancers. You have the radiologists specialized in bone and soft tissue imaging. The pathologist looks at tissue under the microscope and makes diagnoses. We have the radiation oncologist who does radiation therapy, and medical oncologists like myself who do chemotherapy treatments.

All those people sit in a room, review the case history and look at the imaging, and if we have a biopsy already, the pathologist will review [it] with us too.

The value in that comes several ways. The pathologist has tissue and maybe it’s not entirely clear what kind of cancer it is. So the radiologist says, “This tumor is here; it looks like this.” The orthopedic surgeon and radiologists say, “Yeah, that looks pretty typical for this kind of cancer.” The pathologist says, “It could be that for sure.” That kind of collaboration over what things look like can help make a diagnosis in a tricky situation.

Then, in terms of treatment, it’s an efficient way for everybody to say, “Here’s our overall view of this situation. What do we as a group think is the best way to start approaching that?” So [the board is] important for diagnosis, but also important for treatment discussions. 

Because they’re so rare, are sarcomas also more challenging in coming up with that treatment plan? 

Yes. Because it’s a rare cancer — and partly because there are so many different subtypes and presentations — we don’t have as many really big clinical trials to compare Treatment A to Treatment B and say Treatment B is best. There’s less of that to guide us.

For a sarcoma that’s caught at a point where it’s just in one spot and hasn’t spread anywhere, like a lot of other cancer types, we do know that surgery is central to curing that cancer. That’s why it’s important to have orthopedic oncology specialists who are real experts not just in getting these tumors out, but preserving a person’s function. That’s often the central part of the cure of these cancers, and then the appropriate use of radiation therapy and chemotherapy to facilitate that and to make sure we’re maximizing the odds of a cure. Sometimes we do treatments before surgery to help facilitate the surgery by shrinking the tumor down, too.

So we do have protocols. They’re maybe not as well studied or backed up by as many thousands of patients’ research and clinical trials, but we’re gathering some of that data over time. There are cases where surgery doesn’t take place or doesn’t really have as much of a role, especially in a situation where a person’s sarcoma has already traveled from the initial spot to metastasize to other areas of the body. Then things like chemotherapy might take a front seat and be the main treatment. 

There’s variability in how we treat, depending on where we catch the cancer and the extent of the cancer when it’s diagnosed. Hopefully we catch it when it’s still just in one spot, and we can cure it. That’s where the surgeons really are the quarterbacks at the table.

Because the cancers are rare and studies are limited, what does that do for research of new treatments, new ideas and new means of diagnosis?

There are all sorts of ways it impacts that. Partly because it’s such a diverse cancer, there’s no real test for screening for it. We do screening tests for colon cancer with colonoscopy, and for breast cancer with mammogram. The reason is to catch those cancers early, so your odds of curing them are higher. 

Because of the relatively small number of patients and the huge diversity in the cases, it’s hard to run drug clinical trials to identify the very best chemotherapy, just because it’s hard to run studies with these rare cancers to find the right kind of patients to connect with the clinical trials to do those studies.

There are drug companies that pay attention to sarcoma and help develop treatments for our patients. It’s the nature of that industry that they pay more attention to cancers that are more common, which is also very important. But there are improvements all the time and there is investment in research. 

We’re making steps forward with sarcoma care, but those are some of the reasons why it’s a little behind the others. It’s not only the rare cancers that suffer from that, but it causes some extra hurdles.

Step one in overcoming those hurdles?

Maybe we take Sarcoma month in July as a real time to create awareness. Just keep these soft tissue tumors in mind. It’s not all benign lipomas. If it’s growing and hard, we should keep other stuff in our mind.

Patients and doctors should know that if it’s a pulled muscle, then it should get better in time. But if you keep having pain or swelling in a place, maybe it’s not a simple pulled muscle. I certainly don’t want to give your readers the message that everybody needs to get an MRI for every ache and pain. But a collaborative discussion with your doc — “Is there any chance this is something more serious than just a lipoma?” — keep those lines of communication open. 

And we as docs need to do the right thing. If it looks suspicious, get a scan, get a biopsy, so we know what we’re dealing with and then make your treatment plan.

There must also be a challenge in that these tests can be costly and, in the majority of cases, cancer won’t be detected. Trying to keep the patient on board with good news is always news. 

