FOCAL LIVER LESIONS IN A NORMAL LIVER ALEH Fernando Contreras, MD, FACP, FACG, AGAF

Transcription

1 FOCAL LIVER LESIONS IN A NORMAL LIVER ALEH 2016 Fernando Contreras, MD, FACP, FACG, AGAF

2 FOCAL LIVER LESIONS IN A NORMAL LIVER KEY QUESTIONS Is the liver normal? Benign vs Malignant? Need for follow up work up? Differencial diagnosis? Best imaging study? Do we need a biopsy? Surgical consultation?

3 FOCAL LIVER LESIONS IN A NORMAL LIVER EPIDEMIOLOGY Increasing referrals Imaging utilization Imaging quality Benign > Malignant Metastases > HCC/CCA

4 FOCAL LIVER LESIONS IN A NORMAL LIVER Approach to FFLs Risk factors for HHC ( Hep B, Fatty liver, h/o malignancy, elevated tumor markers, weight loss, YES Dynamic CT/MRI (if not performed earlier) NO ( incidentaloma ) Suspect benign lesion Solid Hemangioma Cystic HCC or CCA Metastasis Other Dynamic CT/MRI Central Scar YES NO FNH HCA/other Marrero, j ACG clinical guidelines, Diagnosis and mangement of FLLAm J Gastroenterol 19 August 2014

5 FOCAL LIVER LESIONS IN NORMAL LIVER HEPATIC CYST Incidental > female Asymptomatic Rare RUQ pain Imaging fluid filled lesion US, best imaging No internal echo No or minimal septations No fenestrations No irregular walls No calcifications No doppler flow Charlesworth P, Ade-Ajayi N, Davenport M. Natural history and ong-term follow-up of antenatally detected liver cysts. J Pediatr Surg 2007;42: Marrero, j ACG clinical guidelines, Diagnosis and mangement of FLLAm J Gastroenterol 19 August 2014

6 FOCAL LIVER LESIONS IN NORMAL LIVER SIMPLE/POLYCYSTIC LIVER DISEASE: MANAGEMENT Asymptomatic Conservative No routine aspiration Symptomatic cysts Simple De roofing Resection Polycystic Liver Disease PCLD Resection, Liver transplantation Marrero, j ACG clinical guidelines, Diagnosis and mangement of FLLAm J Gastroenterol 19 August 2014

7 FOCAL LIVER LESIONS IN NORMAL LIVER BILIARY CYSTADENOMA, CYSTADENOCARCINOMA Complexitiy Septation, Irregular wall, Calcification Most are benign CT- MRI No routine aspiration Limited sensitivity Dissemination risk Surgical consultation Marrero, j ACG clinical guidelines, Diagnosis and mangement of FLLAm J Gastroenterol 19 August Garcea G, Rajesh A, Dennison AR. Surgical management of cystic lesions in the liver. ANZ J Surg 2013;83:

8 HEPATIC HEMAGIOMA PATHOPHYSIOLOGY, NATURAL COURSE Most common tumor of the liver (7% on autopsy) Female predominance : 1 Possible hormonal dependence Usually asymptomatic If > 10 cm inflamatory and cuoagulopatthy Kasabach-Merrit Syndrome (KMS) Types: Capillary hemangioma < 3cm Giant hemangioma > 10 cm Cavernous hemangioma Sclerosed hemangioma 1.Rungsinaporn K, Phaisakamas T. Frequency of abnormalities detected by upper abdominal ultrasound. J Med Assoc Thai 2008;91:

9 HEPATIC HEMANGIOMA IMAGING AND DIAGNOSIS Ultrasound for typical Homogenous hyper echoic mass, acoustic, sharp margins Contrast enhancement for atypical: CEUS, CT, MRI MRI with contrast best option Peripheral/globular enhancement on arterial phases Central enhancement on delayed phases MRI: 90% sensitivity and specificity 1.Glinkova V, Shevah O, Boaz M, Levine A, Shirin H. Hepatic haemangiomas: possible association with female sex hormones. Gut 2004;53: Giannitrapani L, Soresi M, La Spada E, Cervello M, D Alessandro N, Montalto G. Sex hormones and risk of liver tumor. Ann N Y Acad Sci 2006;1089:

