Renal Vein Leiomyosarcoma
We describe a 66 year old female who presented with abdominal pain. Histology confirmed what was suggested by surgeon and radiologist to indeed be a leiomyosarcoma, originating from the renal vein.
Authors: Mr Mark Frydenberg , Associate Professor Dept of Surgery Monash University , Chairman Dept of Urology , Monash Medical Centre , Southern Health. Clayton. Australia.
Corresponding Author: Dr Gideon Adam Blecher, MBBS (Hons) Monash University. The Alfred Hospital, Melbourne. Australia, Urology Surgeon in Training, E-mail: [email protected]
Abstract
Leiomyosarcoma is a rare smooth muscle tumour: those with vasculature origin are extraordinarily rare, particularly from the renal vein. In the English literature, there are 32 cases of renal vein leiomyosarcoma. We describe a 66 year old female who presented with abdominal pain. An en-bloc radical nephrectomy was performed. Histology confirmed what was suggested by surgeon and radiologist to indeed be a leiomyosarcoma, originating from the renal vein. A literature review of all cases in English, as well as some non-English cases, is thereafter presented.
Case Report
A 66 year old female presented with left sided loin pain for severalyears. There had been recent change of this pain towards her left upperquadrant. CT scan (Figure 1) showed a lobulated irregular, enhancing 4.5cm massadjacent to the left kidney. Its position was to the left of the aorta,posterior to the pancreas, antero-medial to the kidney and inferior to theadrenal gland. It displaced and partially surrounded the left renal vein andartery. The liver showed no evidence of metastasis.
Figure 1 CT Scan of Left Renal Vein Leiomyosarcoma 69x62mm (300 x 300 DPI)
A doppler ultrasound confirmeda significant vascularity to the lesion and suggested a renal vein origin. CTguided core biopsies showed smooth muscle tumour with mild nuclear atypia.There was insufficient material to distinguish benign from low grademalignancy.
An open left radical nephrectomy was performed with an en blocexcision of renal vein and associated tumour (urologist together with uppergastrointestinal surgeon). The histological specimen was a 35 x 35 x 30mm massseparate to but arising in the hilum of the kidney, appearing to have anattachment to the renal vein. There was no obvious necrosis on slicing and thetumour had a smooth outline (Figure 2).
Figure 2 CT Scan of Left Renal Vein Leiomyosarcoma 69x62mm (300 x 300 DPI)
Microscopy confirmed leiomyosarcoma arising from the renal vein. Thetumour was composed of spindle cells with a mitotic count of 50 per 10 highpower fields (Figure 3). The tumour was cellular but had areas of eosinophilicacellular fibrous tissue. The pathological margins were clear. The adrenalgland was unremarkable.
Figure 3 High power (x400) view of lyomysarcoma
The patient has been reviewed twelve months later and is well withno evidence of disease. The case was discussed at a uro-oncology multidisciplinarymeeting and it was decided not to treat empirically with chemotherapy, givenher negative surgical margins.
Discussion
This review incorporates 48 separate cases of renal veinleimyosarcoma; we report on 32 cases in the English literature and include 16case reports in non-English languages (Table 1). One article reviews a further16 (in the Japanese literature); searches for these were unsuccessful. Searcheswere performed for all published reports via Medline/Embase, CINAHL, and GoogleScholar, using the combined terms “Renal”, “Vein” and “Leiomyosarcoma” as titlewords. The earliest case dates from 1967. In this review, follow up was eightyears at maximum. The longest documented survival was eight years. The vastmajority of cases do not state whether the surgical margins were positive; onlythree of the English articles state that the surgical specimen margins werenegative [1,2,3]. Somepatients had evidence of metastatic disease at diagnosis or laparotomy [3,4]. 13 of 32English cases indicate that adjuvant therapy was used.
Leiomyosarcomata arise from smoothmuscle and have been documented from various tissues, including gastric [5], renal [6], prostate [7], bladder [8], ureter [9] and rectum [10], skin andsubcutaneous [11]. Followingliposarcoma and malignant fibrous histiocytoma, leiomyosarcoma is the thirdmost common primary retroperitoneal malignancy [12].
