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Soft-tissue sarcomas (STS) are malignant tumors of mesenchymal origin with a wide spectrum of biologic behaviors. In the United States, approximately 12,000 new cases of STS are diagnosed annually, with men affected slightly more than women.[1] STS are challenging to evaluate and treat, because they represent a spectrum of histologic subtypes.[2,3] Approximately 40% of STS occur in the extremities, 10% in the trunk, 16% in the retroperitoneum/abdominal cavity, 22% in the viscera, and 12% at other sites, including the head and neck.[4]
Image: Intraoperative photograph of a large liposarcoma of the back (18 x 14 x 6 cm) being removed from an 87-year-old man.
Image courtesy of Paraskeva P, Katsaronis P, Spartalis ED, et al. Cases J. 2009;2:9339. PMID: 20084188. [Open access.]
Most STS present as a painless or minimally symptomatic mass. Size can vary broadly, with about a third of these tumors being over 10 cm at diagnosis.[4] The relationship of STS to vital structures plays an important role in the management of these lesions, and balancing tumor clearance with preservation of function is a critical issue in the management of STS.
Image: Preoperative photograph of the liposarcoma (arrows) seen in the previous slide.
Image courtesy of Paraskeva P, Katsaronis P, Spartalis ED, et al. Cases J. 2009;2:9339. PMID: 20084188. [Open access.]
STS make up more than 50 different histologic subtypes.[2,3] Classification of these tumors is based on their morphologic pattern, features on immunohistochemical (IHC) staining, and cytogenetic abnormalities. The World Health Organization (WHO) uses four categories for STS: benign, intermediate (locally aggressive), intermediate (rarely metastasizing), and malignant.[3] STS may also be divided into those with simple karyotypes and those with highly complex karyotypes. Simple karyotype STS may have single chromosomal translocations or isolated activating mutations (eg, KIT mutation in gastrointestinal (GI) stromal tumors [GIST]); complex karyotype STS usually have multiple derangements. The table lists the most common histologic subtypes of STS.
The American Joint Committee on Cancer (AJCC) staging system (shown) is used to stage STS.[5] T staging is determined by the tumor's size and depth. Lymph node metastases are rare, and the risk of distant metastases varies greatly on the basis of the STS subtype. Unlike other solid tumors, histologic grade is incorporated in the STS staging system. However, the TNM staging system has its limitations because of the many different STS subtypes.[5] For example, the size cutoff of 5 cm is of far greater importance for extremity STS compared with retroperitoneal tumors, which are typically larger.
Tables adapted from National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines): Soft Tissue Sarcoma. V.2.2014.[5]
Undifferentiated pleomorphic sarcomas (previously known as malignant fibrous histiocytomas [MFH]) are among the more common adult STS subtypes. However, they are considered a diagnosis of exclusion.[6] Most undifferentiated pleomorphic sarcomas occur in the extremities and retroperitoneum. Histologically, these tumors are characterized by high cellularity and abundant mitotic activity. Surgical excision with negative margins is the preferred treatment. The images show a radiation-associated undifferentiated pleomorphic sarcoma, which has a particularly ominous prognosis.[7]
Image A: T2-weighted magnetic resonance angiogram (MRA) (coronal reconstruction) of a radiation-associated left axillary undifferentiated pleomorphic sarcoma.
Image B: Intraoperative photograph of the same tumor. The arrow indicates the axillary vessels and brachial plexus.
Images courtesy of Steven C. Katz, MD, FACS.
Liposarcomas occur mostly in middle-aged and older adults. Common sites include the proximal lower extremity and retroperitoneum. Histologic grade significantly influences prognosis. Common variants include well-differentiated, dedifferentiated, pleomorphic, myxoid, and round cell liposarcomas.[4]
Image A: Coronal abdominal computed tomography (CT) scan of a well-differentiated retroperitoneal liposarcoma.
Image B: Micrograph of a dedifferentiated liposarcoma under hematoxylin and eosin (H&E) staining. The magnified section reveals the presence of lipoblasts (yellow arrow) and increased vascularity (green arrows). Nonlipogenic sarcomatous tissue predominates in the presence of adipocytes.
Images courtesy of (A) Steven C. Katz, MD, FACS; (B) Wikimedia Commons | Nephron.
Leiomyosarcomas are derived from smooth muscle cells and account for 5-10% of all STS.[8] Although these tumors may appear at any site, leiomyosarcomas commonly arise from retroperitoneal vascular structures and the uterus. With the advent of KIT (CD117) staining, it has been recognized that GI tract leiomyosarcomas are quite rare, and most of these tumors are more accurately classified as GIST.[9] Surgery remains the mainstay of treatment, although chemotherapy and radiation play an important role in cases of locally advanced and/or metastatic tumors.
