Soft Tissue Sarcoma Subtypes
Soft-tissue sarcomas are more common than bone sarcomas. The 50 different types of soft-tissue sarcomas differ in terms of their tissue of origin, clinical behavior, age of occurrence, aggressiveness, the way they spread, genetic alterations, and their sensitivity to certain therapies. This group of sarcomas comprises less than 1% of all cancers diagnosed nationwide and affects approximately 12,000 people each year.
Endorsed and supported in part by SARC and the NCCN Foundation, the National Comprehensive Cancer Network® recently published NCCN Guidelines for Patients® Soft Tissue Sarcoma.
Below are some specific types of sarcomas:
Alveolar Soft-Part Sarcoma
This extremely rare sarcoma typically arises in the thigh or buttock of patients in their 20s. Men are much more commonly affected than women. While it does not appear particularly aggressive under the microscope, it travels very early to other sites of the body, including lung, chest cavity, liver, and bone, and occasionally to the brain. This form of sarcoma is relatively resistant to standard chemotherapy. Despite its early spread, people with this diagnosis can live for 10-20 years or more after diagnosis, in some cases.
Angiosarcomas and Other Sarcomas of Blood Vessels
This uncommon group of sarcomas appear to arise from the lining of blood vessels (endothelial cells) or their precursors. They include less aggressive (epithelioid hemangioendothelioma or EHE) and more aggressive forms (angiosarcoma)s. Some blood-vessel sarcomas can affect the lymphatic system (which carries fluid from soft tissue to lymph nodes). The vessels of the lymphatic system are lined with cells very similar to those found in blood vessels and give rise to what is termed lymphangiosarcoma. Kaposi sarcoma is a form of blood-vessel sarcoma that is caused by a virus, HHV-8 (also called KSHV), in patients with HIV disease, as well as a group of typically older persons who have intact immune systems. These tumors have a high risk of recurring where they start and can also travel to liver, bone, lung, and other sites.
Even rarer tumors can arise from the sensory organs that regulate blood flow to different parts of the body. These are termed glomus tumors and can be painful. Surgery is usually the best way to treat this rare form of sarcoma. Another group of tumors once thought to arise from cells around blood vessels, hemangiopericytoma, is now termed solitary fibrous tumor/hemangiopericytoma, since the tumors all appear to be very similar in terms of their biology.
An unusual and relatively less aggressive form of sarcoma that shows features of both fibroblasts and cells that retain fat (xanthomas). The primary treatment is surgical. Radiation is occasionally used to try and prevent tumor recurrence, and chemotherapy is largely ineffective for this diagnosis. These tumors metastasize (spread) very, very rarely.
Bone and Cartilage Sarcomas of Soft Tissue
Some sarcomas that arise in soft tissue mimic those that typically arise in cartilage or bone. Many of these sarcomas have some (but not all) features in common with their bone-tumor equivalents, and each has unique characteristics that must be considered in their treatment.
Clear Cell Sarcoma
This unusual hybrid tumor (formerly called melanoma of soft parts) appears to be biologically related to alveolar soft-part sarcoma. It is one of the rare tumors with features of both sarcoma and melanoma, including the ability to travel to lymph nodes (typical of melanoma) and to lung (more common for sarcomas). Surgery and radiation of the primary tumor site provide the best chance for cure.
Another form of tumor with kinship to fibroblasts, the boring cells that hold many parts of our body together. This tumor typically arises in the skin and must be excised by an appropriate expert, as less extensive resections often end in failure. These tumors only rarely (less than 2%) travel to the lungs, even many years after removal of the initial tumor. The mild chemotherapy drug imatinib shows some usefulness for this diagnosis, and SARC members consider it a standard of care for treatment of recurrences.
Desmoplastic Small Round-Cell Tumor (DSRCT)
A sarcoma distantly related to Ewing sarcoma that starts and travels in the abdominal cavity long before it is recognized clinically in the majority of patients. It typically arises in young men between 15 and 35. The tumor can travel not only elsewhere in the abdominal or pelvic cavity where it starts, but it can also spread to liver, lung, or the space between the lungs (mediastinum). Though cure is infrequent because of the early spread of this form of sarcoma, patients who do the best are those who respond well to chemotherapy and have all visible signs of their tumor removed.
Another form of sarcoma that typically affects the extremities (arms and legs) and tends to travel early to other sites of the body, affecting younger people more commonly than older people. Similar to patients with alveolar soft-part sarcoma, patients can live for a long time with this metastatic disease. Unlike other sarcomas, epithelioid sarcoma can travel to lymph nodes and cause side effects in lymph nodes and other body components.
