Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma

INTRODUCTION — Sarcomas are a rare and heterogeneous group of malignant tumors of mesenchymal origin that comprise less than 1 percent of all adult malignancies and approximately 10 percent of pediatric cancers [1-4]. Approximately 80 percent of new cases of sarcoma originate from soft tissue, and the rest originate from bone [1].

The histopathologic spectrum of sarcomas is broad, presumably because the embryonic mesenchymal cells from which they arise have the capacity to mature into striated skeletal and smooth muscle, adipose and fibrous tissue, bone, and cartilage, among other tissues. Although ectodermal in origin, malignant tumors affecting peripheral nerves are included because of similarities in their clinical behavior, management, and outcome.

This topic review will cover the clinical presentation, diagnostic evaluation, and staging of soft tissue sarcoma other than gastrointestinal stromal tumor (GIST), the most common sarcoma, which is discussed in detail elsewhere. Issues specific to soft tissue sarcomas arising in the head and neck, retroperitoneum, and breast are discussed elsewhere, as are bone sarcomas, Kaposi sarcoma, and dermatofibrosarcoma protuberans (DFSP). (See "Head and neck sarcomas" and "Clinical presentation and diagnosis of retroperitoneal soft tissue sarcoma" and "Breast sarcoma: Epidemiology, risk factors, clinical presentation, diagnosis, and staging" and "Osteosarcoma: Epidemiology, pathology, clinical presentation, and diagnosis" and "AIDS-related Kaposi sarcoma: Staging and treatment" and "Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment" and "Dermatofibrosarcoma protuberans: Epidemiology, pathogenesis, clinical presentation, diagnosis, and staging".)

HISTOPATHOLOGY — As classified by the World Health Organization (WHO), the group of soft tissue neoplasms includes more than 100 different histologic subtypes [1]. The most common subtypes that arise in adults are outlined in the figure (figure 1).

WHO classifies most soft tissue neoplasms according to the presumptive tissue of origin (ie, the normal tissues the tumor most closely resembles) [1]. Examples include liposarcoma, synovial sarcoma, leiomyosarcoma, rhabdomyosarcoma (RMS), fibrosarcoma, and angiosarcoma. In some cases, histogenesis is uncertain, and the designation reflects the architectural pattern (eg, alveolar sarcoma of soft parts, epithelioid sarcoma, clear cell sarcoma).

Histologically, the diagnosis of a soft tissue sarcoma is made on the basis of morphologic pattern. Immunohistochemical staining (IHC) often aids in the identification of the presumptive tissue of origin. Some IHC markers are more characteristic than others, and it is the spectrum of markers examined that determines the histological subtype. As examples:

●Desmin is particularly valuable in the identification of myogenic differentiation: RMS and, to a lesser degree, leiomyosarcoma. (See "Rhabdomyosarcoma in childhood and adolescence: Epidemiology, pathology, and molecular pathogenesis", section on 'Tissue diagnosis'.)

●The presence of S100 antigen and neurofilaments suggests cells arising from the neural sheath, but this is also found in tumors with melanocytic differentiation. Among sarcomas, these include clear cell sarcoma and perivascular epithelioid cell tumors (PEComa).

●Cytokeratin is rarely expressed in most sarcomas but can help distinguish between synovial or epithelioid sarcoma (which both contain cytokeratin) and fibrosarcomas (which do not).

●Factor VIII-related antigen identifies tumors of endothelial origin.

Molecular diagnostics — A number of histologic subtypes are associated with specific chromosomal translocations; several examples are provided in the table (table 1), and molecular techniques (including fluorescence in situ hybridization [FISH] and reverse transcriptase polymerase chain reaction [RT-PCR] to detect the protein products of these fusion genes) can aid in the diagnosis of these tumors. A prospective study has shown that molecular methods can modify expert histologic diagnoses in certain sarcomas, and argument has been made that such testing should be considered mandatory [5]. However, in our view, the decision of such testing should be made by an experienced sarcoma pathologist taking into account the clinical information provided by a multidisciplinary care team.

Routine cytogenetics on fresh sarcoma specimens have largely been supplanted by FISH probes that can be performed on paraffin-embedded material. FISH testing can be definitive in ruling-in a specific sarcoma subtype in certain cases when the differential diagnosis has been narrowed but histology and IHC staining remain equivocal (eg, synovial sarcoma). However, when a translocation-associated tumor is highly suspected based upon the clinical presentation (eg, Ewing sarcoma), it is reasonable to send fresh tissue for cytogenetic analysis at the time of biopsy in consultation with the pathologist. This topic is discussed in detail elsewhere. (See "Pathogenetic factors in soft tissue and bone sarcomas", section on 'Chromosomal translocations'.)

Most common subtypes — In a tertiary referral population, the most common soft tissue sarcoma subtypes in adults are liposarcoma (which has three distinct subtypes), leiomyosarcoma, undifferentiated pleomorphic sarcoma, and gastrointestinal stromal tumors (GIST), followed by many others (figure 1) [6,7]. GIST, which are discussed elsewhere, may be underrepresented, since small GIST (eg, <2 cm) are infrequently encountered in a referral population. (See "Clinical presentation, diagnosis, and prognosis of gastrointestinal stromal tumors".)

A brief description of some of the common subtypes follows:

●Liposarcoma – Liposarcomas appear to arise from precursors of adipocytes (fat cells) and are most commonly found in the extremities and retroperitoneum. The three main morphologic subgroups are well-differentiated/dedifferentiated, myxoid/round cell, and pleomorphic liposarcomas [1,8]. There is a great range of biologic behavior amongst these subtypes, spanning from well-differentiated liposarcomas with low metastatic potential to the high-risk round cell or pleomorphic types, which tend to be higher grade and are associated with a high rate of distant metastases [9]. (See 'Histologic grade' below.)

Some well-differentiated liposarcomas arising on the extremities and trunk are referred to as "atypical lipomas" or atypical lipomatous tumors to denote the fact that, at these sites, excision is usually curative and that there is no potential for metastases, as compared with sites in the retroperitoneum, mediastinum, and spermatic cord [10]. However, in our view, this is a confusing name that underestimates the risk of local recurrence of such tumors.