Image A: Sagittal abdominal magnetic resonance image [MRI] of a leiomyosarcoma (double arrow) of the adrenal vein that extends from the superior pole of the right kidney to the right atrium.
Image B: High-power micrograph of a cutaneous leiomyosarcoma that reveals spindle cells with cigar shaped nuclei (white arrow), prominent cytologic atypia, and mitotic figures (black arrows) (H&E stain).
Images courtesy of (A) Wang TS, Ocal IT, Salem RR, Elefteriades J, Sosa JA. World J Surg Oncol. 2007;5:109. PMID: 17910774. [Open access.]; (B) Wikimedia Commons | Nephron.
The term "synovial sarcoma" is a misnomer, as these tumors do not arise from the synovial cells, and the tumor cells do not share the same immunohistochemical and ultrastructural features of the normal synovium.[10] Synovial sarcomas can occur at any age but typically affect young adults; they generally present as high-grade tumors. The diagnosis is confirmed by detection of the characteristic reciprocal translocation t(x;18)(p11.2;q11.2). Surgical resection is undertaken whenever possible, often in conjunction with radiotherapy and systemic chemotherapy to maximize the likelihood of disease control.[11]
Image A: Coronal T2-weighted lower extremity MRI that shows a markedly heterogeneous mass (arrow), with high signal intensity depicting cystic regions of hemorrhage and necrosis. Portions of the mass are hyperintense relative to the subcutaneous fat.
Image B: High-power micrograph of a pulmonary monophasic fibrous synovial sarcoma with sheets of spindle cells (H&E stain).
Images courtesy of (A) Medscape; (B) Wikimedia Commons | Nephron.
The WHO classifies myxofibrosarcomas (MFS) as a spectrum of malignant fibroblastic lesions with variable myxoid stroma and pleomorphism.[4] In the past, these tumors were considered to be a subset of undifferentiated pleomorphic sarcomas; in more recent years, MFS have been recognized as distinct entities. These tumors usually present in elderly patients (age 60-80 years), and they are notorious for high local recurrence rates. Wide surgical margins are necessary for MFS because of their highly infiltrative growth patterns. Moreover, deep tumors with high-grade histology are more likely to metastasize.[12]
Image: Axial T2-weighted lower-extremity MRI showing MFS (arrow).
Image courtesy of Wikimedia Commons | Hellerhoff.
Angiosarcomas are insidious STS of vascular origin. These tumors may occur in any region of the body, although they frequently arise in the head-and-neck region.[13] Angiosarcomas are often misdiagnosed as benign cutaneous lesions, leading to a delay in appropriate care and a poor prognosis. They sometimes arise as a consequence of radiation therapy for other diseases, such as breast carcinoma. Surgery in combination with radiotherapy appears to provide the best local control rates for angiosarcomas;[14] systemic therapy is indicated for metastatic disease.
Image A: Intraoperative photograph of a scalp angiosarcoma that presented as a rapidly enlarging, reddish purple plaque.
Image B: Micrograph of an epithelioid angiosarcoma (H&E stain). Abundant small blood vessels lined by large atypical endothelial cells can be seen. The magnified section reveals atypical mitosis (yellow arrow).
Images courtesy of (A) Steven C. Katz, MD, FACS; (B) Wikimedia Commons | Nephron.
Malignant peripheral nerve sheath tumors (MPNST) originate from peripheral nerves, and they are often associated with neurofibromatosis type 1 (NF1).[15,16] Signs/symptoms may include peripheral edema and pain or discomfort secondary to nerve involvement. Features associated with a poor prognosis include a large primary tumor (>5 cm), high-grade histology, coexistent NF, and the presence of metastases. Surgical resection with wide margins is the first-line treatment. Systemic chemotherapy and radiotherapy are offered as adjuvant or neoadjuvant treatments.
Image A: Coronal MRI of the lower extremities, revealing an MPNST of the left tibia (arrow).
Image B: High-magnification micrograph depicting the herringbone pattern classically seen in MPNST (H&E stain).
Images courtesy of (A) Kosmas C, Tsakonas G, Evgenidi K, et al. Cases J. 2009;2:7612. [Open access.]; (B) Wikimedia Commons | Nephron.
