one of these had been treated for prostate cancer with diethylstilbestrol and leuprolide [2].

Transcription

1 . JOURNAL COMPILATION 2009 BJU INTERNATIONAL Urological Oncology SAHNI et al. BJUI BJU INTERNATIONAL Mixed epithelial and stromal tumour of the kidney: imaging features V. Anik Sahni, Koenraad J. Mortele, Jonathan Glickman* and Stuart G. Silverman Division of Abdominal Imaging and Intervention, Department of Radiology, and *Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA Accepted for publication 26 June 2009 Study Type Diagnosis (case series) Level of Evidence 4 OBJECTIVE To describe the features on ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) of mixed epithelial and stromal tumours of the kidney. PATIENTS AND METHODS Five women with renal mixed epithelial and stromal tumours (mean age 55.6 years, range 49 59) who had preoperative imaging were retrospectively analysed. Three ultrasonograms, five contrast-enhanced CT scans, and one contrast-enhanced MRI examination were available for review. Specific imaging features analysed included lesion size, location, enhancement and cystic composition. The presence of calcification, septation, nodularity and a capsule were also evaluated. RESULTS All mixed epithelial and stromal tumours appeared as well-marginated, multi-septate cystic masses with a nodular component. All lesions were classified as Bosniak category III (three) or IV (two). The presence of calcification (four) or a capsule (three) was variable. Two tumours invaginated into the renal pelvis with no invasion. CONCLUSION Mixed epithelial and stromal tumours of the kidney have a diverse radiographic appearance, indistinguishable from multilocular cystic nephroma and cystic renal cell carcinoma. KEYWORDS mixed epithelial and stromal tumour, kidney, ultrasonography, computed tomography, magnetic resonance imaging INTRODUCTION Mixed epithelial and stromal tumours (MEST) are rare neoplasms of the kidney that have a characteristic histological appearance [1,2]. Their typical composition is an admixture of spindle cells that resemble ovarian stroma and an epithelial component that lines a variable cystic architecture [1,2]. Before 1998, multiple renal tumours with the same histology were assigned a variety of diagnoses [1]. A unifying term was not available until Michal and Syrucek [3] proposed the current name and reported a case with distinctive solid and cystic morphology [2,4]. A strong association with oestrogen exposure was proposed. Of the 90 patients reported who had MEST [1 3,5 18], almost all have been women [2,4]. Many of these patients were perimenopausal with a history of long-term oestrogen replacement at the time of diagnosis [2]. Only six men have been diagnosed with MEST [2,5 7]; one of these had been treated for prostate cancer with diethylstilbestrol and leuprolide [2]. Although there are case reports and series in the pathology literature [1 3,6,7,9 14,16,17] there are few published reports describing the imaging findings of MEST [5,8,19]. To the best of our knowledge, the largest radiological study described the imaging features in three patients [5]. Another series of 10 cystic renal neoplasms included three patients with MEST; the CT features of two were described [8]. Therefore, the objective of this study was to present the radiological findings of MEST of the kidney using ultrasonography (US), CT and MRI. PATIENTS AND METHODS After obtaining Institutional Review Board approval, we retrospectively reviewed the electronic surgical pathology and radiology information databases at our institution, from 1998 to Informed consent was waived. Five pathologically confirmed cases of MEST were identified; all patients underwent preoperative imaging. The mean (range) age of the patients with MEST was 55.6 (49 59) years, and all were women. In all, nine imaging studies were available; three ultrasonograms, five contrast-enhanced CT scans, and one contrast-enhanced MRI examination. For US we used an Acuson Sequoia system (Siemens Medical Solutions, Forchheim, Germany), with a standard convex linear array transducer. Four of five patients were scanned at our institution on either 4-, 16- or 64- detector row CT scanners (Siemens Medical Solutions). A three-scan protocol was used; an unenhanced scan was obtained, then in the nephrographic phase (100 s) and excretory phase (8 15 min) scans were 932 JOURNAL COMPILATION 2009 BJU INTERNATIONAL 105, doi: /j x x

