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Received June 13, 2007; accepted after revision July 16, 2007.
1Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229. Address correspondence to S. R. Prasad ([email protected]).
2Department of Radiology, Mallinckrodt Institute of Radiology, St. Louis, MO.
3Department of Radiology, King Edward Memorial Hospital, Mumbai, India.
CMEThis article is available for CME credit. See www.arrs.org for more information.
OBJECTIVE. A broad spectrum of benign renal neoplasms in adults shows characteristicontogeny, histology, and tumor biology. Benign renal tumors are classified into renal cell tu-mors, metanephric tumors, mesenchymal tumors, and mixed epithelial and mesenchymal tu-mors. Select benign tumors show characteristic anatomic distribution and imaging features.However, because of overlapping of findings between benign and malignant renal tumors, his-tologic evaluation may be required to establish a definitive diagnosis. Accurate preoperativecharacterization facilitates optimal patient management.
CONCLUSION. We attempt to provide a comprehensive, contemporary review of benignrenal neoplasms that occur in adults, focusing on cross-sectional imaging characteristics.
enign renal neoplasms that occurin adults constitute a heteroge-neous group of tumors with char-acteristic histology and variable
clinicobiologic profiles. The 2004 WorldHealth Organization (WHO) classificationschemata categorizes benign renal neoplasmson the basis of histogenesis (cell of origin)and histopathology [1] (Appendix 1). Renalneoplasms are thus classified into renal cell,metanephric, mesenchymal, and mixed epi-thelial and mesenchymal tumors.
Recent advances in imaging technologyhave resulted in the detection of incidental renalmasses in seemingly asymptomatic patients.Although renal cell carcinoma (RCC) is by farthe most lethal urologic malignancy, benign tu-mors constitute a significant proportion ofmasses in patients who undergo surgery. In a re-cent study of 143 patients with presumed soli-tary RCC, the authors found 16.1% of patientswho underwent partial nephrectomy had be-nign masses [2]. Other studies have also foundthat a significant proportion of solid renalmasses are histologically benign [3–5]. Also,percutaneous renal mass biopsy is being in-creasingly performed to preoperatively charac-terize renal masses and to establish definitivediagnoses [3, 4, 6, 7]. Recent advances in histo-pathology, immunocytochemistry, and cytoge-netics assist in fairly accurate characterizationof most renal masses and help guide optimalpatient management [1, 7, 8]. A recent study of66 renal mass biopsies found 98% accuracy and
79% sample adequacy [7]. However, patholo-gists advise caution when interpreting tumors,specifically those with oncocytic features or hy-brid or collision tumors [7, 9]. Laparoscopicpartial nephrectomies and percutaneous abla-tions are being increasingly performed to treatsmall renal tumors and to establish a definitivediagnosis [10, 11].
Renal Cell NeoplasmsOncocytoma
Oncocytoma is a benign renal cell neoplasmthat accounts for approximately 5% of all adultprimary renal epithelial neoplasms in surgicalseries [1]. Oncocytoma is hypothesized tooriginate from or differentiate toward type Aintercalated cells of the cortical collecting duct[12, 13]. The peak age of incidence is in theseventh decade; men are more likely to be af-fected than women. Most tumors occur spo-radically in asymptomatic patients.
Oncocytoma is histologically composed ofnests and acini of large polygonal cells withmitochondria-rich eosinophilic cytoplasm[1]. Oncocytomas do not show diffuse cyto-plasmic Hale colloidal iron staining, in con-tradistinction to chromophobe RCCs.
Oncocytomas typically appear as solitary,well-demarcated, unencapsulated, fairly ho-mogeneous renal cortical tumors. Bilateral,multicentric oncocytomas are seen in heredi-tary syndromes of renal oncocytosis and Birt-Hogg-Dubé syndrome (in association withthe chromophobe subtype and other RCC
B
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subtypes) [14] (Fig. 1). A characteristic cen-tral stellate fibrotic scar (more often seen withlarge tumors) is seen in up to 33% of tumors[1] (Fig. 2). Hemorrhage may be found in upto 20% of cases. A spoke-wheel pattern offeeding arteries associated with a homoge-neous nephrogram is a characteristic findingon catheter angiography [15]. However, on-cocytomas are indistinguishable from renalcell carcinomas on the basis of imaging find-ings alone. In addition, oncocytomas may beassociated with RCCs either as hybrid tumors(pathologic features of both oncocytomas andchromophobe or other RCC subtypes) or ascollision tumors [9]. Thus, despite advancesin histopathologic techniques (including im-munocytochemistry and cytogenetics), a par-tial nephrectomy may be required for accu-rate characterization [7].
