Sarcoma

What is Sarcoma?

Soft tissue sarcomas (STS) are a type of cancer with over 60 different types. They can start in any part of the body and usually affects people at very young or old age. They can occur in different parts of the body including muscles, fat tissues, blood vessels, lymph nodes, connective tissues, and nerves. These cancers can show a wide range of symptoms, from harmless fat tumors known as lipomas, to severe widespread cancer called angiosarcomas.

Diagnosing these conditions can be challenging because many other non-cancerous conditions can look like soft tissue sarcomas. These cancers can also occur in different parts of the body like the trunk and extremities, or behind the abdominal area known as the retroperitoneum. Most of the time, soft tissue sarcomas occur on their own without a clear cause. However, certain inherited genetic changes, exposure to radiation, or certain environmental factors have been known to increase the risk.

What Causes Sarcoma?

Most instances of certain diseases arise by chance, but we have identified several causing factors.

One of these is genetic mutations. For example, a disease called Neurofibromatosis Type 1 (NF1), or Von Recklinghausen Disease, is a hereditary condition caused by changes in a specific gene, called NF1. This gene produces a protein, neurofibromin, which helps keep cell growth in check. However, mutations in the NF1 gene can result in multiple skin growths known as neurofibromas.

Similarly, Li-Fraumeni Syndrome is a rare hereditary disorder caused by changes in the TP53 gene, which produces p53, a protein that helps get rid of damaged cellular DNA. This can lead to various physical characteristics and clinical symptoms, and some patients may develop a type of cancer called rhabdomyosarcoma by the age of 4.

Familial Adenomatous Polyposis (FAP) is another hereditary disorder, caused by changes in the APC gene. This gene normally functions to prevent excessive cell growth. However, mutations can result in uncontrolled cell growth and the formation of numerous polyps in the colon, along with other symptoms like cysts, bone growths, and desmoid tumors.

Exposure to radiation can also significantly increase a patient’s long-term risk of developing soft tissue sarcoma (STS). The effects depend on the dosage and typically occur around the edges of the treated area. Children who develop STS after radiation usually do so about 12 years later.

Certain carcinogens, or cancer-causing substances, can also contribute to disease. For instance, prior use of Thorotrast, a type of contrast used for medical imaging, has been linked to a type of liver cancer known as hepatic angiosarcoma. Extended exposure to polyvinyl chloride, a common plastic, and arsenic can also increase risk.

Chronic Lymphedema, or long-term blockage of the lymphatic system, is thought to stimulate overgrowth of lymphatics and blood vessels or weaken the local immune response, increasing the risk of cancer. This is often seen in people who’ve had extensive surgical procedures, especially if they’ve also had radiotherapy. Infections with parasitic roundworms can also cause this condition, which comes with a high risk of developing a cancer known as angiosarcoma.

Risk Factors and Frequency for Sarcoma

Soft tissue sarcomas are a rare type of cancer. In the United States in 2014, there were 12,020 new cases and 4,740 people died from this disease. It makes up about 1% of all cancer cases and 2% of deaths caused by cancer. Soft tissue sarcomas can occur anywhere in the body, but they are more common in the arms, legs, and torso than the stomach or back of the abdomen. They usually occur closer to the body. Specifically, the thigh is the most common location, accounting for 44% of cases. Certain types of soft tissue sarcomas, like rhabdomyosarcoma, hemangioma, neurofibroma, and alveolar sarcoma, tend to affect children and young adults particularly.

• Soft tissue sarcomas are quite rare.
• In 2014, there were 12,020 new cases and 4,740 deaths in the United States.
• They make up about 1% of all cancer cases and 2% of cancer-related deaths.
• These conditions are more common in the limbs and torso than the inside of the stomach or behind the abdomen, with the thigh being the most common location.
• Types like rhabdomyosarcoma, hemangioma, neurofibroma, and alveolar sarcoma typically affect children and young adults.

