AUTHOR INFORMATION

Section 1 of 11

Authored by Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP, Assistant Professor of Pediatric Hematology-Oncology, Department of Pediatrics, Children's Hospital at Albany Medical Center

Coauthored by Anastasios K Konstantakos, MD, Fellow, Department of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School; David L Dudgeon, MD, Professor, Department of Surgery, Rainbow Babies and Children's Hospital, University Hospitals of Cleveland and Case Western Reserve University

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP, is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Royal College of Physicians

Edited by Stephan A Grupp, MD, PhD, Director, Stem Cell Biology Program, Children's Hospital of Philadelphia; Assistant Professor, Department of Pediatrics, Division of Oncology, University of Pennsylvania; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Steven K Bergstrom, MD, Assistant to the Chairman, Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland, CA; Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida, Clinical Professor, Department of Pediatrics, UNC, Adjunct Professor, Department of Pediatrics, Duke University; and Maureen Strafford, MD, Arnold P Gold Foundation Associate Professor, Departments of Anesthesiology and Pediatrics, Tufts University and Tufts-New England Medical Center

Author's Email:	Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP
Editor's Email:	Stephan A Grupp, MD, PhD

eMedicine Journal, July 20 2006, VOLUME 7, Number 7

INTRODUCTION

Section 2 of 11

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. Surgical excision is the primary treatment, and prognosis is dependent on histologic subtype and degree of resection. For patients with residual disease, radiotherapy has been used.

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.

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. 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. These genetic abnormalities have not been observed in the well-differentiated and pleomorphic subtypes of liposarcoma.

Frequency:

• In the US: Soft tissue sarcomas occur in approximately 5000 patients in the United States per year, and liposarcomas comprise fewer than 20% of them, with an average patient age of 50 years. In children, liposarcomas are rare and comprise fewer than 5% of soft tissue sarcomas. In a review of 2500 cases of liposarcoma, only 17 occurred in patients younger than 16 years. At a large New York Cancer Hospital, only 18 cases of liposarcoma were reported in patients aged 22 years or younger over a period of 4 decades. Overall, fewer than 60 cases of childhood liposarcoma have been reported in the literature, most often in the early part of the second decade of life.

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 a variety of prognostic factors, including stage and grade. The estimated 5-year survival rate for nonmetastatic, completely resected tumors are impacted by histologic subtype and are as follows: 20% for aggressive pleomorphic, 20-50% for round-cell, 70-80% for myxoid, and 100% for well-differentiated.

Local recurrence following resection is common and may be avoided by wide excision or adjuvant radiation.

Metastatic spread is variable, 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, often to extrapulmonary soft tissue sites, such as the retroperitoneum or chest wall.

Race: No racial predilection is apparent.

Sex: Almost two thirds of children with liposarcoma are boys, with a male-to-female ratio of approximately 2:1.

Age: Overall, the average age at presentation is 50 years. However, in children, a bimodal incidence peak has been noted; mean age at presentation in infancy is 14 months, and in early adolescence, mean age at presentation is 13.5 years.

CLINICAL

Section 3 of 11

History:

• In patients, the chief complaints vary, but most commonly the tumor 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, also may 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: While the precise etiology of liposarcomas remains to be 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. Due to the rarity of these tumors, no specific causative environmental factors have been identified.

DIFFERENTIALS

Section 4 of 11

Rhabdomyosarcoma

Other Problems to be Considered:

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

Lipoblastomatosis are important to differentiate in children because lipoblastomatosis is benign, well circumscribed, and does not require wide excision.

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 11

Imaging Studies:

• CT and MRI scans of the primary tumor may provide complementary findings.


• • CT scan 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. However, liposarcomas may have low signals on T1W images and look similar to other soft tissue sarcomas.
  
  
  
• Angiography may demonstrate malignancy based on prominent vascularity and, thus, may be of value in planning surgical resection.



• Chest radiography may be used as initial screening for pulmonary metastases; however, the definitive modality used to detect pulmonary metastases is chest CT. CT scan of 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, but 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.

Several histologic subtypes exist; 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 non–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 a variety of forms based on the degree of cellularity. Basic features of this subtype are (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 show 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, namely, high, intermediate, and low grade.

• High-grade liposarcoma includes the pleomorphic and round-cell types.

• Intermediate-grade lesions encompass the poorly differentiated myxoid 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, which is, unfortunately, 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 11

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.

Open biopsy must be performed meticulously to avoid hematoma, tumor cell spillage, and postoperative infection. The incision must be oriented so that the biopsy site can be encompassed completely 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 scan, MRI, biopsy specimen analysis) suggest a high-grade lesion, either wide en bloc resection or amputation can be planned. It is important to avoid shelling out a high-grade tumor because microscopic disease will be 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 11

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.

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

FOLLOW-UP

Section 8 of 11

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 are highly variable, 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 under 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 11

Medical/Legal Pitfalls:

• While 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. The surgeon needs to place and orient the biopsy incision in a location that allows subsequent curative resection of the liposarcoma.

