Ovarian sex cord-stromal tumors are uncommon neoplasms that

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1 Dign Interv Rdiol DOI /dir Turkish Society of Rdiology 2015 ABDOMINAL IMAGING REVIEW Sex cord-stroml tumors of the ovry: comprehensive review nd updte for rdiologists Mrin Hort, Teres Mrgrid Cunh ABSTRACT Ovrin sex cord-stroml tumors re infrequent nd represent pproximtely 7% of ll primry ovrin tumors. This histopthologic ovrin tumor group differs considerly from the more prevlent epithelil ovrin tumors. Although sex cord-stroml tumors present in rod ge group, the mjority tend to present s low-grde disese tht usully follows nonggressive clinicl course in younger ptients. Furthermore, ecuse the constituent cells of these tumors re engged in ovrin steroid hormone production (e.g., ndrogens, estrogens, nd corticoids), sex cord-stroml tumors re commonly ssocited with vrious hormone-medited syndromes nd exhiit wide spectrum of clinicl fetures rnging from hyperndrogenic virilizing sttes to hyperestrogenic mnifesttions. The World Helth Orgniztion sex cord-stroml tumor clssifiction hs recently een revised, nd currently these tumors hve een regrouped into the following clinicopthologic entities: pure stroml tumors, pure sex cord tumors, nd mixed sex cord-stroml tumors. Moreover, some entities considered in the former clssifiction (e.g., stroml luteom, stroml tumor with minor sex cord elements, nd gynndrolstom) re no longer considered seprte tumors in the current clssifiction. Herein, we discuss nd revise the ultrsonogrphy, computed tomogrphy, nd mgnetic resonnce imging chrcteristics of the different histopthologic types nd clinicopthologic fetures of sex cord-stroml tumors to llow rdiologists to nrrow the differentil dignosis when fcing ovrin tumors. From the Deprtment of Rdiology (M.H. mrin.sf.hort@ gmil.com), Centro Hospitlr Liso Ocidentl, Lison, Portugl; Institute of Antomy (M.H.), Fculdde de Medicin d Universidde de Liso; the Deprtment of Rdiology (T.M.C.), Instituto Português de Oncologi de Liso Frncisco Gentil, Lison, Portugl. Received 14 Septemer 2014; revision requested 25 Novemer 2014; revision received 28 Decemer 2014; ccepted 19 Jnury Pulished online 4 June 2015w. DOI /dir This is preprint version of the rticle; the finl version will pper in the July-August 2015 issue of the Dignostic nd Interventionl Rdiology. Ovrin sex cord-stroml tumors re uncommon neoplsms tht represent pproximtely 7% of ll ovrin tumors (1). These tumors comprise heterogeneous group nd re formed y diverse cell types tht rise from the primitive sex cords or stroml cells (1, 2). The stroml cells include thec cells, firolsts, nd Leydig cells wheres the gondl primitive sex cords include grnulos cells nd Sertoli cells (3). These cell types my e present seprtely or dmixed nd disply different degrees of differentition (4). As some of the constituent cells of these types of tumors re engged in ovrin steroid hormone production (e.g., ndrogens, estrogens, nd corticoids), sex cord-stroml tumors re commonly ssocited with vrious hormone-medited syndromes nd exhiit wide spectrum of clinicl fetures. Tumors formed from ovrin cells (e.g., grnulos cells nd thec cells) re often hyperestrogenic, wheres those comprising testiculr cell types (e.g., Sertoli nd Leydig cells) re usully hyperndrogenic. However, mny tumors re nonfunctioning, nd those comprising femle cells my produce ndrogens nd vice-vers (4). Tumors tht induce hyperndrogenicity my present with viriliztion signs (e.g., hirsutism, cne, irregulr menstrul periods, mle-pttern ldness, loss of femle ft distriution, nd horse voice), wheres tumor sutypes ssocited with norml estrogen production my present with hyperestrogenicity (e.g., isosexul precocity in children, norml uterine leeding, endometril hyperplsi, nd crcinom). The ssocition of ovrin sex cord-stroml tumors with typicl clinicl syndromes is not the only chrcteristic distinguishing these tumors from the more common ovrin epithelil neoplsms. Although sex cord-stroml tumors ffect ptients throughout wide ge rnge, the mjority tend to present in younger ptients nd s low-grde disese (stge I) tht usully follows nonggressive clinicl course. Therefore, the primry tretment is surgicl nd the prognosis is generlly fvorle. Furthermore, ovrin sex cord-stroml tumors my exhiit chrcteristic rdiologicl fetures with which rdiologists should ecome fmilir. Conversely, recognition of the spectrum of the ultrsonogrphy (US), computed tomogrphy (CT), nd mgnetic resonnce imging (MRI) ppernces s well s clinicopthologic fetures of ovrin sex cord-stroml tumors my ssist rdiologists to nrrow the differentil dignosis when fcing ovrin tumors. World Helth Orgniztion clssifiction of sex-cord stroml tumors The World Helth Orgniztion (WHO) clssifiction of sex cord-stroml tumors hs recently een revised in 2014 (5) (Tle 1). In the current revision, these tumors were regrouped into the following clinicopth-

