Myxofibrosarcoma is a cancer that develops from fibroblasts, the cells that make the connective tissue that supports and holds the body together. It is a type of sarcoma, a cancer that begins in the body’s connective tissues. Myxofibrosarcoma makes up about 5% of all soft tissue sarcomas and is one of the most common sarcomas in older adults.
The name describes how the tumor looks under the microscope. “Myxo” refers to the soft, gel-like myxoid tissue that fills much of the tumor. “Fibro” refers to the fibroblasts that make up the tumor cells. Older reports may call this tumor the myxoid type of malignant fibrous histiocytoma, a name that is no longer used.
Myxofibrosarcoma most often affects adults over 50, and it is slightly more common in men. It usually starts in the arms or legs, especially the legs. Many tumors start just under the skin, while others start deeper in the muscle.
This article explains how myxofibrosarcoma is diagnosed and what the grade, margins, and stage in your myxofibrosarcoma pathology report mean.
Myxofibrosarcoma develops when fibroblasts collect many changes in their genes and chromosomes that allow them to grow without control. Unlike some sarcomas, myxofibrosarcoma does not have a single defining genetic change such as a gene fusion. Instead, tumor cells usually have many different changes, and these vary from person to person.
No lifestyle or environmental causes of myxofibrosarcoma are known. It is not inherited.
The most common symptom of myxofibrosarcoma is a painless lump that grows slowly. People often notice tumors just under the skin while they are still small. Deeper tumors may not be noticed until they are larger, and they can cause pain if they press on nearby nerves or muscles.
The diagnosis of myxofibrosarcoma is made after a pathologist examines a sample of the tumor under the microscope. The sample is usually obtained by a core needle biopsy, which removes small pieces of the tumor with a needle. Sometimes the diagnosis is made only after the whole tumor has been removed.
Under the microscope, myxofibrosarcoma is made of abnormal spindle-shaped cells scattered through myxoid tissue. The tumor often grows as several nodules and contains thin, curved blood vessels. In higher-grade tumors, the cells are larger, more crowded, and vary greatly in shape and size. Some cells contain small bubbles of myxoid material and are called pseudolipoblasts.
Myxofibrosarcoma tends to spread out into the surrounding tissue in thin strands, like the roots of a plant. These strands can extend well beyond the edge of the lump seen on imaging or felt at surgery. On MRI, this growth may show up as a “tail” of tissue extending along the thin layers that cover the muscles.
Because myxofibrosarcoma does not have a specific genetic change, the diagnosis is based mainly on how the tumor looks. The pathologist may use immunohistochemistry or molecular tests to rule out other tumors that look similar. Once myxofibrosarcoma is confirmed, doctors usually do a chest CT scan because the lungs are the most common site of spread.
Immunohistochemistry is a test that uses antibodies to show which proteins tumor cells make. For myxofibrosarcoma, no single stain confirms the diagnosis. Instead, the test shows that the tumor is not another type of cancer. Your report may include some of the following:
Not every case of myxofibrosarcoma needs every stain. The pathologist chooses tests based on how the tumor looks, where it started, and which other tumors need to be ruled out.
Histologic grade describes how abnormal the cells of a myxofibrosarcoma look and how quickly they appear to be growing. Grade is one of the most important findings in the report for myxofibrosarcoma, because it strongly predicts whether the tumor will spread. Most pathologists use the FNCLCC system, which adds together scores for three features:
The total score gives the final grade:
Grading myxofibrosarcoma can be difficult, and some pathologists also consider how crowded the cells are and how much of the tumor is solid rather than myxoid. Low-grade myxofibrosarcoma often comes back after surgery, but it rarely spreads to other organs. High-grade tumors are more likely to spread. A tumor that comes back can also be higher grade than the original tumor.
Some myxofibrosarcomas contain round, epithelial-like tumor cells. This type is called epithelioid myxofibrosarcoma, and it behaves like a high-grade tumor.
Tumor size is the greatest dimension of the myxofibrosarcoma, measured in centimeters (cm). The final measurement comes from the tumor removed at surgery rather than from a biopsy. For most body sites, size is used to determine the tumor stage (pT).
Myxofibrosarcomas larger than 5 cm are associated with a less favorable outcome than smaller tumors. Because the tumor spreads out in thin strands, the true extent of the tumor can be larger than the measured size of the main lump.
Tumor depth describes whether the myxofibrosarcoma is located in the tissue just under the skin or deep to the thin layer of tissue covering the muscles, called the fascia. Pathology reports for myxofibrosarcoma often describe depth, because superficial and deep tumors can behave differently. Deep tumors have been associated with a higher risk of spread to other organs.
