Giant dedifferentiated liposarcoma of the retroperitoneum

May 24, 2007
Surgical Rounds®, May 2007, Volume 0, Issue 0

Vahe S. Tateosian, Medical Student IV, Department of Surgery, Flushing Hospital Medical Center, Flushing, NY; Lourdes Castanon, Senior Surgical Resident, Department of Surgery, Brookdale University Hospital & Medical Center, Brooklyn, NY; Charles C. Conte, Surgical Oncology Chairman, Department of Surgery, Flushing Hospital Medical Center, Flushing, NY

Vahe S. Tateosian, BE

Medical Student IV

Department of Surgery

Flushing Hospital Medical Center

Flushing, NY

Lourdes Castanon, MD

Senior Surgical Resident

Department of Surgery

Brookdale University Hospital & Medical Center

Brooklyn, NY

Charles C. Conte, MD

Surgical Oncology

Chairman

Department of Surgery

Flushing Hospital Medical Center

Flushing, NY

Sarcomas are rare tumors that represent less than 1% of all newly diagnosed malignancies in the United States annually.1 These tumors may arise from mesenchymal tissue at any body site, including skeletal and extraskeletal connective tissues and the peripheral nervous system. Most of these tumors (approximately 75%) arise in soft tissue and the remainder in the bones. The majority of soft tissue sarcomas are found in the extremities, with only 13% occurring in the retroperitoneum.2 In a population-based series from the Surveillance, Epidemiology, and End Results (SEER) database, the average annual incidence of retroperitoneal sarcomas was 2.7 cases per million population.3 The majority of retroperitoneal tumors are liposarcomas and leiomyosarcomas. Most patients present with an asymptomatic abdominal mass, but symptoms may include early satiety, obstruction, and bleeding from pressure effects of the mass on neurovascular components.

We report the case of a patient who presented with diffuse abdominal pain and right-sided distention that had been increasing for approximately 8 weeks. Radiographic studies showed a large, heterogeneous, right-sided abdominal mass that extended across the midline and displaced various organs into the left abdomen. Surgical excision yielded a 20.67-lb, high-grade, dedifferentiated retroperitoneal liposarcoma.

Case report

A 53-year-old man with a 30-year undocumented medical history presented to the emergency department with abdominal pain and right-sided distention that had been increasing for approximately 8 weeks. The patient reported a dragging sensation in the right side of the upper abdomen and occasional epigastric pain, which he rated as a 7 out of 10 on a pain intensity scale. The pain was alleviated slightly by laying on his left side. He also reported early satiety and more frequent urination and bowel movements, with the need to empty his bowels forcefully. He also experienced increasing episodes of insomnia, with frequent awakenings throughout the night, and a weight loss of 10 lb over the previous year. He reported no associated chest pain, shortness of breath, fever, nausea, vomiting, diarrhea, or bloody stools. The patient had no surgical history.

Upon physical examination, the upper and lower quadrants of the right side of the abdomen were found to be significantly distended. Bowel sounds with dullness to percussion were auscultated over the entire affected region. There was also notable epigastric tenderness and questionable hepatomegaly on palpation. No lower extremity edema or other positive physical findings were identified.

Upon admission to the hospital, laboratory evaluations yielded the following results: hemoglobin, 8.8 g/dL (normal, 12.5—18 g/dL); white blood cell count, 8.7 x109/L (normal, 4—11 x109/L); platelets, 695 x109/L (normal, 150—400 x109/L); sodium, 130 mEq/L (normal, 136—145 mEq/L); chloride, 92 mEq/L (normal, 101—111 mEq/L); glucose, 454 mg/dL (normal, 70—110 mg/dL); and hemoglobin A1C, 14.1% (normal, < 6%). Based on these results, the initial working diagnosis included an (1) unidentifiable potentially malignant abdominal mass; (2) anemia that might result from an underlying malignancy; and (3) newly discovered diabetes mellitus.