Papillary AdenomaPapillary adenomas are the most common
renal epithelial neoplasms. According to au-topsy series, approximately 40% of patientsolder than 70 years harbor renal adenomas[1]. Papillary adenomas are also commonlyfound in patients with acquired renal cysticdisease and in patients undergoing long-termhemodialysis [16]. A papillary adenoma-to-carcinoma sequence has been described thatis akin to similar transformation in colonicadenomas [17, 18].
By definition, papillary adenomas measure5 mm or less [1]. They are usually subcapsu-lar and solitary. Adenomas are histologicallycharacterized by papillary or tubular cytoar-chitecture and frequent psammoma bodies[1]. Cytogenetic changes of papillary ade-nomas include loss of the Y chromosome andcombined trisomy of chromosomes 7 and 17[19]. Histologic and genetic abnormalities of
renal adenomas are indistinguishable frompapillary RCCs [1, 20].
Papillary adenomas are extremely small(< 5 mm) and may not be distinguished fromother renal tumors (particularly RCC) andpseudotumors on imaging studies.
Metanephric NeoplasmsMetanephric neoplasms are a heteroge-
neous group of benign renal neoplasms thatinclude metanephric adenoma (epithelial tu-mor), metanephric stromal tumor (stromalneoplasm), and metanephric adenofibroma(mixed epithelial and stromal neoplasm) [21].These tumors are histogenetically related toWilms’ tumor and are postulated to representthe most hyperdifferentiated, benign end ofthe nephroblastoma spectrum [21]. Meta-nephric adenofibromas and metanephric stro-mal tumors are essentially pediatric tumorsand will not be discussed in this article.
Metanephric adenoma is a benign renal neo-plasm with peak age of occurrence in the fifthor sixth decade and a 2:1 female preponder-ance [1]. Metanephric adenoma is asymptom-atic in approximately 50% of patients; abdom-inal pain and hematuria are common clinicalsymptoms. Polycythemia, a characteristicfinding seen in approximately 10% of patientswith metanephric adenoma, promptly disap-pears after surgical resection [22].
Metanephric adenoma is histologicallycharacterized by the arrangement of monoto-nous small blue embryonal epithelial cells inan acinar, tubular, or sheetlike configuration[21]. Abundant psammoma bodies are com-monly found.
Metanephric adenoma typically appears asa well-defined, unencapsulated, solitary solidmass [21, 22] (Fig. 3). It commonly appearsas a hyperattenuating mass on unenhanced
CT; large tumors appear as heterogeneous,hypovascular masses with frequent foci ofhemorrhage and necrosis [23, 24]. Calcifica-tion is seen in 20% of cases. Metanephric ad-enoma shows a hypointense signal on T1-weighted MRI and a slightly hyperintensesignal on T2-weighted MRI [25]. Meta-nephric adenoma appears as an expansile hy-poechoic or hyperechoic mass on sonogra-phy. True cystic forms of metanephricadenoma are rare [26].
Mesenchymal NeoplasmsAngiomyolipoma
Angiomyolipoma (AML) is the most com-mon benign mesenchymal neoplasm; it is com-posed of variable proportions of blood vessels,smooth muscle, and adipose tissue [1]. AMLsare now included under the umbrella term“neoplasms of the perivascular epithelioidcells,” which are also referred to as PEComas[27]. Renal AMLs consist of two distinct his-tologic subtypes, classic triphasic and mono-typic epithelioid. Epithelioid AMLs typicallydo not show macroscopic fat and appear assoft-tissue masses and are thus indistinguish-able from other solid renal masses. This raresubtype of AML is potentially malignant andmay exhibit aggressive biology, including re-currence, metastasis, and death. It will not befurther discussed in this article [27, 28].
Classic AML may occur either sporadi-cally or in association with tuberous sclerosiscomplex (TSC). Sporadic renal AMLs show a4:1 female preponderance and are more likelyto be solitary and symptomatic [29]. Patientswith TSC harbor small, multicentric, asymp-tomatic AMLs; 80% of patients with severeTSC have renal AMLs [30]. The morphologyof AMLs depends on the relative proportionsof various components. Profuse elastin-poor,
A B
Fig. 1—72-year-old man with hereditary oncocytosis syndrome. Coronal contrast-enhanced CT scan during nephrographic phase shows bilateral solid renal masses (arrows) that were characterized as oncocytomas on histopathology.