Ewing Sarcoma/Primitive Neuroectodermal Tumor (PNET)
This type of sarcoma typically occurs in children or young adults, although cases in people up to age 80 or more are occasionally seen. There are fewer than 500 cases a year in the United States. Without chemotherapy, the cure rate is at best 10%, but with chemotherapy a cure rate of up to 75% in children and 50-60% in adults is achieved. Surgery and radiation are also commonly used as treatment for the primary tumor, to try to achieve the highest possible cure rate. Ewing sarcomas more commonly affect bone in children and soft tissue in adults, and can be seen in any site of the body. They commonly recur in the lungs and bones.
(Extraskeletal) Myxoid Chondrosarcoma
An unusual form of chondrosarcoma that shows a wide variety of features under the microscope and typically arises in people from 20 to 40 years of age. It grows relatively slowly but has a high risk of recurrence elsewhere in the body, such as the lung. It is largely insensitive to standard chemotherapy drugs.
This sarcoma (also called extraskeletal osteogenic sarcoma) arises in soft tissue but looks just like its counterpart in bone. Like conventional osteogenic sarcomas, it typically arises in older adults, not in children. It does not respond very well to the chemotherapy drugs used in osteogenic sarcoma of bone and is more commonly treated like other soft-tissue sarcomas.
Extrarenal Rhabdoid Tumor
A very aggressive form of sarcoma that nearly always arises in childhood. It affects the kidneys and other structures in the abdomen and has a high risk of early spread to liver, lung, and other sites.
Fibrosarcoma arises from fibroblasts or their precursors and forms a group of tumors that are difficult to diagnose correctly, given their relative scarcity. In decades past, fibrosarcoma was a common name given to sarcomas, but now a true fibrosarcoma is only infrequently diagnosed. These tumors most frequently affect the extremity and trunk, and can metastasize to the lungs, like other sarcomas. There is an “inflammatory” version of this tumor, which appears to have white blood cells coursing throughout the tumor, for unclear reasons. Inflammatory myofibroblastic tumor is a similar tumor to inflammatory forms of fibrosarcoma, in which the tumor cells have both features of connective tissue cells (fibroblasts) and muscle.
Gastrointestinal Stromal Tumor (GIST)
GIST is one of the most common types of sarcoma. It appears to arise from the interstitial cells of Cajal (or its precursors), which are the pacemaker cells of the intestines. In other words, they are responsible for the “peristaltic wave” that pushes food through the intestines. There may be as many as 4,000 new GIST patients per year in the United States. Approximately two-thirds arise in the wall of the stomach, 20% in the small intestine, and the remainder from other places within the abdomen. The common places that GIST recur are in the abdominal cavity or in the liver. GIST tumor cells nearly always show evidence of the KIT molecule or PDGFRA molecule being activated. This is the means by which the three FDA-approved drugs for metastatic GIST, imatinib (Gleevec®), sunitinib (Sutent®), and regorafenib (Stivarga®) appear to function.
Giant Cell Tumors (GCT) of Tendon Sheath
These very rare connective-tissue tumors (some formerly called pigmented villonodular synovitis or PVNS) arise most commonly near the knee joint, but they can also affect large and small joints alike. They are initially removable with surgery, but some have a high risk of recurrence. Very rarely, GCT of tendon sheath can become more aggressive and travel to other organs, such as the lung.
This is a tumor of smooth muscle (or its precursors), and can arise anywhere in the body. This is one of the most common types of sarcoma, and about 3,000 people a year in the United States are affected. Common initial sites for this tumor are the uterus, small intestine or stomach, or the wall of a blood vessel in the abdomen, extremity, or skin. These sarcomas have a highly variable behavior, but when they metastasize they characteristically travel to the lungs and less commonly to the liver, bone, and soft tissues.
A sarcoma that arises from fat cells or their precursors. It is also a fairly common sarcoma, with approximately 2,500 cases per year in the United States. There are three families of liposarcoma: well-differentiated and/or dedifferentiated (~50%), myxoid and/or round cell (~ 40%), and pleomorphic (10%). Each has its own specific biology and risk of recurrence or spread.
Myxoid and/or Round-Cell Liposarcoma
The second-most-common family of liposarcomas. Both forms carry the same translocations (abnormal joining) between two chromosomes, numbers 12 and 16. These tumors typically arise in the leg, with an unusually high risk of recurring in other soft tissue sites or in bones such as the spine and pelvis. Myxoid and/or round-cell liposarcoma appears to be sensitive to eceteinascidin, (Yondelis®), a drug approved in Europe but not in the United States. This type of sarcoma is considered relatively chemotherapy-sensitive.
