AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Liposarcoma is one of the least frequent nonrhabdomyosarcoma soft tissue sarcomas that occur in childhood; it comprises less than 5% of all soft tissue sarcomas in childhood.^{1, 2} 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.³ 

Well-differentiated liposarcomas have ring or marker chromosomes commonly derived from 1q and 12q13–15.⁴

The consistent cytogenetic abnormality in myxoid liposarcoma is translocation t(12;16)(q13;p11.2). This involves fusion of the transcription factor gene CHOP, which is essential for adipocytic differentiation, to the translocated in liposarcoma (TLS) gene on chromosome 16.⁵ In about 2% of cases, CHOP may fuse with the EWS gene on chromosome 22 in translocation t(12;22)(q13;q12).

These cytogenetic abnormalities have also been reported in the more aggressive round-cell liposarcoma; myxoid and round cell liposarcoma form a clear spectrum with regard to disease aggressiveness.⁶

Pleomorphic liposarcoma usually lacks this distinct translocation and appears to be biologically closer to other aggressive pleomorphic sarcomas.

Frequency

United States

In children, liposarcomas are rare and comprise fewer than 5% of soft tissue sarcomas.

Overall, around 100 cases of childhood liposarcoma have been reported in the literature, usually in the second decade of life. 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.⁷

Mortality/Morbidity

Due 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 survival rates for nonmetastatic, completely resected extremity tumors are impacted by histologic subtype and are as follows:⁸

• Pleomorphic tumors - 50%
• Round-cell tumors - 50%
• Myxoid tumors - 80%
• Well-differentiated tumors - 100% 

Metastatic spread varies but commonly occurs to the lungs in high-grade pleomorphic tumors. 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 wall⁹ or even brain and spine.¹⁰

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 10 years. Earlier reports of liposarcoma in infancy were mostly thought to be lipoblastomatosis upon review.³

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Presentation varies, but the tumor usually presents as a painless slow-growing lesion. Only 10-15% patients have a painful rapidly growing mass or functional limitations.
• Depending on the location and involvement of adjacent structures in the extremity, weakness or limitation of motion may be observed.
• Rarely, nonspecific symptoms, such as weight loss, fatigue, and lassitude, may also be observed.

Physical

• Fascial compartmentalization may cause soft tissue sarcomas to adopt awkward discoid and fusiform shapes rather than smooth round forms.
• A fairly well-circumscribed palpable mass slowly increasing in size over many months appears to be the first manifestation of disease in many patients.
• Pain is not often a prominent manifestation.
• Diffuse abdominal enlargement may be observed in patients with retroperitoneal disease.
• Characteristics of the primary tumor, such as size, texture, and mobility, are important to note.
• The neurovascular status of the involved extremities distal to the tumor should be evaluated.
• Palpation of draining lymph nodes usually does not reveal disease.

Causes

• 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.¹¹
• No specific causative environmental factors have been identified because of the rarity of these tumors.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Lipoma is primary in the differential diagnosis and may be difficult to distinguish from liposarcoma.

Lipoblastomatosis is important to differentiate in children because lipoblastomatosis is benign, well circumscribed, and does not require wide excision. It should be suspected in children younger than 8 years. Molecular genetics can be used on tumor tissue to demonstrate rearrangement of chromosome 8q12 involving the PLAG-1 oncogene.¹² 

Other nonrhabdomyosarcoma soft tissue sarcomas of childhood, include the following:

• Malignant fibrous histiocytoma
• Alveolar soft part sarcoma
• Synovial cell sarcoma
• Neurofibrosarcoma

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Imaging Studies

• CT scanning and MRI of the primary tumor may provide complementary findings.
• • CT scanning is superior to MRI in detailing cortical bone erosion and tumor mineralization.
  • MRI is useful in providing views of the long axis of the limb and can sometimes depict the fatty nature of the tumor. Different subtypes exhibit varying signal characteristics.¹³ For example, myxoid liposarcomas have low signal on T1W, high signal on T2W, and thickened septa on postcontrast images. Round-cell liposarcomas and pleomorphic liposarcomas lack characteristic fat signal and look similar to other soft tissue sarcomas.
• Angiography may reveal malignancy based on prominent vascularity and, thus, may be of value in planning surgical resection.
• Fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging may also reveal malignancy, based on intensity of FDG activity.¹⁴
• Chest radiography may be used as initial screening for pulmonary metastases; however, the definitive modality used to detect pulmonary metastases is chest CT scanning. CT scanning of the chest and abdomen may be needed to evaluate for extrapulmonary metastatic spread, which may be seen with myxoid liposarcoma.

