Soft tissue sarcomas (STS) are a group of more than 60 different neoplasms that can originate from any location throughout the human body, and they can affect individuals at the extremes of age. From skeletal muscle, adipose tissue, blood, and lymphatics to connective tissue and peripheral nerves; these neoplasms can span a range of clinical presentations from benign lipomas to aggressive metastatic angiosarcomas. ,, The real challenge in diagnosing these conditions is that there are several, non-neoplastic conditions that mimic STS. Soft tissue sarcomas are separated categorically as trunk and extremity from retroperitoneum. The majority of STS occur spontaneously. However, germline mutations, radiation and environmental exposure(s) have been causative. ,,,
While the majority of these cases occur sporadically, there have been several causative factors identified.
Neurofibromatosis Type 1 (NF1) Von Recklinghausen Disease
Familial Adenomatous Polyposis (FAP)
Soft tissue sarcomas are a rare entity as there were 12,020 new cases and 4740 deaths reported in 2014 in the United States. They account for approximately 1% of all cancer incidence in the United States and represent approximately 2% of cancer-related deaths. As mentioned earlier, they are categorically separated regarding location within the body and extremity, and trunk STS are more common than intraperitoneal and retroperitoneal cases. In regards to the extremities, they occur more frequently on the proximal limb with the thigh being the most common location in 44% of cases. The age at diagnosis and histological subtype are often linked with rhabdomyosarcoma, hemangioma, neurofibroma, and alveolar sarcoma affecting children and young adults more. 
Sarcomas are tumors of the connective tissue, and thus the tumors may occur in bone, cartilage, fat, muscle, or vascular or hematopoietic tissues. Sarcomas are much rarer compared to carcinomas. Most tend to grow locally and invade the adjacent tissues. Most patients present with complaints of a hard mass or a pain, chiefly because of pressure on nearby nerves and soft tissues.
Several different STS subtypes can affect the trunk and, or extremities. The most common presentation is a patient with a painless mass which, upon initial evaluation, requires a detailed history and physical examination. Of note, there are several conditions that may mimic a soft tissue sarcoma. Some of these conditions are hypertrophic scars, hematoma, benign lipoma, cyst, abscess, and melanoma. All of these can confuse the clinician when trying to work up an STS. Neoplasms that are small, superficial, and mobile are highly suggestive of a soft tissue sarcoma. These are separate from skeletal or neurovascular structures and may be surgically resected with grossly wide margins. Tumors which are closer to vital organs or vascular structures are typically referred to a tertiary care center where surgeons specifically trained in such resections can intervene. In such cases, preoperative biopsies are encouraged as there are several factors that may ultimately affect patient outcome.
Indications for preoperative imaging and biopsy takes into consideration the extent of the mass on physical examination as well as the anticipated neurovascular involvement. The clinician also has to consider the likelihood of nodal involvement or distant metastases as well as the relative resectability and potential postoperative functional deficits as seen with STS of the extremities.
In regards to imaging, MRI is generally considered most informative for trunk and extremity STS. Chest CT with contrast is considered in cases where the metastatic potential is high as the lungs are often involved.
If a biopsy is recommended, then the choice is a core-needle biopsy, and if this is nondiagnostic, then an incisional biopsy may need to take place. The core-needle biopsy should be approached such that the entire needle trajectory can be incorporated into the forthcoming surgical resection volume to maximize diagnostic potential. It has been determined that approximately 74% of patients who undergo an unplanned trunk or extremity sarcoma resection have residual disease at the time of the following resection.
The high risk of recurrence warrants close postoperative surveillance with a physical exam every 3 to 6 months for 2 to 3 years and after that every 6 months for the next 2 years and finally annually. Radiographic surveillance of the chest, abdomen, and pelvis and indications for follow-up MRI is based upon individual patient and tumor characteristics.