Rhabdomyosarcomas (RMS) are STS of skeletal muscle origin; these tumors are most commonly seen in children aged 1-5 years. The two most common variants are embryonal RMS and alveolar RMS; other variants include botryoid, spindle cell, and undifferentiated RMS. RMS express MyoD1 and myogenin proteins, which are usually not found in normal skeletal muscle; thus, they can serve as useful immunohistochemical markers.[17] Treatment of RMS is based on the tumor type and its resectability; therapeutic modalities other than surgery include chemotherapy, radiotherapy, and, rarely, high-dose chemotherapy with stem cell transplantation.[18]
Image A: Noncontrast head CT scan depicting a large RMS without any intracranial extension.
Image B: Micrograph of an embryonal RMS that shows many small, round tumor cells with hyperchromatic nuclei, as well as large, polygonal-shaped tumor cells with abundant eosinophilic cytoplasm, which often contain diagnostic cross striations (arrow).
Images courtesy of (A) Vankalakunti M, Das A, Rao NK. Diagn Pathol. 2006;1:37. PMID: 17044930. [Open access.]; (B) Medscape | Scott Kilpatrick, MD.
Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous STS that is notorious for being locally aggressive but rarely metastasizes; approximately 90% of DFSP are low-grade sarcomas.[19] These lesions usually present as an indurated, nodular plaque that slowly grows over years. In advanced cases, DFSP can become fixed to underlying structures, ulcerate, and bleed. More than 90% of DFSP have a chromosomal translocation, t(17;22), that causes fusion of COL1A1 with the gene for platelet-derived growth factor-beta (PDGFβ). DFSP are often positive for CD34.[20] The standard treatment for DFSP is wide surgical resection with margins of 2-4 cm. Targeted therapy with imatinib to block PDGF signaling can be used to induce tumor regression in patients with recurrent, unresectable, or metastatic DFSP.[21]
Image: Photograph of DFSP presenting as a nodular plaque on the chest.
Image courtesy of Medscape.
Workup for STS of the extremities and trunk includes obtaining appropriate imaging studies and usually performing a biopsy. MRI is the preferred imaging modality for extremity (shown) and trunk STS because of its excellent definition of the tumor extent and of the relationship of the mass to the surrounding structures and soft-tissue planes. Although incisional biopsy may be indicated for large, superficial tumors, core needle biopsy is used more often. The biopsy track should be carefully planned for inclusion with the primary tumor during formal surgical resection.[4]
Image: MRI of lower extremities demonstrating a high-grade STS in the posterior calf that abuts the tibial nerve and posterior tibial vessels.
Image courtesy of Medscape | Howard A. Chansky, MD.
In contrast to the means of imaging STS of the extremities and trunk, CT scanning is the imaging modality of choice for visceral or retroperitoneal STS. CT scan–guided core biopsy may be obtained in selected cases. Depending on the patient findings and imaging features, other retroperitoneal tumor types should be among the diagnostic considerations, including germ cell tumors and lymphoma.
Image: CT scan of the abdomen demonstrates a large retroperitoneal dedifferentiated liposarcoma (arrow). Its relationship to critical structures can be clearly seen—including the aorta, inferior vena cava (IVC) (#), superior mesenteric vein (*), and bowel—which helps in surgical planning.
Image courtesy of Steven C. Katz, MD, FACS.
Surgery is the cornerstone of treatment for extremity STS; the goal is complete excision with negative microscopic margins (R0 resection).[5] Frequently, these tumors develop a "pseudocapsule," which arises as a result of the reactive, compressed surrounding tissue. It is desirable to resect a margin of normal tissue around the pseudocapsule plane;[5] microscopically, STS often extend beyond the apparent confines of the pseudocapsule. Although the goal of STS surgery is always complete tumor clearance with a margin of normal tissue, this must be balanced by the need to preserve form and function to the greatest extent possible on the basis of the biologic potential and the tumor anatomy.
Images: Intraoperative photographs of tumor bed after wide surgical excision of STS from a lower extremity (A) and the left axilla (B).
Images courtesy of Steven C. Katz, MD, FACS.
For visceral/retroperitoneal STS, achieving R0 resection (microscopically negative margins) may require resection of the adjacent organs, including the kidney or bowel. Although R0 resection is the goal when resecting STS in the abdominal cavity, an R1 resection (microscopically positive margins) is a reasonable option for low-grade tumors that abut vital organs.[22,23] A true R0 resection may not be possible for large retroperitoneal tumors that abut the aorta, IVC, and other vital structures. The authors advocate uniform levels of surgical aggressiveness on all aspects of a tumor.
Images: Intraoperative photographs of a large retroperitoneal liposarcoma before (A) and after (B) complete resection, which included a right nephrectomy. # = IVC; * = right renal vein stump.
Images courtesy of Steven C. Katz, MD, FACS.
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