Procedures

• The diagnostic procedure of choice is open biopsy. Minimally invasive procedures have been advocated, such as fine needle aspiration; however, experience with these modalities is limited, and results have been equivocal.
• For superficially located small fatty tumors, excisional biopsy is recommended for diagnosis.
• For larger (>3 cm) and deeper tumors, diagnosis and treatment may involve open incisional biopsy followed by definitive resection.

Histologic Findings

Gross appearance can widely vary from tumor to tumor. Usually, the tumor displays smooth, lobulated, or nodular masses that are both encapsulated and freely movable. Upon section, fine fibrous septa can be observed dividing the tumor into smaller lobules. Areas of necrosis and recent and old hemorrhage are not infrequent. Calcification and ossification are uncommon.

Several histologic subtypes are recognized; the 4 primary subtypes are well-differentiated, myxoid, round cell, and pleomorphic. Myxoid is the most common subtype and may be more common in children.

• Well-differentiated liposarcomas are composed of a heterogeneous organization of univacuolate adult lipocytes, chronic inflammatory cells, and fibrous connective tissue. This fibrous matrix harbors an arrangement of fat-storing stellate-shaped cells. Neoplastic cells with large hyperchromatic and pleomorphic nuclei are scattered within the region. Fat necrosis and mitosis usually are not observed. Dedifferentiated lesions may demonstrate a pattern of a densely cellular spindle-shaped sarcoma without fat accumulation.
• Myxoid liposarcomas occur in various forms based on the degree of cellularity. Basic features of this subtype include (1) proliferating lipoblasts in various stages of differentiation, (2) delicate plexiform capillary patterns, and (3) a myxoid matrix containing abundant hyaluronidase-sensitive acid mucopolysaccharides. The least cellular pattern is a low-grade tumor harboring small spindle-shaped cells. These cells surround a plexiform vascular pattern that contrasts with a background of extracellular acid mucopolysaccharide. The most cellular pattern is that of a round-cell liposarcoma containing densely packed uniformly round cells that overcrowd the plexiform vasculature. In reality, most myxoid-type lesions have a mixture of the above features.
• Round-cell liposarcomas are associated with an aggressive clinical course and a high frequency of metastases. The primary feature is an excessive proliferation of uniform and rounded cells with little intercellular myxoid material. Occasionally, cells are arranged in branching rows and strands along abortive capillaries, resulting in a trabecular and adenoid appearance. Large pale polyhedral cells often give a hypernephroid appearance to the tumor.
• Pleomorphic liposarcomas display a disorderly growth pattern, a large degree of cellular pleomorphism, and several bizarre giant cells. Large giant cells may be observed harboring numerous lipid droplets of varying size, giving a moruloid appearance to the cells. Nucleoli vary in occurrence. Numerous small polygonal, round, and spindle-shaped lipoblasts can be observed intermingled with giant cells.

Histologic grade is stratified into 3 broad categories: high, intermediate, and low grade.

• High-grade liposarcoma includes the pleomorphic and round cell types.
• Intermediate-grade lesions encompass the poorly differentiated round-cell component type.
• Low-grade liposarcomas include well-differentiated, myxoid, and lipomatous-type liposarcomas.

Staging

Staging for childhood soft tissue sarcomas follows the standard American Joint Committee on Cancer (AJCC) system; unfortunately, it is of limited value. Liposarcomas do not spread to regional lymph nodes, and lymph node dissection is not indicated. Careful imaging is crucial in staging to assess size and presence or absence of metastases. Considering the possibility that a retroperitoneal or chest wall lesion may have a primary in the lower limb is important.

Grade or histologic subtype impacts significantly on prognosis, and an experienced pathologist needs to be involved. Myxoid liposarcomas that have more than 5-20% round-cell component have a worse outcome.

The AJCC staging system is as follows:

• G1 - Low grade
• G2 - Intermediate grade
• G3 - High grade
• T1a - Noninvasive (<5 cm)
• T1b - Noninvasive (>5 cm)
• T2a - Invasive (<5 cm)
• T2b - Invasive (>5 cm)
• N1 - Regional nodes involved
• M1 - Distant metastases

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Chemotherapy has been shown to be active in these tumors, but its role needs to be defined in clinical trials.

