Alveolar Rhabdomyosarcoma

Alveolar rhabdomyosarcoma is a rare and aggressive form of soft tissue cancer that typically strikes teenagers and young adults. This cancer develops from skeletal muscle cells and often appears in the arms, legs, or trunk, spreading rapidly and presenting unique treatment challenges.

Table of contents

• What is Alveolar Rhabdomyosarcoma?
• Affected Body Parts
• Who Gets This Cancer
• Signs and Symptoms
• Causes and Genetics
• How Doctors Diagnose This Cancer
• Treatment Options
• Outlook and Survival
• Ongoing Research

What is Alveolar Rhabdomyosarcoma?

Alveolar rhabdomyosarcoma, often called “ARMS,” is a type of soft tissue sarcoma—a cancer that develops in the body’s soft tissues rather than in bones^[1]. This cancer specifically starts in skeletal muscle cells, which are the muscles that attach to bones and help the body move^[2].

ARMS gets its name because when viewed under a microscope, the cancer cells have a distinctive pattern that resembles tiny air sacs in the lungs called alveoli^[4]. This appearance helps doctors distinguish ARMS from other types of muscle cancers.

ARMS is one of two main types of rhabdomyosarcoma. The other type, called embryonal rhabdomyosarcoma, is more common in younger children and typically appears in the head, neck, or urinary tract. ARMS, in contrast, is more aggressive, meaning it grows and spreads faster than embryonal rhabdomyosarcoma^[3].

Affected Body Parts

• Arms and legs
• Trunk (torso)
• Head and neck region
• Muscles around the spine
• Area between the genitals and anus

ARMS most commonly develops in the deep soft tissue of the arms or legs^[7]. It can also occur in the trunk of the body, which includes the chest and abdomen. Less frequently, ARMS appears in the head and neck area, in muscles around the spine, or in the perineal region—the area between the genitals and anus^[5].

While ARMS can technically develop anywhere in the body where skeletal muscle exists, it tends to favor the extremities more than other locations. This pattern differs from embryonal rhabdomyosarcoma, which more often affects the head and neck or organs of the urinary and reproductive systems^[8].

Who Gets This Cancer

Alveolar rhabdomyosarcoma is rare. In England, an average of only 31 cases are diagnosed every year, and ARMS makes up just over a quarter of all rhabdomyosarcoma diagnoses^[5]. Across the United States, rhabdomyosarcoma as a whole affects approximately 350 to 500 people each year^[1][3].

ARMS primarily affects older children, teenagers, and young adults, with most cases occurring in people between the ages of 10 and 25 years^[4][14]. This cancer occurs at roughly equal rates in males and females, unlike some other cancers that show a clear gender preference^[4][5].

Although ARMS is most common in adolescents and young adults, a subset of cases has also been observed in adults over 40 years of age^[7]. Children under 10 can also develop ARMS, though they are more likely to develop the embryonal type of rhabdomyosarcoma^[3].

In most cases, ARMS occurs sporadically with no genetic predisposition, accounting for roughly 1 percent of all cancers in children and adolescents^[4].

Signs and Symptoms

The symptoms of alveolar rhabdomyosarcoma vary depending on where the cancer develops and how large the tumor has grown^[5]. Many people first notice a lump or swelling that appears under the skin. This lump often grows larger over time and usually doesn’t go away on its own^[3]. While the lump is often painless initially, it may become painful as it grows^[14].

When ARMS develops in an arm or leg, the main symptom is typically a mass, lump, or swelling in the soft tissue^[1]. This is often the first sign that something is wrong. The lump is usually fast-growing but may not cause pain right away^[5].

If the tumor grows in the head or neck area, symptoms can include loss of hearing or balance, bulging of the eyes, weakness or numbness in the face, pain in the face, or trouble swallowing^[5].

When ARMS develops in the muscles around the spine, it may cause back pain, difficulty walking, or loss of bowel or bladder control^[5][14]. Tumors in the perineal region—the area between the genitals and anus—can lead to constipation, abdominal pain, swelling or bloating in the belly, or blood in the urine or stool^[5].

In cases where the cancer has grown large or spread to other parts of the body, additional symptoms may appear. These can include difficulty urinating or passing stool, blood in the urine, bone pain, persistent cough, weakness, or weight loss^[3][8].