TEST QUESTIONS

Section 10 of 11

CME Question 1: Which of the following is not a histologic subtype of liposarcoma?

A: Well differentiated
B: Myxoid
C: Round cell
D: Pleomorphic
E: Stellate

The correct answer is E: The 4 primary histologic subtypes of liposarcoma include the well-differentiated, myxoid, round-cell, and pleomorphic types. In children, as in adults, the most common type is myxoid.

CME Question 2: Which of the following factors affects prognosis in patients with liposarcoma?

A: Histologic subtype
B: Anatomic location
C: Extent of resection
D: Extent of adjuvant radiotherapy
E: All of the above

The correct answer is E: Prognosis depends on histologic subtype, anatomic location, and overall treatment. The 5-year survival rate for completely resected myxoid lesions is around 80%. Local recurrence may occur irrespective of histologic subtype and is related to the completeness of surgical excision. Typical sites for metastases include the lungs, but myxoid liposarcoma has a propensity to metastasize to unusual soft tissue sites such as retroperitoneum and chest wall.

Pearl Question 1 (T/F): Liposarcoma is diagnosed using MRI findings.

The correct answer is False: Open biopsy is used to make the diagnosis. Biopsy must be performed meticulously to avoid hematoma, tumor cell spillage, and infection. The biopsy incision must be placed so that the biopsy site can be encompassed completely in the definitive resection. Sometimes, performing incisional biopsy and definitive resection is possible during the same procedure, provided that the frozen section is definitive.

Pearl Question 2 (T/F): Axillary lymph node dissection is routinely required in patients with upper extremity or shoulder liposarcoma.

The correct answer is False: In patients with upper extremity tumors, axillary dissection usually is not necessary unless the nodes feel abnormally large or firm. Liposarcoma does not typically spread to regional lymph nodes.

Pearl Question 3 (T/F): Liposarcoma is diagnosed more commonly in females than in males.

The correct answer is False: The male-to-female ratio in liposarcoma is approximately 2:1.

Pearl Question 4 (T/F): Children are more prone to developing liposarcoma than adults.

The correct answer is False: Overall, the average age at presentation for liposarcoma is 50 years. Liposarcomas occur in children much less frequently than in adults; in children, they comprise fewer than 5% of all soft tissue sarcomas. The rare occurrence of this tumor in patients younger than 18 years has made accurate descriptions of the natural history challenging.

BIBLIOGRAPHY

Section 11 of 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 2000 Aug; 2(3): 132-8[Medline][Full Text].
• Castleberry RP, Kelly DR, Wilson ER, et al: Childhood liposarcoma. Report of a case and review of the literature. Cancer 1984 Aug 1; 54(3): 579-84[Medline].
• 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 2005 Nov 1; 104(9): 2006-12[Medline].
• Drevelegas A, Pilavaki M, Chourmouzi D: Lipomatous tumors of soft tissue: MR appearance with histological correlation. Eur J Radiol 2004 Jun; 50(3): 257-67[Medline].
• Engstrom K, Willen H, Kabjorn-Gustafsson C, et al: The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells. Am J Pathol 2006 May; 168(5): 1642-53[Medline].
• Enzinger FM, Weiss SW: Liposarcoma. In Enzinger F, Weiss S, eds. Soft Tissue Tumors. 3rd ed. St Louis Mosby 1995; 431-466.
• Ferrari A, Casanova M, Spreafico F, et al: Childhood liposarcoma: a single-institutional twenty-year experience. Pediatr Hematol Oncol 1999 Sep-Oct; 16(5): 415-21[Medline].
• Gronchi A, Casali PG, Fiore M, et al: Retroperitoneal soft tissue sarcomas: patterns of recurrence in 167 patients treated at a single institution. Cancer 2004 Jun 1; 100(11): 2448-55[Medline].
• Kilpatrick SE, Doyon J, Choong PF, et al: The clinicopathologic spectrum of myxoid and round cell liposarcoma. A study of 95 cases. Cancer 1996 Apr 15; 77(8): 1450-8[Medline].
• Orson GG, Sim FH, Reiman HM, Taylor WF: Liposarcoma of the musculoskeletal system. Cancer 1987 Sep 15; 60(6): 1362-70[Medline].
• Pearlstone DB, Pisters PW, Bold RJ, et al: Patterns of recurrence in extremity liposarcoma: implications for staging and follow-up. Cancer 1999 Jan 1; 85(1): 85-92[Medline].
• Raaf JH, Ragsdale BD: Surgical management of liposarcoma. In: Bogumil GP, Fleegler EJ, eds. Tumors of the Hand and Upper Limb. 1993.
• 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 1999 Dec; 17(12): 3697-705[Medline].

eMedicine Journals > Pediatrics > Oncology > Liposarcoma

Please email us with any comments you have on our new chapter format.

Author Information | Introduction | Clinical | Differentials | Workup | Treatment | Medication | Follow-up | Miscellaneous | Test Questions | Bibliography