Postoperative radiotherapy may be administered (see Further Inpatient Care).

Surgical Care

Surgical objectives include obtaining an accurate histologic diagnosis, minimizing the chance of local recurrence, achieving the best possible functional and anatomic result, and maximizing the probability of survival. Surgery should be performed at a children's cancer center with significant experience dealing with these rare tumors.

Open biopsy must be meticulously performed to avoid hematoma, tumor cell spillage, and postoperative infection. The incision must be oriented so that the biopsy site can be completely encompassed in the definitive resection. A longitudinal incision parallel with the fiber direction of the underlying muscle is used. Under ideal conditions, the surgeon performing the definitive resection also should perform the initial biopsy. Sometimes, performing the incisional biopsy and resection is possible during the same procedure, provided that the frozen section is definitive.

The 3 main techniques of surgical resection used in patients with liposarcoma include simple excision, wide en bloc resection, and amputation. The type of resection used is determined by the tumor's histology and by the anatomic findings at the time of surgery.

• If the lesion appears to be grossly and histologically consistent with lipoma or well-differentiated liposarcoma, simple excision is acceptable.
• If the mass contains areas suggestive of low-grade liposarcoma with clear margins, simple marginal excision can be curative. When evidence suggesting high-grade liposarcoma is present, either a wider resection of the tumor bed may be performed or adjuvant radiotherapy may be added.
• If preoperative studies (CT scanning, MRI, biopsy specimen analysis) suggest a high-grade lesion, either wide en bloc resection or amputation can be planned. Avoid shelling out a high-grade tumor because microscopic disease is left behind. In patients in whom amputation is under serious consideration (either as an initial procedure or following a limb-sparing operation), preoperative education is imperative.
• In upper extremity tumors, axillary dissection is not performed unless the nodes feel abnormal.

Consultations

• Pediatric oncologist: For lesions in which malignancy is strongly suspected or in which a previous incisional biopsy has revealed liposarcoma, consultation with pediatric oncologist is recommended prior to the definitive surgical procedure.
• Radiation oncologist: Adjuvant therapy may be indicated in patients in whom excision is incomplete or when close margins are noted along with concern about microscopic residual disease. Consultation with a radiation oncologist is recommended.

Activity

Consultation with a physical therapist and referral for rehabilitation may be appropriate, depending on the site of the primary and the degree of surgical resection performed.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The role of adjuvant chemotherapy in soft tissue sarcomas is not clearly defined. A definitive survival advantage for patients with incompletely resected tumors who are treated with combination chemotherapy has not been established, despite the fact that the tumors can respond to chemotherapy.¹⁵

Although no definitive chemotherapeutic protocol has been established, doxorubicin and ifosfamide appear to be the most effective cytotoxic agents for nonrhabdomyosarcoma soft tissue sarcomas. In this setting, chemotherapy is investigational and consultation with a pediatric oncologist who has experience with nonrhabdomyosarcoma soft tissue tumors is required.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Consideration for adjuvant therapy for liposarcoma should be based on the degree of residual disease left behind.
• If microscopic disease remains following surgery, postoperative radiation therapy should be administered. External beam radiation doses can range from 4000-6500 centigray, with dosing to be determined in consultation with a radiation oncologist. In children, long-term effects of radiotherapy, such as skeletal and soft tissue deformation, effects on growth, and risk of neoplastic transformation, should be weighed against the child's current physiologic status and potential for remission from liposarcoma.
• If macroscopic disease remains following surgery, radiotherapy, chemotherapy, and second-look surgery should all be considered.

