Soft Tissue Sarcoma Subtypes
Alveolar Soft Part Sarcoma is an extremely rare sarcoma that typically arises in the thigh or buttock of someone in their 20’s. 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 brain. This form of sarcoma is relatively resistant to standard chemotherapy. Despite the early spread of tumor, people with this diagnosis can live for 10-20 years or more after diagnosis, in some cases.
Atypical Fibroxanthoma is 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 felt largely ineffective for this diagnosis. These tumors only very, very rarely metastasize.
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 (melanoma of soft parts) is an unusual hybrid tumor that 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.
Dermatofibrosarcoma Protuberans is another form of tumor with some kinship to fibroblasts. This tumor typically arises in the skin, and must be excised by an appropriate expert, as less extensive resections often times end up failing. These tumors only rarely (5-10%) travel to lungs, even many years after removal of the initial tumor. The mild chemotherapy drug imatinib shows surprising usefulness for this diagnosis, and should be considered a standard of care per members of SARC.
Desmoplastic Small Round Cell Tumor (DSRCT) is 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 ages 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, the people who do the best are those who both have a good response to chemotherapy and can have all visible sign of their tumor removed.
Epithelioid Sarcoma is another form of sarcoma that typically affects tumor of the extremities (arms and legs) and tends to travel early to other sites of the body. Similar to people with alveolar soft part sarcoma, people can live for a long time with despite metastatic disease. Unlike other sarcomas, epithelioid sarcoma can travel to lymph nodes and cause side effects from involving multiple lymph nodes is a given area of the body.
Ewing's Sarcoma / Primitive NeuroEctodermal Tumor (PNET) is another family of sarcomas. This group of sarcomas typically occurs in children or young adults, although cases in people up to age 80 or more are occasionally seen. We estimate 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 seen. Surgery and radiation are also commonly used as treatment for the primary tumor in order to try to achieve the highest cure rate possible. Ewing sarcomas appear to 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 is an unusual form of chondrosarcoma that shows a wide variety of features under the microscope, and arises in people typically from 20-40 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.
Extraskeletal Osteosarcoma (also called extraskeletal osteogenic sarcoma) arises in soft tissue but looks just like its counterpart in bone. It typically arises in older adults, not in children like conventional osteogenic sarcomas. It does not respond very well to the chemotherapy drugs used in osteogenic sarcoma of bone, and is more commonly treated like another soft tissue sarcomas.
Fibrosarcoma arises from fibroblasts or their precursors, and form 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 affect the extremity and trunk most frequently, 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): Some people do not consider this a sarcoma, while others do. If it is considered a sarcoma, it is the most common type. 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 2/3 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 c-kit molecule or PDGFR molecule being activated. This is the means by which the imatinib (Gleevec®) and sunitinib (Sutent®) appear to function, the two FDA-approved drugs for metastatic GIST.
Giant Cell Tumors (GCT) of Tendon Sheath and Pigmented Villonodular Synovitis (PVNS) are very rare connective tissue tumors that arise nearly exclusively from cells near the knee joint. They are initially removable with surgery but have a high risk of recurrence. Occasionally, GCT of tendon sheath and PVNS can become more aggressive and travel to other organs, such as the lung.
Leiomyosarcoma: This is a tumor of smooth muscle (or its precursors), and can arise anywhere in the body. There are approximately 2,500 cases a year of this diagnosis in the United States. Common sites for this tumor to start are the uterus, small intestine or stomach, or from the wall of a blood vessel in the abdomen, extremity or in the 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.
Liposarcoma: This is a sarcoma that arises from fat cells or its precursors. It is also fairly common for a sarcoma, with approximately 2,000 cases per year in the United States. There are three families of liposarcoma: (1) well-differentiated and/or dedifferentiated (~50%); (2) myxoid and/or round cell (~40%); and (3) pleomorphic (10%). Each has its own specific biology and risk of recurrence or spread.
Malignant Extrarenal Rhabdoid Tumor is 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.
Malignant Fibrous Histiocytoma (MFH) is now termed high-grade undifferentiated pleomorphic sarcoma (HGUPS) by pathologists. There are approximately 2,000 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. MFH 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, looking to be sheets and sheets of aggressive looking sarcoma cells, are often times termed "high grade sarcoma, not otherwise specified (NOS)". The most common place for MFH to recur is in the lungs.
Malignant Peripheral Nerve Sheath Tumors (MPNST) are 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 that arise in people with neurofibromatosis type I and spontaneously have 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.
Mesenchymal Chondrosarcoma is another version of chondrosarcoma more common in the soft tissues rather than in the cartilage. Primary therapy is typically surgery and radiation, and some physicians advocate the use of chemotherapy in the primary treatment of this tumor, given its distant kinship with Ewing sarcoma. When such tumors are treated successfully with chemotherapy, often times a less aggressive version of the tumor is left behind, in need of surgical removal to attempt to obtain the best overall outcome for people with this very rare diagnosis.
Myxoid and/or Round Cell Liposarcoma is 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 the presently experimental agent ET-743 (eceteinascidin, Yondelis®). This type of sarcoma is otherwise relatively chemotherapy sensitive.
Paraganglioma is not a sarcoma itself, but is a soft tissue tumor, and is sometimes times treated by sarcoma specialists. It is mentioned here for completeness. It is a tumor of remnants of cells related to the adrenal gland (specifically 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.
Pleomorphic Liposarcoma is the least common form of liposarcoma, and also tends to affect an extremity. It is often times more aggressive than other liposarcomas, and can spread to other sites of the body such as lung and soft tissue.
Rhabdomyosarcoma is a rare sarcoma that typically affects children. Only 20% of rhabdomyosarcomas occur in adults. There are only approximately 250 cases a year in the United States. It is a heterogeneous type of sarcoma, with several recognized subtypes, including Embryonal, Botryoid, Alveolar, and Pleomorphic as its principal types. 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.
Sarcomas of Blood Vessels comprise an uncommon group of sarcomas that appear to arise from the lining of blood vessels (endothelial cells) or their precursors. There are less aggressive (epithelioid hemangioendothelioma or EHE) and more aggressive forms (angiosarcoma) members of this family of sarcomas. Some blood vessel sarcomas can affect the lymphatic system (which carry 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), both in people 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 that were 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.
Solitary Fibrous Tumor, which also encompasses the diagnosis hemangiopericytoma, is an uncommon tumor that is found in the chest cavity, orbit (which contain the eye), coverings of the brain (dura mater) or from 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 cause symptoms of compression of 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 to bone, among other sites.
Synovial Sarcoma is common between ages 15 and 35, and often affects the leg, foot and hand, although other unusual sites such as chest cavity are seen. It is often times 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 appear more like more typical cancers (carcinomas) rather than sarcomas on this basis. We do not have different therapies based on the type of synovial sarcoma, and therapy for a primary leg tumor often times involves surgery, radiation, and sometimes chemotherapy. The lungs are the most common site of recurrence for synovial sarcomas.
Well-differentiated and/or Dedifferentiated Liposarcoma arises in the abdominal cavity or in an extremity, typically. It presents 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 times less aggressive than other so-called "high-grade" sarcomas.