Fig. 2—64-year-old man with histologically proven oncocytoma. K = kidney.A, Axial fat-saturated, T2-weighted gradient-refocused echo image shows expansile, solid right renal mass (arrow) with hyperintense central scar (S).B, Axial fat-saturated, gadolinium-enhanced T1-weighted 3D gradient-refocused echo image shows right kidney mass (arrow) with hypointense central scar (S).
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dysmorphic blood vessels predispose to aneu-rysm formation and hemorrhage [29]. Largetumor size (> 4 cm) and diameter of the in-tralesional aneurysms (> 5 mm) correlate di-rectly with tumor-related hemorrhage inAMLs [31].
On sonography, small AMLs appear uni-formly hyperechoic without a hypoechoic rimor intralesional cysts [32] (Fig. 4). LargeAMLs appear as variegated masses with mac-roscopic fat, hemorrhage, and hypervascularsoft-tissue components. Intralesional aneu-rysms are seen in large tumors as well. Thepresence of macroscopic fat on CT or MRI ischaracteristic of AMLs (Fig. 5). Loss of sig-nal intensity on frequency-selective fat-sup-pressed MRI definitively identifies macro-scopic fat [30] (Fig. 6). However, a multitudeof renal neoplasms, including RCC, oncocy-toma, lipoma, and liposarcoma, may show ei-ther intratumoral fat or engulfed perirenal fat
[33]. Approximately 4.5% of AMLs may notshow identifiable macroscopic fat and are in-distinguishable from RCC on imaging studiesalone (Fig. 7). Recent studies indicate that incontradistinction to RCCs, AMLs with mini-mal fat show uniform, prolonged contrast en-hancement and a higher signal intensity indexon double-echo, chemical shift FLASH MRI[34, 35].
HemangiomaRenal hemangioma is a rare benign mesen-
chymal neoplasm that consists of multipleendothelium-lined, blood-filled vascularspaces [1]. It commonly affects young adultswith no specific sex predilection. Recurrentepisodes of hematuria and renal colic are typ-ical presenting symptoms; however, inciden-tal diagnosis in asymptomatic patients is alsocommon [36]. Hemangiomas of the kidneymay be associated with systemic syndromes
such as Sturge-Weber and Klippel-Trénaunayand with systemic angiomatosis [1]. Cavern-ous hemangiomas are more common than thecapillary variants.
Hemangioma of the kidney occurs as anunencapsulated, unicentric, solitary tumorthat frequently arises from the renal pyra-mids or the pelvis [1, 37]. Hemangiomasshow variable echogenicity on sonographyand hyperintensity on T2-weighted MRI[38] (Fig. 8A). Contrast-enhanced CT andMRI of renal hemangiomas may showearly, intense enhancement (Fig. 8B). Per-sistent contrast enhancement on delayedimages is fairly characteristic of renal he-mangiomas [37].
LymphangiomaLymphangioma of the kidney is a rare be-
nign cystic tumor that most often arises fromthe peripelvic region or renal sinus [1]. It
Fig. 3—Contrast-enhanced axial CT scan in 60-year-old woman with hematuria shows hypoattenuating, expansile solid mass (arrows) in left kidney. Radical nephrectomy showed mass to be metanephric adenoma. K = kidney.
Fig. 4—43-year-old woman with hematuria. Transverse sonogram shows uniformly echogenic mass (arrows) in upper pole of left kidney (K) that was proven to be angiomyolipoma.
Fig. 5—58-year-old woman with angiomyolipoma of kidney. Sagittal contrast-enhanced CT scan shows exophytic renal mass (arrows) with foci of macroscopic fat (arrowhead).
A B
Fig. 6—38-year-old woman with documented tuberous sclerosis complex and renal angiomyolipomas.A, Axial in-phase T1-weighted 2D gradient-refocused echo MR image shows bilateral multicentric renal masses that have increased signal intensity (arrows).B, Axial fat-saturated T2-weighted 2D gradient-refocused echo MR image shows marked drop in signal intensity of masses (arrows).
Fig. 7—55-year-old woman who underwent partial nephrectomy for serendipitously detected renal mass. Axial contrast-enhanced CT scan shows exophytic soft-tissue mass (arrow). Histopathology showed lipid-poor angiomyolipoma.
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may also uncommonly arise from the lym-phatics of the capsule or the cortex [39]. His-tologically, lymphangiomas consist of com-municating endothelium-lined spaces thatcontain clear fluid [1]. The septa may showlymphoid cells.
Renal lymphangioma may occur either asan isolated finding or in association with peri-nephric or systemic lymphangiomatosis [39].It may appear as a localized process or a dif-fusely cystic lesion. Lymphangioma typicallyappears as a well-demarcated, uni- or mul-tilocular cystic neoplasm that most com-monly arises from the renal sinus region or inthe perinephric space [40, 41] (Fig. 9).
