Prepared by Tung V. Huynh, MD and Thomas B. Kinney, MD of the Department of Radiology, and John B. Welsh, MD of the Department of Pathology, at the University of California San Diego Medical Center, San Diego, CA.

CASE SUMMARY

A 52-year-old man presented with worsening left lower extremity swelling despite adequate anticoagulation for a deep venous thrombosis diagnosed 2 months earlier. Physical examination revealed bilateral lower extremity edema, worse on the left. Venous duplex exam (not shown) revealed bilateral thrombi within the superficial femoral and common femoral veins.

Work-up included laboratory evaluation for hypercoagulable state along with imaging workup for occult malignancy as a possible cause of Trousseau syndrome. Initial ultrasonographic abdominal survey reveals right hydronephrosis (not shown) and CT was recommended (figure 1). Figure 2 is a vena cavagram at the time of IVC filter placement and figure 3 is microscopic section of an aspiration biopsy.

DIAGNOSIS

Leiomyosarcoma of the inferior vena cava (IVC) (IVC sarcoma)

IMAGING FINDINGS

The IVC is patent at the level of the renal vein. Right hydronephrosis is demonstrated (figure 1A). More inferiorly, a large 5 cm heterogeneously enhancing retroperitoneal mass extends from the renal hilar level to the iliac bifurcation (figure 1B), centered within and obliterating the IVC. The intraluminal filling defect surrounded by contrast above the iliac bifurcation (figure 1C) could represent an intraluminal component of the tumor mass or bland thrombus.

The patient underwent successful biopsy of the mass percutaneously with CT guidance. The aspirates and cell block (figure 3) demonstrate pleomorphic and cohesive groups of spindle cells, which are positively stained with vimentin and muscle specific actin (special stains not shown) indicating spindle cell neoplasm of smooth muscle differentiation, highly suspicious for leiomyosarcoma.

Laboratory evaluation confirmed antiphospholipid antibody syndrome, which, in combination with the IVC sarcoma, contributed to his recurrent and progressive DVT despite appropriate coumadin therapy. Because of retroperitoneal bleeding related to the biopsy procedure and the concern of possible pulmonary embolism, a suprarenal Greenfield stainless steel IVC filter was inserted. The vena cavogram. at the time of filter placement (figure 2) shows complete occlusion of the IVC just below the renal vein orifices.

DISCUSSION

Leiomyosarcoma of the IVC is an uncommon tumor first reported by Perl in 1871. ¹ Data as of December 1993 from the International Registry of IVC Leiomyosarcoma ² reported a total of 218 cases, inclusive of comprehensive literature review and authors' personal communication. Since then, 35 additional cases have been described, bringing the total number of reported cases to 254, including the current case. ³

Histologically, leiomyosarcoma show a typical pattern of interlacing bundles of spindle-shaped cells with varying degrees of mitotic activity, and cellular and nuclear polymorphism. Differentiation from other types vascular tumors (hemangioendothelioma, angiosarcoma, and fibrosarcoma) is possible by different histologic features and determination of smooth muscle origin by immunohistochemical methods or electron microscopy. ⁴ Generally, there is a poor correlation between the histologic appearance of leiomyosarcoma and clinical outcome; the size and location of the tumor are the most important prognostic factors. ⁵

IVC sarcoma is predominantly a female affliction, with a female to male ratio of approximately 4:1. ² The average age of the patients in the International Registry of IVC Leiomyosarcoma is 54 years (range 15 to 85 years). The presenting symptoms depend somewhat on both the size and location of the tumor and include abdominal pain (67%), palpable mass (43%), leg edema (35%), weight loss (22%), and Budd-Chiari's syndrome (17%). Other less common symptoms (<12%) reported include: weakness, nausea, dyspnea, fever, anorexia, vomiting, jaundice, and night sweat. This tumor has a very poor prognosis and the optimal treatment regimen has not been established. The role of radiation and chemotherapy is not well defined; while surgical resection, when possible, seems to offer the best chance for survival. Comprehensive analysis of the clinical outcome of the 218 patients in the International Registry of IVC leiomyosarcoma (180 with follow-up data) showed a mean survival of 4.7 ± 1.1 months (median 2 months) in patients who were not operated on for curative resection (38.5%). The 5- and 10-year survival rates for patients undergoing radical resection (61.5%) were 49.4% and 29.5% respectively. More than half of these patients had disease recurrence (13.4% with local recurrence, 31.3% with metastasis, and 9% with both) with overall 5- and 10-year disease-free rates of 31.4% and 7.4% respectively.

A statistically significant increased risk of death occurred in patients with tumor involving the upper IVC segment (hepatic vein origin to right atrium) with or without Budd-Chiari's syndrome, IVC occlusion, intraluminal growth, and limb edema. These poor prognostic indicators reflect the critical location of the tumor behind the liver, obligating intraluminal growth and making radical resection of the tumor technically difficult or impossible. In fact, only 14.6% of patients with upper IVC involvement underwent radical resection of the tumor as compared with 70% to 75% of patients with mid IVC (involving renal vein but below hepatic vein) or lower IVC (infrarenal) involvement.

In patients with IVC sarcomas involving the mid and lower segments, good prognostic indicators include presence of abdominal pain and absence of palpable mass at the time of presentation. These parameters likely correlate with earlier detection of the tumor as well as surgical resectability. Tumors in the middle segment of the cava generally cause symptoms earlier due to the rich sensory innervation of the surrounding organs, allowing earlier diagnosis and better 5- and 10-year survival rates (56.7% and 47.3% respectively) compared to tumors in lower IVC segment (37.8% and 14.2%).

Cross-sectional imaging plays a significant role in the early detection and in defining resectability of this tumor. As in the case presented here, heterogeneous contrast uptake on CT is characteristic and allows differentiating tumor mass from bland thrombus. Similar tumor vascularity could be seen with Doppler ultrasound and gadolinium-enhanced MR imaging. These features, along with the pattern of growth (i.e., intraluminal versus extravascular extension), are non-specific and accurate preoperative diagnosis still relies on pathologic examination of the biopsy specimen. Transvenous biopsy, an alternative biopsy technique, may be useful in such cases as this, it might have avoided the bleeding complication this patient developed. ⁶

REFERENCES

1. Perl L : Ein Fall von Sarkom der V cava inferior. Virchows Arch Pathol Anat 53:378-383, 1871.

2. Mingoli A, Cavallaro A, Sapienza P, et al: International registry of inferior vena cava leiomyosarcoma: Analysis of a world series on 218 patients. Anticancer Research 16(5B):3201-3205, 1996.

3. Detailed list of published case reports available from authors upon requests.

4. Leu HJ, Makek M: Intramural venous leiomyosarcomas. Cancer 57:1395-1400, 1986.

5. Wile AG, Evans HL, Romsdahl MM: Leiomyosarcoma of soft tissue: A clinicopathologic study. Cancer 48:1022-1032, 1981.

6. Dake MD, Zernel G, Dolmatch BC, Katzen BT: The cause of superior vena cava syndrome: Diagnosis with percutaneous atherectomy. Radiology 174:975-959, 1990.