Dig Surg 2010;27:46 55 DOI: 10.1159/000268407 Published online: April 1, 2010 Imging Modlities for Focl Nodulr Hyperplsi nd Heptocellulr Adenom Jcomin W. vn den Esschert Thoms M. vn Gulik Sffire S.K.S. Pho b Deprtments of Surgery nd b Rdiology, Acdemic Medicl Center, University of Amsterdm, Amsterdm, The Netherlnds Key Words Liver cell denom Focl nodulr hyperplsi Mgnetic resonnce imging Ultrsound Spirl computed tomogrphy Rdionuclide imging Abstrct Bckground/Aims: There re severl imging modlities vilble for the detection of focl liver lesions. Differentition between focl nodulr hyperplsi (FNH) nd heptocellulr denom (HCA) is importnt becuse of the consequences for mngement. However, differentition bsed on imging lone still shows limittions. Methods: We reviewed the literture for typicl fetures of FNH nd HCA on rdiologic nd nucler imging with emphsis on differentition of both lesions. Results: Seven rticles describe the performnce of n imging modlity for the differentition between FNH nd HCA. Limittions of these studies re the smll smple size nd/or the lck of comprison with the gold stndrd, i.e. histologicl dignosis. No studies re vilble tht compre the ccurcy of severl imging modlities in the differentition of FNH nd HCA. Conventionl ultrsound (US) is not useful in the differentition becuse of the non-specific fetures. On contrst-enhnced US, the rteril filling direction of FNH is centrifugl nd centripetl in cse of HCA. The prenchyml enhncement of FNH is sustined in the portl venous nd delyed phses, but shows rpid wshout in cse of HCA. Multiphse CT scn cn differentite FNH from HCA when there is centrl scr. FNH my hve slightly higher reltive enhncement in the rteril phse. On MRI with heptocyte-specific contrst gents, HCA does not show contrst uptke in the heptobiliry phse in contrst to FNH. Conclusion: We conclude tht there is limited evidence of the dignostic performnce of currently used imging modlities for the differentition of FNH nd HCA. We therefore propose prospective study (DiFA tril) to determine the ccurcy of severl rdiologic nd nucler imging studies in differentiting FNH nd HCA. Introduction Copyright 2010 S. Krger AG, Bsel Due to the incresed use of bdominl imging, benign liver tumors re detected s n incidentl finding more frequently. Focl nodulr hyperplsi (FNH) nd heptocellulr denom (HCA) re both benign lesions which predominntly occur in young nd middle-ged women. Differentition of FNH from HCA is importnt becuse of the consequences for mngement of both these lesions. HCA crries risk of spontneous bleeding nd mlignnt trnsformtion s pointed out elsewhere in this issue [1, 2]. Fx +41 61 306 12 34 E-Mil krger@krger.ch www.krger.com 2010 S. Krger AG, Bsel 0253 4886/10/0271 0046$26.00/0 Accessible online t: www.krger.com/dsu S.S.K.S. Pho, MD, PhD Deprtment of Rdiology, Acdemic Medicl Center Meibergdreef 9, NL 1105 AZ Amsterdm (The Netherlnds) Tel. +31 20 566 9111, E-Mil s.s.pho @ m c.u v. n l
Differentition my be difficult bsed on imging studies lone, becuse of the rdiologicl similrities of both tumors. Biopsy nd histologicl ssessment of the tumor for definitive dignosis of FNH or HCA is mndtory in such cses [3]. In recent yers mny new imging modlities hve been introduced, e.g. MRI with heptobiliry contrst gents nd contrst-enhnced ultrsound (US). The question rises which imging modlity performs best in differentiting FNH from HCA, nd whether we cn rely on imging for dignosis rther thn to obtin histopthologicl confirmtion. We reviewed the literture for studies tht described the typicl fetures of FNH nd HCA on severl imging modlities, nd for studies tht focused on the bility of imging modlities in differentiting FNH from HCA. Methods The literture ws reviewed for typicl fetures of FNH nd HCA on rdiologic nd nucler imging (US, multiphse CT, MRI nd nucler imging) with emphsis on differentition of both lesions. A literture serch ws performed using the Medline dtbse. The pplied serch terms were combintion of the MeSH terms focl nodulr hyperplsi, liver cell denom, mgnetic resonnce imging, ultrsound, spirl computed tomogrphy nd rdionuclide imging with ddition of the