LeiomyomaRenal leiomyomas are rare benign smooth-
muscle neoplasms that mostly occur in adultsas incidental findings [1]. Renal capsule is the
most common target site of leiomyomas;rarely, leiomyomas originate from the renalpelvis or cortex. Intersecting fascicles of spin-dle cells that show immunoreactivity to actinor desmin (smooth-muscle markers) are char-acteristic histologic features [1].
Leiomyomas of the kidney commonly ap-pear as well-circumscribed, homogeneous, ex-ophytic solid masses that show uniform en-hancement on contrast-enhanced CT [42](Fig. 10). Larger tumors are heterogeneous be-cause of hemorrhage and cystic or myxoid de-generation [43, 44]. Calcification is uncom-mon. However, the CT findings of leiomyomasof the kidney may be variable and may includecystic, complex cystic–solid, or purely solidmorphology [44]. Renal leiomyomas mayshow hypervascularity on catheter angiogra-phy because they are predominantly suppliedby capsular vessels [42, 45].
Juxtaglomerular Cell Neoplasm (Reninoma)Juxtaglomerular cell (JGC) neoplasm is an
extremely rare, benign renal neoplasm ofmyoendocrine cell origin [46]. The peak ageof incidence is in the second and third decadesand a 2:1 female preponderance is seen. JGCneoplasm is clinically characterized by a triadof findings: poorly controlled hypertension,hypokalemia, and high plasma renin activity[47]. Histologically, JGC neoplasm consistsof sheets of polygonal or spindle cells and acharacteristic, complex, hemangiopericyticangioarchitecture [1]. The presence of rhom-boid renin protogranules is diagnostic of JGCneoplasm [46].
JGC neoplasm typically appears as a uni-lateral, well-circumscribed, cortical tumorthat usually measures less than 3 cm [13](Fig. 11). Despite profuse vascularity, JGCneoplasms appear hypovascular on contrast-
A B
Fig. 8—60-year-old man with hematuria and histologically proven hemangioma.A, Axial fat-saturated T2-weighted 2D gradient-refocused echo MR image shows hyperintense left kidney mass in renal sinus (arrow).B, Axial fat-saturated gadolinium-enhanced T1-weighted 3D gradient-refocused echo MR image shows contrast enhancement of left renal sinus mass (arrows).
Fig. 9—47-year-old man with bilateral multiple renal sinuses and perinephric lymphangiomatosis. Unenhanced axial CT scan shows multicentric cystic masses in renal sinus and perinephric spaces (arrows).
Fig. 10—43-year-old woman with renal leiomyoma of capsular origin. Axial contrast-enhanced CT scan shows large, fairly homogeneous exophytic mass (arrows) arising from left kidney (K).
Fig. 11—23-year-old woman with hypertension refractory to standard treatment. Axial unenhanced CT scan shows large, expansile right renal mass (arrow) that was histologically proven to be juxtaglomerular cell neoplasm (reninoma). K = kidney, M = mass.
Fig. 12—57-year-old woman with incidental medullary fibroma (arrowhead). Patient underwent radical nephrectomy for renal cell carcinoma (Ca, arrow) of right kidney.
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enhanced CT and MRI, possibly because ofrenin-induced vasoconstriction [48, 49]. JGCneoplasms may show delayed contrast en-hancement. Imaging findings of JGC neo-plasms are nonspecific and indistinguishablefrom other solid renal neoplasms.
Renomedullary Interstitial Cell TumorAlso referred to as medullary fibromas,
renomedullary interstitial cell tumors are be-nign neoplasms that arise from renomedul-lary interstitial cells, small stellate cells thatare thought to play a role in blood pressurehomeostasis [50]. Renomedullary interstitialcell tumors are common incidental findingsthat are present in 50% of adults in autopsyseries [1].
Most renomedullary interstitial cell tumorsare small and typically measure less than 5mm. The renal pyramid is the characteristiclocation of renomedullary interstitial cell tu-mors [1]. Rarely, large renomedullary inter-stitial cell tumors extend into the renal pelvis.They appear as nonenhancing, hypoattenuat-ing renal medullary solid lesions without cal-cification (Fig. 12).
Mixed Epithelial and Mesenchymal Neoplasms
Mixed epithelial and mesenchymal neo-plasms comprise two histologically distinctentities: mixed epithelial and stromal tu-mors and cystic nephromas. However, re-cent studies have found remarkable demo-graphic, clinical, and pathologic similaritiesamong these entities and a new name, renalepithelial and stromal tumor, has been pro-posed [51, 52]. This nomenclature is stillnew and has yet to be universally accepted;we will discuss these two entities separately
in this article according to WHO taxonomicschemata.