This is the least common form of liposarcoma, and it also tends to affect an extremity. It is often more aggressive than other liposarcomas and can spread to other sites of the body such as lung and soft tissue. It has much in common with undifferentiated pleomorphic sarcomas (UPS).
Well-Differentiated and/or Dedifferentiated Liposarcoma
This sarcoma typically arises in the abdominal cavity or in an extremity. It appears as a large painless mass. Primary therapy is surgical, although the recurrence risk in the abdomen is very high, at least 70-80% over 10 years. The less aggressive form of this tumor is termed “well-differentiated”. The more aggressive version of this sarcoma is called “dedifferentiated”, but is often less aggressive than other so-called “high-grade” sarcomas.
Malignant Peripheral Nerve Sheath Tumors (MPNST)
Sarcomas that arise from the insulating cells that surround nerve endings. They can arise in people who have a familial disposition to forming benign versions of these tumors called neurofibromas or schwannomas. This condition is called neurofibromatosis type I and carries with it the risk of developing MPNSTs and other tumors, such as relatively less aggressive tumors that affect the brain or nerve sheaths of nerve endings as they leave the brain, but within the skull (acoustic neuromas). Both MPNSTs arise in patients with neurofibromatosis type I and spontaneous mutations in a gene called neurofibromin (NF1), thus linking these tumors together through a common pathway of activation of the tumor cell. A cousin of this tumor, which appears to arise purely from the neuronal insulating cell, called a Schwann cell, is the malignant granular-cell tumor, which mimics the behavior of an MPNST.
Another unusual version of chondrosarcoma more common in the soft tissues rather than in the cartilage. Primary therapy is typically surgery and radiation, and some doctors advocate the use of chemotherapy in primary treatment of this tumor, given its distant kinship with Ewing sarcoma. When such tumors are treated successfully with chemotherapy, they often leave behind a less aggressive version of the tumor, which should be surgically removed to obtain the best overall outcome for patients with this very rare diagnosis.
This is not a sarcoma itself, but is a soft tissue tumor, and is sometimes treated by sarcoma specialists. It is mentioned here for completeness. It is a tumor of remnants of cells related to the adrenal gland (specifically the adrenal medulla) and specific types of nerve bodies found throughout the body. Treatment is primarily surgical, with chemotherapy and radiation typically held in reserve for any form of later metastatic disease.
This rare sarcoma typically affects children. At most, 20% of rhabdomyosarcomas occur in adults. There are only approximately 350 cases a year in the United States. Rhabdmyosarcomas are themselves a separate family of sarcomas, with several recognized subtypes, including Embryonal, Botryoid, Alveolar, and Pleomorphic. Treatment for these sarcomas nearly always involves surgery, radiation, and chemotherapy. Cure rates are better for children than for adults, for unclear reasons. This is one form of sarcoma that can travel to lymph nodes, though it can also travel to lungs and other sites.
Solitary Fibrous Tumor
This sarcoma, which used to be called hemangiopericytoma by some pathologists, is an uncommon tumor that is found in the chest cavity, the orbits (which contain the eye), the covering of the brain (dura mater) or the pelvis. There are less aggressive and more aggressive versions of this tumor, which can easily grow to a size of 6-10 inches or more in size before they compress other organs. The more aggressive form of this tumor is termed malignant solitary fibrous tumor and is associated with metastatic disease to the lungs or bone, among other sites.
Synovial Sarcoma is usually seen in patients between the ages of 15 and 35, and often affects the leg, foot, and hand, although other unusual sites such as the chest cavity are seen. It is often a chemotherapy-sensitive form of sarcoma. It contains an abnormal joining of two chromosomes in each cell, between chromosomes X and 18. There are two principal forms of synovial sarcoma, monophasic and biphasic. Biphasic tumors have what appear to be glands on microscopic examination and can look like more typical cancers (carcinomas) rather than sarcomas on this basis. Therapy for a primary leg tumor often involves surgery, radiation, and sometimes chemotherapy. The lungs are the most common site of recurrence for synovial sarcomas. This is the subtype of sarcoma about which there is the most interest in using immunotherapy for treatment.
Undifferentiated Pleomorphic Sarcoma (UPS)
UPS used to be called MFH (malignant fibrous histiocytoma) by pathologists. There are approximately 2,500 cases a year of this type of sarcoma in the United States. It tends to affect people over 50 years of age in the leg, trunk, or arm. UPS does not have particular distinguishing characteristics, besides appearing as a relatively aggressive tumor by microscopic examination, with a modest degree of architecture. The cell of origin of such a tumor is unclear. Sarcomas that express no evidence of architecture and look like sheets of aggressive-looking sarcoma cells, are often termed “high-grade sarcoma, not otherwise specified (NOS)”. The most common place for MFH to recur is in the lungs.