Signs and Symptoms of Sarcoma

Soft tissue sarcoma, or STS, can take several forms and affect different parts of the trunk and limbs. Most people with STS initially find a lump that doesn’t hurt. It’s important to fully examine the lump and the person’s medical history because other conditions could mimic STS. These conditions, such as thick scars (hypertrophic scars), blood clots (hematoma), noncancerous fat tissue tumors (benign lipoma), fluid-filled sacs (cysts), pus pockets (abscesses), and skin cancer (melanoma) can all complicate the diagnosis process.

STS tumors are typically small, surface-level, and moveable. They’re not attached to bones or blood vessels, making them easier to surgically remove with a safe margin. However, if the tumors are near vital organs or blood vessels, they’re usually handled by specialized surgeons at a tertiary care center. In these instances, a biopsy before surgery is often recommended because a variety of factors can affect patient outcomes.

Testing for Sarcoma

When a doctor is dealing with a suspected mass, like in the case of soft tissue sarcomas (STS) typically found in the limbs or trunk of the body, they have to consider a number of things before deciding on proper treatment. These may include how big and where the mass is, whether it may have affected nearby nerves and blood vessels, whether the cancer may have spread to lymph nodes or distant parts of the body, and whether the mass can be surgically removed without causing significant harm to the patient’s function.

Different types of scans, like MRI scans, are usually done to get a good look at the STS in the trunk and extremities. A chest CT scan, which uses a special kind of x-ray, is also done if there’s a high risk that the cancer may have spread to the lungs. PET/CT scans, another type of imaging test, have not fully become the standard in evaluating sarcomas as they aren’t as helpful in telling apart benign (not cancer) and malignant (cancer) disease. However, this type of scan could potentially help evaluate how a patient responds to preoperative chemotherapy (drugs given before surgery to shrink the tumor). More studies are needed to determine the part this scan plays in managing sarcomas.

If a biopsy (a test where a small amount of tissue is removed from the body to be examined) is advised, a core-needle biopsy is typically done first. If this doesn’t give a clear diagnosis, then an incisional biopsy (where a piece of the mass is removed) may be done. When performing the core-needle biopsy, doctors keep in mind the eventual surgical removal of the mass, so the path of the biopsy needle falls within the area that will be removed for surgery. This approach maximizes the chance of getting a diagnosis. Unfortunately, even after initial removal of the sarcoma, about 74% of patients still have some residual disease, meaning the surgery didn’t get all of it.

Since there’s a high chance that the sarcoma might come back, doctors keep a close watch after surgery with periodic physical exams. They schedule these exams every 3 to 6 months for 2 to 3 years, every six months for the following two years, and then once per year after that. Radiographic surveillance (watching the body using imaging methods) of the chest, abdomen, and pelvis and possible follow-up MRIs is done based on the specific characteristics of the patient and the tumor.

Treatment Options for Sarcoma

Benign adipocytic tumors, also known as lipomas, are harmless fat cell tumors that can develop anywhere in the body. They generally don’t cause any symptoms unless they are large enough to press against nearby organs or tissues. Lipomas are usually smooth and uniform, encapsulated within a thin layer, and may contain calcified areas or blood from an injury. The typical treatment involves surgically removing the tumor along with its capsule.

However, lipomas can sometimes be confused with a type of malignant tumor known as liposarcoma, the most common type of soft tissue sarcoma. Liposarcomas are characterized by being larger than 10 cm, having thick internal divisions, and containing less than 75% fat cells. Generally, liposarcoma is treated through surgical removal of the tumor with a significant margin of healthy tissue around it to prevent recurrence. However, it can sometimes come back, and this typically happens due to an increase in certain genes (12q13-15) leading to an overactive growth path.

For extremity liposarcomas (those present on arms or legs), the main aim is to remove the tumor while retaining the function of the limb. In the case of retroperitoneal liposarcomas (those occurring in the abdominal cavity), the objective is total removal of the tumor. The conventional treatment is surgery, but sometimes radiation therapy is also employed before surgery to potentially make the tumor easier to remove.