Benign adipocytic tumors that can arise from any part within the body and can cause symptoms primarily through mass effect. They are usually encapsulated, homogenous without evidence of nodularity or septations and may contain calcifications or hemorrhage as a result of trauma. Treatment consists of excision beyond the capsule of the tumor. There is some degree of clinical overlap with the potentially malignant form and most common soft tissue sarcoma, the liposarcoma. Liposarcomas are defined as those tumors which are greater than 10 cm in size, has thick internal septations and those lesions that are generally less than 75% adipose tissue. They represent 45% of retroperitoneal sarcomas. Treatment for the liposarcoma is surgical resection with wide margins. Local recurrence is common. Malignant behavior attributed to the amplification of (12q13-15), which leads to the upregulation of MDM2 and CKD4. Tumor-promoting pathways MET, RET and PI3K/Akt are thought to be activated. Liposarcomas of the extremities, the goal of care is limb-sparing resection with a gross negative margin. Retroperitoneal liposarcomas the goal is complete resection. Typically, well-differentiated liposarcomas have a low risk of distant metastases whereas de-differentiated extremity liposarcoma are generally benefit from neoadjuvant radiation therapy.
Trunk and Extremity Sarcoma
There is a fine balance between preserving limb function and tumor control. Many types are chemoresistant, and several studies have reported conflicting results regarding the utility of neoadjuvant and adjuvant chemotherapy. Several studies have supported a surgical margin of 1 cm in regards to adequate resection.
An rare form of fibroblastic tumors. Approximately 80% are sporadic, whereas others are related to familial adenomatous polyposis (FAP). Sporadic cases are related to pregnancy and prior trauma. They are 2 to 3 times more common in women than men and usually diagnosed between the ages of 30 to 40. They can originate in the extremities, intraperitoneal space, abdomen, and/or chest wall. They are usually slow growing, however can be quite aggressive. They utilize the WNT signaling pathway. Clinically, they can range from an asymptomatic firm mass to a painful mass resulting in bowel obstructions or ischemia. Radiographically they are usually homogenous and solid in appearance with a distinct or infiltrating boundary. Despite resection these tumors have a high incidence of recurrence.
Malignant tumor arising from the endothelial lining of blood vessels and can arise from essentially any region within the body. Two percent are considered soft tissue sarcomas, and 40% are radiation-induced. They usually occur in the scalp, head, neck (scalp), and viscera and generally occur during the seventh or eighth decade of life. There is usually regional lymphatic nodal involvement. Histologically they can range from well-differentiated to poorly differentiated. Again, therapy is aimed at surgical resection with negative margins. Tumors that are larger than 5 cm and with evidence of epitheliod are considered indicators of poor prognosis. These tumors are often locally advanced and beyond resection at presentation; however, there has been some noted benefit from chemoradiation. 
Retroperitoneal and Visceral Sarcomas
Retroperitoneal sarcomas represent approximately 15% of all soft tissue sarcomas with the average tumor size at presentation measuring 15 cm. Average age at presentation is 54 with an equal male to female distribution. There are a variety of clinical presentations depending on the size and location of the tumor. Many are asymptomatic and only incidentally discovered. Symptoms can range from abdominal pain, weight loss, early satiety, nausea, emesis, back or flank pain, paresthesias and weaknesses. CT is the study of choice. Gross resection is the treatment of choice with or without neoadjuvant or adjuvant chemoradiation. Most frequent subtype is the liposarcoma. Predominant intraperitoneal subtype is the Gastrointestinal stromal tumor. Despite optimal surgical resection, approximately 70% will relapse. 