2 ologic entities: pure stroml tumors, pure sex cord tumors, nd mixed sex cord-stroml tumors. The pure stroml tumors ctegory comprises entities from the previous thecom-firom group, which hd een clssified under the grnulos-stroml cell tumor group division, s well s entities from the previous steroid cell group division (6) (Tle 2). In the recent clssifiction, luteinized thecom is no longer considered seprte entity from the thecom group, nd therefore this term should only e used when ssocited with sclerosing peritonitis. Insted, seprte histopthologic entity titled luteinized thecom ssocited with sclerosing peritonitis now exists. A distinct rre ovrin neoplsm, which ws recently nmed microcystic stroml tumor, ws dded to this ctegory wheres the denomintion Dignostic nd Interventionl Rdiology stroml tumor with minor sex cord elements is not encompssed y this clssifiction. Moreover, in terms of steroid cell tumors, the term stroml luteom, which ws used to designte smll steroid tumors confined to the ovrin cortex, hs lso een discrded. The sudivision of pure sex cord tumors now comprises tumors tht were previously ctegorized seprtely, including dult grnulos cell tumors (GCTs), juvenile GCTs, Sertoli cell tumors, nd sex cord tumors with nnulr tuules. The different types with respect to Sertoli-Leydig cell tumor (SLCT) differentition s well s sex cord-stroml tumors, not otherwise specified re ctegorized s mixed sex cord-stroml tumors. Stroml-Leydig cell tumor nd gynndrolstoms re no longer considered in the current clssifiction. Tle 1. WHO clssifiction scheme for ovrin sex cord-stroml tumors (2014) Pure stroml tumors Firom Cellulr firom Thecom Luteinized thecom ssocited with sclerosing peritonitis Firosrcom Sclerosing stroml tumor Signet-ring stroml tumor Microcystic stroml tumor Leydig cell tumor Steroid cell tumor Steroid cell tumor, mlignnt Pure sex cord tumors Adult grnulos cell tumor Juvenile grnulos cell tumor Sertoli cell tumor Sex cord tumor with nnulr tuules Mixed sex cord-stroml tumors Sertoli-Leydig cell tumors - Well-differentited - Modertely differentited with heterologous elements - Poorly differentited with heterologous elements - Retiform with heterologous elements Sex cord-stroml tumours, NOS* WHO, World Helth Orgniztion; NOS, not otherwise specified. Pure stroml tumors Firom, cellulr firom, nd firosrcom Firoms re lmost lwys endocrine-inert tumors composed of spindle stroml cells tht produce collgenous strom (5, 7, 8). These re undenily the most common sex cord-stroml tumors, representing 4% of ll ovrin neoplsms (4, 5, 9) (Fig. 1). Firoms cn present t ny ge, lthough the men ge of occurrence is in the lte forties, nd re ssocited with nevoid sl crcinom syndrome (5). Firoms rnge in size from smll to lrge lesions. Smll lesions re frequently symptomtic, ut women cn present with pelvic discomfort or cute dominl pin due to ovrin torsion s the size increses. Firoms cn mimic mlignncy when present in the clssic Meigs syndrome (hydrothorx, scites, nd enign ovrin tumor), which typiclly disppers fter tumor removl (3, 4, 10, 11). The tumor size is known to correlte with the presence of scites. Hypercellulr firoms re clssified s either cellulr firoms or firosrcoms. Cellulr firoms constitute 10% of ll ovrin firoms nd hve low mlignnt potentil, exhiit mild nucler typi, nd my present more thn four mitotic figures per 10 high-powered fields (5). These generlly exhiit the sme clinicl mnifesttions ut tend to e lrger thn firoms, thus potentilly leding to necrosis nd hemorrhge, prticulrly due to torsion (4, 5) (Fig. 2). Ovrin firosrcoms re rre entities tht follow mlignnt clinicl course nd tend to exhiit moderte-to-severe nucler typi nd mitotic figures (5, 12). These tumors usully present in postmenopusl women s lrge unilterl msses, often with necrosis nd hemorrhge (4, 5, 12). Although different ovrin firom US ptterns my e encountered, the US ppernce is usully solid hypoechoic ttenuting ovrin mss (13). On CT, firoms usully pper s homogeneous solid ovrin msses with delyed contrst enhncement (3, 13) (Fig. 1). Clcifiction my e present nd widespred throughout the tumor (13). Given their predominnt collgenous nd firous compo- Hort nd Cunh

3 Tle 2. Former WHO clssifiction scheme for ovrin sex cord-stroml tumors (2003) Grnulos-stroml cell tumors Grnulos cell tumor group Adult grnulos cell tumor Juvenile grnulos cell tumor Thecom-firom group Thecom, NOS - Typicl - Luteinized Firom Cellulr firom Firosrcom Stroml tumor with minor sex cord elements Sclerosing stroml tumor Signet-ring stroml tumor Unclssified (firothecom) Sertoli-stroml cell tumors Sertoli-Leydig cell tumors group (ndrolstom) Well-differentited Of intermedite differentition - vrint with heterologous elements Poorly differentited (srcomtoid) - vrint with heterologous elements Retiform - vrint with heterologous elements Sertoli cell tumor Stroml-Leydig cell tumor Sex cord-stroml tumors of mixed or unclssified cell types Sex cord tumor with nnulr tuules Gynndrolstom Sex cord-stroml tumor, unclssified Steroid cell tumors Stroml luteom Leydig cell tumor group Hilus cell tumor Leydig cell tumor, non-hilr type Leydig cell tumor, NOS Steroid cell tumor, NOS Well-differentited Mlignnt WHO, World Helth Orgniztion; NOS, not otherwise specified. nents, firoms exhiit