There are several other types of soft tissue tumors as well, each presenting its own unique challenges. Some may respond poorly or not at all to chemotherapy, which makes the surgical process critical for treatment.

Desmoid tumors, for example, are fibrous growths that are sporadic in most cases but can sometimes be associated with a genetic condition known as familial adenomatous polyposis (FAP). Despite resection or removal, these tumors have a high chance of recurrence.

Another example is an angiosarcoma, malignant tumors originating from blood vessel linings. They can occur anywhere in the body but are often triggered by radiation exposure. While larger or epithelioid (resembling normal skin cells) angiosarcomas signal a more severe prognosis, surgical resection remains the primary treatment, sometimes alongside chemoradiation.

Some rare soft tissue tumors are found in the stomach lining, known as GISTs (Gastrointestinal Stromal Tumors). These tumors often spread to the liver and the surface of the abdomen. Besides surgery, they can also be treated with a specific targeted therapy medicine called Imatinib.

Leiomyosarcomas are another kind of malignant tumor that originates from smooth muscle cells in any part of the body. These are the second most common type of soft tissue sarcoma, but unlike other sarcomas, can also originate in the uterus. Treatment again primarily involves surgical removal of the tumor with a clear margin, potentially followed by radiation therapy to aid local control.

Remember, early detection and treatment are pivotal in the management of any kind of tumor, benign or malignant. If you’re experiencing any unusual symptoms or have found any lumps in your body, it’s important to seek medical advice promptly.

What else can Sarcoma be?

When a doctor comes across a mass in the soft tissues of the body, there are several possible causes that they must consider. These causes can vary from harmless conditions to severe illnesses such as cancer. Usually, benign or harmless lumps are found near the surface of the skin or under it. However, a near-surface location doesn’t always mean the lump is harmless. To make a correct diagnosis, doctors rely on methods like performing an excellent biopsy or using imaging techniques. Some of the conditions that can cause a soft tissue mass are listed below, categorized as benign, infectious, or malignant:

• Benign Conditions:
• Acrochordons (skin tags)
• Lipoma (fatty lump)
• Myositis ossificans (usually related to physical injury)
• Hemangioma (birthmark that looks like a rubbery bump)
• Keloids (raised, overgrown scars)
• Dermoid cyst (a lump under the skin that can contain teeth, hair, etc.)
• Ganglion cyst (noncancerous lumps typically located near joints)
• Pilonidal cyst (skin infection near the tailbone)
• Angiofibroma (small, red bumps)
• Neurofibromas (lump beneath the skin)
• Rickets (softening and weakening of the bones)
• Infectious Conditions:
• Abscess (swollen, pus-filled lump)
• Cellulitis (skin infection, usually in the lower leg)
• Malignant (Cancerous) Conditions:
• Squamous cell carcinoma (a type of skin cancer)
• Melanoma (the most serious type of skin cancer)
• Basal cell carcinoma (the most common type of skin cancer)
• Merkel cell carcinoma (a rare type of skin cancer)
• Skin metastasis (skin cancer that originated from other parts of the body)
• Keratoacanthoma (type of skin growth that resembles skin cancer)
• Cutaneous lymphoma (cancer in the lymphocytes)
• Nonrhabdomyosarcoma soft tissues sarcoma (cancer that grows in connective tissues)
• Kaposi sarcoma (cancer that causes lesions in the skin and mouth)
• Pediatric neuroblastoma (cancer that involves certain types of nerve tissues)
• Pediatric non-Hodgkin lymphoma (cancer in a type of white blood cells)
• Pediatric osteomyelitis (bone infection in children)
• Pediatric osteosarcoma (bone cancer in children)
• Pediatric rhabdomyosarcoma (cancer that forms in soft tissues)
• Ewings sarcoma (type of tumor that occurs in the bone or soft tissue)
• Soft tissue sarcoma (cancer that develops in the soft tissues)

Surgical Treatment of Sarcoma

Surgical removal or resection is often the primary method for treating sarcoma, a type of cancer. Before the 1980s, this treatment often involved limb amputation. Though it controlled the cancer effectively, it often resulted in significant physical impairments. Nowadays, fewer than 5% of sarcoma surgeries involve amputation.

