Epidemiologic and Clinical Features
Sarcomas constitute a heterogeneous group of rare solid tumors of mesenchymal cell origin with distinct clinical and pathological features, collectively accounting for approximately 1% of all adults malignancies and 15% of pediatric malignancies; they are usually divided into two broad categories:
- Sarcomas of soft tissues (including fat, muscle, nerve and nerve sheath, blood vessels, and other connective tissues); and
- Sarcomas of bone.
Soft tissue sarcomas are the most frequent sarcomas, with the majority (60%) arising in the extremities. Fifteen percent of all soft tissue sarcomas originate in the retroperitoneum, with liposarcoma being the most common histologic subtype, accounting for approximately 40%, followed by leiomyosarcoma (30%). Primary mesenteric and primary peritoneal liposarcomas are rare.
Most patients with liposarcoma are 50-70 years-old, and the tumor has no gender predilection.
Most liposarcomas occur in deep soft tissue, in contrast to lipomas, which more commonly occur in superficial soft tissue.
The retroperitoneal cavity can accommodate a large volume of growing tumor mass. Retroperitoneal liposarcomas are often very large before producing any symptoms or signs. The late presenting signs and symptoms are usually vague and nonspecific, resulting in a delay in diagnosis.
CT and MR can define the extent of the primary tumor and assess for involvement of adjacent organs and vessels. Features that suggest unresectable disease include extensive vascular involvement, peritoneal implantation, and distant metastatic disease.
Although the World Health Organization identifies five subtypes (well-differentiated, myxoid, round cell, dedifferentiated, and pleomorphic), the liposarcomas may be conceptually divided into three subgroups. These subtypes have radiologic, clinical, pathologic, and genetic distinctions.
Well-differentiated and dedifferentiated liposarcomas comprise one subgroup (the most common), since over time a subset of well-differentiated liposarcomas histologically can progress to dedifferentiated sarcomas, which have metastatic potential. Well-differentiated liposarcomas without associated areas of dedifferentiation rarely, if ever, metastasize.
A second subgroup is composed of the myxoid and round cell liposarcomas, with the continuum of lesions ranging from pure myxoid liposarcoma at one end to round cell (poorly differentiated myxoid) liposarcomas at the other.
The third subgroup – pleomorphic liposarcoma – exhibits unusual features or combines patterns not accounted for in the above classifications.
Retroperitoneal liposarcoma usually presents as a huge mass (mean diameter of 20 cm), and complete surgical resection is often not possible, giving rise to recurrence rates that approach 100% within 6 months–2 years of initial surgical resection. Local recurrence of tumor is responsible for most morbidity and mortality.
Pathologic Features
Liposarcomas originate from primitive mesenchymal cells rather than from mature fat cells.
Well-differentiated liposarcoma is an adipocytic tumor with widened fibrous septa and enlarged, hyperchromatic atypical lipocytes within both the septa and the fat. Lipoblasts need not be present for the diagnosis of a well-differentiated liposarcoma. When the tumor contains an area of well-differentiated liposarcoma that abruptly changes to a solid, alipogenic area that measures more than a 10x power field, the lesion is defined as dedifferentiated liposarcoma.
Myxoid liposarcoma is composed of myxoid lobules with delicate plexiform vessels, predominantly monovacuolated and bivacuolated lipoblasts, and a paucity of round to stellate stroma cells. The stromal cells may coalesce and form sheets of round cells. These sheets constitute the round cell component of round cell liposarcoma that portends a worse prognosis.
Pleomorphic liposarcoma is a spindle cell, malignant fibrous histiocytoma–like sarcoma that is characterized by bizarre, large lipoblasts, with enlarged hyperchromatic and sometimes multinucleated nuclei with abundant large clear vacuoles that scallop the nucleus.
Treatment
Chemotherapy for retroperitoneal soft-tissue sarcoma is not effective, and adjuvant radiation is limited by toxicity to adjacent intra-abdominal structures.
Surgery remains the mainstay of therapy for both primary and recurrent retroperitoneal liposarcomas, but it is often impossible or difficult to perform owing to the deep anatomic location with proximity to vital retroperitoneal structures, the frequent late presentation, and the frequent invasion of adjacent retroperitoneal structures. Therefore, the practical surgical goal is wide excision of the tumor or tumor recurrence with resection of adherent structures if a tumor-free margin can be achieved.
In patients with unresectable retroperitoneal liposarcoma, incomplete resection or debulking provide improvement in survival in addition to symptom palliation, particularly in patients resected for primary disease.
Prognosis
Retroperitoneal sarcomas are staged according to GTNM system, incorporating tumor grade, size, location, and regional nodal and distant metastasis [Fig. 1].
Fig.: (1) 2002 American Joint Committee on Cancer GTNM Classification and Stage Grouping of Soft Tissue Sarcomas. *Superficial tumor is located exclusively above the superficial fascia without invasion of the fascia; deep tumor is located either exclusively beneath the superficial fascia, superficial to the fascia with invasion of or through the fascia, or both superficial yet beneath the fascia. Retroperitoneal, mediastinal, and pelvic sarcomas are classified as deep tumors. †Presence of positive nodes (N1) is considered stage IV.
References: Adapted from AJCC Cancer Staging Manual, Sixth Edition. New York, Springer-Verlag, 2002.
Surgical resection of a localized tumor with grossly negative margins remains the standard, potentially curative treatment for retroperitoneal liposarcoma. Complete primary tumor resection is the most important factor contributing to long-term disease-free survival.
Following complete resection of a retroperitoneal sarcoma, histologic grade is the most important prognostic factor in regard to local recurrence and overall survival.
Local recurrence of retroperitoneal liposarcomas approaches 50% at 5 years for all patients but is 75% for patients with high-grade tumors.
Regional lymphadenopathy is uncommon in soft tissue sarcomas, occurring in less than 10% of cases.
The rate of distant metastasis to both liver and lung is less than 10%, significantly lower comparing with other types of retroperitoneal sarcomas.
The prognosis of patients with liposarcomas varies with the histologic subtype.
The well-differentiated variant is considered a low-grade malignancy and, although prone to local recurrence, has little or no metastatic potential and a 5-year survival rate near 90%. Dedifferentiation of well-differentiated liposarcomas is thought to be time-dependent and has been reported to occur in 15% of patients at a median time of 8 years. Dedifferentiated liposarcomas of both high and low grade course with substantially higher rates of recurrence and metastatic spread than their well-differentiated counterparts, which rarely if ever metastasize.
The myxoid or round-cell subtypes have intermediate prognosis and metastatic potential, with an estimated 5-year survival rate of 60-90%.
Pleomorphic liposarcomas have the highest metastatic potential, with 5-year survival rates of 30%-50%.