chrcteristic MRI fetures such s hypointensity on T1-weighted imges nd mrked hypointensity on T2-weighted imges s well s wek nd delyed enhncement fter gdolinium dministrtion (3) (Fig. 1, 1c). Notwithstnding, edem nd cystic degenertion my e encountered in firoms; these pper s dispersed hyperintense res on T2-weighted imges (8, 10, 13). These chrcteristics re most frequently oserved in lrge lesions nd firosrcoms (8, 10, 13). Both predominntly cystic firoms nd firoms with T1 nd T2 hyperintensity/isointensity hve lso een descried (9, 14). Regrding the reltionship etween ovrin firoms nd the ovry, Oh et l. (9) reported tht exophytic firom growth from the ovrin periphery without ltering the norml form of the ipsilterl ovry is not uncommon (46%) nd tht depicting the rest of the ipsilterl ovry in premenopusl women is norml (83%). In ddition, 67% of the 24 studied firoms exhiited order of T2 hypointensity or pseudocpsule round the outer ovrin mrgin tht reflected compression of the ovrin tissue (9). The MRI-sed differentil dignosis includes essentilly firous ovrin tumors such s Brenner tumors nd denofiroms s well s pedunculted nondegenertive suserosl nd rod ligment leiomyoms (15). Depiction of the tumor-feeding ovrin rteries or vsculr signl voids etween the uterus nd leiomyom might help to differentite these entities (16). Thomssin-Nggr et l. (17), in retrospective study tht ccessed the ccurcy of dynmic MRI for differentiting ovrin firoms from uterine suserosl leiomyoms, reported tht the dynmic-contrst MRI enhncement of uterine leiomyoms ws higher in terms of mximl enhncement nd enhncement t 30, 60, nd 90 seconds. However, no significnt sttisticl difference existed in delyed T1 post-contrst sequence (17). Firom my induce dnexl torsion. In such cses, hemorrhgic infrction or necrosis my occur (3, 10). Hemorrhgic infrction my e difficult to define ecuse of the solid nture of the tumor. Nonetheless, n eccentric hyperintense re on T1-weighted imges my llow this dignosis (3). Excepting few cellulr firoms nd firosrcoms, these types of tumors hve typiclly enign courses nd re curle vi surgicl excision (7). Thecom nd luteinized thecom ssocited with sclerosing peritonitis Thecoms re composed of lipid-lden stroml cells tht resemle thec Sex cord-stroml tumors of the ovry

4 cells, which usully encircle the ovrin follicles, nd exhiit estrogenic ctivity in most cses (4, 7, 18) (Fig. 3). Thecoms ccount for 0.5% 1% of ll primry ovrin tumors (19). These tumors re more likely to occur in postmenopusl women nd, with rre exceptions, re considered enign neoplsms (5). Affected women experience estrogen-relted symptoms such s uterine leeding, endometril hyperplsi, nd endometril crcinom; the ltter hs een reported to occur in 21% of cses (4, 8) (Fig. 3). Thecoms ssocited with ndrogen production my contin steroid-type cells (lutein cells) nd were previously formlly clssified s luteinized the- c Figure 1. c. A 77-yer-old femle ptient with right ovrin firom. Coronl delyed contrst-enhnced computed tomogrphy imge () shows solid, well-defined, homogeneous right ovrin mss isodense to the uterus with very sprse contrst uptke (rrow). This firom is hypointense on oth xil T1-weighted () nd T2-weighted imges (c). A smll mount of scites is oserved in the pelvic recesses (sterisks). c Figure 2. c. A 50-yer-old femle ptient with right ovrin cellulr firom. Axil T1-weighted (), T2-weighted () nd gdolinium-enhnced ft-suppressed T1-weighted (c) imges show lrge, heterogeneous nd well-defined tumor of the right ovry. The tumor fetures lrge-centred cystic/necrotic re with T2 hyperintensity nd T1 hypointensity (open rrows). The solid components exhiit n intermedite T2 signl nd T1 isointensity to the muscle s well s vid contrst uptke (rrows). c Figure 3. c. A 61-yer-old postmenopusl femle ptient who presented with metrorrhgi nd ws dignosed with right ovrin thecom nd endometril polyps. Axil T1-weighted imge () shows lrge homogeneous right ovrin mss isointense to the myometrium. Axil T2-weighted imge of the tumor () revels res of isointense nd hyperintense signl reltive to the myometrium, wheres xil gdolinium-enhnced ftsuppressed T1-weighted imge (c) shows wek contrst-enhncement of the tumor (*). Endometril polyps disply hypointensity on T2-weighted imge (), isointensity to the endometrium on T1-weighted imge (), nd homogeneous gdolinium uptke (rrowheds). Dignostic nd Interventionl Rdiology Hort nd Cunh