Mixed Epithelial and Stromal TumorThe entity mixed epithelial and stromal tu-
mor was previously called by several descrip-tive names reflecting variegated tumor histol-ogy. It is now thought that mixed epithelialand stromal tumor was previously referred toas leiomyomatous renal hamartoma, mul-tilocular cyst with ovarian stroma, cystichamartoma of the renal pelvis, and adult me-soblastic nephroma [53–55]. The unifyingterm, mixed epithelial and stromal tumor, wasfirst coined by Michal and Syrucek in 1998[56]; two recent large series have largely con-tributed to our understanding of mixed epithe-lial and stromal tumors [57, 58].
Mixed epithelial and stromal tumors occuralmost exclusively in perimenopausal women(6:1 female preponderance); most patients arereceiving estrogen therapy [57, 58]. Twenty-five percent of the tumors present as inciden-tal findings; most patients manifest nonspe-cific symptoms of flank pain and hematuria.Pathologically, mixed epithelial and stromaltumor is a benign, bimorphic solid–cysticneoplasm that consists of epithelium-linedcysts or microcysts and variably cellular spin-dle-cell, ovarianlike (estrogen- or progester-one-receptor positive) stroma [57, 58].
On imaging, mixed epithelial and stromaltumors typically appear as expansile, com-plex, cystic–solid masses with heterogeneousand delayed enhancement [59] (Fig. 13). Theproportion of cystic and solid constituentsvaries in any given case. The stromal compo-nent of the tumor is thought to be responsiblefor the hypointense signal on T2-weightedMRI with delayed contrast enhancement [59].
Large mixed epithelial and stromal tumorsmay herniate into the renal pelvis. The tumorstypically show benign biologic behaviorwithout recurrence or metastasis; however,aggressive mixed epithelial and stromal tu-mors with sarcomatous transformation of thestromal component have been described [60].
Cystic NephromaCystic nephroma is a benign cystic neo-
plasm that affects predominantly middle-aged,perimenopausal women [1]. Adult-onset cysticnephroma is histogenetically and morphologi-cally different from pediatric cystic nephroma[39, 61]. Morphologically, cystic nephromasare composed of encapsulated, noncommuni-cating cysts with thin septations. By definition,cystic nephromas are characterized by the ab-sence of a solid component or necrosis [1]. Onhistology, the cysts are lined by a monolayer ofhobnail epithelium; the fibrous septa may bepaucicellular or cellular [1].
Cystic nephroma appears as a well-demar-cated, solitary, multilocular cystic lesion withthin septations (Fig. 14A). The cystic massmay protrude into the renal pelvis and causehemorrhage or urinary obstruction [62](Fig. 14B).
ConclusionBenign renal tumors that occur in adults
cover a wide spectrum and show character-istic histology, histogenesis, and anatomicdistribution. Some benign tumors of the kid-ney (such as angiomyolipomas, mixed epi-thelial and mesenchymal tumors, leiomyo-mas, and hemangiomas) show characteristicimaging findings and regional distributionthat permit their diagnosis (Appendix 2). Al-though leiomyomas originate from the renal
A B
Fig. 13—40-year-old woman with histologically proven mixed epithelial and stromal tumor of kidney. Axial contrast-enhanced CT scan shows large complex cystic left kidney (K) mass (arrows) with septations and solid components.
Fig. 14—50-year-old woman with cystic nephroma.A, Coronal contrast-enhanced CT scan shows lobulated, expansile, cystic mass (M) in left kidney (arrow) that compresses calyces (C).B, Coronal T2-weighted MR image shows multilocular, septated cystic mass in left kidney (arrow) that herniates into renal pelvis. C = calyces.
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capsule, hemangiomas typically arise fromthe renal sinus. Renomedullary interstitialcell tumors (also known as medullary fibro-mas) are commonly confined to the renalmedulla. Approximately one third of largeoncocytomas typically show a central stel-late scar. Cystic nephromas show septatedcysts, macroscopic fat predominates in mostangiomyolipomas, and metanephric ade-nomas are commonly solid. Mixed epithelialand stromal tumors consist of solid areas andcysts that may herniate into the renal pelvis.However, most benign renal tumors appearas solid enhancing masses and are thus indis-tinguishable from the more common malig-nant renal neoplasms, notably RCCs. Biopsyof the renal mass may help establish the de-finitive diagnosis and may obviate aggres-sive treatment.
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