Approach

The most common presentation of soft-tissue sarcoma (STS) is extremity soft-tissue swelling, which may or may not be painful. Other sites of presentation include retroperitoneal/abdominal, chest wall, and head and neck. As a group there are >50 different histologic subtypes; therefore, expert pathologic review of biopsy is essential for confirmation and subtyping of the malignancy.[5][6][7][8]

History and physical exam

Depending on the location of the primary tumor, the patient history and physical exam may differ:

Soft-tissue extremity tumors

Patients with soft-tissue extremity tumors typically present with a painless mass, usually 5 cm or larger, that they report has been enlarging. Some tumors may have been present for many years. It is important that the physician enquires about features of metastases, including weight loss, fatigue, and anorexia. Fever is rarely noted.

There is no age or sex in which extremity STS is particularly seen, although the median age of onset is younger than for many other cancers.

Neuropathic pain is particularly seen with neural tumors, and can be elicited by percussion. It may also be seen with tumors invading the brachial or pelvic nerve plexi or any nerve outflow foramina.

Retroperitoneal/abdominal tumors

Patient with retroperitoneal/abdominal tumors may complain initially of intra-abdominal symptoms such as obstruction, bloating, and discomfort or pain, or may describe increased abdominal girth. On examination of the abdomen, the physician should look for signs of obstruction, which include abdominal distention and tenderness. The patient may complain of constipation. Perforation may be noted by the physician as rebound tenderness and guarding, tachycardia, and hypotension (signs of sepsis). On examination, the physician may find an abdominal mass.

These tumors usually do not arise within intestinal viscera, but are more frequently retroperitoneal or mesenteric. Although these tumors can occur in patients of any age, notably desmoplastic small round cell tumors (a variant on primitive neuroectodermal tumor) are seen in adolescent male patients.

Gastrointestinal stromal tumors

Because they arise in the wall of the intestine, gastrointestinal stromal tumors (GIST) may only present once they have caused obstruction or perforation. However, initially, the patient may present with symptoms of anemia (fatigue, palpitations, dizziness, tachycardia, pallor), weight loss, abdominal pain or swelling, and upper or lower gastrointestinal bleed.

Initial workup imaging

Imaging of the primary tumor is recommended for all lesions with a reasonable chance of being malignant.[11] Imaging studies should include cross-sectional imaging (MRI with and without contrast and/or CT with contrast) to provide details about the size of tumor and contiguity to nearby visceral structures and neurovascular landmarks.[11] Other imaging studies such as angiogram and plain x-ray may be warranted in selected circumstances.[11]

Contrast improves differentiation of benign from malignant soft-tissue masses. If available, diffusion-weighted MR imaging, dynamic contrast-enhanced perfusion imaging and MR spectroscopy may also aid differentiation of benign from malignant masses.[38]

MRI with and without intravenous contrast is the preferred imaging modality for the evaluation of primary soft-tissue tumors of the extremities, pelvis, and trunk.[11][38][39][40]​​

Computed tomography (CT) with intravenous contrast is the preferred method to evaluate primary retroperitoneal sarcomas, and GIST.[11][38][41]​​​​​ Typically, a CT scan will provide more valuable information than an MRI scan within the abdomen, but either is recommended for the evaluation of primary GIST.[41] FDG-PET/CT scan can also be considered for retroperitoneal/intra-abdominal tumors.[11]

If any primary lesion appears to be malignant according to imaging criteria, a chest CT scan should be mandatory for all patients.[41][42][43]

Consider FDG-PET/CT as part of initial workup to differentiate between neurofibroma(s) and malignant peripheral nerve sheath tumor (MPNST) in people with NF1.

Biopsy

In order to establish the histologic subtype and grade of a sarcoma, a core needle biopsy, fine needle biopsy, or fine needle aspiration should be done in all patients after adequate diagnostic imaging.[11]​​[38][39][44]​​​​​ Functional imaging should be used to guide the biopsy to the highest-grade element of the lesion.[44] An experienced pathologist should review the histopathology of sarcoma specimens. 

In addition to histology, the specimen should be processed for molecular pathology, in which case an open biopsy may be required.[39] The treating specialist needs to consider a number of critical points in determining the optimal site and direction of biopsy, as the decision may be influenced by proposed treatment. Issues to take into consideration include avoiding compromise of fascial planes important to surgical reconstruction, and avoiding contamination of a field that could render the patient inoperable.[39]

Fine-needle aspiration is only used in institutions that have developed specific expertise with this procedure.

Ancillary techniques

Diagnosis of STS with microscopic examination of histology sections remains the gold standard, however several ancillary techniques may be useful in supporting the diagnosis including:[11]

  • Immunohistochemistry

  • Classical cytogenetics

  • Electron microscopy

  • Molecular genetics

Molecular testing utilizes multiple techniques, including next-generation sequencing (NGS) - based methods (including DNA and RNA sequencing) which can determine patient eligibility for clinical trials, identify actionable mutations that may not have been targeted previously, and select patients who may benefit from immunotherapy.[11]

If the physician or pathologist is suspicious of a translocation-associated sarcoma, then appropriate gene rearrangement testing should be carried out to accurately diagnose the sarcoma subtype, for example:[45]

  • KIT and platelet-derived growth factor receptor alpha (PDGFRA) mutations are associated with gastrointestinal stromal tumors (GIST). Patients with GIST lacking a KIT or PDGFRA mutation may have a succinate dehydrogenase (SDH) gene mutation or another rare mutation (e.g., BRAF, NF1, NTRK, and FGFR fusions) and may need further evaluation to guide treatment, including immunohistochemistry testing for SDH deficiency and testing for alternative mutations.[41]

  • Desmoid tumor is associated with Gardner syndrome 5q21-5q22.

  • In cases of clear cell sarcoma, the EWSR1 fluorescence in situ hybridization (FISH) assay should not routinely be performed if another molecular testing modality has been used to detect the translocation. In cases of dermatofibrosarcoma protuberans, the t(17;22) FISH assay should not routinely be performed if another testing modality has been used to detect the translocation.[46]

Full staging workup

Once the primary tumor has been confirmed as malignant, tumor stage should be determined. The following imaging is recommended:[11]

  • Chest CT without contrast: given the risk of hematogenous spread from high-grade sarcoma to the lungs, this is essential for accurate staging.

  • Abdominal/pelvic CT: should be considered for patients with angiosarcoma, leiomyosarcoma, myxoid liposarcoma or epithelioid sarcoma, as well as STS without definitive pathology.

  • MRI of the total spine: should be considered for patients with myxoid cell liposarcoma due to a higher risk of metastasis to the spine compared with other STSs.

  • PET or FDG-PET/CT scan: may be useful for initial staging of STS at any site.

Additional tests

Patients presenting with gastrointestinal bleeding should have a complete blood count (CBC) and coagulation profile performed to determine if there is any anemia or clotting abnormality requiring correction. These patients should be referred for endoscopy as part of the workup.

CBC, liver function tests, and renal function (blood urea nitrogen, creatinine) should be ordered for all patients prior to chemotherapy. In some cases, where treatment may involve cumulative doses of doxorubicin, formal evaluation of cardiac function (e.g., by gated blood pool scan or echocardiogram) may be indicated.[47][48][49]​ This may particularly apply to patients receiving curative treatments for the pediatric sarcomas (rhabdomyosarcoma and Ewing sarcoma).[50][51]

For information on additional testing for Kaposi sarcoma, see Kaposi sarcoma.

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