2 TABLE 1 The CT imaging features TABLE 2 Description of the imaging features for each patient Imaging feature N (of five) Exophytic location 3 Renal sinus invagination 2 Presence of calcification 4 Presence of septa 5 Presence of capsule 3 Presence of nodules 5 Enhancement of nodules 2 Bosniak category III 3 Bosniak category IV 2 Variable Patient Age, years Maximum size, cm N/A Side R R L R L Exophytic Yes No Yes Yes No Renal sinus invagination No No No Yes Yes Calcifications Yes No Yes Yes Yes Septa (n) > >10 Yes Capsule Yes No Yes Yes No Cystic composition, % >75 > >75 >75 Nodules Yes Yes Yes Yes Yes Enhancement No Yes No Yes No Bosniak III IV III IV III obtained after 100 ml of iopromide (Ultravist 300, Bayer Healthcare, Seattle, WA) was administered at 3 ml/s. Patients received 900 ml of water by mouth before the investigation. Images were obtained at 120 kv and ma and reconstructed at 3 5 mm. One patient was scanned at an outside institution and therefore protocol information was not available. For MRI we used a 1.5 T unit (GE Excite, GE Medical Systems, Waukesha, WI, USA) using a phased-array torso coil. T1-weighted imaging was acquired with a breath-hold spoiled gradient-echo dual-echo in-phase and outof-phase sequence (TR/TE, 230/ ms; flip angle, 90 ). T2-weighted imaging was obtained in the axial and coronal planes using a single-shot fast-spin echo sequence (TR/TE, / ms) and a fast-recovery fast-spin echo sequence (TR/TE, 2500/87 ms). Intravenous gadolinium was administered with a power injector in a bolus of 20 ml of gadopentetate dimeglumine (Magnevist, Bayer Healthcare, Seattle, WA, USA) at 2 ml/s, followed by a saline flush. Four sets of breath-hold serial axial T1-weighted threedimensional spoiled gradient-echo fatsuppressed images (TR/TE, 3.95/1.85 ms; flip angle, 12 ) were acquired before administering i.v. contrast medium, and during the contrast-enhanced corticomedullary, nephrographic and excretory phases. Section thickness was 4 8 mm, and the matrix size was for all sequences. Two abdominal radiologists evaluated in consensus all images retrospectively on a picture archiving and communication system workstation. The maximum diameter of the mass was determined in three orthogonal N/A, not available. planes. Location was evaluated for side (left or right), renal pole (upper, interpolar or lower), and whether the tumour was primarily exophytic, intraparenchymal or central, and whether it invaginated into the renal pelvis. Imaging characteristics reviewed included: margin (poorly or well-marginated), calcification (size and distribution), capsule (presence and thickness), nodules (size and location), cystic component (<25%, 26 50%, 51 75% and >75% of the total volume), and septa (number and thickness). Cystic was defined as an attenuation of <20 Hounsfield units (HU) on the unenhanced scan. Septa were considered thin when they were 2 mm, and thick when they were >2 mm. The number of septa was categorized as two or fewer, three to 10, or >10. MRI signal characteristics of the mass on T1- and T2- weighted sequences (as compared to renal cortex) were evaluated. All lesions were assigned a Bosniak category [20]. The remainder of the kidneys were evaluated for other focal lesions. CT attenuation (HU) or MRI signal intensity (units) were obtained of both cystic and solid components using a region of interest of at least three pixels, on the unenhanced, nephrographic and excretory phases. Masses were considered enhancing if after contrast medium there was an increase in attenuation of 20 HU [21], or a 20% increase in signal intensity [22]. Enhancement was deemed equivocal if the increase in CT attenuation was HU, and if the increase in signal intensity was 15 20%. RESULTS All MEST appeared as well-marginated, multi-septate cystic masses with a nodular component. The presence of calcification (four) or a capsule (three) was variable. Two tumours invaginated into the renal pelvis with no invasion and three arose exophytically. The lesions were classified as Bosniak category III (three) or IV (two). Tables 1 and 2 summarize the imaging features as observed on CT. Patient 1 was a 59-year-old woman who presented with an incidental right renal mass detected on imaging for her lumbar spine at an outside institution. On CT a cm mass was seen to arise from the upper and interpolar regions anteriorly of the right kidney (Fig. 1a c). It was an exophytic mass located in the renal parenchyma with entrapment of a calyx in the interpolar region. It was well-marginated with a 2.4-mm capsule. Peripheral calcifications were present of up to 2 mm. The cystic component comprised >75% of the mass and contained >10 thin septa. A non-enhancing cm nodule was present at the anteromedial aspect of the lesion. The Bosniak category was III. There were no ipsilateral or contralateral renal lesions. The patient had a partial nephrectomy; grossly, the tumour was JOURNAL COMPILATION 2009 BJU INTERNATIONAL 933