Gastrointestinal Stromal Tumor (GIST)
GIST tumors are the most common visceral soft tissue sarcoma. The majority occur sporadically. They originate from the interstitial cells of Cajal within the gastrointestinal myenteric plexus and can occur any location along the GI tract. The most prevalent location is the stomach, small bowel, and rectum. They function as the pacemaker cells of the bowel. GIST tumors have a marker for CD117 (also known as KIT gene), which codes for a tyrosine kinase transmembrane receptor called c-kit. Classically a spindle cell neoplasm of smooth muscle origin. Clinically, they can range from asymptomatic to symptomatic with pain, nausea, hematemesis and gastrointestinal (GI) blood loss. Endoscopically they appear as a smooth submucosal tumor that can impinge on the visceral lumen. Radiographically, it appears well encapsulated with heterogeneous areas of enhancement secondary to patchy necrosis within the tumor. Metastases are common with common sites being the liver and peritoneal surface. Localized lesions are taken to the operating room for complete excision with negative margins with empiric lymphadenectomy. Adjuvant therapy after resection and neoadjuvant therapy for unresectable or locally advanced disease requires Imatinib (an oral tyrosine kinase inhibitor of c-kit).
Malignant smooth muscle tumor that can originate from any part of the body. It is the second most common soft tissue sarcoma subtype. They occur during the sixth and seventh decades. The retroperitoneum and uterus are the most common locations in women; whereas, in males, they originate in other locations. On gross inspection, they are heterogeneous, well-circumscribed tumors with cystic or necrotic central areas. They stain positive for desmin and smooth muscle actin. First-line therapy is surgical resection with negative margins.
Current recommendations for sarcomas are as follows:
Sarcomas are heterogeneous lesions, and the response to radiation is dependent on the type of lesion. While overall these lesions are less sensitive to radiation, refinements and advances have improved outcomes. Radiation helps improve local control and is of most benefit when surgical margins are not clear.
Not all sarcomas respond to chemotherapy. However, because of their heterogeneous nature, some may respond. The 2 chemotherapeutic drugs approved to manage sarcomas include ifosfamide and doxorubicin. Current, standard, second-line therapy is fixed dose rate gemcitabine with or without docetaxel. Recently, the targeted agents eribulin and trabectedin have also been approved for managing patients with liposarcoma and leiomyosarcoma. However, the response depends on optimal dosing and timing. While the role of adjuvant chemotherapy remains questionable, most oncologists administer it.
For localized and early-stage lesions, curative resection can be done with good long-term survival, but recurrences are common. The risk of recurrence even persists after 10 to 15 years, and patients need indefinite follow up.
The majority of recurrences occur within the first 5 years.
For those with advanced disease, a cure is not possible, and the median survival is 12 to 18 months, depending on the subtype.
The majority of sarcomas show a poor response to chemotherapy (10% to 50% response). The response also depends on histological subtype, grade, and patient.
Besides the invasion of the sarcoma into the adjacent tissues and causing neurovascular compromise, the tumor has many other complications.
All patients with sarcoma should enter a rehabilitation program after surgery. These patients often have marked functional deficits and can be confined to a bed or chair. To regain some functionality rehab is vital.
The staging of STS is based on the American Joint Committee on Cancer (AJCC) Staging System where multiple histological subtypes are considered together. Various scoring systems have been employed that essentially take into account the same key elements or different tumor characteristics such as the following:
There are limitations to the current system as the 7th edition AJCC encompasses the diverse heterogeneity of all soft tissue sarcomas, which decreases their prognostic potential and does not differentiate between categorical differences, for example, extremity and retroperitoneum. Of importance, tumor depth is not relevant to visceral or retroperitoneum STS. In regards to the extremities, superficial and deep refer to their relationship with the fascial plane. There has been shown to be a statistically significant decrease regarding disease-free survival when considering an extremity STS that is deep to the fascial layer and larger than 5 cm in size.
