About Sarcoma

Sarcomas occur when the DNA in a patient’s cells develops mutations that disrupt the cellular instructions that would determine the growth rate and subsequent death in normal cells. Cancer cells grow at a much higher rate than normal cells, producing an aggressive primary tumor mass that invades and destroys adjacent normal tissues and cells, resulting in cellular and tissue death, or necrosis. 

The primary tumor represents the starting point for a malignant tumor. As the primary tumor grows larger, it sends out aggressive metastatic cancer cells through the vascular system to the heart, lungs, skeleton, and organs. These metastatic cells find a home in their new location, enlarging and causing pain and dysfunction as the metastasis invades its new location.  

All cancers result primarily from genetic disruptions associated with isolated or multiple DNA mutations, including: 

• Bacterial or viral infections (e.g., Kaposi’s sarcoma) or autoimmune deficiencies
• Dietary and lifestyle causes such as excess intake of sugar, fat, and alcohol; obesity; and lack of daily exercise
• Environmental carcinogens, including smoking (causes lung and other cancers), excessive exposure to the sun (causes melanoma), exposure to asbestos (causes lung cancer), and exposure to chemicals such as arsenic, DDT, and pesticides
  
• Cancer-causing familial genetic mutations that can be passed along from parents to their children
  • Some of the conditions that put families at risk for sarcomas include Li-Fraumeni syndrome (soft tissue sarcoma/osteosarcoma), neurofibromatosis type 1 (peripheral nerve tumors that become sarcomas), multiple hereditary exostoses (benign tumors that slowly evolve into chondrosarcoma) and retinoblastoma of the eye (associated with osteosarcoma)
    
• The normal process of aging significantly increases our risk of developing most cancers, especially over the age of 60

Within the two categories of soft tissue sarcoma and bone sarcoma there are many subtypes. For example, there are more than 80 different soft tissue sarcoma subtypes including rare and ultra-rare sarcomas.

Not all sarcomas subtypes are aggressive, high-grade malignancies with a significant risk for developing metastases. Many (30-40%) malignant sarcomas of bone or soft tissue are low-grade or intermediate-grade malignancies that may carry only a small risk for metastatic disease. 

In addition, there are many more benign tumors of bone and soft tissue in children and adults than there are malignant tumors.

Timely and correct subtype diagnosis is critical and is the key to determining the best systemic therapies and treatment protocols.

Sarcomas represent one of the most common rare cancers. 

• There are approximately 15,000 new adult soft tissue sarcomas and 4,000 new bone sarcomas diagnosed in the U.S. per year, representing only 1% of all U.S. adult cancers. 
• There are approximately 750 pediatric bone sarcomas and 1,000 pediatric soft tissue sarcomas diagnosed in the U.S. per year, that represent 15% of all pediatric malignancies.
• Young adults (18-25 years) with sarcomas of bone or soft tissue represent approximately 15% of new U.S. sarcoma diagnoses in young adults; this includes many high-grade soft tissue and bone sarcomas that require a timely diagnosis.

Rare Sarcomas are defined as malignancies that occur with an incidence of greater than one per 1,000,000 per year and represent 80% of all soft tissue sarcomas.

Rare soft tissue diagnoses include:

• Gastrointestinal Stromal Tumors (GIST)
• Undifferentiated Pleomorphic Sarcoma (UPS)
• Differentiated (Low-Grade) Liposarcoma (WDLPS)
• High-Grade Dedifferentiated Liposarcoma (DDLPS)
• Leiomyosarcoma (LMS)
• Dermatofibrosarcoma Protuberans (DFSP)
• Solitary Fibrous Tumor (SFT)
• Angiosarcoma
• Myxofibrosarcoma
• PVNS and Tenosynovial Giant Cell Tumor
• Myxoid Liposarcoma (MLPS)

Ultra-Rare Sarcomas are defined as malignancies with an incidence of less than one per 1,000,000 per year, accounting for 20% of all soft tissue sarcomas and involving 50 ultra-rare soft tissue sarcoma diagnoses.