3 SAHNI ET AL. well-circumscribed and was predominantly composed of innumerable cysts measuring up to 1 cm in diameter (Fig. 1d). Patient 2 was a 49-year-old woman who was noted to have a right renal mass as an incidental finding on abdominal US at an outside institution. She had had a previous history of nephrolithiasis but had no genitourinary symptoms. US showed a wellmarginated mass of cm in the interpolar region of the right kidney (Fig. 2a). It was centred in the renal parenchyma and abutted renal sinus fat. No capsule or calcification was identified. The cystic component comprised <25% of the mass, contained >10 septa, and a central nodule. No other lesions were identified in either kidney. FIG. 1. A 59-year-old woman with MEST of the right kidney. Axial CT scans during unenhanced (a), nephrographic (b), and excretory (c) phases show a 6.4-cm exophytic low-attenuation mass (10 HU) with peripheral calcifications and multiple thin septa (white arrows). The mass is entrapping interpolar calyx (black arrow, c). d, Gross specimen of tumour shows well-circumscribed tumour with multiple noncommunicating cysts. CT showed a well-marginated mass in the interpolar region posteriorly of the right kidney (Fig. 2b,c). The mass was confined to the renal parenchyma and abutted the collecting system but did not distort the calyces. There was no exophytic component, calcification or capsule. The mass appeared predominantly (>75%) cystic and contained 3 10 thin septa. A central enhancing nodule measured mm. A 5-mm lowattenuation lesion, probably representing a simple cyst, was noted in the upper pole of the right kidney. There was no focal mass in the left kidney. On MRI, the lesion was well-marginated and located in the interpolar region posteriorly of the right kidney (Fig. 2d f). It was centred in the renal parenchyma and abutted the renal pelvis with no exophytic component. There was no capsule. There were 3 10 thin septa and the lesion was >75% cystic. A central nodule measured 7 7 mm. The cystic region appeared hypointense on T1-weighted images and hyperintense on T2-weighted images. The central nodular component was hyperintense on the T1-weighted images, hypointense on the T2-weighted images, and enhanced by 117% and 63% in the nephrographic and excretory phases, respectively. The Bosniak category was IV. A 4-mm, T2-hyperintense probable cyst was noted in the upper pole of the right kidney. No lesions were identified in the left kidney. The patient had a US-guided partial nephrectomy. Patient 3 was a 52-year-old woman who presented with left upper quadrant pain. CT showed a cm well-marginated mass arising exophytically from the interpolar region of the lateral aspect of the left kidney (Fig. 3a d). It had a capsule of 3.4 mm. Linear peripheral and septal calcifications were present. The cystic component comprised 51 75% of the mass, and contained 3 10 septa that were both thick and thin, the thickest being 2.5 mm. A non-enhancing cm nodule was located at the anterior lateral margin. The Bosniak category was III. No ipsilateral renal lesions were identified. A thick-walled cystic mass of cm was present in the interpolar region of the right kidney. The patient had a left partial nephrectomy; grossly, the tumour was well-circumscribed and consisted of a dominant thick-walled cyst, with several smaller peripheral cysts (Fig. 3e). Microscopically, similar to the other cases, the cysts were lined by benign cuboidal epithelium, and the cyst walls contained a cellular spindle-cell stroma growing in short fascicles (Fig. 3f). Patient 4 was a 59-year-old woman who was found to have an incidental cystic lesion in the right kidney on staging CT for laryngeal carcinoma at an outside institution. On US the mass was well-marginated and was cm (Fig. 4a). It was located in the interpolar region and lower pole of the right kidney, and invaginated into the renal sinus fat. No calcification or capsule was present. The lesion was >75% cystic and contained >10 thick and thin septa. Some locules contained low-level internal echoes. Mural nodules were identified. No additional ipsilateral lesion was noted but in the lower pole of the left kidney there was a cm cystic lesion with internal echoes. CT showed a well-marginated mass arising from the right interpolar region (Fig. 4b e). The mass was exophytic but invaginated into the pelvis and compressed several calyces. 934 JOURNAL COMPILATION 2009 BJU INTERNATIONAL

