Dermatology

Liposarcoma

Are You Confident of the Diagnosis?

Size greater than 5cm, tumor depth to deep fascia, relatively fast-growing, concerning clinical features such as firmness or irregularity and attachment to the underlying tissue.

Characteristic findings on physical examination

A growing large deep tumor on extremities, very rarely in skin. The thigh is the most common site for soft tissue sarcomas including liposarcoma. The myxoid variant is located more than two thirds of the time in the deep musculature of the thigh. The well-differentiated type is most common in the extremities and retroperitoneum. Since most liposarcomas are located in deep tissue, ulceration is rarely reported.

Expected results of diagnostic studies

Preoperative core needle biopsy (image-guided) has an accuracy of 73%. Histology demonstrates different variants: well-differentiated (lipoma-like but with significant variations in cell size/pleomorphism and at least focal atypia in both adipocytes and stromal cells; some consider lipoblasts as a marker when differentiating the lesion from an atypical lipoma); myxoid type (uniform round to oval primitive non-lipogenic mesenchymal cells and variable number of small signet-ring lipoblasts in a prominent myxoid stroma with characteristic branching vasculature pattern); round cell variant (with greater than 5% round cells seen in given tumor) and; pleomorphic (variable number of pleomorphic lipoblasts)(Figure 1, Figure 2).

Figure 1.

Liposarcoma, magnification 40x. (Courtesy of Cloyce L Stetson, MD)

Figure 2.

Liposarcoma, magnification 10x. (Courtesy of Cloyce L Stetson, MD)

Imaging (CT or MRI) may reveal heterogeneity and wider septae (also seen with a deep atypical lipoma).

Diagnosis confirmation

Lipomas are usually superficial compared with liposarcomas and are histologically distinct; other (deep) soft tissue sarcomas are also histologically distinct but should be considered in the clinical differential diagnosis.

Open biopsy should be done to confirm the diagnosis. This allows for adequate tissue sampling and is superior to fine needle biopsy.

Who is at Risk for Developing this Disease?

Risk factors for liposarcoma are summarized in Table I.

Table I.

Risk factors for liposarcoma
Subtype Develops when Additional Comment
Well differentiated (40-50%) tend to occur in the 6th decade of life considered most common soft tissue sarcomas in adults and are rare in children; most common in the extremities and retroperitoneum; good prognosis
De-differentiated associated with well-differentiated subtype  most commonly seen in the retroperitoneum
Myxoid (> 33%) usually 4th to 5th decade of life located > 2/3 of time in the deep musculature of thigh; overall 1/3 metastatic rate
Pleomorphic (5%) after age 50 years (especially elderly) high grade and aggressive

What is the Cause of the Disease?

Etiology

Pathophysiology

Well-differentiated types are associated about 80% of the time with supernumerary ring, giant chromosomes, and double minutes. These changes are associated with 12q13-15 region (including MDM2) amplification; myxoid and round cell types are associated with t(12;16)(q13;p11) resulting in TLS (also known as FUS at 16p11)/ CHOP (also known as DDIT3 at 12q13) fusion protein in greater than 90% of cases. Rarely associated with t(12;22)(q13;q12) resulting in EWS (highly related to FUS-CHOP fusion protein); pleomorphic type is associated with high chromosomal counts and complex structural rearrangements.

Liposarcomas arise most often de novo. Rarely if ever do they arise from lipomas.

Systemic Implications and Complications

Well-differentiated type (40% to 45% of liposarcomas), like deep atypical lipomas, have a good prognosis. The presence of lipoblasts is used by some to differentiate liposarcomas from lipomas. Lesions recur locally but are not associated with metastasis or death from distant disease. Histologic subtypes of lipoma-like, sclerosing, and inflammatory (lymphocyte-rich) variants all have the same prognosis. De-differentiated types (90% de novo, 10% recurrent) have a 15% to 20% metastatic rate.

The myxoid type (>33% of liposarcomas) has an overall one third metastatic rate. Metastases most commonly affect soft tissue and bone (especially spine) before the lung. There is a higher chance of multifocal disease at presentation. A hypercellular or round-cell morphology (15% of liposarcomas and a variant of myxoid type) is associated with a poorer prognosis. There is a 70% to 90% 5-year survival if myxoid; 20% to 50% 5-year survival for the round cell component.