word differentition. The serch ws limited to English lnguge. Additionl rticles were reviewed from the bibliogrphy of rticles cited. R e s u l t s Of the 55 hits, 7 studies specificlly ssessed the use of n imging modlity in the differentition of FNH nd HCA. These studies re discussed below. U lt r soun d Both FNH nd HCA show non-specific fetures on gry-scle US. FNH is usully slightly hypo- or isoechoic nd very rrely hyperechoic. Sometimes the lesion is only detected by visuliztion of pseudocpsule which is due to compression of the surrounding liver tissue or vessels. A centrl scr nd septe re typicl findings of FNH, but more thn hlf of the FNH re devoid of centrl scr [4 8]. HCA is lso hypoechoic in the mjority of cses. However, HCA my pper hyperechoic becuse of bundnt ft, fibrosis, or bleeding inside HCA. Clcifictions my be present nd show up s hyperechoic foci with coustic shdowing [9, 10]. Color Doppler US is ble to show peri- nd intrtumorl vessels [10 12]. Brtolozzi et l. [13] performed Doppler US study in which they compred power Doppler nd color Doppler sonogrphy in 29 ptients with 22 histologiclly proven FNHs nd 9 HCAs. FNH ws chrcterized by the presence of multiple well-defined vessels with pulstile Doppler spectrum rditing from the center to the periphery of the lesion. This finding ws present in 91% of the lesions on power Doppler nd in 68% on color Doppler sonogrphy. In contrst, HCA showed vessels running long the periphery of the lesion ssocited with multiple vsculr pedicles in the centrl portion with venous Doppler spectrum, in 89 nd 67% on power Doppler nd color Doppler sonogrphy, respectively. Power Doppler imging ppered to be superior to color US in the depiction of those intrtumorl flow chrcteristics. To improve the chrcteriztion of liver lesions on US, contrst gents consisting of microbubbles hve been developed. Nowdys, second-genertion contrst gents (e.g. Sonovue; Brcco Imging, Miln, Itly) nd continuous (rel-time) US scnning re often used. Burns nd Wilson [14] ssessed the concordnce of enhncement ptterns of focl liver lesions on contrst-enhnced US with ptterns on contrst-enhnced CT nd MRI. They concluded tht US showed high concordnce with rteril phse CT or MRI. This concordnce ws much less for the portl phse, probbly due to lck of diffusion of the microbubbles into the interstitium. After contrst dministrtion, FNH typiclly shows centrifugl filling preceded by spoke-wheel pttern enhncement in the erly rteril phse. This spoke-wheel pttern is less present in lesions! 3 cm. During the portl venous nd delyed phses, FNH ppers hyper- or isoechoic in comprison with surrounding liver prenchym. The presence of non-enhncing centrl scr ws found to be distinctive feture of FNH [15 23]. HCA shows subcpsulr feeding rteries with mixed or centripetl filling. The cler enhncement in the rteril phse becomes less intense in the portl venous nd delyed phses [24]. Dietrich et l. [25] performed study in 32 ptients to differentite FNH from HCA with contrst-enhnced US. All lesions showed pronounced enhncement in the rteril phse. In the portl phse, 96% of ptients with FNH showed sustined enhncement. In contrst, ll ptients with HCA showed rpid wshout of the contrst leding to no enhncement during the portl venous phse. Kim et l. [26] performed retrospective study to determine the differentil fetures of FNH nd HCA on Imging of FNH nd HCA Dig Surg 2010;27:46 55 47
contrst-enhnced US. Their conclusion ws tht the fetures in the erly rteril phse contributed most to the differentition of FNH nd HCA by showing the rteril phse filling direction nd rteril morphology. FNH showed centrifugl filling (74 91%) nd stellte vsculrity (60 67%), wheres HCA ws less relibly predicted by centripetl or mixed filling (86%) without stellte vsculrity (11 16%). They concluded tht sustined portl enhncement ws more common in FNH (86 91%) thn in HCA (47 63%). In short, conventionl US is not useful in differentiting FNH from HCA becuse of the non-specific fetures, except for centrl scr. On Doppler US nd contrstenhnced US, FNH typiclly shows centrifugl, rteril vsculrity nd HCA typiclly shows centripetl vsculrity