Your pathology report for alveolar rhabdomyosarcoma

By Jason Wasserman MD PhD FRCPC and Bibianna Purgina MD FRCPC
December 8, 2025

Alveolar rhabdomyosarcoma is an aggressive type of cancer that develops from immature skeletal muscle cells. Although muscle is found throughout the body, this tumor can arise in places with little or no actual muscle. Alveolar rhabdomyosarcoma is most commonly found in the arms or legs, but it may also occur in the head and neck, spine, pelvis, or perineum.

This tumor grows quickly and has a higher risk of spreading to lymph nodes, lungs, bones, and other organs compared with other types of rhabdomyosarcoma. Most tumors contain a specific genetic change involving the FOXO1 gene, which plays an important role in diagnosis, prognosis, and treatment planning.

What causes alveolar rhabdomyosarcoma?

Most cases are caused by a genetic change called a fusion, where two genes break apart and rejoin in the wrong way. In alveolar rhabdomyosarcoma, the FOXO1 gene fuses with PAX3 or PAX7, creating a new fusion gene called PAX3–FOXO1 or PAX7–FOXO1.

This fusion gene produces an abnormal protein that “switches on” growth signals and prevents normal cell death, allowing tumor cells to multiply rapidly.

Doctors do not yet know why these fusion events occur. They are not inherited, meaning they are not passed down through families.

What are the symptoms?

The symptoms of alveolar rhabdomyosarcoma depend on the size and location of the tumor. People usually notice symptoms only when the tumor becomes large enough to push on surrounding tissues or organs.

Symptoms based on location include:

  • Arms or legs: A growing mass, swelling, pain, or difficulty moving the limb.

  • Head and neck: Headaches, facial pain, nasal obstruction, nosebleeds, loss of smell, ear fullness, or vision problems.

  • Near the spine: Numbness, weakness, or pain in the legs, or difficulty walking.

  • Perineum/pelvis: Problems with urination or bowel movements, pelvic pain, or constipation.

Because the tumor can grow quickly, symptoms may worsen over weeks to months.

How is this diagnosis made?

Imaging

The process often begins with imaging, such as an MRI, CT scan, or ultrasound. These tests help doctors:

  • Identify the tumor’s size and location.

  • Determine whether it involves muscles, nerves, or bones.

  • Look for signs of spread, especially to lymph nodes or lungs.

MRI is beneficial because it provides soft-tissue detail and helps guide biopsy and surgical planning.

Biopsy

The diagnosis is confirmed after a biopsy, where a small sample of the tumor is removed. A pathologist examines this tissue under the microscope to determine that the tumor is a rhabdomyosarcoma and to identify the specific subtype.

After a biopsy, treatment often begins with chemotherapy and sometimes radiation therapy. Surgery to remove the tumor may follow, and the entire tumor is then sent to pathology for detailed examination.

Microscopic features

Under the microscope, alveolar rhabdomyosarcoma consists of small, round, blue cells, a term pathologists use to describe primitive-appearing cells with dark blue nuclei.

Common microscopic features include:

  • Nests of tumor cells separated by thin fibrous bands.

  • Tumor cells in the center of nests appear loosely attached or separate from one another. This resembles the small spaces (“alveoli”) in the lung, which is why the pattern is called alveolar.

  • Frequent mitotic figures, which are tumor cells seen dividing, are a sign of rapid growth.

  • Cells are described as discohesive, meaning they do not stick together well.

These features help distinguish alveolar rhabdomyosarcoma from other small round blue cell tumors.

Immunohistochemistry (IHC)

Immunohistochemistry is a test that uses antibodies linked to colored dyes to detect specific proteins in tumor cells. These proteins help identify the tumor’s cell of origin.

Alveolar rhabdomyosarcoma typically shows strong positivity for muscle markers:

  • Desmin.

  • Myogenin.

  • MyoD1.

These results support the conclusion that the tumor arises from skeletal muscle–type cells.

Molecular tests (FISH and NGS)

Alveolar rhabdomyosarcoma almost always contains a translocation involving FOXO1. A translocation is a type of genetic change where two chromosomes break and rejoin in the wrong places, creating a new fusion gene. This new fusion gene produces an abnormal protein that drives tumor growth.

Pathologists test for these genetic changes using:

  • FISH (fluorescence in situ hybridization), which uses fluorescent probes to detect breaks or fusions involving FOXO1, PAX3, or PAX7.

  • Next-generation sequencing (NGS), which reads the tumor to identify the exact fusion gene present.

Your pathology report will state which test was performed and whether a PAX3–FOXO1 or PAX7–FOXO1 fusion was detected.

Grade

Pathologists do not assign an FNCLCC grade to alveolar rhabdomyosarcoma. This is because the tumor is already considered high-grade due to its rapid growth rate and tendency to spread.

Tumor size

Tumor size is important because tumors smaller than 5 cm are less likely to spread and are associated with a better prognosis. Tumor size also affects the pathologic tumor stage (pT).