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 tend to 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.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Although liposarcoma is an extremely rare lesion in the pediatric population, considering liposarcoma in the differential diagnosis of lipoma is important. Careful pathologic analysis of all excised specimens that clinically resemble lipoma is essential to avoid misdiagnosing a potentially lethal condition.
• Lipoblastomatosis and liposarcoma should be differentiated in younger children to avoid unnecessarily mutilating surgery.
• The surgeon needs to place and orient the biopsy incision in a location that allows subsequent curative resection of the liposarcoma.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Marcus KC, Grier HE, Shamberger RC, Gebhardt MC, Perez-Atayde A, Silver B. Childhood soft tissue sarcoma: a 20-year experience. J Pediatr. Oct 1997;131(4):603-7. [Medline].
2. Spunt SL, Poquette CA, Hurt YS, et al. Prognostic factors for children and adolescents with surgically resected nonrhabdomyosarcoma soft tissue sarcoma: an analysis of 121 patients treated at St Jude Children's Research Hospital. J Clin Oncol. Dec 1999;17(12):3697-705. [Medline].
3. Shmookler BM, Enzinger FM. Liposarcoma occurring in children. An analysis of 17 cases and review of the literature. Cancer. Aug 1 1983;52(3):567-74. [Medline].
4. Italiano A, Cardot N, Dupre F, et al. Gains and complex rearrangements of the 12q13-15 chromosomal region in ordinary lipomas: the "missing link" between lipomas and liposarcomas?. Int J Cancer. Jul 15 2007;121(2):308-15. [Medline].
5. Crozat A, Aman P, Mandahl N, Ron D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. Jun 17 1993;363(6430):640-4. [Medline].
6. Fiore M, Grosso F, Lo Vullo S, et al. Myxoid/round cell and pleomorphic liposarcomas: prognostic factors and survival in a series of patients treated at a single institution. Cancer. Jun 15 2007;109(12):2522-31. [Medline].
7. La Quaglia MP, Spiro SA, Ghavimi F, Hajdu SI, Meyers P, Exelby PR. Liposarcoma in patients younger than or equal to 22 years of age. Cancer. Nov 15 1993;72(10):3114-9. [Medline].
8. Chang HR, Hajdu SI, Collin C, Brennan MF. The prognostic value of histologic subtypes in primary extremity liposarcoma. Cancer. Oct 1 1989;64(7):1514-20. [Medline].
9. Cheng EY, Springfield DS, Mankin HJ. Frequent incidence of extrapulmonary sites of initial metastasis in patients with liposarcoma. Cancer. Mar 1 1995;75(5):1120-7. [Medline].
10. Schwab JH, Boland PJ, Antonescu C, Bilsky MH, Healey JH. Spinal metastases from myxoid liposarcoma warrant screening with magnetic resonance imaging. Cancer. Oct 15 2007;110(8):1815-22. [Medline].
11. Antonescu CR, Elahi A, Humphrey M, et al. Specificity of TLS-CHOP rearrangement for classic myxoid/round cell liposarcoma: absence in predominantly myxoid well-differentiated liposarcomas. J Mol Diagn. Aug 2000;2(3):132-8. [Medline]. [Full Text].
12. Brandal P, Bjerkehagen B, Heim S. Rearrangement of chromosomal region 8q11-13 in lipomatous tumours: correlation with lipoblastoma morphology. J Pathol. Feb 2006;208(3):388-94. [Medline].
13. Song T, Shen J, Liang BL, Mai WW, Li Y, Guo HC. Retroperitoneal liposarcoma: MR characteristics and pathological correlative analysis. Abdom Imaging. Sep-Oct 2007;32(5):668-74. [Medline].
14. Brenner W, Eary JF, Hwang W, Vernon C, Conrad EU. Risk assessment in liposarcoma patients based on FDG PET imaging. Eur J Nucl Med Mol Imaging. Nov 2006;33(11):1290-5. [Medline].
15. Cecchetto G, Alaggio R, Dall'Igna P, et al. Localized unresectable non-rhabdo soft tissue sarcomas of the extremities in pediatric age: results from the Italian studies. Cancer. Nov 1 2005;104(9):2006-12. [Medline].
16. Castleberry RP, Kelly DR, Wilson ER, et al. Childhood liposarcoma. Report of a case and review of the literature. Cancer. Aug 1 1984;54(3):579-84. [Medline].
17. Enzinger FM, Weiss SW. Liposarcoma. In: Enzinger F, Weiss S, eds. Soft Tissue Tumors. St Louis, MO: Mosby; 1995:431-66.
18. Ferrari A, Casanova M, Spreafico F, et al. Childhood liposarcoma: a single-institutional twenty-year experience. Pediatr Hematol Oncol. Sep-Oct 1999;16(5):415-21. [Medline].
19. Gronchi A, Casali PG, Fiore M, et al. Retroperitoneal soft tissue sarcomas: patterns of recurrence in 167 patients treated at a single institution. Cancer. Jun 1 2004;100(11):2448-55. [Medline].
20. Raaf JH, Ragsdale BD. Surgical management of liposarcoma. In: Bogumil GP, Fleegler EJ, eds. Tumors of the Hand and Upper Limb. 1993.

Article Last Updated: Jun 4, 2008