5 coms (5). This histopthologic clssifiction is no longer recommended nd should only e used if there is n ssocition with sclerosing peritonitis. However, luteinized thecom ssocited with sclerosing peritonitis is usully ilterl hormonlly inert tumor tht occurs in younger women t n verge ge of 28 yers (5). Thecoms tht mnifest in comintion with firous tissue my e clssified s firothecoms (5). Generlly, pure thecoms or thecoms with scnty firotic components do not hve distinct US nd CT ppernces nd mimic other solid ovrin tumors (13). A recent study y Zhng et l. (19) prospectively evluted the MRI chrcteristics of 18 thecoms/firothecoms, nmely the diffusion-weighted imging (DWI) fetures nd pprent diffusion coefficients (ADC) t 3.0 T, nd correlted these with the fetures of other solid ovrin tumors nd dnexl leiomyoms. The uthors concluded tht most thecoms/firothecoms (61.1%) were homogenous msses nd isointense to the myometrium on DWI-MRI nd tht the ADC vlues of thecoms/firothecoms did not significntly differ from those of other ovrin solid tumors nd leiomyoms (19). When compred with predominnt firous tumors, pure thecoms tend to exhiit greter hyperintensity on T2-weighted imges; more vid contrst-enhncement my e oserved ecuse thec cells re gretly vsculrized (13, 18) (Fig. 3). Sclerosing stroml tumor Sclerosing stroml tumor (SST) is enign neoplsm tht ccounts for less thn 5% of ovrin sex cord-stroml tumors (20) (Fig. 4). Unlike firom, thecom, nd dult GCTs, SSTs re more likely to occur in young women; pproximtely 80% of reported cses re under 30 yers of ge (13, 21). Although SSTs most commonly occur fter menrche, few cses hve een reported in premenrchl girls (22). Typiclly, SSTs mnifest s unilterl msses. To our knowledge, only two cses of ilterl SSTs hve een descried: one in n 11-yer-old premenrchl girl nd the other in pregnnt womn with Gorlin syndrome fter clomiphene therpy for infertility (21, 23). Pelvic pin nd menstrul irregulrities re frequent symptoms (20, 24). A few hormonlly ctive tumors tht produced ndrogens nd/or estrogens hve een documented in the literture (18). SSTs of the ovry hve lso een ssocited with pregnncy (25). Although rre, scites my e present (3). Upon gross exmintion, SSTs re mostly solid msses with yellowish foci, edem, nd cystic res (4). The histopthology is chrcterized y the presence of n ill-defined pseudoloulr pttern in the cellulr res, which re seprted y edemtous firous res. These nodulr portions contin collgen-producing spindle-shped cells nd vcuolted lipid-contining lutein cells. Prominent vsculriztion is seen within these res (4, 24). Both these typicl fetures nd the edem present in SSTs re thought to result from the expression of vsculr permeility fctor/ vsculr endothelil growth fctor in lutein cells nd its receptor fms-like tyrosine kinse 1 in smll to middle-sized lood vessels (4, 24, 26). The imging findings of SSTs reflect their chrcteristic histologic fetures. US commonly revels unilterl tumors with str-shped hypoechoic res enclosed y solid res or solid tumors with medilly locted multiple smll round or cleft-like hypoechoic res (15, 24). Multiloculr heterogeneous cystic msses nd irregulr septe hve lso een descried (15). Color Doppler imging revels intrtumorl lood vessels in the periphery nd etween the centrl cystic spces. Low-resistnce wveforms re visile on pulsed Doppler US (24). The descried US fetures my mimic those of mlignnt ovrin tumors; therefore, further MRI-sed rdiologic evlution is usully necessry. On MRI, heterogeneous solid tumor with iso- to hyperintensity is oserved on T2-weighted imging (Fig. 4) (3). The pseudoloulr res in the outer prt of the lesion commonly exhiit spoke-wheel pttern nd iso- to hypointensity on T2-weighted imging in contrst with the hyperintense sept (15, 18) (Fig. 4). Cystic res re hyperintense on T2-weighted imging nd hypointense on T1-weighted imging (15) (Fig. 4, 4). A thick, hypointense rim tht outlines the tumor on T2-weighted imging reflects compression of the ovrin cortex y the slow-growing tumor (3). Dynmic contrst-enhnced MRI nd CT imges revel erly nd vid peripherl contrst uptke, reflecting prominent vsculture in the cellulr res, with centripetl progression on lte imges (16, 18, 20) (Fig. 4c). - To our knowledge, ll ovrin SSTs descried in literture were enign, did c Figure 4. c. A 14-yer-old femle ptient with left ovrin sclerosing stroml tumor. Sgittl T2-weighted imge () revels left ovrin mss with pseudoloulr spoke-wheel pttern chrcterized y intermedite-signl intensity of the outer nodules (open rrow) surrounding centrl hyperintense cystic re (rrowhed). Axil T1-weighted imge () shows well-defined, slightly loulted, smooth-ordered hypointense mss (rrow). Axil gdolinium-enhnced ft-suppressed T1-weighted imge (c) shows erly nd vid contrst uptke y the solid portions of the tumor (rrows). Sex cord-stroml tumors of the ovry

6 not recur, nd were treted successfully vi surgicl excision. Steroid cell tumor nd Leydig tumor Steroid cell tumors re very uncommon neoplsms tht ccount for 0.1% of ll ovrin tumors (5). These re defined s ovrin neoplsms composed exclusively of cells resemling steroid-secreting cells without Reinke crystls (5). In contrst, intrcytoplsmtic Reinke crystls my chrcteristiclly e present in Leydig cell tumors, which re formed from Leydig cells nd represent pproximtely 20% of ll steroid cell tumors (5) (Fig. 5). Approximtely 80% of steroid tumors re steroid cell tumors, not otherwise c d Figure 5. d. A 53-yer-old femle ptient, who ws eing monitored for hirsutism, dignosed with right ovrin Leydig cell tumor. Axil T1-weighted imge () shows n incresed in size right ovry (rrow). Axil T2-weighted imge () demonstrtes hypointense, smll solid lesion in the right ovry (rrow). Axil gdolinium-enhnced T1-weighted imge (c) demonstrtes