Ultra-rare soft tissue sarcomas include: 

• Adult Fibrosarcoma
• Alveolar Rhabdomyosarcoma (ARMS)
• Alveolar Soft Part Sarcoma (ASPS)
• Clear Cell Sarcoma (CCS)
• Desmoplastic Small Round Cell Tumor (DSRCT)
• Epithelioid Sarcoma (ES)
• Extraskeletal Soft Tissue Ewing Sarcoma
• Histiocytic Sarcoma
• Inflammatory Myofibroblastic Tumor (IMT)
• Intimal Sarcoma of the Pulmonary Artery
• Glomus Tumor (malignant)
• Extraskeletal Osteosarcoma
• Hemangioendothelioma
• Infantile Fibrosarcoma
• Pleomorphic Liposarcoma

Sources

Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025; 75(1): 10-45. doi:10.3322/caac.21871

Stacchiotti S, Frezza AM, Blay JY, Baldini EH, Bonvalot S, Bovée JVMG, Callegaro D, Casali PG, Chiang RC, Demetri GD, Demicco EG, Desai J, Eriksson M, Gelderblom H, George S, Gounder MM, Gronchi A, Gupta A, Haas RL, Hayes-Jardon A, Hohenberger P, Jones KB, Jones RL, Kasper B, Kawai A, Kirsch DG, Kleinerman ES, Le Cesne A, Lim J, Chirlaque López MD, Maestro R, Marcos-Gragera R, Martin Broto J, Matsuda T, Mir O, Patel SR, Raut CP, Razak ARA, Reed DR, Rutkowski P, Sanfilippo RG, Sbaraglia M, Schaefer IM, Strauss DC, Sundby Hall K, Tap WD, Thomas DM, van der Graaf WTA, van Houdt WJ, Visser O, von Mehren M, Wagner AJ, Wilky BA, Won YJ, Fletcher CDM, Dei Tos AP, Trama A. Ultra-rare sarcomas: A consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities. Cancer. 2021 Aug 15;127(16):2934-2942. doi: 10.1002/cncr.33618. Epub 2021 Apr 28. PMID: 33910263; PMCID: PMC8319065.

Shimada E, Nakagawa M, Endo M, Yokoyama N, Nabeshima A, Fujiwara T, Kawai A, Nakashima Y. Landscape of ultra-rare sarcomas: a nationwide study for epidemiology and prognosis. ESMO Open. 2025 May;10(5):105097. doi: 10.1016/j.esmoop.2025.105097. Epub 2025 May 12. PMID: 40359706; PMCID: PMC12141934.

WHO Classification of Tumors Editorial Board: Soft Tissue and Bone Tumors,” Lyon (France): International Agency for Research on Cancer; 2020 [March 15, 2021]. (WHO Classification of Tumors Series, 5th ed.; vol. 3). 

Ultra-rare sarcomas: A consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities. Cancer. 2021 Aug 15;127(16):2934-2942. doi: 10.1002/cncr.33618. Epub 2021 Apr 28. PMID: 33910263; PMCID: PMC8319065.

The typical soft tissue sarcoma is a soft tissue mass that is larger than 5 cm (2 inches) in diameter and has a soft tissue consistency or density that is firmer or more dense than normal muscle. 

Soft tissue sarcoma frequently presents as a painless soft tissue mass that may be confused with a lipoma, the most common benign soft tissue tumor. Magnetic resonance imaging (MRI) can usually distinguish between a benign lipoma and a malignant soft tissue sarcoma.

• Patients of any age with a soft tissue mass measuring 5 cm (2 inches) or more in diameter should have an MRI, computed tomography (CT) scan, or ultrasound. MRIs provide greater sensitivity and accuracy of diagnosis.
• The initial image, when reviewed by an experienced sarcoma radiologist, surgeon, or oncologist, is 80-90% accurate in diagnosing a soft tissue sarcoma.
• If the mass is suggestive of a soft tissue sarcoma on the scan, the patient should be seen by a sarcoma specialist.
• A sarcoma surgeon (orthopedic or general surgery) and/or a medical oncologist will discuss the findings with the patient and determine the possible need for a needle biopsy. While the scan may provide an accurate image of the tumor, a needle biopsy will confirm a possible sarcoma diagnosis.
• If the initial needle biopsy is not clearly diagnostic, the biopsy may need to be repeated to obtain additional tissue for evaluation.
• Patients with a confirmed high-grade sarcoma will frequently be treated with 2-3 months of systemic chemotherapy and/or immunotherapy prior to tumor excision.
• Treatment progress should be assessed with a repeat MRI, CT scan, or positron emission tomography (PET) scan within three to four months.