Because ARMS is aggressive and can spread quickly, approximately 25 to 30 percent of patients already have the cancer in distant parts of the body or nearby lymph nodes when they are first diagnosed^[7].

Causes and Genetics

The exact cause of alveolar rhabdomyosarcoma is not fully understood^[8]. Like many cancers, ARMS develops when normal muscle cells undergo changes that cause them to grow and multiply uncontrollably. In most cases, the disease occurs sporadically, meaning there is no clear genetic predisposition or family history^[4].

However, scientists have discovered specific genetic changes that are present in most cases of ARMS. The majority of alveolar rhabdomyosarcoma cases—about 60 percent—involve a genetic change called the PAX3-FOXO1 fusion gene^[4]. Another 20 percent of cases involve a similar genetic change called the PAX7-FOXO1 fusion gene^[4]. The remaining 20 percent of ARMS cases do not have either of these genetic fusions^[4].

These fusion genes form when pieces of different chromosomes break off and attach to each other in an abnormal way. For PAX3-FOXO1, part of chromosome 13 moves to chromosome 2. For PAX7-FOXO1, part of chromosome 13 moves to chromosome 1^[4]. When these abnormal gene combinations form, they create proteins that disrupt normal cell growth and cause cancer to develop^[4].

People with certain rare inherited genetic syndromes have an increased risk of developing rhabdomyosarcoma, although the risk remains low even with these conditions^[1][8]. These syndromes include:

• Li-Fraumeni syndrome
• Beckwith-Wiedemann syndrome
• Neurofibromatosis type 1
• Costello syndrome
• Dicer1 syndrome
• Noonan syndrome

In most cases, however, rhabdomyosarcoma develops in people with no family history of these genetic conditions or cancer^[8].

How Doctors Diagnose This Cancer

Diagnosing alveolar rhabdomyosarcoma requires multiple tests and procedures. A doctor will start by asking about symptoms and conducting a physical examination to look for lumps or other signs of disease^[1][5].

If a tumor is suspected, doctors use various imaging tests to see inside the body and determine the tumor’s location and size. These tests may include X-rays, CT scans (computed tomography scans), MRI scans (magnetic resonance imaging), PET scans (positron emission tomography), or ultrasound^[5][8].

To confirm the diagnosis, doctors must perform a biopsy, which means removing a small sample of the tumor tissue for examination under a microscope^[5]. A specialized doctor called a pathologist examines this tissue sample to determine whether it is ARMS and to look for the characteristic genetic changes^[5].

Because ARMS can spread to other parts of the body, additional tests are often needed to check whether the cancer has moved beyond its original location. If the tumor is near the spine, doctors may perform a lumbar puncture, also called a spinal tap, which uses a small needle to collect fluid from around the spine and check it for cancer cells^[5][14].

Since ARMS sometimes spreads to the bone marrow—the spongy tissue inside bones where blood cells are made—doctors may also perform bone scans and bone marrow biopsies to check for cancer in the bones^[5][8].

Using specialized molecular testing of the tumor tissue, pathologists can identify whether the PAX3-FOXO1 or PAX7-FOXO1 fusion genes are present. This information helps doctors understand how aggressive the cancer is and plan the best treatment^[4][7].

Treatment Options

Treating alveolar rhabdomyosarcoma typically requires a combination of three main approaches: surgery, chemotherapy, and radiation therapy^[3][5]. The specific treatment plan depends on several factors, including the tumor’s size, location, stage, and whether the cancer has spread to other parts of the body^[3].

Doctors often categorize ARMS as low-risk, intermediate-risk, or high-risk based on these factors, and this classification helps determine the most effective treatment approach^[3].

Surgery is typically the first treatment method. The surgeon attempts to remove the entire tumor along with an area of normal tissue around it, called “taking a margin.” This helps ensure that all cancer cells have been removed^[5]. Because ARMS commonly affects the arms and legs, surgeons work to perform limb-sparing surgery so that the limb can continue to function normally^[5]. Very rarely, if the cancer has spread extensively throughout a limb, a partial or full amputation may be necessary to stop the cancer^[5].

Sometimes surgery alone cannot completely remove the tumor because of its location or size. In these cases, doctors may use chemotherapy or radiation therapy before surgery to shrink the tumor and make it easier to remove^[3].

