Hepatocellular adenomas (HCAs) are uncommon primary benign tumours. They are constantly monoclonal tumours.

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1 Hepatocellular adenoma: Evaluation with contrast enhanced ultrasound, MRI And Correlation with pathologic and phenotypic classification. About 26 lesions. Poster No.: C-1561 Congress: ECR 2011 Type: Scientific Exhibit Authors: A.-F. Manichon, M. Durieux-Millon, B. Bancel, Y. Berthezène, A. Rode; Lyon/FR Keywords: Pathology, Biopsy, Ablation procedures, Ultrasound, MR,, Liver DOI: /ecr2011/C-1561 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 32

2 Purpose To review the contrast enhanced ultrasonographic (CEUS) and magnetic resonance (MR) imaging findings in 25 patients with 26 hepatocellular adenomas (HCA) and to compare imaging features with histopathologic results from resected specimen (or biopsy sample) considering the new immunophenotypical classification. Hepatocellular adenomas (HCAs) are uncommon primary benign tumours. They are constantly monoclonal tumours. They can be solitary or multiple. They typically occur in young women (sex ratio 9/1), in the presence of a long history of oral contraceptives (OCs) use (>2 years). In 2006, Bioulac Sage described a new histological/molecular classification of HCA with 4 subtypes: HCA with mutations of HNF1# gene or steatotic HCA HCA with mutations of #-catenin gene or atypical HCA HCA without mutations of HNF1# or #-catenin genes and with inflammatory features or inflammatory/telangiectatic HCA HCA without mutations of HNF1# or #-catenin genes nor specific features or unspecified HCA 1. HCAs with mutations of HNF1# gene or STEATOTIC HCAs: on page 7 Observed in 30-50% of HCAs Homogeneous group Often multiple Characterized by marked steatosis, no cytological abnormalities and no inflammatory infiltrate No association with hepatocellular carcinoma (HCC) Page 2 of 32

3 Fig.: Steatotic HCA References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR 2. HCAs with mutations of #-catenin gene or ATYPICAL HCAs on page % of HCAs Mainly in men Characterized by the occurrence of cytological abnormalities and acinar pattern They are less frequently steatotic More frequently associated with the development of HCC Page 3 of 32

4 Fig.: Atypical HCA References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR 3. HCAs with inflammatory features or INFLAMMATORY/TELANGIECTATIC HCAs: on page 8 Previously called telangiectatic focal nodular hyperplasia 35-50% of HCAs Occur in overweight or obese patients Often associated with a biological inflammatory syndrome Characterized by their vascular changes including abnormal arteries, prominent sinusoidal dilatation, and marked ectasia with inflammatory infiltrate Increased risk of complications: haemorrhagic risk and HCC. Page 4 of 32

5 Fig.: Inflammatory/telangiectatic HCA References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR 4. Hepatocellular adenomas without mutations of HNF1# or #-catenin genes nor specific features: Represents less than 5%-10% of cases No specific features Each HCA subtype is associated with different evolutive risk factors: -HCC for atypical HCA and inflammatory/telangiectatic HCA -Haemorrhage for inflammatory/telangiectatic HCA -No particular risk for steatotic HCA So the question is: Page 5 of 32

6 Can we establish correlation between the imaging appearance (CEUS and MRI) and the pathological features of each HCA subtype to have an optimal management of patients? Page 6 of 32

7 Images for this section: Fig. 0: Steatotic HCA Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Page 7 of 32

8 Fig. 0: Atypical HCA Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Page 8 of 32

9 Fig. 0: Inflammatory/telangiectatic HCA Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Page 9 of 32

10 Methods and Materials Retrospective unicentric study ( ) 25 patients: 23 undergoing surgery and 2 with liver biopsy 26 HCA analysed: with hepatic MRI and CEUS focused on the lesion 1.Clinical and Biological Analysis: Age, Sex, BMI, OCs use?, diabetes? Circumstances of diagnosis (pain, by chance..) Biological inflammatory syndrom? 2.Pathologic Analysis: All cases were reviewed retrospectively by one pathologist with expertise in hepatic pathology. Features evaluated: Steatosis (%) Telangiectasia (%) Inflammation (4 grade scale: 0= absent; 1= few inflammatory infiltrates without any foci; 2= one lymphocytic foci/10 septas; 3=2 and more lymphocytic foci/10 septas) Cytological aspect of hepatocytes, and adjacent non tumoral liver Immunohistochemistry for subtyping HCA on the basis of phenotypical features (anti-liver fatty acid binding protein (LFABP) antibody for steatotic HCA, anti-serum amyloid A (SAA) antibody for inflammatory HCA, #-catenin for atypical HCA) was performed in a subset of patients with HCA (n = 11). This subset was selected among recent cases and according to easy access and availability of tissue material. 3.Imaging Analysis: CEUS: B mode administration of 2.4 ml of sulfur hexafluoride-filled microbubbles (Sonovue, Bracco) Tape recorded Page 10 of 32