with flt continuous Doppler spectrum. The dditionl vlue of rel-time US with microbubble contrst lies in the enhncement pttern of the liver prenchym. Both lesions show pronounced enhncement in the rteril phse. In cse of FNH, prenchyml enhncement sustins in the portl venous nd delyed phses, but in cse of HCA wshes out rpidly. Multiphse CT Scn Mny studies ssessed the use of multiphse CT scn for the detection of focl liver lesions, including FNH nd HCA. On plin CT scn, FNH is usully homogeneous nd iso- or slightly hypointense compred to norml liver tissue. In cse of stetosis of the liver prenchym, FNH my pper hyperintense due to the low ttenuting ftty liver [27, 28]. Clcifictions re rrely seen [27, 29, 30]. HCA my show vriety of density ptterns on plin CT scn due to ft, necrosis or hemorrhge. Clcifictions re more common thn in FNH nd re present in 5 15% of the lesions [31]. After contrst dministrtion, rpid homogeneous enhncement of well-delineted, lobulr-shped FNH is seen in the rteril phse with hypodense centrl scr in some cses. An enlrged feeding rtery is often visible. In the portl venous nd delyed phse, the FNH becomes isodense nd my be difficult to detect. The centrl scr nd septtions typiclly show lte enhncement due to diffusion of the contrst mteril into the strom of the lesion [4, 27, 28, 30, 32 37]. A centrl scr is seen on CT in pproximtely 50% of the lesions. Lrge FNHs ( 1 3 cm) re significntly more likely to revel centrl scrring, vsculr displcement nd bnorml vessels round the lesions thn smller lesions [27, 38]. A pseudocpsule is seen in 8% of the FNHs [27]. A well-circumscribed HCA lso becomes hyperdense in the erly rteril phse nd slightly hyper- to isodense in the portl phse. Peripherl enhncement my be seen reflecting the presence of the lrge subcpsulr feeding vessels [10]. On delyed phse imging, wshout phenomenon my occur when contrst wshout is rpid, rendering the lesion hypodense in comprison to the surrounding liver tissue. A pseudocpsule is present in 25 30% of the HCAs [10, 31]. Ruppert et l. [36] performed study in 45 histologiclly proven FNHs nd 27 HCAs to evlute the use of triphsic CT imging for differentiting FNH nd HCA. They found centrl scr in 65% of ll FNHs (29% in FNH! 3 cm nd 82% in FNH 1 3 cm) nd none in cse of HCA. Subcpsulr rteries were detected in none of the FNHs nd in 39% of the HCAs. In ddition, they quntified dynmic enhncement ptterns. FNH enhnced more homogeneously nd rteril enhncement ws stronger thn in HCA. HCA showed more wshout in the portl phse; 22% of the HCAs were hypodense, wheres FNH remined iso- or hyperdense. They concluded tht FNH cn relibly be dignosed if reltive enhncement is 1 1.6 in the rteril phse. In conclusion, multiphse CT scn cn differentite FNH from HCA bsed on the presence of centrl scr, the slightly higher reltive enhncement in the rteril phse nd the presence of centrl feeding rteries. However, these findings re not lwys present or visible on CT ( fig. 1, 2 ). HCA shows heterogeneous densities on plin CT due to ft, necrosis, hemorrhge or clcifictions nd wshout phenomenon my occur. MRI Scn Owing to high soft-tissue contrst of MRI, FNH nd HCA cn be depicted on non-enhnced MRI. Almost ll FNH lesions re slightly hyper- or isointense or not visible on T 2 imges of unenhnced MRI. A centrl scr, typiclly hyperintense, my be seen in pproximtely 30% of the lesions, mostly in the lesions 1 3 cm. On the T 1 imges, most lesions re iso- or slightly hypointense while the centrl scr ppers hypointense [39 48]. HCA is lso minly slightly hyper- to isointense on T 2 imges. On T 1 imges, ll possible signl intensities re mentioned in the literture. For exmple, Grzioli et l. [41] showed tht HCA ws iso- or slightly hypointense in 74% nd slightly hyperintense in 20% of the lesions. Chung et l. [49] lso showed tht the minority of the lesions were hyperintense (35%), while ccording to Pulson et l. [50] nd Arrive et l. [51], HCA ppered hyperintense in 51 nd 59% of the cses, respectively. HCA my show more heterogeneous signl intensity thn FNH due to hemorrhge, ft or ne- 48 Dig Surg 2010;27:46 55 vn den Esschert /vn Gulik /Pho