The metastatic pattern of the various subtypes of liposarcomas is also unique, with metastases to other soft tissue sites and bone marrow (myxoid/round cell liposarcoma, dedifferentiated liposarcoma) more common than metastases to liver or lung (as may occur for pleomorphic liposarcomas or undifferentiated/unclassified sarcomas). (See 'Pattern of recurrence' below.)

Myxoid and round cell liposarcomas share the same reciprocal translocation t(12;16)(q13;p11), in which the CHOP gene (also called the DNA damage inducible transcript 3 [DDIT3] gene or GADD153) is inserted adjacent to a novel gene called FUS or TLS (translocated in liposarcoma). While no specific chromosomal translocations have been identified in well-differentiated/dedifferentiated liposarcomas, amplification of MDM2 and CDK4 is very frequent in these subtypes, and their identification may be useful diagnostically. Furthermore, overexpression of the MDM2 and CDK4 genes is also being exploited for therapeutic gain [8,11]. Pleomorphic liposarcomas genetically most closely resemble the pleomorphic variant of undifferentiated/unclassified sarcomas. (See "Pathogenetic factors in soft tissue and bone sarcomas", section on 'Myxoid liposarcomas' and "Pathogenetic factors in soft tissue and bone sarcomas", section on 'Somatic gene mutations'.)

●Leiomyosarcoma – Leiomyosarcomas, which are characterized by smooth muscle differentiation, can be found throughout the body. In addition to presentation in the extremities, they can arise from a branch of the inferior vena cava, the gastrointestinal tract, or the uterus. Leiomyosarcomas that originate in the uterus may be a distinct subgroup of tumors as they have different gene expression patterns when compared with nonuterine leiomyosarcomas [12]. Uterine leiomyosarcomas are discussed in detail separately. (See "Uterine sarcoma: Classification, epidemiology, clinical manifestations, and diagnosis", section on 'Leiomyosarcoma'.)

Unlike superficial and deep tumors, cutaneous leiomyosarcomas typically have a more indolent course and are less likely to metastasize [13].

●Undifferentiated/unclassified soft tissue sarcoma – This subgroup was formerly included in a broad category of soft tissue sarcomas that were termed malignant fibrous histiocytoma (MFH), which was formerly the most common subtype of soft tissue sarcoma [7]. However, many sarcomas that were previously identified as MFH have been reclassified to other subtypes when reanalyzed using histology and IHC [14]. The term undifferentiated/unclassified soft tissue sarcoma is now reserved specifically for sarcomas that lack specific lines of differentiation [1], although some pathologists use the term "sarcoma, not otherwise specified (NOS)" for these sarcomas.

Subsets of undifferentiated/unclassified soft tissue sarcomas include the pleomorphic (undifferentiated pleomorphic sarcoma), round cell, and spindle cell variants, which simply describe histological morphology. One version of what was formerly termed myxoid MFH is now classified as a distinct sarcoma subtype, myxofibrosarcoma. In comparison with undifferentiated/unclassified soft tissue sarcoma, myxofibrosarcomas may be associated with a greater local recurrence risk than other histologies [15-17].

●Synovial sarcoma – Synovial sarcoma initially derived its name from a histologic resemblance to synovial cells, but its cell of origin is unknown. There are two morphologic subtypes, monophasic and biphasic. The most common presentation is a soft tissue tumor of the extremities in young adults.

The majority of synovial sarcomas are characterized by the chromosomal translocation t(X;18)(p11;q11). The breakpoint of this translocation fuses the SS18 (previously called SYT) gene from chromosome 18 to one of three homologous genes, SSX1, SSX2, and SSX4 on the X chromosome. SS18-SSX1 is associated with biphasic tumors (glandular epithelial differentiation on a background of spindle tumor cells), while SS18-SSX2 is associated with monophasic tumors that lack glandular epithelial differentiation.

Cytogenetic analysis, FISH, or RT-PCR can be used to detect the translocation or the protein product of the fusion gene, thus aiding in the diagnosis of synovial sarcoma. The specific SS18-SSX fusion type may have prognostic importance, with better outcomes reported for patients with the SS18-SSX2 fusion in many, but not all, reports. (See "Pathogenetic factors in soft tissue and bone sarcomas", section on 'Synovial sarcoma'.)

●Malignant peripheral nerve sheath tumor (MPNST) – MPNSTs are of ectodermal origin and originate from peripheral nerves. Approximately 50 percent of these tumors occur in patients with neurofibromatosis type I and result from degeneration of plexiform neurofibromas. (See "Peripheral nerve tumors", section on 'Malignant peripheral nerve sheath tumors' and "Pathogenetic factors in soft tissue and bone sarcomas", section on 'Neurofibromatosis' and "Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis", section on 'Soft tissue sarcomas'.)

MPNSTs are commonly found in the trunk, extremities (image 1), and head and neck. The diagnosis of an MPNST can be difficult due to variable histomorphology. There are no characteristic chromosomal translocations. The presence of S100 protein can aid in the diagnosis, but it is not uniformly expressed in these tumors, since the line of differentiation appears to be lost to some degree in many.

●Angiosarcoma – Angiosarcomas are uncommon tumors that arise in the subcutaneous tissue of many sites of the body, typically head and neck, or breast. It is one of the most common tumors caused by therapeutic radiation, often after treatment of breast cancer or Hodgkin lymphoma, with a median time of development of 8 to 10 years. (See "Breast sarcoma: Epidemiology, risk factors, clinical presentation, diagnosis, and staging", section on 'Ionizing radiation' and "Head and neck sarcomas", section on 'Angiosarcoma'.)

In IHC, the tumor cells stain positive for vascular markers such as CD31 and factor VIII. Mutations in the vascular endothelial growth factor receptor-2 (VEGFR2; also called Flk1/KDR) are seen in a subset of these patients, with unclear clinical implications. (See "Overview of angiogenesis inhibitors", section on 'VEGF receptors'.)

●Solitary fibrous tumor (SFT) – SFTs are slow-growing tumors that arise most commonly in the pleura, pelvis, or dura, where they can reach a very large size before detection due to their slow change over time. (See "Solitary fibrous tumor" and "Uncommon brain tumors", section on 'Solitary fibrous tumor'.)