11 MRI: 1,5 T Axial T1W FFE Axial in-phase and out-phase chemical shift GRE T1W Fat suppressed T2W FSE Fat-suppressed dynamic gadolinium-enhanced T1W All images reviewed by 2 radiologists (with expertise in digestive radiology) separately and analysed: Size, location, US: echogenicity, enhancement pattern, direction of filling... MRI: signal intensity, presence of drop out signal, enhancement pattern 4.Stastistical analysis Page 11 of 32

12 Results 1. PATHOLOGICAL FINDINGS: Among the 26 lesions analysed: 16 inflammatory/telangiectatic HCAs: Inflammation and telangiectasias varied among cases 3 displayed marked steatosis No cytological abnormalities were seen 6 steatotic HCAs: Steatosis diffuse in 5, patchy for 1 No cytological abnormalities nor inflammation were seen 4 atypical HCAs: One had important steatosis One was associated with a well differenciated HCC No unspecified HCA Page 12 of 32

13 Fig.: Main pathological findings of the 26 HCAs References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR 2. IMAGING FINDINGS: A. AMONG THE 16 INFLAMMATORY HCAs: 2 different imaging features: Inflammatory HCAs with typical imaging features: 7/16 They all displayed these following criteria: CEUS: moderate to strong arterial enhancement on page 23 persistent enhancement at delayed phase on page 23 centripetal filling on page 23 Page 13 of 32

14 Fig.: Inflammatory HCA with typical imaging features CEUS: strong arterial enhancement (0'17), persistent at delayed phase (1'30) References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR MRI: Hyperintense T2W, hyperintense T1W (only 2/7) on page 24 Strong arterial enhancement on page 24 Persistent at delayed time on page 24 Page 14 of 32

15 Fig.: Inflammatory HCA (typical): Iso T1W, no drop out signal, hyper T2W, strong arterial enhancement, persistent on delayed time References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR This group is correlated on histology with a strong amount of telangiectasia (>30%) and a high grade of inflammation (#2). Page 15 of 32

16 Fig.: Inflammatory HCA (typical): Macroscopic view of the lesion well encapsulated, inflammatory foci (arrow) and telangiectasia (arrow head) on microscopic view References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Inflammatory HCAs without typical imaging features: 9/16 More heteregeneous group: CEUS: on page 25 Moderate to strong arterial enhancement (6/9) on page 25 Centripetal filling (7/9) on page 25 Vanished (hypo or iso) at delayed time on page 25 Page 16 of 32

17 Fig.: Inflammatory HCA (less typical): CEUS: The lesion is isoechoic on B mode, with a moderate arterial enhancement, and becomes isoechoic on late phase References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR IRM: 3/9: drop out signal on page 25 Hyperintense T2W (5/9), hyperintense T1W (4/9) on page 25 Strong arterial enhancement (5/9) on page 25 Persistant enhancement at delayed time (3/9) on page 25 Page 17 of 32

18 Fig.: Inflammatory HCA (less typical): The lesion of the left liver shows a drop out signal on chemical shift sqce, hyposignal on T2W, a slight arterial enhancement, vanishing on delayed phase References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR All the HCAs from this group had either important amount of telangiectasia or high score of inflammation, but not both of them. Fig.: Inflammatory HCA (less typical): The lesion is well encapsulated, yellow, with telangiectasia (arrow head) and area of steatosis (black arrow) on microscopic view References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR B. AMONG THE 6 STEATOTIC HCAS: Six present a drop out signal on chemical shift images Six have a slight to moderate arterial enhancement (CEUS + MRI) No enhancement persistant at delayed time (CEUS +MRI) (lesions are hypo or iso) Page 18 of 32

19 Fig.: Steatotic HCA: CEUS: The lesion is hyperechoic on B mode, with a slight arterial enhancement and becomes isoechoic on late phase References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Fig.: Steatotic HCA: The lesion (black arrow) shows a drop out signal on chemical shift sqce, hyposignal on T2W, a slight arterial enhancement, vanishing on delayed phase References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR They all showed important amount of steatosis on histology. on page 28 Page 19 of 32

20 Fig.: Steatotic HCA: The lesion is well encapsulated, yellow, with important area of steatosis (black arrow) micro and macro vesicular on microscopic view References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR on page 28 C. FOUR ATYPICAL HCAs: on page 28Four lesions with no specific imaging features. on page 29 Page 20 of 32