enhncement of the lesion. Note tht the hyperintense mss is well delineted ginst the ovrin strom (rrow, c). The section surfce of the right dnexl specimen (d) contins n ill-defined rown yellow hilr tumor with long xis of 10 mm (rrowheds). specified (5) (Fig. 6). Formlly, the term stroml luteom ws used to designte smll steroid cell tumor confined to the ovrin cortex; however, this designtion ws discrded in the most recent WHO clssifiction of ovrin tumors (5). Steroid cell tumors occur t n verge ge of 43 yers (5). The mjority is ndrogenic, nd ptients exhiit virilizing symptoms (50% of cses). Occsionlly, these tumors re ssocited with estrogenic mnifesttions, nd few cses hve een ssocited with hypercortisolism nd progesttionl chnges (3, 5, 7). Leydig tumors usully occur in older women, most of whom exhiit hyperndrogenicity (7). Estrogenic Leydig tumors re less frequent ut my lso occur. Wheres Leydig tumors re enign, pproximtely one-third of steroid cell tumors, not otherwise specified, re cliniclly mlignnt (5). During imging evlutions, Leydig nd steroid cell tumors pper s unilterl solid msses. Leydig tumors tend to e smll (men, 2.4 cm) nd re reportedly isoechoic to the uterus on US nd hypottenuting on CT (5, 27, 28). The signl intensity on T2-weighted imging differs depending on the mount of firous strom (10, 28). Hyperintense res my e oserved on T1 nd T2-weighted imges; these reflect the presence of lipid components (10) (Fig. 5). Smll virilizing Leydig tumors re sometimes difficult to identify on CT nd trnsdominl US. Trnsvginl US with color Doppler nd MRI re importnt c Figure 6. c. A 19-yer-old femle ptient who presented with menorrhe nd hirsutism nd ws dignosed with left ovrin steroid cell tumor, not otherwise specified (NOS). Axil T1-weighted imge () shows smll solid tumor in the left ovry hyperintense to the ovrin strom (rrow); this lesion displys intermedite/low signl intensity on xil T2-weighted imge () (rrow); xil gdolinium-enhnced T1-weighted imge (c) demonstrtes enhncement of the lesion (rrow). Mteril reproduced from Mrtins I, et l. (50), with permission. Dignostic nd Interventionl Rdiology Hort nd Cunh

7 tools for dignosing these tumors, which often cn only e identified y depicting morphologic chnges within the ovry (13). Few cses of steroid cell tumors, not otherwise specified, hve een reported in the literture. These hve een descried s lrger tumors (verge size, 8.4 cm) tht vry from solid msses to multiloculr cystic msses with nodulr wlls (29, 30). On MRI, isointensity on T2-weighted imging nd vid contrst uptke my e oserved (18, 28) (Fig. 6). Pure sex cord tumors Adult nd juvenile grnulos cell tumors GCTs re low-grde mlignnt ovrin sex cord-stroml tumors tht represent less thn 5% of ll mlignnt ovrin tumors (3). Clinicopthologiclly, these tumors re divided into two histologic sutypes, dult nd juvenile, of which the former ccounts for 95% of the neoplsms (13, 16). The incidence of dult GCT peks strikingly in erly postmenopusl women, wheres the juvenile form occurs predominntly in children nd young women (<30 yers) (13, 31). Although GCTs re the most common estrogen-producing tumors, smll suset is ndrogenic (13, 18, 31, 32). Women typiclly present with hyperestrogenicity, including vginl leeding nd rest tenderness during the postmenopusl stge. During the reproductive yers, women frequently present with ltered menstrul ptterns rnging from menorrhe to excessive uterine leeding (4, 13, 31). In the peditric popultion, isosexul pseudoprecocity is common (13). Estrogen overproduction is lso responsile for endometril hyperplsi nd concomitnt endometril cncer, which ccording to the literture occur in 32% 85% nd 3% 22% of cses, respectively (33, 34). Uterine cncer is nerly lwys low-grde, low-stge endometrioid denocrcinom (35). Moreover, women with GCT hve higher risk of rest cncer development (36, 37). Unregulted inhiin production cn cuse infertility, nd ndrogen secretion my induce virilizing symptoms in smll group of ptients (31, 32). Most ptients hve plple pelvic msses upon clinicl exmintion. Mss enlrgement nd the compression of djcent structures cn occsionlly cuse dominl symptoms (4). Mss rupture nd consequent hemoperitoneum my e seen t presenttion (3, 4, 13). Despite the different ges of onset, clinicl findings, nd histologic chrcteristics, the dult nd juvenile sutypes of GCT hve similr imging fetures (13). GCTs differ from epithelil ovrin neoplsms vi predominnt unilterlity nd confinement to the ovry with no peritonel seeding t the time of the dignosis in most cses (3, 31). Moreover, GCTs usully do not feture intrcystic ppillry projec- tions nd rrely contin intrtumorl clcifictions (13, 31, 38). GCTs re typiclly unilterl msses (verge size, 12 cm) nd cn mcroscopiclly rnge from solid msses to multiloculr cystic lesions with solid components lesions nd exclusively cystic msses, lthough homogeneous solid lesions nd uniloculr cysts re less common (3, 4, 13, 18, 31) (Figs. 7 9). The imging ppernces of these tumors vry ccording to the gross pthologic tumor chrcteristics. US nd CT imging usully revel multicystic msses with