Leiomyosarcoma of the renal vein: analysis of outcome and prognostic factors in the world case series of 67 patients

Leiomyosarcoma (LMS) is a rare malignant mesenchymal tumour of smooth muscle origin. It represents only 5–7% of soft tissue sarcomas.¹Approximately 2.0% of LMS originate from the smooth muscle of vessel walls, predominantly veins and 60.0% of these originate from inferior vena cava (IVC).¹ According to Gage et al. ¹, the most common location of extracaval venous LMS is the renal vein, followed by the great saphenous, pulmonary and femoral vein. Leiomyosarcoma of the renal vein (LRV) is extremely rare. There have been some cases reported in the literature, but no analysis of data and search for prognostic factors have been done so far. The first case was reported by Lopez Varela and Pereira Garro in 1967.² We present an additional case, world literature overview and the outcome of these patients.

On the basis of limited data, univariate analysis was used to evaluate the following potential prognostic factors for overall survival (OS), local recurrence free survival (LRFS) and distant metastases free survival (DMFS): age, gender, tumour site, dissemination, weight loss, palpable mass, operation type, tumour thrombus IVC luminal extension, tumour size, grade, margin status, number of mitoses and neoadjuvant or adjuvant treatment. OS and LRFS were compared using log-rank test. All comparisons were two sided. P-value of 0.05 was considered statistically significant. Survival curves were calculated and plotted using Kaplan-Meier method. Cox′s multivariate regression was used to identify independent prognostic variables of OS, LRFS and DMFS. The statistical program SPSS® version 22 was used for analysis.

Points to be discussed about the case from our institution are biopsy, surgery, adjuvant RT and treatment of liver metastases.

The patient presented to the Institute of Oncology Ljubljana because of retroperitoneal location of the tumour and cytological suspicion for LMS. Ultrasound guided FNAB was performed in another hospital. At the MDT it was not decided for CNB, because the mass was a spindle cell tumour, suspicious for LMS, with the renal vein not identified on CT, indeed suspicious for primary LRV, and because the tumour was deemed resectable and not disseminated, as such not planned for neoadjuvant treatment.

The tumour was removed with compartment resection with negative margins, in separately removed satellite margins were positive. Analysing the CT scans again after the histological report, the satellite was found on CT and it seems that the tumour was invading the psoas muscle in continuity. Surgery was planned as wide resection but was marginal and R1. The operation would be optimal if both specimens would be removed en bloc, but the margins on the vertebra would probably be positive anyway. Because reoperation with clear margins on vertebra in case of local recurrence would probably not be possible, we decided for adjuvant RT.

According to magnetic resonance imaging liver metastases were small and resectable and that was the reason at the MDT to decide for metastasectomy.

LRV is very rare. Cases from the last literature overview in 2010 ⁵⁰, cases from nonenglish literature, new reports from 2010–2015 and present case were summarised. From data gathered from these case reports, subsequent analysis and with respect to sarcoma guidelines, several observations can be made.

From the clinical point of view, LRV presents difficulties in making diagnosis, because it is uncommon, has no specific symptoms and no pathognomonic radiological features. It predominantly occurs in women (76.1%), on the left side (68.7%) and affects older population, with the peak occurring at age 60–69 years. Presenting symptoms are unspecific, abdominal pain was reported in 49.3%. Hematuria was reported in a single case (1.5%) of LRV patients, but is present in more than one third of the cases (34.8%) of renal cell carcinoma (RCC) with venous extension.⁵¹ Genetic predisposition may play a role in development of primary LRV, with two patients being treated for retinoblastoma and one patient having Li Fraumeni syndrome.

From the point of imaging, location of LRV is more important than the size of the tumour. It can overlap with much more common RCC with venous extension. LRV is usually located in the hilum of the kidney. The bulk of the tumour lies predominantly or entirely outside the hilar parenchyma or the tumour is limited to the renal vessels [46]. The mean tumour size in this LRV group is 8.9 cm. In a study group of 1192 patients with RCC with extension into the renal vein (23.0%) and IVC (7.0%) the mean tumour size was 8.9 cm as well.⁵² It may not be possible to distinguish between these two entities by imaging. Other diagnoses considered in this location are metastatic lymph node in a patient with a history of malignancy, renal pelvis leiomyosarcoma, extremely rare as well, with around 10 cases reported in the literature⁵³, lymphoma, adrenal gland tumour, upper tract urothelial carcinoma, granulomatous disease and renal vein thrombus.⁴⁶