Primary leiomyosarcomata arising from veins are rare; most originatefrom the inferior vena cava [13]. Butany etal described 230 cases of malignant smooth muscle neoplasms of vascular origin.Their review showed a significant proportion (70%) arising from IVC (162/230),with renal vein origin only making up for one of the 230 cases (0.4%) [14].
Renalvein leiomyosarcomata are commoner in women 29:5 (85%) and tend to occur on theleft side (64%) [3], as was the case with our patient. Thelateralisation may be secondary to the simple physical difference in length ofthe left and right renal veins. It has been suggested that there is a hormone-dependantgrowth mechanism for benign leiomyomatosis [14]; perhaps this accounts forthe female preponderance in leiomyosarcoma. Retroperitoneal leiomyoma cases demonstratea 40% rate of concurrent uterine leiomyoma (or a remote history of hysterectomy)[15] and there is documentation of benignmetastasizing uterine leiomyoma [16]. Uterine leiomyomata have also been shown toundergo dysplasia and malignant transformation to leiomyosarcoma followingtotal hysterectomy [17].There is no evidence yet to suggest renal vein leiomyosarcomata arise from abenign metastasizing lesion with subsequent dysplasia.
Leiomyosarcoma has been described as a slowly developing tumour,often encapsulated and compressing, rather than invading adjacent structures [18]. They have ahigh mortality because their presentation is often late, variable ornon-specific [19]. Presentingsymptoms include abdominal, back or pelvic pain, weight loss, evidence ofmalignancy as well as incidental findings [20].
US, CT and MR have all shown to be useful for diagnosis and surgicalplanning. US is helpful; a rounded, uniform echogenic mass is typical [20], whilst CT and MR have non-specificcharacteristics [12]. Angiography combined with CT or MR can assist in demonstrating tumourvascularity, collateral blood supply as well as resectability [12].
Gold standard treatment includes enbloc surgical resection, with nephrectomy [3,12]. When tumour does not involve renal parenchyma, some investigatorshave argued for kidney sparing surgery [21]. Cocuzza etal suggest partial nephrectomy as another option for smaller leiomyosarcomata [22].
Surgical treatment in metastatic context has been employed severaltimes: both Brandes [3] and Pelton [4] reported hepatic lobectomy and intraoperative radiotherapy forisolated hepatic metastasis.Lipton [23] reported another case comprising nephrectomy,splenectomy and renal vein thrombectomy. For extensive local invasion González-Rodríguez [24] reportednephrectomy accompanied by caudal pancreatectomy,splenectomy and right hemicolectomy.The survival in these contexts was generally poor; ranging from 17 to 54 months.
Some investigators recommend complete surgicalresection, with subsequent chemotherapy, as the most appropriate treatment plan[25,26]. A variety of chemotherapeutic agents have beenused; primarily cyclophosphamide [20,25,26] adriamycin [3,28], doxorubicin [2,20,26,27] ifosfomide [3] as well as dacarbizine [3,26,27]. Radiotherapy has been utilised both intra [3,4] and post operatively[28,29]. It has been used to irradiate the tumour bed as well asfor treatment of metastatic spread, months or years after the primary tumourremoval [4,30]. Due to small numbers of cases and lack of controlledstudies, chemotherapy thus far remains an adjuvant, rather than neoadjuvanttreatment.
Traditional chemotherapy has not shown to behighly effective against leiomyosarcomata. Newer agents such as tyrosine kinaseinhibitors have shown effectiveness against gastro-intestinal stromal tumours (GISTs),however there are no reports of this treatment for leiomyosarcoma.
Prognostic indicators of leiomyosarcoma arestill debated; Gustafson et al [11] claimedpatient age of 60 years or greater, tumour necrosis, vascular invasion, morethan five mitoses per ten high power fields, and local recurrence werecorrelated with decreased survival. They also mentionedthat tumour depth, tumour size, compartmentalization, malignancy grade,DNA ploidy status, type of surgical margin and type of surgical proceduredid not influence survival. Bevilacquaet al [31]reviewed prognostic factors in retroperitoneal soft tissue sarcomas, concludingthat the major factor in survival outcome was complete lesion resection.Histological grade, provided complete removal has been obtained, is a majorprognostic indicator; 90 to 95% 5 year disease free survival for low grade and30 to 35% for high grade tumours [32].Regarding malignancy potential, some studies suggest mitotic rate as the bestindicator, however others show poor correlation for leiomyosarcoma [19,33,34].