solid components nd either irregulr thickened or thin septtions (38) (Fig. 9). On MRI, the tumor usully presents Figure 7.,. A 50-yer-old postmenopusl femle ptient with right ovrin dult grnulos cell tumor nd prolifertive endometrium who presented with metrorrhgi. Trnsvginl US imges (, ) show heterogeneous nd pprently complex mss tht is predominntly solid with focl cystic res (rrow, ). Note the thickness of the endometrium, which exceeded 8 mm (rrowhed, ). Figure 8.,. A 40-yer-old femle ptient with right ovrin dult grnulos cell tumor. Axil T1-weighted () nd ft-suppressed T2-weighted () imges show lrge, well-defined, multiloculted cystic tumor with septtions of vrying thicknesses. Axil T1-weighted imge () depicts res of hyperintensity within the cystic locules tht reflect hemorrhgic res (rrow). Sex cord-stroml tumors of the ovry

8 sponge-like ppernce, indicting multiloculr cystic mss (18) (Fig. 8). On T2-weighted imges, the solid tumor component is usully isointense ut thickened septtions my e hypointense (15, 38). The cystic portions my exhiit fluid-fluid levels nd res of intrcystic hemorrhge re typiclly hyperintense on T1-weighted imges (15, 38). Solid components tend to exhiit contrst uptke on gdolinium-enhnced imges, wheres cystic res re nonenhncing (15). Continuous estrogenic stimultion is responsile for endometril thickening, endometril hemorrhge, nd uterine enlrgement (31). Becuse of the ssocited hormonl ctivity, the mjority of GCTs re detected erly nd present s stge I disese (>80%), leding to reported five-yer survivl rte exceeding 90% (32, 39). Chrcteristiclly, recurrence exhiits lte pttern nd hs een reported in less thn 40% of ptients with stge I disese, of whom 56% hd ftl outcomes (40). Given the long nturl history nd rrity of these tumors, informtion regrding fctors tht might e predictive of recurrence is limited. Still, the disese stge t presenttion hs een shown to e the most importnt fctor (40). Most juvenile GCT cses present with stge I disese nd re less likely to recur fter simple resection; however, the occsionl cliniclly mlignnt tumors usully exhiit fst growth nd erly intr-dominl spred (13, 38). Mixed sex cord-stroml tumors Sertoli Leydig cell tumor SLCT is rre sex cord-stroml tumor tht ccounts for pproximtely 0.5% of ll ovrin neoplsms (3, 18) (Fig. 10). SLCT nd SST occur predominntly in the sme ge group; pproximtely 75% of SLCTs re encountered in women younger thn 30 yers (13). However, few cses hve een descried in postmenopusl women (41, 42). For SLCT, nerly ll cses re unilterl (98%) nd 80% re restricted to the ovry t dignosis (4, 18). SLCT is the most common virilizing ovrin tumor, s pproximtely 30% 50% of these tumors produce ndrogens (testosterone nd ndrogen precursors) nd more thn one-third of Dignostic nd Interventionl Rdiology cses develop symptoms of viriliztion (4, 15, 18). Notwithstnding, SLCT is rre cuse of viriliztion in premenopusl women. In this ge group, other differentil dignosis such s polycystic ovry syndrome nd drenl ndrogen-secreting tumors should e considered. In cses of ndrogen-secreting SLCTs, the lortory dt normlly indicte elevted serum testosterone levels ut, in contrst to msculinizing drenl tumors, norml or slightly elevted urinry 17-ketosteroid levels (4). Mny SLCTs re hormonlly inctive nd smll sugroup is estrogenic. Sudden dominl pin nd swelling re frequent symptoms of nonfunctioning tumors. Very rrely, SLCT hve een reported to ssocite with elevted lph-fetoprotein serum levels; this is typicl feture of germ cell tumors such s yolk sc neoplsm. Although only pproximtely 30 cses hve een descried to dte, SLCT is the most commonly reported ovrin nongerm cell tumor ssocited with elevted serum lph-fetoprotein levels (43, 44). SLCT hs nonspecific ppernce. On US, these tumors usully present either s distinct hypoechoic mss or heterogeneous mss tht is primrily solid with multiple cystic spces. Smll virilizing SLCTs my e esily detected using color Doppler US rther thn trnsvginl US lone (13, 45, 46). On CT imges, soft-tissue ttenuting dnexl mss is usully seen (15). The solid tumor portions chrcteristiclly exhiit vid contrst uptke. Figure 9.,. A 17-yer-old femle ptient with right ovrin juvenile grnulos cell tumor. A trnsdominl US imge () shows multiloculr cystic ovrin mss. An xil contrstenhnced CT imge (), shows multiloculted low ttenuting mss with thin septtions (rrow). Note the presence of undnt scites (sterisks). Figure 10.,. A 13-yer-old femle ptient with right ovrin Sertoli-Leydig cell tumor. Sgittl T2-weighted () nd xil ft-suppressed T1-weighted () imges show well-defined, heterogeneous, pprently complex tumor. The solid portions re iso- to hyperintense on T2- weighted imge (), nd the cystic portions re hyperintense on T2-weighted imge () nd hypointense on ft-suppressed T1-weighted imge (). Hort nd Cunh