While many SFTs are classified as benign tumors with a very low risk of metastasis, others are classified as malignant because of hypercellularity, at least focal cytologic atypia, tumor necrosis, numerous mitoses, and/or infiltrative borders [18]. These lesions have a greater ability to metastasize, usually at an interval of several years, most commonly to bone, liver, and lung. Tumor cells stain positive for stem cell marker CD34.

Rare patients will present with hypoglycemia on the basis of overexpression of a form of insulin-like growth factor 2 (IGF-2). This finding resolves with resection of the tumor.

These tumors are commonly associated with an NAB2-STAT6 fusion gene, which functions as a chimeric transcription factor. (See "Solitary fibrous tumor", section on 'Molecular pathogenesis and molecular diagnostics'.)

●Desmoid tumor/deep fibromatosis – Desmoid tumors, also referred to as aggressive or deep fibromatosis, are not sarcomas, but they represent neoplasms of fibroblastic tissue that lack the ability to metastasize. However, desmoid tumors have a propensity for local recurrence, even after complete resection, and they have the capacity to cause local morbidity and death in rare cases. (See "Desmoid tumors: Epidemiology, molecular pathogenesis, clinical presentation, diagnosis, and local therapy".)

Desmoid tumors typically arise in the extremity in sporadic cases or in the abdominal wall in association with pregnancy (where they usually improve postpartum) and arise in the mesenteric root in the setting of familial adenomatous polyposis (FAP). FAP is characterized by loss of expression of the gene APC. The development of desmoid tumor in the setting of FAP is a characteristic of Gardner syndrome, a specific version of FAP. Mesenteric desmoids are those with the highest degree of mortality.

CTNNB1 gene mutations are found in most sporadic desmoids, although some, instead, have loss of the APC gene. The specific type of CTNNB1 mutation may predict for risk of recurrence.

Among children, who account for 10 to 15 percent of all cases of soft tissue sarcoma, the "small round blue cell" sarcomas predominate, such as Ewing sarcoma and related tumors (eg, peripheral primitive neuroectodermal tumor [PNET]), CIC-DUX4 tumors (table 1) [19], and rhabdomyosarcoma subtypes more commonly seen in children (embryonal and alveolar). Central (supratentorial) PNET tumors are discussed separately. (See "Clinical presentation, staging, and prognostic factors of Ewing sarcoma" and "Epidemiology, pathology, and molecular genetics of Ewing sarcoma" and "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging" and "Uncommon brain tumors", section on 'Embryonal tumors'.)

It is important to differentiate between the various subtypes of sarcoma for both prognosis and potential differences in treatment. This is especially true for typical pediatric tumors that arise in adults, such as RMS. Both embryonal and alveolar RMS are more susceptible to chemotherapy and carry a better prognosis than many types of adult soft tissue sarcomas. Nevertheless, pleomorphic RMS has a relatively poor prognosis compared with other RMS subtypes and predominates in adults, and outcomes are worse than in children. (See "Rhabdomyosarcoma in childhood and adolescence: Epidemiology, pathology, and molecular pathogenesis", section on 'Histologic classification' and "Rhabdomyosarcoma in childhood, adolescence, and adulthood: Treatment".)

Histologic grade — Several grading systems have been developed to increase the prognostic value of histologic assessment, some of which use a three-tier system (ie, grade 1 [well differentiated, low grade], 2 [moderately differentiated] or 3 [poorly differentiated, high grade]) and others a four-tier system. The three-tiered system is incorporated into the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system for soft tissue sarcomas and is preferred [1,20]. (See 'Staging' below.)

The French Federation of Cancer Centers Sarcoma Group (FNCLCC) grading system is preferred by the College of American Pathologists (CAP), and is based on three parameters: differentiation, mitotic activity, and necrosis [21,22]. Grading should be used only for untreated primary soft tissue sarcomas. The histologic grade does not differentiate between benign and malignant soft tissue tumors and is not a substitute for morphologic diagnosis.

Grading is not applicable to all soft tissue sarcomas. It is of little prognostic value for MPNST (the majority of which are considered high grade [23,24]), and it is not recommended for angiosarcoma, alveolar soft part sarcoma, extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and epithelioid sarcoma [1,20]. The impact of histologic grade on prognosis is discussed below. (See 'Prognostic factors' below.)

ETIOLOGY AND PATHOGENESIS — In nearly all instances, sarcomas are thought to arise de novo and not from a preexisting benign lesion. Most cases have no clearly defined etiology, but a number of associated or predisposing factors have been identified. In addition to long-recognized genetic predisposition syndromes such as Li-Fraumeni syndrome and neurofibromatosis type I, there is increasing recognition that pathogenic germline variants may be present in a significant proportion of sarcoma patients [25]. Additional predisposing factors include retinoblastoma, exposure to radiation therapy or chemotherapy, chemical carcinogens, chronic irritation, and lymphedema. In addition, human immunodeficiency virus (HIV) and human herpes virus 8 have been implicated in the pathogenesis of Kaposi sarcoma. These topics are discussed separately. (See "Pathogenetic factors in soft tissue and bone sarcomas" and "AIDS-related Kaposi sarcoma: Clinical manifestations and diagnosis" and "Classic Kaposi sarcoma: Epidemiology, risk factors, pathology, and molecular pathogenesis" and "Retinoblastoma: Treatment and outcome", section on 'Second malignancies'.)

CLINICAL PRESENTATION — The most common presenting complaint for a soft tissue sarcoma is a gradually enlarging, painless mass. These tumors can become quite large, especially in the thigh and retroperitoneum. Some patients complain of pain or symptoms associated with compression by the mass, including paresthesias or edema in an extremity. Rarely, a patient may present with constitutional symptoms, such as fever and/or weight loss.

Distribution — Soft tissue sarcomas occur at all anatomic body sites, but the majority are in the extremities. The anatomic distribution of soft tissue sarcomas in 4550 adults reviewed by the American College of Surgeons was as follows [26]:

●Thigh, buttock, and groin – 46 percent

●Upper extremity – 13 percent

●Torso – 18 percent

●Retroperitoneum – 13 percent

●Head and neck – 9 percent

Some histologic types of soft tissue sarcoma have a predilection for certain anatomic sites. As examples:

●While only 14 percent of all soft tissue sarcomas present in the upper extremity, 40 to 50 percent of all epithelioid sarcomas arise on the forearm and finger [27-29].