Despite relatively littledocumentation in the literature of renal vein tumours and survival rates,prognosis overall, seems poor. Leiomyosarcoma patients, in general, havedemonstrated survival of 16 to 38 months after diagnosis [35]. A review ofthree patients with vascular leimyosarcoma demonstrated three and five-yearsurvival rates of 76% and 33%, respectively [18]. In a reviewof 29 renal vein leiomyosarcoma cases, follow up was no longer than 96 months.The longest documented duration of ‘alive free of disease’ state was 78 months [36]. Of thosewho died from disease, the mean duration of life was 43 months [20].
Adjuvant chemotherapy was given in 11 of 32 cases. Of these, onecase incorporated both pre and post operative chemo, for known local invasion [2]. Two cases involved empiric post operativeadjuvant treatment; in the remaining nine cases, chemotherapy treatedsubsequent metastasis or local recurrence. It is not clear in the remainingcases whether chemotherapy was given.
Conclusion
Renal vein leiomyosarcoma is a rare tumour which has a non-specific, often late stage presentation, it normally occurs when people don’t choose the best options for vein treatments. It has a female preponderance. Radical resectionwith nephrectomy represents the gold-standard treatment. Both pre and postoperative chemotherapy and radiation have been utilised as adjuncts totreatment, however it is difficult to assess its effectiveness given thelimited number of cases. Newer molecular therapy may play a future role,although there are currently not enough studies to demonstrate strong evidencefor this.
TABLE 1
Known Cases of Renal Vein Leiomyosarcoma
| Year of Publication | Author | Age | Sex | SurgicalTreatment | Adjuvant/Neo Adjuvant Therapy | Margins | Survival |
| 1967 | Lopez-Varela [37] | 40 | F | N | No | ? | 8yr DOD |
| 1972 | Bathena [1] | 50 | F | N | No | Negative | 36month Mets7yr NED |
| 1976 | Montgomery [38] | 51 | F | N | ? | ? | 3yr DOD |
| 1976 | Gierson [36] | 54 | F | LE | No | ? | 6.5yr NED |
| 1977 | Appel [27] | 60 | F | N | DC Dac, Dox | ? | 4month NED16month DOD |
| 1977 | Stringer [28] | 59 | F | LE | DC Vin, dactinomycin, Cytoxin, Ad.XRT: 4500rad | ? | 3yr Rec.6yr DOD |
| 1978 | Rhadakrishanan[39] | 88 | F | N | ? | ? | 7.5yr DNED |
| 1981 | Kaufman [2] | 42 | F | NUreterectomy
IVC resection |
PrOC: Dox, Radio 1600radPOC: Dox, Met, Vin | Negative | 4yr NED |
| 1986 | Martin [40] | 54 | F | N | Chemo | ? | ? |
| 1988 | Martin | 64 | M | N | Chemo | ? | 24month NED |
| 1988 | Phoa [29] | 60 | F | N | PO XRT | ? | 48month Mets DOD |
| 1988 | Vos [30] | 65 | F | N | Delayed XRT | ? | 24month Mets45month DOD |
| 1989 | Farah [41] | 40 | M | N | ? | ? | ? |
| 1989 | Martin [42] | 48 | F | N | No | ? | 4yr NED |
| 1990 | Ball & Fisher [43] | 58 | F | N | ? | ? | 12month MetsDOD |
| 1990 | Ball & Fisher | 53 | F | N | ? | ? | 4month Mets30month DOD |
| 1991 | Grignon [25] | 61 | F | N | Adjuvant Chemo Act,Vin,Cyc | ? | 31 month |