Fig. 1. Multiphse CT scn of typicl FNH. On plin CT: slightly hypodense lesion is visible in liver segment 4 ( ). In the rteril phse, the hypervsculr lesion b ppers hyperdense with hypodense centrl scr ( b ). In the portl venous phse, the FNH becomes iso- to hypodense nd the centrl scr is still hypodense ( c ). In the equilibrium phse, n isodense lesion is seen. The centrl scr shows contrst enhncement nd is therefore poorly recognized ( d ). Fig. 2. Multiphse CT scn of n typicl FNH without centrl scr. On the rteril phse imges, homogeneous enhncement of the lesion ( 13 cm) is seen without centrl scr ( ). The FNH sustins enhncement in the portl venous (b) nd equilibrium phse (c) without signs of c d centrl scr. 1 b c 2 crosis. MRI is superior to CT in detecting smll mounts of ft in the liver or in focl liver lesion, using in- nd out-of-phse imging sequences. Old bleeding in the lesion my cuse scr-like ppernce ( fig. 3 ). There re severl liver-specific contrst gents vilble for MRI. Superprmgnetic iron oxide (SPIO) nd USPIO (ultrsmll SPIO) prticles re tken up by the reticuloendothelil system. Uptke by Kupffer cells will led to loss of signl of the liver on T 2 -weighted MR imges [47, 53, 54]. The iron oxide prticles re used to better detect lesions in the liver tht do not contin Kupffer cells, e.g. metstsis. In FNH the mount of functionl Kupffer cells is higher thn in HCA. Therefore, FNH demonstrtes more signl loss on MRI fter ferumoxide Imging of FNH nd HCA Dig Surg 2010;27:46 55 49
b c Fig. 3. MRI denom with old centrl bleeding. On the T 1 -weighted imge (ft st) in the rteril phse, strong enhncement of the lesion is seen except for the centrl re ( ). On T 2 -weighted MR imge the centrl scr shows low signl which is not consistent with scr in FNH ( b ). An unenhnced T 1 -weighted MR imge of the sme ptient 3 months erlier shows lrge centrl re with high signl which is consistent with n cute bleeding. At tht time, the ptient did not hve cute symptoms ( c ). compred to HCA. However, the dignosis of FNH cnnot relibly be mde on the bsis of ferumoxide s contrst gent [39, 55, 56]. Mngfodipir trisodium (Teslscn; Amershm Helth, Oslo, Norwy) is MR contrst gent tht is selectively tken up by heptocytes, leding to incresed signl intensity on T 1 -weighted imges in norml liver prenchym. It is excreted vi the biliry system. With this contrst gent, heptocyte-contining liver tumors cn be differentited from tumors of non-heptocyte origin, e.g. metstses [55, 57]. Gdobente dimeglumine (Gd-BOPTA, Multihnce; Brcco Imging) nd gdoxetic cid (Gd-EOB-DTPA, Primovist; Schering) re both contrst medi with combined perfusion nd heptocyte-selective properties. Firstly, these contrst medi re visible during the vsculr phse due to the non-specific gdolinium cheltes. Secondly, they re prtly tken up by heptocytes nd excreted into the bile ducts [58]. The ltter property is of importnce in the differentition of FNH nd HCA, becuse HCA does not contin bile ducts in contrst to FNH (fig. 4, 5 ). Grzioli et l. [41] performed prospective, multicenter study to differentite FNH from HCA with MRI nd Gd-BOPTA in 73 ptients with FNH, 27 with HCA, nd 8 with denomtosis. On T 1 -weighted imges, 95% of the FNHs ppered homogeneously hyperintense in the rteril phse. In the portl venous nd equilibrium phses, the FNHs remined slightly hyperintense (47 nd 33%, respectively) or becme isointense compred to the surrounding liver prenchym. The centrl scr ws minly seen s hypointense feture in the rteril phse nd becme hyperintense in the equilibrium phse. The enhncement pttern of HCA ws similr to tht of FNH fter contrst dministrtion, i.e. hyperintense in the rteril phse (96%) nd hyper- to isointense in the portl venous nd equilibrium phses. In the heptobiliry phse, when contrst is tken up by the heptocytes nd excreted vi the bile ducts, FNH ppered hyperintense (68%) or isointense (29%). In contrst, ll HCAs ppered hypointense in this delyed phse. Recently, Zech et l. [48] performed prospective study to evlute the dignostic performnce of MRI with Primovist in comprison to pre-contrst MRI nd dynmic CT in the dignosis of FNH. They concluded tht