●Desmoplastic small round cell tumors, which have a predilection for adolescent and young adult males, primarily involve the abdominal cavity and pelvis [30,31].

The anatomic distribution of histologic subtypes is not a simple function of abundance of the tissue type. Liposarcomas are not common in the large fatty deposits of the abdominal wall, while in the thigh, a frequent site, they often arise deep in the muscle mass, rather than in the subcutaneous fat.

Clinical presentation of retroperitoneal sarcomas, uterine sarcomas, and sarcomas of the head and neck is discussed in more detail elsewhere. (See "Clinical presentation and diagnosis of retroperitoneal soft tissue sarcoma" and "Uterine sarcoma: Classification, epidemiology, clinical manifestations, and diagnosis" and "Head and neck sarcomas".)

Pattern of growth — Soft tissue sarcomas grow at various rates depending on the aggressiveness of the tumor. Tumors tend to grow along tissue planes and only rarely traverse or violate major fascial planes or bone. The growing tumor compresses surrounding normal tissue, leading to the formation of a so-called pseudocapsule that is comprised of compressed normal tissue with poorly defined margins and fingerlike tumor projections that infiltrate adjacent tissues. Dissection along the pseudocapsule plane will invariably leave residual disease and should be avoided. (See "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and superficial trunk", section on 'Resection'.)

Pattern of spread — The most common pattern of spread is hematogenous, predominantly to the lung, though metastatic patterns are also linked to specific sarcoma histology. (See 'Pattern of recurrence' below.)

The presence of distant metastatic disease at the time of initial diagnosis is uncommon, but is more likely in large, deep, high-grade sarcomas and with specific histologies. In a retrospective review of 1170 patients over a 7.5-year period, the following were noted [32]:

●The incidence of distant metastatic disease at the time of diagnosis was 10 percent, and 83 percent of metastases were located in the lungs.

●There was a higher risk of lung metastases in tumors that were deep to the fascia (9 versus 4 percent).

●The risk of having lung metastases at diagnosis also increased with higher histologic grade of differentiation (12, 7, and 1.2 percent for high-grade, intermediate-grade, and low-grade tumors, respectively).

●The histologic subtypes most likely to present with lung metastases were soft tissue Ewing sarcoma, malignant peripheral nerve sheath tumor (MPNST), and extraskeletal chondrosarcoma (25, 16.2, and 13.6 percent respectively). (See "Chondrosarcoma".)

Regional nodes — Overall, spread to regional nodes is infrequent for soft tissue sarcomas. An analysis of 1772 sarcoma patients in a prospective database at Memorial Sloan-Kettering Cancer Center (MSKCC) identified 46 (2.6 percent) with lymph node metastases [33]. However, certain histologies have a higher risk of nodal metastases than do others. The histologies with the greatest risk of lymph node metastases are rhabdomyosarcoma, synovial sarcoma, epithelioid sarcoma, clear cell sarcoma, and the vascular sarcomas (including angiosarcomas) [27-29,33-40].

Nodal metastases carry a poor prognostic implication but somewhat less than do overt bloodborne metastases in soft tissue sarcoma [34,35,37,38]. This finding prompted a change in the 2010 joint American Joint Committee on Cancer (AJCC)/Union for international Cancer Control (UICC) staging system (which covered all soft tissue sarcomas regardless of primary location) to reclassify N1 disease as stage III instead of stage IV [41]. However, in the 2017 revision of the AJCC/UICC staging system, this is only the case for soft tissue sarcomas arising in the retroperitoneum (table 2); nodal metastases are once again classified as stage IV disease for primary sites in the extremity and trunk (table 3) [42,43]. (See 'Staging' below.)

Management of the regional lymph nodes, including the role of sentinel node biopsy, is discussed elsewhere. (See "Surgical resection of primary soft tissue sarcoma of the extremities", section on 'Lymphadenectomy'.)

Pattern of recurrence — Recurrent disease after treatment of a soft tissue sarcoma can present as a local recurrence or metastatic disease [44,45]. The incidence of local recurrence depends on anatomic location, extent of resection, use of perioperative radiation therapy, and histology. (See "Surgical resection of primary soft tissue sarcoma of the extremities", section on 'Recurrence' and "Initial management of retroperitoneal soft tissue sarcoma".)

Overall, approximately 25 percent of patients will develop distant metastatic disease after successful treatment of their primary tumor; the incidence increases to 40 to 50 percent with tumors that are >5 cm in size, deep to the fascia, and intermediate or high grade [46,47].

In 70 to 80 percent of cases, metastatic disease is to the lungs [32,45,48,49]. Rare sites of metastatic disease spread include the skin, soft tissues, bone, liver, and brain [44,45,50,51].

There are some exceptions to the typical pattern of metastatic disease:

●In round cell/myxoid liposarcomas, where extrapulmonary metastases to the retroperitoneum, abdomen, bone (particularly the spine), and paraspinal soft tissue are common [52,53].

●Retroperitoneal sarcomas, in particular leiomyosarcomas, also commonly metastasize to the liver as well as the lung. Conversely, retroperitoneal liposarcomas, nearly all the well-differentiated/dedifferentiated subtype, recur local-regionally instead of with metastatic disease. (See "Clinical presentation and diagnosis of retroperitoneal soft tissue sarcoma".)

DIAGNOSTIC EVALUATION — Histologic examination of a soft tissue mass is essential for diagnosis and treatment planning. Radiographic imaging is used to assist in defining the etiology of a soft tissue mass, determining the extent of a primary tumor for surgical planning, and establishing the presence or absence of metastatic disease.

The initial evaluation of a patient with a suspected soft tissue sarcoma begins with a history of when the mass was first noticed, how quickly it has been growing, and whether there are symptoms to suggest distal neurovascular compromise. The physical examination should focus on the size and depth of the mass, fixation to adjacent structures, and associated edema or signs of nerve impingement.

Delay in diagnosis of soft tissue sarcomas is common [54]. Patients frequently do not seek prompt medical attention due to the painless nature of the tumor, and delays on the part of the physician are likewise common due to assumptions of benignity [55].