It’s a tough issue. The vast majority of these lumps and bumps are benign. So if we MRIed every lump and bump, that’s a huge cost to patients and creates all sorts of additional workup that has costs and even risks associated with it. It’s just having a little bit of caution: If it’s not behaving in a benign manner, we have to think about it.

… and remember that if it is a sarcoma, they are often highly treatable.

It’s not uniformly a bad prognosis. If they’re caught at a relatively early stage, a lot of them are very curable. It depends at the stage at which they’re diagnosed. Under the care of surgeons with good expertise and the right teams that know how to treat them, these are curable cancers.

Our feeling is it makes sense to involve a team that has sarcoma experience when you’re treating these. Knowledge about how the disease behaves and knowledge about how the different treatment modalities affect different aspects of the cancer is valuable in these situations. It’s a unique surgical training and experience to treat some of these tumors in the extremities or deep in the abdomen. But we have a lot of patients that are cured of this.

Is there some sort of uniformity or commonality in how sarcomas take shape and grow because they are rare? 

For the majority of these sarcomas, we don’t really know why people get them. In most cases, there aren’t risk factors that we can identify that would have been the cause of the person getting a sarcoma. There’s some instances [such as] Kaposi sarcoma, where we know it’s driven by a specific virus — human herpesvirus-8 — usually in the setting of an immune system that’s not functioning normally.

That’s the unique example. For most of the sarcomas, we don’t really have a specific thing that triggered it. There are patterns we can identify with certain types of sarcoma, but sometimes those are specific-to-specific subtypes.

For instance, there’s a sarcoma called myxoid liposarcoma. We know that if it’s going to spread, it might spread in odd ways. It might spread to the tissues around the spine — most of our other sarcomas don’t do that. So there are some patterns that we’re aware of. But not a lot of big, generalized patterns.

I’m guessing that beyond removing the mass, treatments are widely varied as well?

Immune-based therapies are really making a huge impact in a lot of different cancer types. The common immunotherapy drugs aren’t approved for use in sarcoma yet, but we’ve seen some early studies where certain subtypes of sarcomas looked like they might respond well to some of these immunotherapy drugs — for instance, angiosarcoma. There’s a clinical trial going on that explores that further. 

There are several other sarcoma types where they’ve identified specific targets in the cancer cell. There are studies where we take out a patient’s T-cells — some of their immune cells — and they get genetically reprogrammed to attack these cancer targets better. Then the T-cells are given back to the patient as the treatment, modifying the patient’s immune system to more effectively attack the cancer. That’s happening in several sarcoma types now in clinical trials, and that’s really exciting as well.

There’s a type of sarcoma called GI stromal tumor, or gastrointestinal stromal tumor (GIST). In the past several years, there have been a couple new drug approvals for new drugs that were designed specifically to bring us more effective treatments for GIST. 

There are exciting advances happening for patients, and there’s a lot of room to go yet. 

Is there anything specifically going on through Froedtert & the Medical College, or is it just constant communication with your colleagues here and elsewhere?

We’re collaborating with some of our colleagues at other institutions in clinical trials and participating in some of the big studies that are going on at multiple centers around the country and around the world. We do try to participate in that kind of research and have those study options open for our patients here to the extent that we can.

The Medical College hired a new lab-based researcher who’s gotten to research background with specific type of tumors driven by mutations in neurofibromatosis 1 gene, or NF1. His interest and his expertise is going to add another facet to the sarcoma program here. We’re trying to help make our contribution to understanding the cancers a little better, and helping to explore new treatments for them as well. 

We’re certainly not as big as the MD Andersons or the Dana Farber Cancer Institutes. But we’re trying. MKE

By the Numbers:

The American Cancer Society’s estimates for soft tissue sarcomas in the United States for 2021 are:

• About 13,460 new soft tissue sarcomas will be diagnosed (7,720 in males and 5,740 in females).

• About 5,350 people (2,840 males and 2,510 females) are expected to die of soft tissue sarcomas. 

The most common types of sarcoma in adults are:

• Undifferentiated pleomorphic sarcoma (previously called malignant fibrous histiocytoma)

• Liposarcoma — malignant tumor that develops in fatty tissue

• Leiomyosarcoma — rare tumors that grow in the smooth muscles