MRI with Primovist ws superior to pre-contrst MRI lone nd to dynmic CT. However, mixed uptke in FNH still resulted in misdignosis of FNH for HCA in 25 of 59 lesions by 1 of the 3 blinded rdiologists. To sum up, MRI with heptocyte-specific contrst gents performs better in dignosing FNH thn multiphse CT scn. The typicl enhncement ptterns of both FNH nd HCA re similr in the rteril nd portl venous phse. In contrst to FNH, HCA does not show contrst uptke in the heptobiliry phse. However, contrst uptke in FNH my show mixed response mking chrcteriztion difficult ( fig. 6 ). The centrl scr in FNH is typiclly hyperintense on T 2 -weighted imges nd is minly seen s hypointense feture on T 1 -weighted imges in the rteril phse fter which it becomes hyperintense in the equilibrium phse. One should lso be wre of other hypervsculr tumors. Fibrolmellr heptocellulr crcinom (HCC) my, like FNH, show centrl scr tht is more corse nd irregulr ( fig. 7 ). These scrs 50 Dig Surg 2010;27:46 55 vn den Esschert /vn Gulik /Pho
Fig. 4. MRI with heptobiliry contrst gent of typicl FNH. On the blnk T 1 - weighted MRI, the lesion is visible, lthough isointense with centrl scr ( ). After contrst the lesion shows strong enhncement with exception of the centrl scr ( b ). In the portl venous phse, the lesion is slightly hyperintense with hypointense centrl scr ( c ). In the heptobiliry phse, the lesion is still hyperintense compred to the norml liver tissue ( d ). c b d b Fig. 5. MRI with heptobiliry contrst gent of typicl HCA. MRI of multiple typicl denoms in symptomless femle ptient. In the rteril phse, there is strong enhncement of the lesion ( ). In the portl venous phse, the lesion is isointense ( b ). Due to rpid wshout of contrst (wshout phenomenon), the lesion becomes hypointense in the equilibrium phse ( c ). In the heptobiliry phse, there is no enhncement of the heptospecific contrst ( d ). c d do not show lte enhncement nd the tumor often shows inhomogeneous enhncement nd clcifictions [29, 59]. Metstsis of renl cell crcinom my lso simulte FNH with fibrotic centrl scr ( fig. 8 ). These scrs, however, do not show lte enhncement. In HCA, n old centrl bleed my mimic centrl scr. Heterogeneity, peripherl rim nd wshout phenomen re common for both HCA nd well-differentited HCC ( fig. 9 ). Furthermore, HCA nd well-differentited HCC occsionlly show uptke of heptocyte-specific contrst medi, mking definitive dignosis bsed on imging lone impossible [58, 60, 61]. Metstsis from other hypervsculr tumors (e.g. neuroendocrine tumors, crcinoid tumors nd renl cell crcinom) will, just s typicl HCA, not show Imging of FNH nd HCA Dig Surg 2010;27:46 55 51
Fig. 6. MRI with heptobiliry contrst gent of typicl FNHs. On T 1 -weighted rteril phse imges, two smll lesions with strong homogeneous enhncement re visible (rrows) ( ). During the heptobiliry phse, only slight ring-like enhncement is shown in the FNH ( b ). b Fig. 7. MRI with lesion found in 15-yerold femle with vgue bdominl complints. In the rteril phse, on T 1 -weighted imging, strong enhncement of the lesion is seen except for the stellte centrl re ( ). O n t he T 2 -weighted imge, low signl of the centrl scr nd corse irregulr spect is clerly visible ( b ). The finl dignosis ws fibrolmellr HCC. b b c d e Fig. 8. MRI of solitry lesion in femle ptient. The lesion existed for 3 yers nd ws considered n FNH. The lesion hd incresed in size. T 1 -weighted unenhnced MRI ( ). After gdoxetic cid dministrtion, there is strong enhncement of lesion with exception of the centrl stellte re in the rteril nd portl venous phse ( b, c ). On the T 2 -weighted imge, high signl of centrl scr is visible ( d ). In the heptobiliry phse, there is however no enhncement of contrst ( e ). The finl dignosis ws solitry metstsis of renl cell crcinom, 14 yers fter resection of t he pr i m r y t u mor. 52 Dig Surg 2010;27:46 55 vn den Esschert /vn Gulik /Pho