With regard to biopsy, retroperitoneal mass is usually detected on abdominal CT scans. When imaging is not diagnostic of a retroperitoneal liposarcoma, image-guided CNB of retroperitoneal tumour is strongly recommended to obtain the sample for diagnosis. Correct diagnosis may significantly affect surgical decision and neo/adjuvant therapy.^54,55 Wilkinson et al.⁵⁶ from Royal Marsden, London reported, that preoperative CNB for retroperitoneal sarcoma (RPS) is safe and does not affect oncological outcome. Patients with intermediate and high-grade RPS were included. There were no intra-abdominal complications requiring early operation. The group of 90 patients with preoperative CNB was compared to a group of 60 patients, who did not have preoperative CNB. There was no significant difference in local recurrence (p = 0.101) or OS (p = 0.191). FNAB in retroperitoneal tumours rarely yields diagnostic information and should be avoided⁵⁵, but it can be performed in RCC in spite of danger of haemorrhage. In the present review preoperative histological biopsy was performed in 13.4% of cases only and FNAB in 3.0%.

With regard to treatment, the only potentially curative treatment for RPS is surgery with macroscopically complete resection.^54,55,57 The role of ChT and RT in RPS is not proven and still under investigation. It is generally recommended, that in case of RT administration, it should be delivered in the preoperative setting and possibly within a clinical trial.⁵⁴ Postoperative RT should not be administered routinely in R0 and R1 resections.⁵⁴ ChT is an option in the preoperative setting of resectable disease, is an option after surgery in case of R2 resection and is an option in case of unresectable or metastatic disease.⁵⁴

Because of complex evaluation and treatment options patients with RPS should be managed by sarcoma MDT in a specialized reference center.^54,55

Histologic subtype is one of the major determinants of the oncologic outcome in RPS. The most common location of LMS is the retroperitoneum⁵⁸, where it represents the second most common histological subtype after liposarcoma, accounting for 14–36% of patients in major series.^59,60 Retroperitoneal LMS has a high propensity for distant recurrence. The reported rate of distant metastases for retroperitoneal LMS at 5 years is around 40–50% and for local recurrence at 5 years around 5%.⁶¹ Similar results are present in the present review, with the rate of local recurrence of 4.5% (3/67), distal metastases of 29.9% (20/67) and both in 14.9% (10/67), but in much shorter period of follow up.

And finally, in the present review of the literature 79.5% of the LRV patients survived at 2 years. A 5-year OS, LRFS and DMFS was not performed because of the inadequate sample size at that length of follow up. Retrospective comparisons of series of RPS patients have demonstrated 5-years OS rates of 50–70% and 5-years local control rates of 40–80%.⁵⁷ In the IVC LMS series 5-year survival has been reported between 33.0% and 53.0%.²⁶ Data from different large series of RPS patients have demonstrated tumour grade and surgical margin status as independent prognostic factors of OS and LRFS.^62,63 Cases from this review are dispersed world wide and through half of the century, lacking data for tumour grade (58.2%; 39/67), surgical margin status (73.1%; 49/67) and follow up (16.4%; 11/67). Because of insufficient histologic data and truncated follow up, we were not able to identify prognostic factors of OS, LRFS and DMFS in multivariate analysis.

As a retrospective analysis this study has limitations. Most of the information collected was from case reports, without significant follow up and lacking histological data. As a consequence, there was a limitation in the statistical analysis and the conclusions that could be drawn from it, particularly in patients’ outcome. However, to our knowledge, this is the largest study on this topic, and even this limited survey expands our understanding of the natural history of this rare sarcoma.

LRV is usually located in the hilum of the kidney. It should be considered in differential diagnosis of renal and retroperitoneal masses, particularly in women over the age of 40, on the left side and in the absence of hematuria. Core needle biopsy should be performed. Patients should be managed by sarcoma MDT. For optimal clinical outcomes, LRV should be surgically removed, with negative margins. After a median follow up of 24 months OS was 79.5%, LRFS was 83.5% after a median follow up of 21.5 months and DMFS was 76.1% after a median follow up of 22 months. Factors predictive of OS in univariate analysis were surgical margins, while factors predictive of LRFS were inferior vena cava luminal extension and grade. No factors predictive of DMFS were identified. Because of insufficient histologic data and follow up, we were not able to identify prognostic factors of OS, LRFS and DMFS in multivariate analysis.