Chemotherapy uses powerful drugs to kill cancer cells throughout the body. All children with rhabdomyosarcoma receive chemotherapy^[3]. The type of chemotherapy drugs used and the doses given depend on whether the cancer is categorized as low-risk, intermediate-risk, or high-risk^[3]. The standard chemotherapy approach for rhabdomyosarcoma typically includes a combination of three drugs: vincristine, actinomycin, and cyclophosphamide or ifosfamide^[9].

Radiation therapy uses high-energy radiation beams to destroy cancer cells. Radiation can be used either before or after surgery^[5][14]. When used before surgery, radiation therapy aims to shrink the tumor to make it easier to remove. When used after surgery, radiation helps destroy any remaining cancer cells. Radiation is often combined with chemotherapy and surgery to target and eliminate cancer cells more effectively^[3].

The treatment process can be long and difficult. It may involve months of chemotherapy, including many nights in the hospital, along with surgery and radiation treatments^[3]. These treatments can cause significant side effects, which can be especially challenging given how young many patients are when diagnosed.

Outlook and Survival

The outlook for someone with alveolar rhabdomyosarcoma depends on several factors. These include the child’s age, where the tumor started in the body, the tumor’s size, whether the cancer has spread, whether the tumor can be completely removed, and which type of rhabdomyosarcoma it is^[21].

Children between the ages of 1 and 9 years tend to have a better outlook than children who are 10 years or older or younger than 1 year^[21]. The location where the tumor started also affects the prognosis. Tumors that begin around the eye, in certain areas of the head and neck, or in organs of the genitourinary system generally have a better prognosis^[21].

Smaller tumors—those that are 5 centimeters or less in diameter—are associated with better outcomes than larger tumors^[21]. Children whose tumors can be completely removed during surgery usually have a better outlook than those whose tumors cannot be fully removed^[21].

Unfortunately, alveolar tumors tend to be more aggressive than embryonal tumors and generally have a poorer prognosis^[21]. Children whose cancer has already spread to distant parts of the body or to lymph nodes when it is first diagnosed face greater challenges^[21].

The overall survival rates vary considerably based on risk level. For low-risk rhabdomyosarcoma, the five-year survival rate is approximately 80 to 95 percent. The majority of cases are intermediate-risk, with a survival rate of 50 to 70 percent. However, once the cancer has spread to distant parts of the body—which occurs in about 10 to 15 percent of cases—the survival rate drops to 20 to 30 percent^[19].

Nearly all recurrences of rhabdomyosarcoma occur within three years of diagnosis^[19]. While many patients with localized rhabdomyosarcoma can be cured, long-term outcomes for patients with cancer that has spread to other parts of the body remain poor^[9].

Even when treatment is successful, survivors may experience long-term side effects from chemotherapy and radiation therapy that can affect their health and quality of life for years^[3].

Ongoing Research

Research into alveolar rhabdomyosarcoma is ongoing, with scientists working to find better ways to treat this challenging cancer. Over the past few decades, research has improved treatment options for rhabdomyosarcoma, but significant challenges remain—especially for children with aggressive ARMS^[3].

Current research priorities include finding new targeted therapies that can improve survival rates while reducing harmful side effects^[3]. Scientists are also working to identify biomarkers—measurable indicators in the blood or tissue that can help doctors better diagnose ARMS, determine its risk level, and predict how well it will respond to treatment^[3].

Researchers are developing more effective treatments specifically for high-risk cases or when the cancer comes back after initial treatment^[3]. New treatments being explored include molecular targeted drugs and immunotherapies—treatments that help the body’s own immune system fight cancer^[9].

Understanding the PAX3-FOXO1 and PAX7-FOXO1 fusion genes has opened new avenues for research. Scientists now know that the PAX3-FOXO1 fusion protein drives cancer-promoting genes through the creation of special genetic elements called super enhancers^[4]. This knowledge is helping researchers develop drugs that specifically target these abnormal proteins and the genetic programs they control.

Clinical trials continue to test modifications to standard chemotherapy protocols to find combinations that work better with fewer side effects^[9]. These studies are essential for improving outcomes and quality of life for children facing this challenging disease.