Management of sarcomas involves an interprofessional team of doctors and nurses. The team should discuss each patient should before making any treatment decisions. In addition to the oncologist, a surgeon, an orthopedist, neurologist, pain consultation, an internist, and a plastic surgeon should be consulted before any major surgery. When a patient is suspected of having a sarcoma, a referral to an oncologist should be the first step. Sarcomas are resistant to chemotherapy and radiation and surgery is the definitive treatment. However, they are known to occur and the prognosis for most patients is guarded. (Level V)
|||Singhi EK,Moore DC,Muslimani A, Metastatic Soft Tissue Sarcomas: A Review Of Treatment and New Pharmacotherapies. P [PubMed PMID: 30013298]|
|||Duncan MA,Lautner MA, Sarcomas of the Breast. The Surgical clinics of North America. 2018 Aug [PubMed PMID: 30005780]|
|||Skoda J,Veselska R, Cancer stem cells in sarcomas: Getting to the stemness core. Biochimica et biophysica acta. 2018 Jul 9 [PubMed PMID: 30003939]|
|||Grünewald TGP,Cidre-Aranaz F,Surdez D,Tomazou EM,de Álava E,Kovar H,Sorensen PH,Delattre O,Dirksen U, Ewing sarcoma. Nature reviews. Disease primers. 2018 Jul 5 [PubMed PMID: 29977059]|
|||Kondo T, Current status of proteomics in Ewing's sarcoma. Proteomics. Clinical applications. 2018 Jul 10 [PubMed PMID: 29992772]|
|||Tenneti P,Zahid U,Iftikhar A,Yun S,Sohail A,Warraich Z,Anwer F, Role of High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation for Children and Young Adults with Relapsed Ewing's Sarcoma: A Systematic Review. Sarcoma. 2018 [PubMed PMID: 29973774]|
|||Vangipuram R,Tyring SK, Epidemiology of Kaposi sarcoma: review and description of the nonepidemic variant. International journal of dermatology. 2018 Jun 11 [PubMed PMID: 29888407]|
|||Yarchoan R,Uldrick TS, HIV-Associated Cancers and Related Diseases. The New England journal of medicine. 2018 Mar 15 [PubMed PMID: 29539283]|
|||von Mehren M,Randall RL,Benjamin RS,Boles S,Bui MM,Ganjoo KN,George S,Gonzalez RJ,Heslin MJ,Kane JM 3rd,Keedy V,Kim E,Koon H,Mayerson J,McCarter M,McGarry SV,Meyer C,Morris ZS,O'Donnell RJ,Pappo AS,Paz IB,Petersen IA,Pfeifer JD,Riedel RF,Ruo B,Schuetze S,Tap WD,Wayne JD,Bergman MA,Scavone JL, Soft Tissue Sarcoma, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN. 2018 May [PubMed PMID: 29752328]|
|||Torres JC,Xin C, An unusual finding in a desmoid-type fibromatosis of the pancreas: a case report and review of the literature. Journal of medical case reports. 2018 May 12 [PubMed PMID: 29751773]|
|||Tambe SA,Nayak CS, Metastatic Angiosarcoma of Lower Extremity. Indian dermatology online journal. 2018 May-Jun [PubMed PMID: 29854638]|
|||Wang QM,Ning XH,Liu XH,Li HH, [Practice of Palliative Care:Experience of a Patient with Advanced Retroperitoneal Sarcoma at the End of Life]. Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae. 2018 Jun 28 [PubMed PMID: 29978800]|
|||Hirota S, Differential diagnosis of gastrointestinal stromal tumor by histopathology and immunohistochemistry. Translational gastroenterology and hepatology. 2018 [PubMed PMID: 29971258]|
|||Fucà G,de Braud F,Di Nicola M, Immunotherapy-based combinations: an update. Current opinion in oncology. 2018 Jul 9 [PubMed PMID: 29994900]|