9 On MRI, the T2 signls of the solid components differ ccording to the extent of firous components. Nonetheless, strong hypointensity on T2-weighted imges is not chrcteristic (13, 18) (Fig. 10). Hypointense res on T1-weighted imges nd hyperintense res on T2-weighted imges reflect cystic res. Cysts my lso exhiit mild hyperintensity on T1-weighted imges (47). Striking homogeneous or heterogeneous contrst enhncement of the solid res is oserved on gdolinium-enhnced imges. The prognosis of SLCT is good, nd 92% of tumors mnifest s stge I (13). The most importnt prognostic fctors re the stge nd degree of histologic differentition (3, 13, 48). In previous report y Sigismondi et l. (49), five-yer survivl rtes of 92.3% nd 33.3% were reported for ptients with stge I nd stge 2 disese, respectively. In the sme report, ptients with well-differentited tumors hd five-yer survivl rte of 100% versus 77.8% for ptients with modertely nd poorly differentited tumors. In contrst to GCTs, which tend to recur lte, mlignnt SLCTs usully recur erly in the pelvic nd dominl cvity, with reported relpse rte of 71.4% within two yers fter dignosis (49). Conclusion Ovrin sex cord-stroml tumors re infrequent tumors tht differ from the more frequent epithelil neoplsms vi strong ssocitions with hormone-medited syndromes, presenttion in rod ge rnge, nd the ner-uiquitous dignosis of low-stge disese with good outcome. These tumors, which develop from cells rising from the primitive sex cords or stroml cells, comprise diverse group. As result, these tumors re currently sudivided s pure stroml tumors, pure sex cord tumors, or mixed sex cord-stroml tumors. The rdiologic ppernces of these tumors vry long with their morphologies. Notwithstnding, some rdiologic fetures previl in certin types of tumors. Firoms typiclly present s solid hypoechoic nd homogenously isodense msses with chrcteristic hypointensity on T1-weighed imges, strong hypointensity on T2-weighted imges, nd delyed enhncement fter contrst dministrtion. Thecoms nd GCTs typiclly ssocite with hyperestrogenic sttes tht my induce endometril hyperplsi nd endometril crcinom. Steroid cell tumors, Leydig tumors, nd SLCTs re chrcteristic virilizing neoplsms. Leydig cell tumors re usully smll tumors tht my e difficult to depict vi different imging methods; therefore, rdiologists should note morphologic chnges within the ovry, especilly on MRI nd trnsvginl US with color Doppler. SSTs frequently mnifest on US s unilterl tumors comprising str-shped hypoechoic res enclosed y solid res. On MRI, the pseudoloulr solid res exhiit spoke-wheel pttern nd disply iso- to hypointensity on T2-weighted imges nd erly nd vid contrst uptke. The rrity of sex cord-stroml tumors contriutes to low index of suspicion; therefore, thorough knowledge of the clinicopthologic nd rdiologicl findings of these tumors is importnt nd llows rdiologists to nrrow the differentil dignoses for ovrin tumors, thus fcilitting surgicl plnning nd the voidnce of inpproprite tretments. Conflict of interest disclosure The uthors declred no conflicts of interest. References 1. Hroon S, Zi A, Idrees R, Memon A, Ftim S, Kyni N. Clinicopthologicl spectrum of ovrin sex cord-stroml tumors; 20 yers retrospective study in developing country. J Ovrin Res 2013; 6: Shim SH, Kim DY, Lee SW, et l. Lproscopic mngement of erly-stge mlignnt non-epithelil ovrin tumors: surgicl nd survivl outcomes. Int J Gynecol Cncer 2013; 23: Jung SE, Rh SE, Lee JM, et l. CT nd MRI findings of sex cord-stroml tumor of the ovry. Am J Roentgenol 2005; 185: Prtt J. Pthology of the ovry. 1st ed. Phildelphi: Sounders, 2004; Kurmn RJ, Crcngiu ML, Herrington CS, Young RH. Clssifiction of tumours of the ovry. In: WHO Clssifiction of Tumours, Volume 6. 4 th ed. Lyon: IARC, 2014; Tvssoli FA, Devilee P. Tumours of the ovry nd the peritoneum. In: WHO Clssifiction of Tumours; Tumours of the Brest nd Femle Genitl Orgns. 3 th ed. Lyon: IARC, 2003; Chen VW, Ruiz B, Killeen JL, Coté TR, Wu XC, Corre CN. Pthology nd clssifiction of ovrin tumors. Cncer 2003; 97: Shingre AB, Meylerts LJ, Lury AR, Mortele KJ. MRI fetures of ovrin firom nd firothecom with histopthologic correltion. AJR Am J Roentgenol 2012; 198:W Oh SN, Rh SE, Byun JY, et l. MRI fetures of ovrin firoms: emphsis on their reltionship to the ovry. Clin Rdiol 2008; 63: Montoriol PF, Mons A, D Ines D, Bourdel N, Tixier L, Grcier JM. Firous tumours of the ovry: etiologies nd MRI fetures. Clin Rdiol 2013; 68: Yzdni S, Alijnpoor A, Shrtdrn M, et l. Meigs syndrome with elevted serum CA125 in cse of ovrin firom /thecom. Cspin J Intern Med 2014; 5: Ry S, Bisws BK, Mukhopdhyy S. Gint primry ovrin firosrcom: Cse report nd review of pitflls. J Cytol 2012; 29: Outwter EK, Wgner BJ, Mnnion C, McLrney JK, Kim B. Sex cord-stroml nd steroid cell tumors of the ovry. Rdiogrphics 1998; 18: Yen P, Khong K, Lm R, Corwin MT, Gerscovich EO. Ovrin firoms nd firothecoms: sonogrphic correltion with computed tomogrphy nd mgnetic resonnce imging: 5-yer single-institution experience. J Ultrsound Med 2013; 32: Hrick H. Firothecom nd Sclerosing Stroml Tumor. In: Hrick H, Akin O, Sl E, Ascher SM, Levine D, Reinhold C, Eds. Dignostic Imging: Gynecology, 1st ed. Slt Lke City: Amirsys, 2007; Jung SE, Lee JM, Rh SE. CT nd MR imging of ovrin tumors with emphsis on differentil dignosis. Rdiogrphics 2002; 22: Thomssin-Nggr I, Drï E, Nssr-Sl J, Cortez A, Mrsult