4 FIG. 2. A 49-year-old woman with MEST of the right kidney. a, Sagittal intraoperative US image shows a well-marginated multiseptate cystic mass (black arrows). Axial CT scans during unenhanced (b) and nephrographic (c) phases show a intraparenchymal 2.5-cm low-attenuation mass (9 HU) with a central enhancing nodule (white arrows). d, Coronal (d) single shot fast spin-echo T2-weighted MR images show T2-hyperintense intraparenchymal lesion with T2-hypointense central nodule (white arrow). e and f, Axial T1-weighted three-dimensional fast-acquisition multiecho fat-suppressed sequence in unenhanced (e) and nephrographic (f) phases shows T1-hyperintense nodule (black arrow, e), which enhances. Linear calcification was present in the wall. The lesion had a 2.1-mm capsule. The mass was >75% cystic and contained >10 thick and thin septa, the thickest being 3.7 mm. There were enhancing nodules; the two largest areas measured cm and cm. The Bosniak category was IV. No ipsilateral renal lesions were present. In the left kidney, 3- and 4-mm low-density lesions were identified in the upper pole and interpolar region, respectively. A cm septated cystic lesion was visualized in the lower pole of the left kidney. The patient had a right nephrectomy. Patient 5 was a 59-year-old woman who was found to have a left renal mass on US, for chronic UTIs and persistent microhaematuria, at an outside institution. She had CT at the same outside institution but only selected images were available for review. A wellmarginated lower pole mass invaginated into the renal pelvis with distortion of the lower pole calyces and hydronephrosis (Fig. 5). There was no exophytic component. There were predominantly peripheral calcifications with a few foci of small central calcifications. Renal calculi were also noted. The mass was >75% cystic and contained thin septa. The lower pole portion contained a non-enhancing nodule. The Bosniak category was III. Retrograde pyelography and ureteroscopy confirmed the presence of a large lower pole mass invaginating into a lower pole calyx and the renal pelvis. The patient had a laparoscopic left nephrectomy. DISCUSSION MEST of the kidney is a relatively recently described neoplasm [3]. A specific, pathological diagnosis depends on the detection of both spindle-cell stromal components and adenomatous epithelium, and the exclusion of other entities [1,2]. Before 1998, multiple renal tumours with the same histology were assigned a variety of diagnoses, including, among others, adult mesoblastic nephroma, cystic hamartoma of the renal pelvis, and leiomyomatous renal hamartoma [1]. These tumours are now believed to have been MEST of the kidney. Published imaging appearances of these entities are limited to small series and descriptions found only in case reports [23 26]. Freeby et al. [23] and Groves et al. [24] described the CT and MRI appearances, respectively, of single cases of adult mesoblastic nephroma. The radiological appearance of both tumours was concordant with our series; both lesions were wellcircumscribed, cystic lesions with solid enhancing components. Neither lesion had JOURNAL COMPILATION 2009 BJU INTERNATIONAL 935

5 SAHNI ET AL. FIG. 3. A 52-year-old woman with MEST of the left kidney. Axial CT scans during unenhanced (a) and nephrographic (b) phases show a 4.1-cm exophytic multiseptate cystic mass with multiple thick septa and nodular components (white arrows). c, Axial CT scan in excretory phase shows a mass abutting opacified interpolar calyx (black arrow). d, Coronal CT scan in nephrographic phase shows a multiseptate cystic mass arising from left interpolar region. e, Gross specimen of the tumour shows a multicystic mass with large central cyst and several smaller peripheral cysts. f, Photomicrograph shows cellular spindle-cell stroma growing in short fascicles (S) and benign-appearing cuboidal epithelial lining (black arrow). lymphadenopathy or extrarenal involvement. The reported imaging features of cystic hamartoma of the renal pelvis are also very similar [25]. CT and MRI show a multilocular cystic lesion with thick septa and enhancement of the solid