b c Fig. 9. CT scn of mle bodybuilder using steroids who presented with n cute bleeding. In the rteril phse, bleeding nd multiple enhncing lesions were seen (only one shown) ( ). The portl venous nd equilibrium phse imges showed n inhomogeneous lesion with wshout phenomenon (rrow) ( b, c ). This wshout phenomenon ws not found in the other lesions. The presumptive dignosis ws steroid-induced multiple denoms, but t he f i n l d i g no s i s w s HC C w it h me t s t s e s. uptke of heptospecific MR contrst gents. Of note is recent rticle in which correltion is shown between fetures on MRI nd the pthologicl subclssifiction of HCAs [62]. A detiled description of this study is however beyond the scope of this rticle. Nucler Imging On 99m Tc-sulfur-colloid scintigrphy FNH usully shows norml or incresed uptke, while HCA shows no uptke due to lck of functionl Kupffer cells [63]. However, contrry to expecttions, severl studies showed tht 30 36% of FNH hve decresed uptke [32, 64, 65]. Hermn et l. [66] used the 99m Tc-sulfur-colloid scn preopertively for the dignosis of FNH (n = 13) nd HCA (n = 10). Atypicl findings were tht 1 of the 13 FNH showed decresed uptke nd 4 HCAs showed norml uptke. The heptobiliry trcer 99m Tc-mebrofenin (HIDA) is, like the heptobiliry MR contrst gents, tken up by functionl heptocytes nd excreted into the bile [64]. Since biliry dringe in FNH is reduced compred to norml liver prenchym, the trcer is retined nd visible s hot spot on delyed imges [65]. Evidence on the use of this imging technique for the differentition between FNH nd HCA is however not vilble. In 2007, Bumsel et l. [67] showed promising results in 14 ptients in differentiting FNH from HCA using positron emission tomogrphy (PET/CT) in combintion with the use of the trcer fluoromethylcholine. So fr, no series hve however been published using this modlity. Discussion Mny imging modlities re used to visulize FNH nd HCA. Bsed on the typicl fetures, especilly FNH cn be dignosed with high certinty on severl imging studies. However, there re typicl findings in both FNH nd HCA tht preclude definitive dignosis nd my resemble other tumors. While reviewing the literture, we found mny cse reports nd studies which describe the fetures of FNH nd HCA. However, there is little evidence on the dignostic performnce of imging modlities in the differentition of FNH nd HCA. In mny studies the finl dignosis ws often only bsed on imging nd follow-up, while the gold stndrd is histopthologicl confirmtion of the tumor. Moreover, the histopthologicl dignosis of telngiecttic FNH hs recently been reclssified s HCA on the bsis of clinicl nd moleculr fetures [68]. Brtolozzi et l. [13], Dietrich et l. [25] nd Ruppert et l. [36] performed performnce study of Doppler-, contrst-enhnced US nd multiphse helicl CT scn, respectively, in ptients with histology proven FNH or HCA. The smple sizes, especilly for HCA, were however smll. A lrge prospective, multicenter study conducted by Grzioli et l. [41] ssessed the use of Gd- BOPTA MRI for the differentition of FNH nd HCA. They reported sensitivity of 96.9% nd specificity of 100%. However, limittion of their study ws tht the gold stndrd, i.e. the histologicl dignosis, ws only vilble in less thn 30% of the FNH lesions. The lck of histologicl confirmtion of ll lesions lso pplies to the Imging of FNH nd HCA Dig Surg 2010;27:46 55 53
retrospective study of Kim et l. [26]. No study compred the use of more thn one imging modlity in the differentition of FNH nd HCA. Becuse of the lck of relible evidence, we strted prospective tril to ssess the ccurcy of severl imging studies for the differentition of FNH nd HCA, termed the DiFA tril which stnds for the cronym di fferentition of f ocl nodulr hyperplsi nd heptocellulr d- enom. The im of the DiFA tril is to compre the ccurcy of multiphse CT scn, MRI with Primovist, PET scn with fluoromethylcholine nd contrst-enhnced US for the differentition of FNH nd HCA. The dignosis bsed on the different imging studies is compred with the histologicl outcome (core biopsy nd/or resection specimen). The finl im is to develop dignostic lgorithm for ptients with suspicion of either FNH or HCA in order to obtin correct dignosis nd provide proper tretment. References 1 Huurmn VAL, Schpherder AFM: Mngement of ruptured heptocellulr denom. 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