Tumor extension

Alveolar rhabdomyosarcoma often starts in a muscle but can grow into surrounding organs, bones, nerves, or soft tissues. The pathologist carefully examines the tissue around the tumor to see whether it has invaded nearby structures.

Extension into other tissues increases the pT stage and may require additional treatment.

Perineural invasion

Perineural invasion (PNI) means tumor cells grow along or around a nerve. This is important because tumor cells can travel along nerves into deeper tissues, increasing the likelihood of recurrence.

Lymphovascular invasion

Lymphovascular invasion (LVI) means tumor cells are found in a blood vessel or lymphatic channel. This increases the risk that cancer cells have spread to lymph nodes, lungs, or other organs. Alveolar rhabdomyosarcoma frequently spreads through these pathways.

Margins

A margin is the edge of the tissue removed during surgery. Margins are only assessed after surgery that removes the entire tumor (such as an excision or resection). They are not evaluated after a biopsy, because a biopsy removes only a small sample rather than the whole tumor.

Pathologists examine all margins to determine whether any cancer cells extend to the cut edges.

  • A negative margin means no tumor cells are seen at the edge, suggesting the tumor was removed entirely.

  • A positive margin means tumor cells reach the cut surface, raising the possibility that cancer remains in the body.

The report may also describe how close the tumor comes to the margin. Margin status helps your surgeon decide whether additional surgery or radiation therapy is needed.

Margin

Treatment effect

If chemotherapy and/or radiation therapy were given before surgery, the pathologist will evaluate how much of the tumor is still alive. A tumor that is dead appears as necrosis.

A good response to therapy means 90% or more of the tumor is dead, and 10% or less is still viable. A strong treatment response is associated with a better outcome.

Lymph nodes

Lymph nodes are small, bean-shaped immune structures found throughout the body. They filter lymph fluid and help the immune system recognize infections and abnormal cells. Many cancers, including alveolar rhabdomyosarcoma, can spread to lymph nodes through tiny lymphatic channels.

If lymph nodes are removed during surgery, a pathologist examines them under the microscope to look for tumor cells. The report will describe whether cancer was found, how many lymph nodes were involved, and whether tumor cells have spread outside the lymph node capsule (extranodal extension). This information helps determine the nodal stage (pN) and guides treatment planning.

Pathologic stage (pTNM)

Staging describes how advanced the cancer is, based on tumor size, local growth, lymph node involvement, and distant spread. Staging is necessary because it helps predict prognosis and guides decisions about treatment intensity.

The pathologic stage is based on the TNM system, which evaluates:

  • T (tumor): size of the tumor and how far it has grown into nearby tissues.

  • N (nodes): whether cancer has spread to lymph nodes.

  • M (metastasis): whether cancer has spread to distant organs.

Your pathologist assigns a number to each part. In general, higher numbers mean more advanced disease.

Adults (standard TNM system)

The T stage depends on where the tumor began and its size.

Trunk and extremities

  • T1 – 5 cm or smaller

  • T2 – 5–10 cm

  • T3 – 10–15 cm

  • T4 – larger than 15 cm

Thoracic visceral organs

  • T1 – tumor limited to one organ

  • T2 – tumor has grown into the connective tissue around that organ

  • T3 – tumor has grown into at least one other organ

  • T4 – multiple tumors present

Retroperitoneum

  • T1 – 5 cm or smaller

  • T2 – 5–10 cm

  • T3 – 10–15 cm

  • T4 – larger than 15 cm

Nodal stage (pN)

  • N0 – no tumor in any lymph nodes

  • N1 – tumor found in at least one lymph node

Children (IRSG system)

Children are staged using a modified system (Intergroup Rhabdomyosarcoma Study Group) that considers tumor location, extent of resection at surgery, and whether lymph nodes or distant sites are involved. This staging helps determine treatment intensity and long-term prognosis.

What happens after the diagnosis?

After the diagnosis is confirmed, treatment usually begins with multi-agent chemotherapy, which is essential for all patients with alveolar rhabdomyosarcoma. Radiation therapy is often added to control the tumor locally, especially if complete surgical removal is not possible. Surgery may be performed before or after chemotherapy, depending on the tumor’s location. Because this cancer can spread, follow-up imaging of the lungs, lymph nodes, bones, and other organs is required at regular intervals. The treatment plan is tailored to your age, tumor stage, and molecular findings, including whether the tumor contains the PAX3–FOXO1 or PAX7–FOXO1 fusion.

Questions to ask your doctor

  • What fusion gene was found in my tumor, and what does it mean for my treatment?

  • Has the tumor spread to lymph nodes or other organs?

  • What treatments do I need first—chemotherapy, radiation, or surgery?

  • Was the tumor completely removed, and were the margins negative?

  • How often will I need imaging after treatment?

  • What symptoms should I watch for that might indicate recurrence or progression?

  • Are there clinical trials that might be appropriate for me?

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