element. No capsule or calcification could be identified, which can be variable features, as noted in our study. Interestingly, a case report of leiomyomatous renal hamartoma [26] showed a purely solid mass with capsular disruption, a feature not identified in any of the present cases. There was no evidence of lymphadenopathy and the patient was followed for 54 months after resection with no evidence of recurrence. In addition, another cystic neoplasm, cystic nephroma, is thought to have many similarities and represent part of the same spectrum of cystic renal neoplasms [7,9,10]. Both MEST and cystic nephroma share a similar age and sex distribution, and have similar morphology and immunohistochemical profiles. They differ in that cystic nephromas typically contain larger cysts, thinner septa, and a lower stromal-toepithelial ratio [7,9]. MEST occur almost exclusively in perimenopausal women; many patients have a previous history of long-term oral oestrogen use or contraceptives [11]. As a result, a hormonal aetiology has been hypothesized [2]. Further evidence for this is that the stroma found in MEST resemble ovarian stroma and often expresses oestrogen and progesterone receptors. However, a hormonal aetiology does not appear to explain all cases. MEST of the kidney has been identified in six men [2,5 7] and only one was exposed to exogenous oestrogens. In addition, MEST has been reported in a 12-year-old girl; the patient was pre-menarchal and had not been treated with oestrogen [11]. MEST are classified as benign tumours with virtually no predilection for metastatic spread or recurrence. However, malignant cases have been reported [12 14]. Svec et al. [12] described a malignant MEST in a 46-yearold woman. The multicystic component was benign, but there was malignant transformation of the solid, mesenchymal component. There were no metastases. 936 JOURNAL COMPILATION 2009 BJU INTERNATIONAL

6 FIG. 4. A 59-year-old woman with MEST of the right kidney. a, Transverse US shows a multiseptate cystic mass with thick septa. Low-level echoes are noted within several locules (white arrow). Axial CT scans during unenhanced (b), nephrographic (c), and excretory (d) phases show a 11.3-cm exophytic multiseptate cystic mass (black arrows) with a solid component (white arrow, b). The mass compresses interpolar calyx (white arrow, d). e, Coronal nephrographic CT scan shows a mass adjacent to the renal pelvis (white arrow). Nakagawa et al. [13] described two cases of malignant MEST; both patients developed local recurrence at the resection site that ultimately led to the death of the patients. Malignant transformation has also been reported in the solid, stromal component of a MEST in a 84- year-old woman [14]. In all malignant cases [12 14] the epithelial lining of the multicystic component had no evidence of malignancy. In our study, all five patients were more typical; all were women and within the perimenopausal age group, and all tumours were histopathologically confirmed to be benign, with no invasion of the renal pelvis. Hora et al. [8] reported three perimenopausal women with MEST; CT scans of two tumours were reported and showed large, exophytic cystic masses with internal septa, findings similar to our cases. Park et al. [5] described US, CT and MRI findings in three cases, but the imaging findings were not systematically reviewed. Two of their patients were atypical; one was a 26-year-old woman and another a man. Unlike in the present study, tumours showed delayed enhancement (qualitatively) and one was entirely solid. A uniformly solid, mildly enhancing 9-cm lesion has also been reported in a 35-year-old woman [15]. Invagination into the renal pelvis has been described as a feature that can be used to suggest the diagnosis of a cystic nephroma [27]. This feature could also be used to consider MEST, but it was seen in only two of the present cases, and is not diagnostic. A limitation of our study was that it was retrospective; as a result, data from all three imaging methods were not available for each patient. In addition, because MEST are rare, only a few cases were available for review. However, to the best of our knowledge, our study is the largest published radiological review of MEST. In summary, MEST have a diverse radiological appearance, but most present as multiseptate cystic renal masses with thick septa and nodular components. Imaging features do not allow discrimination between other multilocular cystic lesions such as cystic nephroma and RCC. As a result, when encountering a mass with a multiseptate appearance, surgical resection is generally recommended. The role of percutaneous biopsy in such lesions is limited [28]. Biopsy could be considered; the retrieval of ovarian stroma could potentially be used to suggest the diagnosis, but ovarian stroma could be found in cystic nephroma [29] and rarely in the malignant form of MEST [12 14]. CONFLICT OF INTEREST None declared. JOURNAL COMPILATION 2009 BJU INTERNATIONAL 937