Differential diagnosis — The differential diagnosis of a soft tissue mass includes benign soft tissue tumors, such as a lipoma, as well as malignant tumors, including sarcoma, metastatic carcinoma, melanoma, or lymphoma.

Given that benign soft tissue masses are at least 100 times more common than malignant soft tissue sarcomas [1], it can be difficult to determine which soft tissue masses warrant further evaluation. The United Kingdom Department of Health has published criteria for urgent referral of a patient with a soft tissue lesion [56]:

●Soft tissue mass >5 cm (golf ball size or larger)

●Painful lump

●Lump that is increasing in size

●A lump of any size that is deep to the muscle fascia

●Recurrence of a lump after previous excision

In a prospective review of 365 patients with confirmed soft tissue sarcoma, tumor depth was found to be the most sensitive marker of malignancy, followed by size >5 cm and a history of rapid growth [57].

Importance of biopsy planning — Because the diagnosis of soft tissue sarcoma is often unsuspected, unplanned and inappropriate excisions of these tumors frequently occur before a proper pathologic diagnosis has been made [58]. Partial excision of the tumor before referral to a tertiary center does not appear to compromise limb preservation, local control, or in most series, survival. However, a higher incidence of distant metastatic disease has been reported in such patients [59], and reresection may entail a larger procedure than a de novo procedure and impact the functional result. These data underscore the importance of transferring patients with soft tissue masses of uncertain identity to centers that specialize in treating sarcomas so that they can undergo adequate initial resection. Studies have shown improved outcomes in patients treated at a specialist sarcoma center [60,61]. (See 'Biopsy' below and "Surgical resection of primary soft tissue sarcoma of the extremities", section on 'Inadequate initial resection'.)

Radiographic studies — Various imaging techniques are used to assist in defining the etiology of a soft tissue mass, determining the extent of a primary tumor for surgical planning, and establishing the presence or absence of metastatic disease.

Imaging of the primary tumor — Our practice for the diagnostic workup of a soft tissue mass includes cross-sectional imaging with magnetic resonance imaging (MRI) for a primary extremity or trunk lesion and contrast-enhanced multidetector-row computed tomography (CT) for a primary abdominal, visceral, or retroperitoneal lesion.

Plain radiography — Plain films of the primary site can be useful to rule out soft tissue masses that arise from bone and to detect intratumoral calcifications such as those that appear within soft tissue (extraskeletal) osteosarcomas and synovial sarcomas.

MRI and CT — MRI is the preferred imaging modality for the evaluation of soft tissue masses of the extremities, trunk, and head and neck, while CT is the most commonly used imaging technique for retroperitoneal and visceral sarcomas. Several studies report that MRI is superior to CT in evaluating soft tissue sarcomas of the extremity as MRI provides multiplanar images with better spatial orientation. MRI is superior for delineating the extent of the neoplasm and the relation to surrounding structures, especially individual muscle involvement (image 2) [62-64]. However, a multicenter prospective study that included 133 patients who underwent both CT (image 3) and MRI within four weeks of surgery for a soft tissue sarcoma of the arm, shoulder, pelvis, hip, or lower extremity found no statistically significant difference between the two modalities in determining tumor involvement of muscle, bone, joints, or neurovascular structures [65]. Combined interpretation of CT and MRI did not improve accuracy of preoperative assessment.

PET and PET/CT — A number of studies report that positron emission tomography (PET) and integrated PET/CT using fluorodeoxyglucose (FDG) can distinguish benign soft tissue tumors from sarcomas with the greatest sensitivity for high-grade sarcomas [66-68]. However, the ability to differentiate benign soft tissue tumors from low- or intermediate-grade sarcomas is limited, and PET and PET/CT are not routinely recommended for the initial workup of a soft tissue mass [69-71].

PET/CT may have a role in distinguishing well-differentiated from dedifferentiated retroperitoneal liposarcomas [72]. The modality may also have a role in characterization of a suspected peripheral nerve sheath tumor in a patient with neurofibromatosis; in this scenario, PET imaging can be helpful in distinguishing a malignant peripheral nerve sheath tumor (MPNST) from a neurofibroma [73-75]. Gallium scans may also differentiate between neurofibromas and MPNSTs [76]. (See "Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis", section on 'Soft tissue sarcomas'.)

Consensus guidelines for workup of a soft tissue sarcoma of the extremity and trunk issued by the National Comprehensive Cancer Network (NCCN) suggest that PET scan may be useful in prognostication, grading, and determining response to neoadjuvant chemotherapy in patients with soft tissue sarcoma [77]. However, this recommendation is based upon a single study demonstrating that FDG-PET was useful to predict the outcomes of patients with high-grade extremity soft tissue sarcomas who were treated initially with chemotherapy [78]. Patients with a baseline tumor standard uptake value (SUV) maximum ≥6 who had a <40 percent decrease in FDG uptake after neoadjuvant chemotherapy were found to be at high risk of systemic disease recurrence.

The clinical utility of having this information prior to surgical treatment is unclear. At present, the use of PET for prognostication or assessment of treatment response is not considered routine at most institutions.

Functional imaging with PET/CT may have a role in patients with a clinical suspicion of recurrent sarcoma. In one study, the sensitivity of FDG-PET for recurrence of soft tissue sarcoma was higher than that of contrast-enhanced CT (83 versus 50 percent), though specificity was equally good (100 percent with both tests) [79]. However, MRI is still considered the most useful modality for detecting local recurrences [80].

Evaluation for metastatic disease — Imaging studies to evaluate for metastatic disease are typically influenced by tumor histology and patterns of disease spread. Since sarcomas are a rare and heterogenous group of cancers, clinicians may consult with an expert center to define the most appropriate imaging follow-up. (See 'Pattern of spread' above.)

Our general approach to evaluating for metastatic disease is as follows:

CT imaging

●CT chest – We recommend chest imaging to evaluate for pulmonary metastatic disease for all newly diagnosed patients with soft tissue sarcoma of the extremity/trunk, given the propensity for lung metastases [77]. We suggest a chest CT rather than chest radiograph (CXR) in patients with a high risk of pulmonary metastases (eg, tumors >5 cm or deep seated, or intermediate or high grade).