21 Fig.: Atypical HCA: CEUS: one atypical HCA with a slight arterial enhancement, vanishing on delayed phase References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Fig.: Atypical HCA: The lesion (black arrow) within a steatotic liver, shows a hypersignal on T2W, a intense arterial enhancement, persistent on delayed phase References: Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Page 21 of 32

22 One HCC developped on a atypical HCA, it was not suspected on usual radiological criteria for HCC. Page 22 of 32

23 Images for this section: Fig. 0: Main pathological findings of the 26 HCAs Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Fig. 0: Inflammatory HCA with typical imaging features CEUS: strong arterial enhancement (0'17), persistent at delayed phase (1'30) Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Page 23 of 32

24 Fig. 0: Inflammatory HCA (typical): Iso T1W, no drop out signal, hyper T2W, strong arterial enhancement, persistent on delayed time Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Page 24 of 32

25 Fig. 0: Inflammatory HCA (typical): Macroscopic view of the lesion well encapsulated, inflammatory foci (arrow) and telangiectasia (arrow head) on microscopic view Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Fig. 0: Inflammatory HCA (less typical): CEUS: The lesion is isoechoic on B mode, with a moderate arterial enhancement, and becomes isoechoic on late phase Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Page 25 of 32

26 Fig. 0: Inflammatory HCA (less typical): The lesion of the left liver shows a drop out signal on chemical shift sqce, hyposignal on T2W, a slight arterial enhancement, vanishing on delayed phase Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Page 26 of 32

27 Fig. 0: Inflammatory HCA (less typical): The lesion is well encapsulated, yellow, with telangiectasia (arrow head) and area of steatosis (black arrow) on microscopic view Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Fig. 0: Steatotic HCA: CEUS: The lesion is hyperechoic on B mode, with a slight arterial enhancement and becomes isoechoic on late phase Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Page 27 of 32

28 Fig. 0: Steatotic HCA: The lesion (black arrow) shows a drop out signal on chemical shift sqce, hyposignal on T2W, a slight arterial enhancement, vanishing on delayed phase Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Fig. 0: Steatotic HCA: The lesion is well encapsulated, yellow, with important area of steatosis (black arrow) micro and macro vesicular on microscopic view Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Page 28 of 32

29 Fig. 0: Atypical HCA: CEUS: one atypical HCA with a slight arterial enhancement, vanishing on delayed phase Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Fig. 0: Atypical HCA: The lesion (black arrow) within a steatotic liver, shows a hypersignal on T2W, a intense arterial enhancement, persistent on delayed phase Radiology, Hospices civils de Lyon, Croix Rousse - Lyon/FR Page 29 of 32

30 Conclusion This study shows us that we can easily detect on imaging: - some inflammatory HCAs (this is correlated with the amount of telangiectasia (>30%) and the score of inflammation (#2)). Their imaging features are: moderate to strong arterial enhancement on CEUS and MRI persistant enhancement at delayed phase on CEUS and MRI centripetal filling on CEUS hyperintense T2W on MRI - the steatotic HCAs But some HCAs can display important amount of steatosis without belonging to the steatotic group! The presence of a drop out signal is not enough, all the imaging features must be observed before a conclusion of a steatotic HCAs can be made. The atypical group (more at risk of HCC) doesn't have in this study typical imaging features because of the low number of cases. Page 30 of 32

31 References 1. Bioulac-Sage P, Blanc JF, Rebouissou S, Balabaud C, Zucman-Rossi J. Genotype phenotype classification of hepatocellular adenoma. World J Gastroenterol May 21;13(19): Bioulac-Sage P. Les tumeurs hépato-cellulaires bénignes, données morphologiques et moléculaires: Une nouvelle classification. Acta endoscopica. 2006;36(3): Paradis V, Champault A, Ronot M, Deschamps L, Valla DC, Vidaud D, et al. Telangiectatic adenoma: An entity associated with increased body mass index and inflammation. Hepatology Jul;46(1): Dokmak S, Paradis V, Vilgrain V, Sauvanet A, Farges O, Valla D, et al. A single-center surgical experience of 122 patients with single and multiple hepatocellular adenomas. Gastroenterology Aug Zucman-Rossi J, Jeannot E, Nhieu JT, Scoazec JY, Guettier C, Rebouissou S, et al. Genotype-phenotype correlation in hepatocellular adenoma: New classification and relationship with HCC. Hepatology Mar;43(3): Farges O, Dokmak S. Malignant transformation of liver adenoma: An analysis of the literature. Dig Surg. 2010;27(1):32-8. Page 31 of 32

32 Personal Information Page 32 of 32