To identify the tumor better, a series of radiographic studies was undertaken. Abdominal ultrasonography showed an irregularly marginated mass within the right mid-abdomen, which caused obstruction of the right urinary collecting system, and hydronephrosis on the ipsilateral side. Abdominal radiographs showed no evidence of bowel obstruction, ileus, or free air in the abdomen. Stool was observed in the descending colon, but the tumor appeared only as a hazy density within the abdomen. Computed tomography (CT) scans of the chest, abdomen, and pelvis showed a large, heterogeneous,?right-sided abdominal mass that extended across the midline into the left abdomen (Figure 1). The mass was approximately 31.5 cm long, and its greatest axial dimension measured 23.5 x 17 cm. There was a deformity of the right renal contour at the mid- and lower poles, and the mass arose from?within the right kidney. There was mild-to-moderate hydronephrosis of the right kidney and likely obstruction of the ureter. The mass displaced the ascending and transverse colon anteriorly and pushed most of the bowel into the left abdomen, but there was no evidence of bowel obstruction. The right renal artery and vein were found to be patent; however, the superior mesenteric vein was displaced into the left upper quadrant, and the inferior vena cava was compressed against the aorta. There was no evidence of liver or lung metastases. Magnetic resonance imaging (MRI) of the abdomen and pelvis was suggestive of sarcoma (Figure 2).

Exploratory laparotomy, right nephrectomy, and resection of the tumor and mesenteric lymph nodes were undertaken (Figure 3). Upon surgical excision, the mass was found to be a 9,395-g (20.67 lb) retroperitoneal tumor. It was circumscribed, well-encapsulated, and encased the kidney without directly infiltrating the parenchyma. Microscopic examination showed predominantly vascular myxoid stroma scattered with pleomorphic neoplastic cells and multinucleated giant cells with areas of increased cellularity, confirming a neoplasm (Figure 4). There were frequent atypical mitotic figures and extensive tumor necrosis. A diagnosis of high-grade dedifferentiated retroperitoneal liposarcoma was made.

Postoperative radiation therapy was not undertaken due to the large affected surface area (tumor bed) and the relative intolerance of normal surrounding tissue to radiation. Radiographic studies at the patient’s 3-month follow-up did not show any previous or newly developed metastases.

Discussion

Soft tissue sarcomas are almost always thought to arise de novo and not from pre-existing benign lesions. They are classified according to their presumptive tissue of origin. Although most cases have no clearly defined etiology, an array of predisposing risk factors has been described, including genetic predisposition; chronic irritation; and previous exposure to radiation, chemotherapy, or chemical carcinogens. In addition to the potential for local growth and destruction, the risks of recurrence and distant metastasis are substantial. Liposarcomas pose many challenges with respect to early detection, clinical behavior, and treatment.

Classification and staging Currently, liposarcomas are generally classified into four types based on their morphologic features and cytogenic aberrations; these are (1) well-differentiated, (2) dedifferentiated, (3) myxoid/round cell, and (4) pleomorphic.4 The extent of differentiation affects the clinical course of the disease and the patient’s prognosis after resection. Using the American Joint Committee on Cancer (AJCC) staging system, our patient had a stage III, malignant, soft tissue sarcoma, which was histologically classified as a dedifferentiated liposarcoma.5 To determine staging, the AJCC system considers histologic grade, tumor size, tumor depth, and the presence or absence of lymph node and distant metastasis.6 Stage III disease is characterized by the presence of a poorly differentiated primary tumor larger than 5 cm in its greatest diameter and no distant or histologically verified metastasis to regional lymph nodes. In stage IV disease, there is regional lymph node involvement or evidence of distant metastatic disease, regardless of the tumor’s histologic grade, size, or site.

Dedifferentiated liposarcoma refers to the development of a high-grade nonlipogenic sarcoma juxtaposed with a well-differentiated liposarcoma.7 Dedifferentiated liposarcomas generally have a worse prognosis than other sarcoma variants, with an overall 5-year survival rate of approximately 20%.8 There is local recurrence in 40% to 83% of cases and distant metastasis in 15% to 30% of cases.8

Diagnosis When liposarcoma is suspected, a thorough history and physical examination should be undertaken to determine which major vessels, organs, nerves, or bones may be affected, and to assess regional lymph node status. CT scanning of the abdomen and pelvis are useful in evaluating the primary site and offer clues regarding intraperitoneal seeding, regional lymph node involvement, and whether there is distant metastasis to the liver. CT scanning of the chest should also be undertaken to check for possible metastasis to the lungs. While CT scanning cannot indicate the histologic grade of the tumor, it can show features that may be suggestive of a higher grade (such as necrosis), thereby offering some insights. The increased use of CT scanning has allowed liposarcomas to be detected earlier in both symptomatic and asymptomatic patients; however, despite the increased use of this modality, most retroperitoneal liposarcomas are detected as locally advanced tumors.