7 SAHNI ET AL. FIG. 5. A 59-year-old woman with MEST arising from the left kidney. a, Retrograde pyelogram shows distortion of lower pole calyces (white arrow) and large apparent intrapelvic mass (black arrow). Axial CT scans obtained immediately after retrograde pyelogram during unenhanced (b), nephrographic (c), and excretory (d) phases show an intraparenchymal lower-pole mass with polypoid low attenuation component (16 HU) that appears to protrude into pelvis (black arrow). There is a higher attenuation component in parenchyma (white arrow). There is mild hydronephrosis in upper pole; gas in the collecting system was introduced during the retrograde pyelogram. REFERENCES 1 Michal M, Hes O, Bisceglia M et al. Mixed epithelial and stromal tumors of the kidney. A report 22 cases. Virchows Arch 2004; 445: Adsay NV, Eble JN, Srigley JR, Jones EC, Grignon DJ. Mixed epithelial and stromal tumor of the kidney. Am J Surg Pathol 2000; 24: Michal M, Syrucek M. Benign mixed epithelial and stromal tumor of the kidney. Pathol Res Pract 1998; 194: Michal M. Benign mixed epithelial and stromal tumor of the kidney. Pathol Res Pract 2000; 196: Park HS, Kim SH, Kim SH et al. Benign mixed epithelial and stromal tumor of the kidney: imaging findings. J Comput Assist Tomogr 2005; 29: Mai KT, Elkeilani A, Veinot JP. Mixed epithelial and stromal tumour (MEST) of the kidney: report of 14 cases with male and PEComatous variants and proposed histopathogenesis. Pathology 2007; 39: Jevremovic D, Lager DJ, Lewin M. Cystic nephroma (multilocular cyst) and mixed epithelial and stromal tumor of the kidney: a spectrum of the same entity? Ann Diagn Pathol 2006; 10: Hora M, Hes O, Michal M et al. Extensively cystic renal neoplasms in adults (Bosniak classification II or III) possible common histological diagnoses: multilocular cystic renal cell carcinoma, cystic nephroma, and mixed epithelial and stromal tumor of the kidney. Int Urol Nephrol 2005; 37: Turbiner J, Amin MB, Humphrey PA et al. Cystic nephroma and mixed epithelial and stromal tumor of kidney: a detailed clinicopathological analysis of 34 cases and proposal for renal epithelium and stromal tumor (REST) as a unifying term. Am J Surg Pathol 2007; 31: Antic T, Perry KT, Harrison K et al. Mixed epithelial and stromal tumor of the kidney and cystic nephroma share overlapping features: reappraisal of 15 lesions. Arch Pathol Lab Med 2006; 130: Hara N, Kawaguchi M, Murayama S, Maruyama R, Tanikawa T, Takahashi K. Mixed epithelial and stromal tumor of the kidney in a 12 year-old girl. Pathol Int 2005; 55: Svec A, Hes O, Michal M, Zachoval R. Malignant mixed epithelial and stromal tumor of the kidney. Virchows Arch 2001; 439: Nakagawa T, Kanai Y, Fujimoto H et al. Malignant mixed epithelial and stromal tumours of the kidney: a report of the first two cases with a fatal outcome. Histopathology 2004; 44: Sukov WR, Cheville JC, Lager DJ, Lewin JR, Sebo TJ, Lewin M. Malignant mixed epithelial and stromal tumor of the kidney with rhabdoid features: report of a case including immunohistochemical molecular genetic studies and comparison to morphologically similar renal tumors. Hum Pathol 2007; 38: Thyavihally YB, Tongaonkar HB, Desai SB. Benign mixed epithelial stromal tumor of the renal pelvis with exophytic growth: case report. Int Semin Surg Oncol 2005; 2: Bisceglia M, Bacchi CE. Mixed epithelialstromal tumor of the kidney in adults: two cases from the Arkadi M. Rywlin Slide Seminars. Adv Anat Pathol 2003; 10: Buritica C, Serrano M, Zuluaga A, Arrabal M, Regauer S, Nogales FF. Mixed epithelial and stromal tumour of the kidney with luteinised ovarian stroma. J Clin Pathol 2007; 60: Sharma JB, Aruna J, Mittal S, Sharma MC. Mixed epithelial and stromal tumor of the kidney in a puerperal woman. J Obstet Gynaecol Res 2007; 33: Prasad SR, Surabhi VR, Menias CO, Raut AA, Chintapalli KN. Benign renal neoplasms in adults: cross-sectional 938 JOURNAL COMPILATION 2009 BJU INTERNATIONAL

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