Practice Essentials
Liposarcoma is one of the least frequent nonrhabdomyosarcoma soft tissue sarcomas to occur in childhood; it comprises less than 5% of all soft tissue sarcomas in childhood. [1, 2, 3] Surgical excision is the primary treatment, and prognosis depends on the histologic subtype and degree of resection. For patients with residual disease, radiotherapy has been used. [1]
Pathophysiology
Liposarcoma is a lipogenic tumor of large deep-seated connective tissue spaces. The 3 major locations in which liposarcomas are found are the lower extremities, the retroperitoneal region, and the shoulder area. The favored sites of occurrence in the lower extremities include the popliteal fossa and medial thigh. The most common retroperitoneal location is the perineal region. Occasionally, tumors may originate in the subcutis of shoulder, neck, and facial areas. Children tend to have a higher incidence of lower extremity tumors. [4]
Three distinct subgroups based on clinicopathologic and cytogenetic features have been identified: well-differentiated/dedifferentiated, myxoid/round-cell, and pleomorphic.
Well-differentiated/dedifferentiated liposarcoma has amplification of region 12q13–15, which includes the genes MDM2 and CDK4. [5] Next generation sequencing identified 27 mutations in addition to amplification of MDM2 and CDK4. Two of these mutations, NF2 and EGFR, were driver mutations and potentially actionable. [6]
Myxoid liposarcoma has the translocation t(12;16)(q13;p11.2). This involves fusion of the transcription factor gene CHOP (DDIT3), which is essential for adipocytic differentiation, to the translocated in liposarcoma (TLS) or FUS gene on chromosome 16. [7] In about 2% of cases, a variant translocation t(12;22)(q13;q12) that involves fusion of CHOP (DDIT3) with the EWSR1 gene on chromosome 22 is noted. These cytogenetic abnormalities have also been reported in the more aggressive round-cell liposarcoma; myxoid and round-cell liposarcoma form a spectrum with regard to disease aggressiveness. [8]
Pleomorphic liposarcoma lacks identifiable translocations or gene amplification and was characterized by its clinical and pathologic aggressiveness. The introduction of molecular biological analysis suggests that many of these tumors express MDM2 and CDK4 and may better be described as dedifferentiated liposarcoma. [9]
In retrospective review of 331 liposarcoma samples, the use of molecular techniques in addition to standard histology resulted in a change in the type of liposarcoma diagnosed in approximately one-quarter of patients. [9]
Etiology
Although the precise etiology of liposarcomas is not yet defined, the presumed origin likely involves terminal dedifferentiation of mesenchymal cellular components. For myxoid/round-cell liposarcomas, the TLS-CHOP oncoprotein plays a key role in tumor formation. [10, 11] No specific causative environmental factors have been identified because of the rarity of these tumors.
Epidemiology
United States statistics
In children, liposarcomas are rare and comprise fewer than 5% of soft tissue sarcomas.
Overall, less than 150 cases of childhood liposarcoma have been reported in the literature, usually in the second decade of life. [12, 13] At a large New York Cancer Hospital, 18 cases of liposarcoma were reported in patients aged 22 years or younger over a period of 4 decades. [14] A multi-institutional study reviewed 82 patients younger than 22 years diagnosed over a 27-year period. [15]
International statistics
Liposarcomas account for fewer than 2% of all pediatric soft tissue malignancies worldwide, and almost 90% of pediatric liposarcomas occur during the second decade of life. [3, 16, 17]
Race-, sex-, and age-related demographics
Race
No racial predilection is apparent.
Sex
In the several small series reported, gender predominance varies; assessing an accurate male-to-female ratio is not currently possible.
Age
Overall, the average age at presentation is 50 years. Liposarcomas are rarely seen in the teenage years and are almost never found in patients younger than 8 years. Earlier reports of liposarcoma in infancy are now mostly thought to be lipoblastomatosis. [4]
Prognosis
Prognosis depends on the stage, histologic subtype or grade, anatomic location of the tumor, tumor size, and the overall treatment regimen used.
Five-year survival rates range widely vary, depending on histologic subtype.
Based on histologic characteristics alone, myxoid lesions, which occur commonly in children, have 5-year survival rates approaching 80%.
In contrast, rare highly-aggressive pleomorphic lesions have 5-year survival rates around 20%
With any histologic subtype, local recurrence is common and is related to the completeness of surgical excision. If metastases occur, they typically involve the lungs, but unusual extrapulmonary soft tissue sites such as retroperitoneum or chest wall may be involved.
Morbidity/mortality
Owing to its rarity, survival data for liposarcoma patients are often extrapolated from small series or from adult data. As with other childhood nonrhabdomyosarcoma soft tissue sarcomas, outcome is linked to various prognostic factors, including stage and grade. Complete surgical resection is crucial. The estimated 5-year overall survival rates are impacted by histologic subtype and are as follows [9] :
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Pleomorphic tumors - 40%
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Round-cell tumors - 40%
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Myxoid tumors - 80%
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Well-differentiated tumors - 80-100%
Local recurrence following resection is common and may be avoided by wide excision or adjuvant radiation. Thus, an extremity location, which allows aggressive surgery, is a favorable prognostic feature as opposed to a retroperitoneal location.
Metastatic spread varies but commonly occurs to the lungs in high-grade pleomorphic tumors. [18] Lymphatic spread is not seen. Myxoid liposarcoma is often considered intermediate grade but may still metastasize in 10-35% patients, sometimes to extrapulmonary soft tissue sites, such as the retroperitoneum or chest wall [19] or even brain and spine. [20]