The morphologic variability of liposarcomas may lead to nonspecific imaging features that reflect the coexistence of a nonlipomatous mass and predominantly fatty tumor. Although MRI is sensitive enough to detect minute fat deposits or immature fatty components, liposarcomas may contain various amounts of myxoid matrix composed of hyaluronic acid, which often has a similar signal intensity to that of fatty tissue, confounding the diagnosis.9

The collaborative use of CT scanning and MRI have revealed well-defined, nonlipomatous masses associated with fatty tumor, where the transition between the two components has been found to be characteristically abrupt in most cases.9 Another characteristic imaging pattern of dedifferentiated liposarcoma is calcification or ossification, which may be suggestive of metaplasia within the tumor. The effect of metaplasia on prognosis is not fully understood.9

Treatment Complete surgical resection of the primary lesion at initial presentation is critical to achieving a cure or long-term survival.10 The histologic grade of the liposarcoma is more indicative of prognosis than histologic type. Traditionally, patients with retroperitoneal liposarcomas have been more likely to die from local recurrence than from distant metastasis.11 Because the risk of local recurrence is attributed to surgical margins, complete excision is imperative to avoid this complication. Complete resection of these tumors is challenging, because these lesions are usually large (> 10 cm) when diagnosed and the lack of distinct anatomic compartments within the retroperitoneum allows these tumors to extend and involve many adjacent organs and structures. Retroperitoneal liposarcomas also have a high degree of adipocyte differentiation, which makes it difficult to distinguish tumor from retroperitoneal fat; thus, the determination of negative microscopic margins is a difficult and imprecise task.

The role of radiation therapy for retroperitoneal liposarcomas is unclear, because there is a paucity of data substantiating favorable impact with this therapy on recurrence rates or on overall patient survival.10,11 A randomized trial evaluating radiation therapy in the management of retroperitoneal sarcomas compared intraoperative and low-dose postoperative radiation with high-dose postoperative radiation.12 Patients in the intraoperative radiation therapy arm had significantly better control of local disease but showed no improvement in overall survival. Despite the lack of controlled trials confirming the efficacy of radiation therapy for retroperitoneal sarcomas, it has been hypothesized that adjuvant radiation still may play a role in controlling local disease, potentially enhancing long-term survival.10

An important consideration of postoperative radiation therapy is the relative intolerance of normal surrounding tissues to this therapy, including the loops of bowel, which may become fixed due to postoperative adhesions. Preoperative radiation may be a safer alternative since it allows for more accurate targeting of the volume around the tumor. Because the normal surrounding tissues and bowel are displaced by the tumor, a higher dose of radiation may be used directly at the site. A randomized trial that evaluated intraoperative radiotherapy as an adjuvant treatment showed improvement in local control but failed to show a significant increase in patient survival.12 The optimal treatment regimen for local tumor control may be a combination of surgical resection and radiation therapy, but further trials are necessary to determine this definitively. While the best outcomes are observed in patients with negative surgical margins, and the importance of obtaining clear surgical margins is accepted, the highly aggressive nature of sarcomas and their propensity for local recurrence and distant metastasis create a fundamental need for enhanced adjuvant therapy.

Conclusion

The histopathologic spectrum of sarcomas is extensive, presumably because they are composed of embryonic mesenchymal cells, which have the ability to differentiate. We reported a case of a dedifferentiated liposarcoma, which has a significantly worse prognosis than other variants of sarcoma. Adequate surgical resection with negative microscopic margins remains the highest priority for long-term survival. Neoadjuvant radiation and chemotherapy have been used for limb salvage in unresectable extremity sarcomas, but the role of these therapies for retroperitoneal liposarcomas requires further evaluation. The highly aggressive nature of these tumors supports the need for more effective adjuvant therapies.

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