C, Bzot M. Vlue of dynmic enhnced mgnetic resonnce imging for distinguishing etween ovrin firom nd suserous uterine leiomyom. J Comput Assist Tomogr 2007; 31: Tnk YO, Tsunod H, Kitgw Y, Ueno T, Yoshikw H, Sid Y. Functioning ovrin tumors: direct nd indirect findings t MR imging. Rdiogrphics 2004; 24:S Zhng H, Zhng GF, Wng TP, Zhng H. Vlue of 3.0 T diffusion-weighted imging in discriminting thecom nd firothecom from other dnexl solid msses. J Ovrin Res 2013; 6: Khnn M, Khnn A, Mnjri M. Sclerosing stroml tumor of ovry: cse report. Cse Rep Pthol 2012; 2012: Chng YW, Hong SS, Jeen YM, Kim MK, Suh ES. Bilterl sclerosing stroml tumor of the ovry in premenrchl girl. Peditr Rdiol 2009; 39: Yen E, Deen M, Mrshll I. Youngest reported ptient presenting with n ndrogen producing sclerosing stroml ovrin tumor. J Peditr Adolesc Gynecol 2014; 27:e Ismil SM, Wlker SM. Bilterl virilizing sclerosing stroml tumours of the ovry in pregnnt womn with Gorlin s syndrome: implictions for pthogenesis of ovrin stroml neoplsms. Histopthology 1990; 17: Lee MS, Cho HC, Lee YH, Hong SR. Ovrin sclerosing stroml tumors: gry scle nd color Doppler sonogrphic findings. J Ultrsound Med 2001; 20: Sex cord-stroml tumors of the ovry

10 25. Clrese M, Zndrino F, Gisotto V, Rissone R, Fulcheri E. Sclerosing stroml tumor of the ovry in pregnncy: clinicl, ultrsonogrphy, nd mgnetic resonnce imging findings. Act Rdiol 2004; 45: Kwuchi S, Tsuji T, Kku T, Kmur T, Nkno H, Tsuneyoshi M. Sclerosing stroml tumor of the ovry: clinicopthologic, immunohistochemicl, ultrstructurl, nd cytogenetic nlysis with specil reference to its vsculture. Am J Surg Pthol 1998; 22: Souto SB, Bptist PV, Brg DC, Crvlho D. Ovrin Leydig cell tumor in post-menopusl ptient with severe hyperndrogenism. Arq Brs Endocrinol Metol 2014; 58: Skmoto K, Fujimitsu R, Id M, Horiuchi S, Hmd Y, Yoshimitsu K. MR dignosis of steroid cell tumor of the ovry: vlue of chemicl shift imging. Mgn Reson Med Sci 2009; 8: Sid T, Tnk YO, Minmi M. Steroid cell tumor of the ovry, not otherwise specified: CT nd MR findings. AJR Am J Roentgenol 2007; 188:W [Cross- Ref] 30. Jing W, To X, Fng F, Zhng S, Xu C. Benign nd mlignnt ovrin steroid cell tumors, not otherwise specified: cse studies, comprison, nd review of the literture. J Ovrin Res 2013; 6:53. [Cross- Ref] 31. Kottrthil VD, Antony MA, Nir IR, Pvithrn K. Recent dvnces in grnulos cell tumor ovry: review. Indin J Surg Oncol 2013; 4: Crew KD, Cohen MH, Smith DH, Tiersten AD, Feirt NM, Hershmn DL. Long nturl history of recurrent grnulos cell tumor of the ovry 23 yers fter initil dignosis: cse report nd review of the literture. Gynecol Oncol 2005; 96: Lee IH, Choi CH, Hong DG, et l. Clinicopthologic chrcteristics of grnulos cell tumors of the ovry: multicenter retrospective study. J Gynecol Oncol 2011; 22: Putier P, Lhommé C, Culine S, et l. Adult grnulos-cell tumor of the ovry: retrospective study of 45 cses. Int J Gynecol Cncer 1997; 7: Rn J, Gupt D, Zloudek CJ, Chen L. Synchronous ovrin grnulos cell tumor nd uterine serous crcinom: A rre ssocition of high-risk endometril cncer with n estrogenic ovrin tumor. Gynecol Oncol 2006; 103: Hmmer A, Luszus FF, Petersen AC. Ovrin grnulos cell tumor nd incresed risk of rest cncer. Act Ostet Gynecol Scnd 2013; 92: Ohel G, Kneti H, Schenker JG. Grnulos cell tumors in Isrel: study of 172 cses. Gynecol Onc 1983; 15: Gittlemn AM, Price AP, Coren C, Akhtr M, Donovn V, Ktz DS. Juvenile grnulos cell tumor. Clin Imging 2003; 27: Mlmström H, Högerg T, Riserg B, Simonsen E. Grnulos cell tumors of the ovry: prognostic fctors nd outcome. Gynecol Oncol 1994; 52: Rosrio R, Wilson M, Cheng WT, et l. Adult grnulos cell tumours (GCT): clinicopthologicl outcomes including FOXL2 muttionl sttus nd expression. Gynecol Oncol 2013; 131: Cringell A, Loizzi V, Rest L, Ferreri R, Loverro G. A cse of Sertoli-Leydig cell tumor in postmenopusl womn. Int J Gynecol Cncer 2006; 16: Nicoletto MO, Cltross E, Donch M, Nrdelli GB, Prenti A, Amrosini A. Sertoli cell tumor: rre cse in n elderly ptient. Eur J Gynecol Oncol 2006; 27: El-Bhrwy M. Alph-fetoprotein-producing non-germ cell tumours of the femle genitl trct. Eur J Cncer 2010; 46: Jshnni KD, Hegde CV, Munot SP. Alf-fetoprotein secreting ovrin sex cord-stroml tumor. Indin J Pthol Microiol 2013; 56: Outwter EK, Mrchetto B, Wgner BJ. Virilising tumors of the ovry: imging fetures. Ultrsound Ostet Gynecol 2000; 15: Ynushpolsky EH, Brow DL, Smith BL. Locliztion of smll ovrin Sertoli-Leydig cell tumors y trnsvginl sonogrphy with color Doppler. Ultrsound Ostet Gynecol 1995; 5: Hmm B, Forstner R, Bert AL, Knuth M, Srtor K. CT nd MRI in ovrin crcinom. In: MRI nd CT of the femle pelvis. New York: Springer, 2007; Bht RA, Lim YK, Chi YN, Ym KL. Sertoli-Leydig cell tumor of the ovry: nlysis of single institution dtse. J Ostet Gynecol Res 2013; 39: Sigismondi C, Gdducci A, Lorusso D, et l. Ovrin Sertoli-Leydig cell tumors. retrospective MITO study. Gynecol Oncol 2012; 125: Mrtins I, Félix A, Cunh TM. Steroid cell tumour of the ovry - cse report {Online}. Aville t: org/cse.php?id= Dignostic nd Interventionl Rdiology Hort nd Cunh