| 1990 | Pelton [4] | 27 | F | NLiver nodule resection | Intraoperative XRTDC
Delayed XRT |
? | 20month Rec30month DOD
|
| 1993 | Herman [26] | 48 | F | N | DC Dox, Cyc, Dac (4yr post op) | ? | 23month NED4yr |
| 1994 | Inoue [44] | 75 | F | N | No | ? | 4month NED |
| 1995 | Lipton [23] | 64 | F | N/Splenectomy/Thrombectomy | ? | ? | ? |
| 1996 | Brandes [3] | 71 | M | N/LND (Already metastatic) | Delayed XRTDC Ad, ifosfamide,2-mercaptoethane | ? | 25month DOD |
| 1996 | Brandes [3] | 72 | M | N+LND | ? | Negative | 51month NED |
| 1996 | Brandes [3] | 27 | F | NHepatic LE | Intraoperative XRT 2750cGyDC: Ad, ifosfamide,Dac,Mesna
Palliative XRT |
? | 30month Mets54month DOD |
| 1997 | Polsky [45] | 56 | F | N | No | ? | 12month NED |
| 2001 | Hiratuka [46] | 54 | F | N | No | ? | 22 month NED |
| 2002 | Kaushik [12] | 49 | F | N | ? | ? | 3.5 month NED |
| 2003 | Lemos [32] | 47 | M | N | No | ? | ? |
| 2005 | Aguilar [20] | 76 | F | N | Chemo Cyc, DoxXRT | ? | 5month Mets24month DOD |
| 2006 | Mansencal [47] | ? | M | ? | ? | ? | 12 month |
| 2006 | Maeda [48] | 67 | F | N | ? | ? | 24 month NED |
| 2009 | Ikegami [49] | 40 | F | N | No | ? | ? |
| 2010 | Blecher | 66 | F | N | No | Negative | 12month NED |
| Non English Reports | |||||||
| 1982 | Dufour [50] | 73 | F | LE | (French) | ? | 12month Mets18month DOD |
| 1984 | Hisa [51] | 52 | F | LE | (French) | ? | 8month NED |
| 1986 | Farges [52] | 54 | F | N | (French) | ? | 6month AWD |
| 1990 | Maglione [53] | ? | ? | ? | |||
| 1992 | Lakhloufi [54] | 60 | F | NJejunal resection | (French) | ? | ? |
| 1996 | Alcover [55] | ? | ? | ? | (Spanish) | ? | ? |
| 2001 | Hiratsuka [56] | 54 | F | N | Japanese | ? | 22 month NED |
| 2001 | Soulie [57] | ? | ? | ? | (French) | ? | 9 month DOD |
| 2003 | Mugitani [58] | 64 | F | N | Japanese | ? | 8 month DOD |
| 2004 | Kolodziejski [59] | 75 | F | LE | (Polish) | Positive | 24 month NED |
| 2004 | Colon-Rodriguez[60] | 63 | F | N | ? | ? | ? |
| 2006 | Ueda [61] | ? | ? | ? | ? | ? | ? |
| 2006 | Mssrouri [62] | 54 | ? | N | French | ? | ? |
| 2008 | Nalan [63] | 62 | F | N | Turkish | Negative | 24 month NED |
| 2009 | Kato [64] | 52 | M | N | Japanese | ? | 24 month NED |
| 2009 | González-Rodríguez [24] | 59 | F | Ncaudal pancreatectomy, splenectomy, right hemicolectomy | XRT (45g) | Negative | 17 month NED |
Dac: Dacarbizine,Dox: Doxorubicin, Vin: Vincristine, Cyc: Cyclophosphamide, Met: Methotrexate,Act: Actinomycin, Ad: AdriamycinN: RadicalNephrectomy, LE: Local Excision, LND: Lymph node dissection
PrOC: Preoperative chemotherapy, POC: Postoperative chemotherapy, DC: DelayedChemotherapy, Chemo: Chemotherapy – unspecified.
NED: No evidenceof disease, AWD: Alive with disease, DOD: Died of disease, DNED: Dead with noevidence of disease, Mets: Metastatic spread, Rec: Recurrence (local)
? Information Unavailable
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Date added to bjui.org: 20/10/2010
DOI: 10.1002/BJUIw-2010-046-web