Before any surgery, it’s important for doctors to thoroughly understand the cancer location and extent. This usually involves an MRI scan. The goal in modern surgical approaches is to remove the tumor along with an ‘all around’ safe margin of at least 1cm of healthy, uninvolved tissue. For tumors with irregular borders, this safe margin may need to be 2cm. However, certain constraints such as the spread of the disease or close proximity to crucial nerves and blood vessels may limit this.

If the tumor is near or pressing onto nerve structures, these structures may be left intact, provided their outermost layers are peeled off. In some rare cases, if the bone is infected, it may also need to be removed to get the proper margins. After surgery, additional treatment may be needed, especially if the surgical margins were smaller than planned.

Unplanned removal of these tumors, often occuring in less specialized settings, has been shown to increase the risk of local recurrence and potentially spread (22% vs. 7%).

Leaving tumors partially inside the body after surgery can lead to poor outcomes. Tumor margins, the boundaries of the tumor and surrounding tissue, can vary. Margins labelled as “Intralesional” leave some tumor behind, whereas “marginal” include the cancer’s reactive zone – the area around the tumor where normal tissue is attempting to fight the cancer. “Wide” margins involve normal tissue surrounding the cancer. With “radical” resections, the whole tumor-infected compartment is removed. The surrounding skin should also be removed. If the resulting wound is likely to be large, a tissue graft may be required.

Even for sarcomas that return after treatment, surgery may still be an option. This could involve another wide excision or amputation. The choice of surgery will be based on the location and size of the tumor, how close it is to vital structures, and whether limb function can be preserved.

For large or non-operable tumors, or for patients not suitable for surgery, the cancer may be monitored if there are no symptoms. Yet, for those with symptoms, surgery to reduce discomfort and improve quality of life may be done.

Recurrence rates for low-grade sarcomas after surgery are around 5%, and these are typically treated with surgery alone. However, high-grade sarcomas have a recurrence rate of 33% at five years after surgery, and radiotherapy is generally recommended after surgery. In recurring cases, surgery alone also had a local recurrence rate of 33% at five years.

As these tumors are rare and treatment requires a team of specialists, it is recommended that patients are treated at high-volume centers with specific expertise. Following treatment, rigorous follow-up, particularly in the first few years, and continued physical therapy are crucial.

What to expect with Sarcoma

Sarcomas are a diverse group of cancers, but the most important factors that affect prognosis are the tumor’s grade, which tells us how aggressive the cancer is, and its size. The grade of the sarcoma can predict if the cancer will spread to distant parts of the body (metastasis) and affect survival. The size of the primary (or initial) tumor can predict if the cancer will come back (local recurrence) and also if it will spread.

There are several tools (nomograms) that help predict the chance of local recurrence, distant metastasis, and overall survival for sarcoma patients. For example, the Sarcoma nomogram from Memorial Sloan Kettering, compiled from their experience treating non-metastatic sarcomas from 1982 to 2006, predicts the chance of local recurrence at 3 and 5 years based on grade, depth, size, margin status, age, and type of sarcoma. In these patients, surgery was the only form of treatment.

Additional prediction tools for overall survival and distant metastasis were created from data of patients who underwent surgery for sarcomas from 1994 to 2013 at a single institution. These tools were then tested and validated on separate groups of patients from other institutions.

Factors like age, tumor size, sarcoma grade, and type of sarcoma were found to significantly affect both overall survival and distant metastasis. Generally, for localized and early-stage sarcomas, complete removal of the tumor can be done with good long-term survival, but it’s common for the cancer to come back. For people with advanced disease, a cure is usually not possible, and the median survival is around 12 to 18 months, depending on the type of sarcoma. The risk of the cancer coming back can continue for 10 to 15 years, so patients need to be followed up indefinitely. Most recurrences happen within the first five years. Unfortunately, most sarcomas don’t respond well to chemotherapy, with only 10% to 50% showing improvement. The response can also depend on the type of sarcoma, its grade, and the specific patient’s characteristics.