While CT scan is often preferred due to its greater sensitivity in detecting small lung nodules, it is unknown whether this provides benefit over CXR alone. Both modalities are considered highly appropriate for this purpose by the American College of Radiology (ACR) [81]. A retrospective review performed in the United Kingdom found that CXR alone detected two-thirds of pulmonary metastases in patients with soft tissue sarcoma; when compared with CT as the "gold standard," the sensitivity, specificity, positive predictive value, and negative predictive value of CXR were 60.8, 99.6, 93.3, and 96.7 percent, respectively [32]. The use of CXR only to stage the lungs would have missed one-third of all patients with lung metastases, but because of the infrequency of lung metastases overall (96 of 1170 patients), the initial staging would have been inaccurate in only 3.1 percent of cases. A greater proportion (4.9 percent) would have been incorrectly staged if CXR alone had been used in patients with high-grade, large, deep tumors. The authors recommended that all patients with a suspected soft tissue sarcoma should have a CXR, with chest CT reserved for those with an abnormality on CXR or who have the highest risk of pulmonary metastases (primary tumor >5 cm and deep-seated, or intermediate/high grade). We agree with this recommendation.

However, we note that recommendations for chest imaging from expert groups differ:

•Consensus-based NCCN guidelines [82] suggest chest imaging with either CXR or CT for soft tissue sarcoma of the extremity or trunk, but chest CT (not CXR) for retroperitoneal/abdominal soft tissue sarcoma.

•On the other hand, guidelines from the European Society of Medical Oncology (ESMO) recommend spiral chest CT for all patients with newly diagnosed soft tissue sarcoma, regardless of site of origin [83].

•The most recent eighth edition of the American Joint Committee on Cancer (AJCC) staging manual suggests the use of chest CT to assess for pulmonary metastases [84].

●CT abdomen pelvis – We recommend CT imaging of the abdomen and pelvis in round cell/myxoid liposarcomas due to the common presentation of extrapulmonary metastases to the abdomen and retroperitoneum [85,86]. Some clinicians may also offer this approach to patients with select histologies involving the lower extremities (eg, angiosarcomas, epithelioid sarcoma, and clear cell sarcoma) who are at risk for lymph node metastases [87-89].

We do not typically offer routine CT imaging of the abdomen and pelvis for other sarcomas of the extremities, as the risk of abdominal and retroperitoneal involvement for these other histologies is low overall [86,90].

CNS imaging — We suggest imaging of the brain with MRI (with CT as an alternative if MRI is contraindicated) for patients with cardiac angiosarcoma and alveolar soft part sarcoma due to the high propensity of these tumors for central nervous system metastases [91,92]. For non-cardiac angiosarcomas and other soft tissue sarcoma histologies, we do not pursue CNS imaging unless there are concerning neurologic signs or symptoms.

Bone imaging — Although it is not our routine practice, some clinicians obtain MRI of the spine for patients with round cell/myxoid liposarcomas, given the risk of bony metastases in this histology and the lack of sensitivity of bone scan (ie, bone scintigraphy) [85,93].

In other histologies, bone metastases are relatively unusual and we do not offer routine baseline bone imaging in the absence of symptoms.

Is there a role for PET/CT? — We do not routinely pursue positron emission tomography (PET) or integrated PET/computed tomography (CT) as a component of the initial staging workup of soft tissue sarcoma for evaluation of either pulmonary or extrapulmonary metastatic disease.

PET scanning can achieve whole body imaging, and it is widely considered to be more sensitive than CT for the detection of occult distant metastases in a variety of solid tumors (image 4). However, the utility of PET alone or with integrated CT for staging of distant disease extent in soft tissue sarcoma is unclear, as evidenced by the following reports [94-98]:

●In several reports, chest CT is more sensitive than PET for detection of thoracic metastases in patients with sarcoma [94,96,98,99]. In the largest report of 106 patients with bone or soft tissue sarcomas who had PET or integrated PET/CT, pulmonary metastases were found in 40 [96]. CT identified 17 lesions larger than 1 cm, while PET identified only 13 of them. The authors concluded that subcentimeter CT lesions should not be considered false-positive if inactive on PET and that a negative PET scan in the presence of suspicious CT findings in the chest cannot reliably exclude pulmonary metastases.

●One purported benefit of PET is its ability to detect additional sites of extrapulmonary metastatic disease [94,97]. However, the risk of extrapulmonary metastases is so low with most soft tissue sarcomas that the routine use of PET for this purpose is unlikely to change the therapeutic plan. This was illustrated in a report of 75 patients who underwent PET during staging evaluation for a soft tissue sarcoma [98]. Only one patient was upstaged as a result of PET imaging, and PET did not alter the management of patients already known to have metastatic disease (ie, no new organ sites were identified).

Biopsy — Histologic examination of a soft tissue mass is essential for diagnosis and treatment planning. Our preferred method for obtaining tissue is with a core needle biopsy, if technically feasible. If incisional biopsy is required, it should be carefully planned and performed by the surgeon who will be doing the definitive resection. A poorly placed initial biopsy may preclude subsequent surgical resection, preparation of flaps, and/or cosmetic repair, or result in the need for a more extensive surgery to encompass the biopsy site at the time of definitive resection. We recommend that all pathology specimens of suspected soft tissue sarcoma be reviewed by a pathologist who specializes in the evaluation of soft tissue tumors.

There are several methods for obtaining a diagnostic biopsy, which are reviewed below. Ideally, the biopsy should be performed after an MRI has been obtained, as postprocedural edema may make the MRI difficult to interpret.

The diagnostic biopsy must be carefully planned to ensure that adequate tissue is obtained in a manner that does not compromise definitive therapy.

Incisional biopsy — Although incisional biopsy was the historic gold standard procedure for obtaining diagnostic tissue for a suspicious soft tissue mass, core needle biopsy has become the most common procedure used for diagnosis in recent years (see 'Core needle biopsy' below). A biopsy that contains enough material to ascertain the histologic subtype and grade of the tumor is essential prior to commencement of therapy [100].

If definitive diagnosis may require flow cytometry, cytogenetics, or molecular analysis for chromosomal translocations, an incisional biopsy may be preferred. The larger sample provides the pathologist with more tissue and a greater degree of confidence in the diagnosis, in part because of the degree of morphologic heterogeneity throughout the tumor.