Pleomorphic types (5% of liposarcomas) are high grade and aggressive with a metastatic rate up to 50% (lung particularly, 90%); overall tumor-associated mortality is 40% to 50%.

Treatment Options

Patients with liposarcomas should be referred to facilities that specialize in soft tissue sarcomas.

Complete excision is first-line for treatment. A wide local excision with 1 to 2cm of normal tissue should be perfomed.

Well-differentiated liposarcomas are generally treated only with excision. Adjuvant radiation may be used, especially if the lesion is close to critical neural structures.

Due to high recurrence rate, chemotherapy should be considered, especially in higher grade types. Since these tumors are rare, studies are extremely difficult to conduct. Overall for soft tissue sarcomas, anthracyclines (doxorubicin and epirubicin) and ifosfamide are considered first-line for stage 3 and retroperitoneal disease. Chemotherapy is used as adjuvant to surgery and as palliative treatment if the lesion is nonresectable (especially stage 4)

Radiation therapy has shown to improve local control compared with surgery alone but does not improve overall survival. Preoperative treatment is complicated by poor wound healing. Postoperative treatment is associated with increased fibrosis, edema, and joint stiffness.

Optimal Therapeutic Approach for this Disease

The recommendation is that these patients be referred to facilities that specialize in soft tissue sarcomas. Referral to a surgical oncologist, radiation oncologist and a medical oncologist are required.

Wide-local excision is the first-line treatment.

To date, there are no clinical trials providing evidence that nonsurgical interventions have a significant impact on overall survival.

Chemotherapy is considered for intermediate- to high-grade malignancy if lesions are retroperitoneal or stage 3 or higher. Chemotherapy is used palliatively for stage 4 disease. One can review the National Comprehensive Cancer Networks (NCCN) guidelines for the most current treatment of these tumors. www.NCCN.org

Radiation is best used for local disease control if a complete wide local excision is not attainable due to close critical structures.

Patient Management

These patients shoud be referred to facilities that specialize in soft tissue sarcomas. Because of their high rate of recurrence, close follow-up is necessary. Patients should be followed by an oncologist, every 3 to 6 months for a history and physical examination for the initial 2 to 3 years, then annually. Consider magnetic resonance imaging posttreatment, twice a year for the first 2 to 3 years, then annually thereafter. Follow-up should be for at least 8 years for high-grade tumors and longer for low-grade tumors since the latter are associated with late relapses.

Obtain a chest X-ray for high-grade types or stage 2 or higher disease every 3 to 6 months for 2 to 3 years, then twice yearly for 2 more years, then annually.

Retroperitoneal disease is associated with the de-differentiated subtype if original tumor is well-differentiated-type.

Unusual Clinical Scenarios to Consider in Patient Management

A patient with Bazex syndrome (acrokeratosis paraneoplastica) has been reported to be associated with a retroperitoneal liposarcoma. Primary periorbital liposarcomas have been reported in the Li-Fraumeni familial cancer syndrome.

What is the Evidence?

Serpell, JW, Chen, RYY. "Review of large deep lipomatous tumours". ANZ J Surg. vol. 77. 2007. pp. 524-9.

(Retrospective review of large deep lipomatous tumors reflecting on behavior with a summary discussing the workup and management of such tumors.)

Sandberg, AA. "Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: liposarcoma". Cancer Genet Cytogenet. vol. 155. 2004. pp. 1-24.

(Review of liposarcoma with focus on associated cytogenetic abnormalities.)

Demetri, GD, Antonia, S, Benjamin, RS, Bui, MM, Casper, ES. National Comprehensive Cancer Network clinical practice guidelines in oncology: Soft tissue sarcoma. 2010 v2. http://www.nccn.org.

(Consensus statement outlining management of soft tissue sarcoma. Updated yearly)

Grimer, R, Judson, I, Peake, D, Seddon, B. "Guidelines for the management of soft tissue sarcomas". Sarcoma. 2010. pp. 1-15.

(Guidelines for management from a consensus meeting of sarcoma specialists from the United Kingdom.)
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