Possible Complications When Diagnosed with Sarcoma

Chemotherapy

Initial treatments for sarcoma often had severe side effects like low blood counts and sometimes resulted in patient deaths. Modern treatments are often better tolerated without the same harmful effects on the blood cells. The main side effects of today’s go-to treatments, often doxorubicin/ifosfamide, are:

• Low blood counts
• Mouth sores
• Hair loss
• Tiredness
• Nausea and vomiting
• Heart damage
• Blood in urine
• Waste salt kidney disease
• Central nervous system damage

Damage to the heart can be particularly severe. Doctors try to limit heart damage through several methods, such as:

• Restricting the lifetime dose
• Infusing instead of injecting the drug
• Utilizing heart-protecting strategies like beta-blockers, cholesterol-lowering drugs, and antioxidant supplements

However, despite these measures, the risk of heart failure still remains.

Dexrazoxane is the only medication approved by the FDA to protect against heart damage caused by this specific chemotherapy, but its use is limited to patients with advanced breast cancer who have received a certain amount of doxorubicin and plan to continue treatment. It was found to be the only drug to reduce heart failure risk in these patients. Receiving these drugs after radiation treatment might result in skin reactions such as blistering and peeling.

Medication is typically combined with ifosfamide to decrease the risk of blood-filled blisters in the bladder. Other treatment regimens can cause side effects like:

• Low blood counts
• Fluid retention
• Redness and swelling of the hands and feet
• Nail bed separation
• Increased liver enzymes
• Protein in the urine
• Shortness of breath
• Neuropathy

Taking oral drugs that inhibit tyrosine kinase, a protein involved in cell growth and division, can lead to diarrhea, changes in taste, a skin reaction that’s sensitive to sunlight or heat, high blood pressure, high liver enzymes, low bone marrow function, and swelling.

Radiotherapy

External beam radiotherapy is usually well-tolerated. The risk for certain side effects depends on when the radiation is given and how much radiation is used. With pre-operation radiation, wound complications are more common. Post-operation radiation increases the risk for bone fractures, tissue hardening, joint stiffness, and swelling. There’s also a risk of developing secondary cancers after several years. Side effects associated with brachytherapy, a type of internal radiation therapy, are generally mild. However, certain factors increase the risk for complications:

• Diabetes
• Smoking history
• Larger tumor size
• Radiation dose
• Removal of the outer layer of bone
• Kind of surgical wound closure used

About half of the time, this can result in delayed wound healing. Other complications include thickening of the skin and underlying tissues, decreased joint mobility, and lymph fluid buildup called lymphedema. There’s also a chance of bone fractures but this is more common with EBRT than BRT. The removal of the outer layer of bone seems to be the only risk factor for this outcome.

Recovery from Sarcoma

After surgery, all patients diagnosed with sarcoma, a type of cancer, should participate in a rehabilitation program. These individuals often experience severe impairment in their daily functions, and may be limited to staying in a bed or chair. Undergoing rehabilitation is key to helping them recover some of their lost abilities.

Preventing Sarcoma

If you’re being treated for a certain type of cancer called sarcoma, you’ll need to have regular check-ins with your doctor. These appointments might include physical check-ups and blood tests to make sure the cancer hasn’t come back. Depending on where the sarcoma was and what type it was, your doctor might also want to do imaging tests like X-rays or MRIs.

At first, these appointments could be every few months. But as time goes by, and the chance of the cancer coming back gets smaller, you’ll need to go less often. It’s important to remember that high-risk types of sarcoma are more likely to come back in the first two or three years after treatment. Some types of sarcoma come back later, but the chances are lower.

The specific schedule and type of tests you’ll need will depend on things like the grade of the tumor (how abnormal the cancer cells look under a microscope), its size, and where it was located in your body.