|||Probst U,Fuhrmann I,Beyer L,Wiggermann P, Electrochemotherapy as a New Modality in Interventional Oncology: A Review. Technology in cancer research [PubMed PMID: 29986632]|
|||Adult Soft Tissue Sarcoma Treatment (PDQ®): Health Professional Version null. 2002 [PubMed PMID: 26389481]|
|||Bagaria SP,Chang YH,Gray RJ,Ashman JB,Attia S,Wasif N, Improving Long-Term Outcomes for Patients with Extra-Abdominal Soft Tissue Sarcoma Regionalization to High-Volume Centers, Improved Compliance with Guidelines or Both? Sarcoma. 2018 [PubMed PMID: 29849479]|
|||Villalobos VM,Byfield SD,Ghate SR,Adejoro O, A retrospective cohort study of treatment patterns among patients with metastatic soft tissue sarcoma in the US. Clinical sarcoma research. 2017 [PubMed PMID: 29152166]|
|||Chakravarty D,Gao J,Phillips SM,Kundra R,Zhang H,Wang J,Rudolph JE,Yaeger R,Soumerai T,Nissan MH,Chang MT,Chandarlapaty S,Traina TA,Paik PK,Ho AL,Hantash FM,Grupe A,Baxi SS,Callahan MK,Snyder A,Chi P,Danila D,Gounder M,Harding JJ,Hellmann MD,Iyer G,Janjigian Y,Kaley T,Levine DA,Lowery M,Omuro A,Postow MA,Rathkopf D,Shoushtari AN,Shukla N,Voss M,Paraiso E,Zehir A,Berger MF,Taylor BS,Saltz LB,Riely GJ,Ladanyi M,Hyman DM,Baselga J,Sabbatini P,Solit DB,Schultz N, OncoKB: A Precision Oncology Knowledge Base. JCO precision oncology. 2017 Jul [PubMed PMID: 28890946]|
|||Voss RK,Chiang YJ,Torres KE,Guadagnolo BA,Mann GN,Feig BW,Cormier JN,Roland CL, Adherence to National Comprehensive Cancer Network Guidelines is Associated with Improved Survival for Patients with Stage 2A and Stages 2B and 3 Extremity and Superficial Trunk Soft Tissue Sarcoma. Annals of surgical oncology. 2017 Oct [PubMed PMID: 28741122]|
|||George S, Evolving Treatment of Soft Tissue Sarcoma. Journal of the National Comprehensive Cancer Network : JNCCN. 2017 May [PubMed PMID: 28515258]|
|||Hoefkens F,Dehandschutter C,Somville J,Meijnders P,Van Gestel D, Soft tissue sarcoma of the extremities: pending questions on surgery and radiotherapy. Radiation oncology (London, England). 2016 Oct 12 [PubMed PMID: 27733179]|
|||von Mehren M,Randall RL,Benjamin RS,Boles S,Bui MM,Conrad EU 3rd,Ganjoo KN,George S,Gonzalez RJ,Heslin MJ,Kane JM 3rd,Koon H,Mayerson J,McCarter M,McGarry SV,Meyer C,O'Donnell RJ,Pappo AS,Paz IB,Petersen IA,Pfeifer JD,Riedel RF,Schuetze S,Schupak KD,Schwartz HS,Tap WD,Wayne JD,Bergman MA,Scavone J, Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN. 2016 Jun [PubMed PMID: 27283169]|
|||Smeland S,Bielack SS,Whelan J,Bernstein M,Hogendoorn P,Krailo MD,Gorlick R,Janeway KA,Ingleby FC,Anninga J,Antal I,Arndt C,Brown KLB,Butterfass-Bahloul T,Calaminus G,Capra M,Dhooge C,Eriksson M,Flanagan AM,Friedel G,Gebhardt MC,Gelderblom H,Goldsby R,Grier HE,Grimer R,Hawkins DS,Hecker-Nolting S,Sundby Hall K,Isakoff MS,Jovic G,Kühne T,Kager L,von Kalle T,Kabickova E,Lang S,Lau CC,Leavey PJ,Lessnick SL,Mascarenhas L,Mayer-Steinacker R,Meyers PA,Nagarajan R,Randall RL,Reichardt P,Renard M,Rechnitzer C,Schwartz CL,Strauss S,Teot L,Timmermann B,Sydes MR,Marina N, Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. European journal of cancer (Oxford, England : 1990). 2019 Jan 24; [PubMed PMID: 30685685]|