If needed, incisional biopsy should ideally be performed by the surgeon planning the definitive resection. Errors, complications, and changes in patient outcome occur more frequently when an incisional biopsy is performed in a referring institution instead of a treatment center [101,102]. Open biopsy incisions should be placed longitudinally along the extremity so that the scar can be resected along with the tumor at the time of definitive surgical resection. Adequate hemostasis is important to prevent dissemination of tumor cells.

Core needle biopsy — Core needle biopsy is considered the preferred method to achieve an initial biopsy in most cases due to its low incidence of complications and high diagnostic accuracy [103-106]. In a study of 530 patients with suspected soft tissue tumors, core needle biopsy differentiated malignant soft tissue sarcomas from benign soft tissue tumors in 97.6 percent of patients. Histologic grade was accurately determined in 86.3 percent of patients, and the subtype was accurately identified in 88 percent [104].

CT or ultrasound guidance can assist in the biopsy of deep lesions and improve the diagnostic accuracy in lesions with cystic areas and necrosis by allowing the operator to select the site to be biopsied [107,108]. In cases where core needle biopsy is unsuccessful in obtaining adequate material for diagnosis, a subsequent incisional biopsy is usually considered. The incidence of follow-up biopsy has been reported as high as 20 percent [109].

Fine needle aspiration — Fine needle aspiration (FNA) is not recommended in the initial diagnostic evaluation of a suspicious soft tissue mass as it has a lower diagnostic accuracy than core needle biopsy [110,111]. In addition, FNA may not provide the histologic subtype or grade of the sarcoma, which are both important for treatment planning. FNA can be useful in confirming disease recurrence, however [112].

STAGING — The most widely used staging system for soft tissue sarcomas is the tumor, node, metastasis (TNM) system developed as a collaborative effort of the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC). The AJCC TNM system uses tumor size (T), lymph node involvement (N), presence or absence of distant metastases (M), and histologic grade (G) to determine the stage grouping for soft tissue sarcomas.

The most recent (eighth edition, 2017) version of the TNM staging classification contains separate T staging criteria and prognostic stage groups for soft tissue sarcomas arising in the extremity/trunk (table 3) and retroperitoneum (table 2); there are also unique primary tumor definitions for soft tissue sarcoma of the viscera of the abdomen and thorax but no recommended prognostic stage groupings at this site (table 4) [42,113].

The AJCC staging system has not been in widespread use for retroperitoneal sarcomas. It does not account for disease site or histology, two major prognostic indicators. In addition, its ability to discriminate outcome based on tumor size alone is limited [114,115]. Because of this, the AJCC specifically recommends the use of a prognostic nomogram to estimate the likelihood of postoperative survival (figure 2) [116]. Given that histologic grade, the presence or absence of metastatic disease, and achieving macroscopic total resection are the major determinants of survival for patients with retroperitoneal sarcoma, alternative staging systems have been proposed, but they are not in widespread use. (See "Clinical presentation and diagnosis of retroperitoneal soft tissue sarcoma", section on 'Staging'.)

PROGNOSTIC FACTORS — A number of prognostic factors have been identified in patients with soft tissue sarcoma, the most important of which are histologic grade, tumor size [6,117-119], and pathologic stage at the time of diagnosis. These factors are the main determinants of the primary tumor (T) stage (see 'Staging' above). In a series derived from Memorial Sloan Kettering Cancer Center (MSKCC) and using the tumor, node, metastasis (TNM) stage groupings from the 2010 seventh edition, five-year rates disease-free survival for stage I, II, and III disease were 86, 72, and 52 percent, respectively [120]. The corresponding values for overall survival were 90, 81, and 56 percent.

Histologic grade — Histologic grading is an independent indicator of the degree of malignancy and the probability of distant metastases and death from sarcoma [1,6,7,121]. In contrast, histologic grade is a poor predictor of local recurrence, which is mainly a function of surgical margins.

A histologic grade should be assigned to all sarcomas. Comprehensive grading incorporates differentiation (which is histology specific), mitotic rate, and the extent of necrosis. In accordance with recommendations from the College of American Pathologists (CAP) [122], the 2017 American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) cancer staging manual recommends use of the three-tiered French Federation of Cancer Centers Sarcoma Group (FNCLCC) grading schema, which is based on the resected tumor or pretreatment biopsy material, for soft tissue sarcomas at all sites (table 5) [84].

Tumor size — The risk of developing a local recurrence and distant metastases increases substantially as tumor size increases [117,123,124]:

●In a review from Massachusetts General Hospital (MGH), the frequency of distant metastases in high-grade tumors as a function of tumor size was [123]:

•Tumors ≤2.5 cm – 6 percent

•Tumors 2.6 to 4.9 cm – 23 percent

•Tumors 5 to 10 cm – 38 percent

•Tumors 10.1 to 15 cm – 49 percent

•Tumors 15.1 to 20 cm – 58 percent

•Tumors >20 cm – 83 percent

●Another study grouped 316 patients with soft tissue sarcomas into four subgroups on the basis of tumor size (less than 5 cm, 5 to less than 10 cm, 10 to less than 15 cm, and greater than 15 cm). Each subgroup was found to have a different prognosis, with five-year survival rates of 84, 70, 50, and 33 percent, respectively [117].

●The impact of tumor size category on local disease-free survival, overall recurrence-free interval, and disease-specific survival in a series of 5267 patients with soft tissue sarcoma of the extremities or trunk is illustrated in the figure (figure 3) [124].

These data form the basis of the primary tumor (T) stage classification in the 2017 AJCC/UICC cancer staging manual for extremity/trunk (table 3) and retroperitoneal (table 2) primary soft tissue sarcomas.

Prognostic tools — Clinical nomograms can estimate the prognosis of patients with soft tissue sarcoma [125-130]. Estimating prognosis is important for individual patient counseling and therapeutic decision-making. Major clinical determinants of survival include stage, tumor size, grade, anatomic site, age, and histologic subtype. Other important prognostic factors include the presence or absence of metastatic disease and ability to achieve macroscopic total resection.