Tumor extension describes whether the myxofibrosarcoma has grown into nearby structures such as the skin, muscle, bone, or blood vessels. For tumors in the head and neck, the orbit (the space around the eye), and internal organs, growth into nearby structures raises the tumor stage. For tumors of the trunk, arms, legs, and retroperitoneum, the stage depends on size alone.
Some people with myxofibrosarcoma receive radiation therapy, and less often chemotherapy, before surgery. This is called neoadjuvant or pre-operative treatment. When this happens, the pathologist estimates what percentage of the removed tumor is non-viable (dead) and what percentage is still viable (alive).
A tumor that is 90% or more non-viable is often considered a strong response to pre-operative treatment. For soft tissue sarcomas, including myxofibrosarcoma, experts have not agreed on a single cut-off that predicts outcome. Your doctors interpret the percentage together with the other findings in your report.
Treatment changes how tumor cells look under the microscope. For this reason, the grade is usually taken from the biopsy done before treatment. If no treatment was given before surgery, the report may say there was no known presurgical therapy.
Lymphovascular invasion means that cells from the myxofibrosarcoma are seen inside a small blood vessel or lymphatic channel. These vessels give cancer cells a route to other parts of the body. Current reports may list this finding as “lymphatic and/or vascular invasion.”
Perineural invasion means tumor cells are growing around or along a nerve. It is not a standard item in soft tissue sarcoma reports, but a pathologist may mention it when it is seen in myxofibrosarcoma. When present, it suggests the tumor may extend beyond its visible edge and may raise the risk of the tumor coming back in the same place.
A margin is the edge of tissue cut by the surgeon to remove a myxofibrosarcoma. The pathologist examines each margin to see whether tumor cells reach it. Margins are especially important for myxofibrosarcoma because its thin strands of tumor cells make it harder to remove completely than most other sarcomas.
A positive margin is one of the strongest predictors that myxofibrosarcoma will come back in the same place. During surgery, the pathologist may examine some margins right away using a rapid test called a frozen section. This helps the surgeon decide whether to remove more tissue.
Lymph nodes are small immune organs that filter fluid from the tissues. Myxofibrosarcoma very rarely spreads to lymph nodes. For this reason, lymph nodes are usually removed only if they look enlarged or suspicious on imaging.
If lymph nodes are examined, the report states how many were examined and how many contain tumor cells. Tumor cells in a lymph node change the nodal stage to pN1.
The pathologic stage for myxofibrosarcoma is assigned using the TNM system from the American Joint Committee on Cancer (AJCC), 8th edition. The tumor stage (pT) is based on the tissue removed at surgery, and the nodal stage (pN) describes the lymph nodes. The metastasis stage (M) is usually determined by imaging and is often not included in the pathology report.
If you received treatment before surgery, the stage may begin with the letter “y,” as in ypT2. A stage beginning with “r” describes a tumor that has come back after treatment.
The tumor stage (pT) for myxofibrosarcoma depends on where the tumor started in the body.
Trunk and extremities (chest, back, abdominal wall, arms, and legs):
Retroperitoneum (the space at the back of the abdomen):
Head and neck:
Abdominal and thoracic visceral organs (internal organs such as the stomach, intestines, and lungs):
Orbit (the space around the eye):
A stage of pT0 means no tumor was found in the tissue removed, which can happen after treatment before surgery. If the tumor cannot be assessed, for example because it was removed in many pieces, the report may say that pT was not assigned.
The nodal stage (pN) for myxofibrosarcoma describes whether tumor cells were found in the lymph nodes:
If no lymph nodes were removed, which is common for myxofibrosarcoma, the report will usually say that pN was not assigned. Older reports may show pNX, but current reporting standards no longer use this term for soft tissue sarcomas.
The outlook for a person with myxofibrosarcoma depends mainly on the grade of the tumor, its size, and whether it can be completely removed. In the largest study to date, which included 908 people, about 68% were alive five years after diagnosis. This figure includes deaths from all causes, and many people with myxofibrosarcoma are older adults.
Myxofibrosarcoma comes back in the same place more often than most other sarcomas. Reported rates of local recurrence range from about 16% to 61%, compared with around 10% for soft tissue sarcomas overall. In one detailed group from the large study, 39% of people had the tumor come back in the same place and 28% developed spread to other organs.
Features associated with the outcome of myxofibrosarcoma include:
After myxofibrosarcoma is confirmed, a team at a center experienced in treating sarcoma usually plans care. In one study, complete removal with negative margins was achieved much more often when surgery was done at a sarcoma center. The findings in your report, especially the grade, size, and margin status, help the team decide which options to consider.
No biomarker test is currently used to choose a targeted treatment for myxofibrosarcoma. Because the tumor can come back in the same place, follow-up usually includes regular examination and imaging of the area where it started. Chest imaging is also usually part of follow-up.