Several available prognostic nomograms are as follows:

●Memorial Sloan Kettering Cancer Center nomogram – The MSKCC postoperative nomogram for 12-year sarcoma-specific death applies to all anatomic sites (figure 4) [125,126], and is also available online [131]. This nomogram has been validated with an external cohort of patients who were treated at University of California-Los Angeles (UCLA) [132]. Histologic grade in the MSKCC nomogram was defined as high or low according to previously published criteria [133]. A subsequent adapted nomogram has been published incorporating the FNCLCC three-grade classification [127].

●"Sarculator" – The "Sarculator" prognostic tool is available online and incorporates externally validated nomograms for overall survival and risk of distant metastases in soft tissue sarcoma of the extremities [134]. This prognostic tool was developed by Istituto Nazionale Tumori, Mount Sinai Hospital (Toronto), Royal Marsden Hospital NHS Foundation Trust, and Institut Gustave Roussy. The tool also includes an externally validated nomogram for retroperitoneal sarcomas that predicts seven-year overall and disease-free survival (figure 2) [116]. (See "Clinical presentation and diagnosis of retroperitoneal soft tissue sarcoma".)

●The Helsinki University sarcoma nomogram [129].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Soft tissue sarcoma".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Soft tissue sarcoma (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Histopathology – Soft tissue sarcomas are a rare and heterogeneous group of tumors of mesenchymal origin, which includes more than 100 different histologic subtypes. (See "Pathogenetic factors in soft tissue and bone sarcomas".)

●Clinical presentation – Soft tissue sarcomas most commonly present as an enlarging, painless mass in the extremities or trunk. The presence of distant metastatic disease at the time of initial diagnosis is uncommon but more likely in large, deep, high-grade sarcomas. Approximately 80 percent of metastases are located in the lungs. (See 'Clinical presentation' above.)

●Diagnostic evaluation – Our practice for the diagnostic workup of a soft tissue mass includes (see 'Diagnostic evaluation' above):

•Imaging – MRI of a primary extremity lesion and CT of a primary abdominal, visceral, or retroperitoneal lesion. (See 'Imaging of the primary tumor' above.)

•Tissue sampling

-Importance of biopsy planning – The diagnosis of a soft tissue sarcoma is often unsuspected. Partial excision of the tumor before referral may be associated with a higher incidence of distant metastatic disease and the need for an extensive reresection that may impact the functional result. In addition, an inappropriately placed diagnostic biopsy may preclude subsequent surgical resection, preparation of flaps, and/or cosmetic repair, or result in the need for a more extensive surgery to encompass the biopsy site at the time of definitive resection. Because of these issues, early referral of a patient with a suspicious soft tissue mass to a specialized center with a multidisciplinary sarcoma team is recommended. (See 'Importance of biopsy planning' above.)

-Biopsy methods – Our preferred method of obtaining tissue is with a core needle biopsy, if technically feasible. If incisional biopsy is required, it should be carefully planned and performed by the surgeon who will be doing the definitive resection. A poorly placed initial biopsy may preclude subsequent surgical resection, preparation of flaps, and/or cosmetic repair, or result in the need for a more extensive surgery to encompass the biopsy site at the time of definitive resection. We recommend that all pathology specimens of suspected soft tissue sarcomas be reviewed by a pathologist who specializes in the evaluation of soft tissue tumors. (See 'Biopsy' above.)

●Diagnosis – The diagnosis of soft tissue sarcoma is made definitively with biopsy and histopathologic evaluation of the tumor. Pathologic diagnosis is based on histologic morphology, immunohistochemistry, and sometimes, molecular testing. (See 'Histopathology' above.)

●Evaluating for metastatic disease – Imaging studies to evaluate for metastatic disease are typically influenced by tumor histology and patterns of disease spread. Clinicians may consult with an expert center to define the most appropriate imaging follow-up. Our general approach to evaluating for metastatic disease is as follows (see 'Pattern of recurrence' above and 'Evaluation for metastatic disease' above):

•Once the diagnosis of a sarcoma is established, we recommend chest imaging to evaluate for pulmonary metastatic disease in all patients; we use chest CT rather than chest radiograph in patients with a high risk of pulmonary metastases (tumors >5 cm, deep-seated, or intermediate or high grade). (See 'CT imaging' above.)

•We recommend CT of the abdomen and pelvis in patients with round cell/myxoid liposarcomas due to the risk of extrapulmonary metastases to the abdomen and retroperitoneum in these histologies. Some clinicians may also offer this approach to patients with select histologies involving the lower extremities (eg, angiosarcomas, epithelioid sarcoma, and clear cell sarcoma) who are at risk for lymph node metastases. (See 'CT imaging' above.)

•Imaging of the brain is suggested for patients with cardiac angiosarcoma and alveolar soft part sarcoma due to the high propensity of these tumors for central nervous system metastases. (See 'CNS imaging' above.)

•Although it is not our routine practice to obtain MRI of the spine for patients with round cell/myxoid liposarcomas, some clinicians obtain it for such patients, given the risk of bony metastases in this histology. Bone scan is usually not helpful for initial staging of soft tissue sarcomas. (See 'Bone imaging' above.)

•We do not routinely perform positron emission tomography (PET) or PET/CT in the initial staging evaluation of a newly diagnosed soft tissue sarcoma. (See 'PET and PET/CT' above and 'Is there a role for PET/CT?' above.)

●Staging – Soft tissue sarcomas are staged according to the combined American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor, node, metastasis (TNM) system, which is based on tumor size (T), lymph node involvement (N), distant metastases (M), and histologic grade (G).

•The eighth edition version of the AJCC/UICC staging manual has separate T staging criteria and prognostic stage groups for soft tissue sarcoma arising in the extremity/trunk (table 3) and retroperitoneum (table 2); in addition, there are unique primary tumor definitions for sarcomas of the viscera of the abdomen and thorax but no recommended prognostic stage groupings at this site (table 4) [42,113]. (See 'Staging' above.)

•The TNM staging system is not in widespread use for retroperitoneal sarcomas. It does not account for disease site or histology, two major prognostic indicators. In addition, its ability to discriminate outcome is limited. Because of this, the AJCC specifically recommends the use of a prognostic nomogram to estimate the likelihood of postoperative survival (figure 2) [116].

●Prognostic factors – In addition to tumor stage, other prognostic variables include anatomic site, patient age, and histologic subtype. Several nomograms are available online to aid in predicting survival and treatment decision-making for individual patients. (See 'Prognostic factors' above.)