10 HEPATIC HEMANGIOMA IMAGING AND DIAGNOSIS CT AND CEUS

11 HEPATIC HEMANGIOMA IMAGING AND DIAGNOSIS: MRI

12 HEPATIC HEMANGIOMA MANAGEMENT Typical lesion Conservative Imaging follow up NOT need it Pregnancy and OCP are NOT contraindicated Refer to MDT KMS Increasing size and symptoms of compression Giant hemangioma Liver transplantation for large un-resectable tumor Biopsy rarely need it, but NOT contraindicated Miura JT, Amini A, Schmocker R, Nichols S, Sukato D, Winslow ER, et al. Surgical management of hepatic hemangiomas: a multiinstitutional experience. HPB (Oxford) 2014;16: Ebina Y, Hazama R, Nishimoto M, Tanimura K, Miyahara Y, Morizane M, et al. Resection of giant liver hemangioma in a pregnant woman with coagulopathy: case report and literature review. J Prenatal Med 2011;5: Giuliante F, Ardito F, Vellone M, Giordano M, Ranucci G, Piccoli M, et al. Reappraisal of surgical indications and approach for liver hemangioma: single-center experience on 74 patients. Am J Surg 2011;201:

13 FOCAL NODULAR HYPERPLASIA EPIDEMIOLOGY Second most frequent benign liver lesion Prevalence 0.03% 90% female, y/o Most < 5cm, 20-30% multiple 20% associated to hemangioma Hereditary hemorrhagic telangiectasia Pregnancy or OCP Do NOT play a role Dystrophic artery, benign appearing hepatocytes CENTRAL FIBROUS SCAR Marrero JA, Ahn J, Rajender Reddy KA. Am J Gastroenterol 2014;109:

14 FOCAL NODULAR HYPERPLASIA IMAGING AND DIAGNOSIS Contrast enhancement imaging (CEUS, CT, MRI) Lesion homogeneity, except in the central scar Strong homogenous enhancement on arterial fase with central vascular supply Central scar: Enhancement hepatobiliary phase MRI: sensitivity: 70-80% (less in <3cm), specificity: 100% Hepatobiliary contrast increase sensitivity up to 90% CEUS more sensitive in lesion < 3cm Liver biopsy is indicated only Atypical cases on imaging: 49.Bioulac-Sage P, Laumonier H, Rullier A, Cubel G, Laurent C, Zucman-Rossi J, et al. Over-expression of glutamine synthetase in focal nodular hyper- plasia: a novel easy diagnostic tool in surgical pathology. Liver Int 2009;29: Ramirez-Fuentes C, Marti-Bonmati L, Torregrosa A, Del Val A, Martinez C. Variations in the size of focal nodular hyperplasia on magnetic resonance imaging. Radiologia 2013;55:

15 FOCAL NODULAR HYPERPLASIA IMAGING AND DIAGNOSIS-MRI

16 FOCAL NODULAR HYPERPLASIA IMAGING AND DIAGNOSIS CT Arterial phase Central Scar Isointense PVP

17 FOCAL NODULAR HYPERPLASIA MANAGEMENT Conservative Suspected FNH Contrast enhanced imaging preferably MRI Rarely complication Follow up imaging NOT necessary Underling vascular disease (exception Refer to MDT Symptoms Pedunculated Exophytic Expanding Pregnancy or OCP: NOT contraindicated Diagnosis FNH - certain Discharge no follow-up needed CEUS Diagnosis uncertain Diagnosis FNH - doubtful <3cm >3cm Biopsy Confirmed FNH Easl clinical practice guidelines, in press

18 HEPATOCELLULAR ADENOMA EPIDEMIOLOGY Prevalence % Female-male 10: y/o OCP: fold increase Increase in Males Anabolic steroids Polycystic ovary Klinefelter syndrome Obesity and metabolic syndrome MODY 3 (maturity onset DM3) Iron overload Glycogen storage disease Rooks JB, Ory HW, Ishak KG, Strauss LT, Greenspan JR, Hill AP, et al. Epidemiology of hepatocellular adenoma. The role of oral contraceptive use. JAMA 1979;242: Edmondson HA, Henderson B, Benton B. Liver-cell adenomas associated with use of oral contraceptives. N Engl J Med 1976;294: Edmondson HA, Reynolds TB, Henderson B, Benton B. Regression of liver cell adenomas associated with oral contraceptives. Ann Intern Med 1977;86:

19 HEPATOCELLULAR ADENOMA PATHOPHYSIOLOGY AND NATURAL COURSE Proliferation of benign hepatocytes in trabecular pattern and small thin vessels, no bile ducts 4 types of clonal benign proliferations Different morphological features and significant complications Hemorrhage Molecular classification Related to tumor > 5 cm Malignant transformations Molecular classification Male 100.Bioulac-Sage P, Laumonier H, Couchy G, Le Bail B, Sa Cunha A, Rullier A, et al. Hepatocellular adenoma management and phenotypic classification: the Bordeaux experience. Hepatology 2009;50: 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 2006;43:

20 HEPATOCELLULAR ADENOMA MOLECULAR CLASIFICATION

21 HEPATOCELLULAR ADENOMA HCA INACTIVATED FOR HNF-1A (H-HCA) Represent 30-40% of all HCA Transcription factor: metabolism and differentiation Inactivation of HNF-1A Absence of liver fatty acid binding protein (LFABP) Mostly somatic mutation Germline mutation MODY3, Adenomiosis Prominent steatosis 100.acq Y, Jacquemin E, Balabaud C, Jeannot E, Scotto B, Branchereau S, et al. Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation. Gastroenterology 2003;125:

22 HEPATOCELLUAR ADENOMA INFLAMATORY ADENOMA (I-HCA) 40-55% of all HCA Heterogeneous subgroup Activation of JAK/STAT pathway Obese and metabolic syndrome High alcohol consumptions Elevated CRP, fibrinogen levels Cluster of small arteries, extracellular matrix, inflammatory cell and sinusoidal dilatation IHC: cytoplasmic expresión of serum amyloid A (SAA) and CRP Pilati C, Amessou M, Bihl MP, Balabaud C, Nhieu JT, Paradis V, et al. Somatic mutations activating STAT3 in human inflammatory hepatocellular ade- nomas. J Exp Med 2011;208:

23 HEPATOCELLULAR ADENOMA B-CATENIN ACTIVATED HCA (B-HCA) 10-20% of all HCA Mutations of B-catenin gen (CTNNBI) exon 3 50% of B-HCA are also inflammatory (JACK/STAT) Males over represented HIGH RISK OF MALIGNANT TRANSFORMATION B-catenin mutations in exon 7-8: no malignant transformation Cellular atypias,pseudoglandular formation and cholestasis ICH: Diffuse and strong GS and B-catenin nuclear expression Pilati C, Letouze E, Nault JC, Imbeaud S, Boulai A, Calderaro J, et al. Genomic profiling of hepatocellular adenomas reveals recurrent FRK-activating mutations and the mechanisms of malignant transformation. Cancer Cell 2014;25: Chen YW, Jeng YM, Yeh SH, Chen PJ. P53 gene and Wnt signaling in benign neoplasms: beta-catenin mutations in hepatic adenoma but not in focal nodular hyperplasia. Hepatology 2002;36:

24 HEPATOCELLULAR ADENOMA IMAGING AND DIAGNOSIS MRI superior Fat, vascular space Heterogenous arterial enhancement Classified subtypes up to 80% HNF-1A and IHCA classified 90% B-catenin activated HCA, Difficult distinction: Unclassified HCC

25 HEPATIC ADENOMA FNH VS HA HEPATOBILIARY CONTRAST FNH HA Roux M, Pigneur F, Calderaro J, Baranes L, Chiaradia M, Tselikas L, et al. Differentiation of focal nodular hyperplasia from hepatocellular adenoma: role of the quantitative analysis of gadobenate dimeglumine-enhanced hepatobiliary phase MRI. J Magn Reson Imaging 2015;42:

26 HEPATOCELLULAR ADENOMA MANAGEMENT LIVER CELL ADENOMA: MRI Male Gender Female Gender Radical management Hormonal Therapy cessation Single lesion Multiple lesions Size 5cm Hemorrhage Size > 5 cm Lesions 5cm Surveillance TAE B catenin subtype HNF1 α subtype Surveillance Persistance > 3 cm Biopsy Radical management Surveillance Agrawal, S,clinical gast and hepatology, 13, 2015

27 HEPATOCELLULAR ADENOMA WHEN TO BIOPSY Early biopsy if: Equivocal imaging Cannot exclude malignancy Avoid if: Obvious diagnosis by imaging Most FLL have characteristic MRI/CT/US Risks Biopsy: bleeding, pain, seeding, false negative Not biopsy: uncertainly, ongoing imaging

28 HEPATOCELLULAR ADENOMA WHEN TO REFER TO SURGERY Symptomatic Exclude other causes Growing Size > 5 cm Bleeding Male sex of HCA B-catenin HCA Huurman VA, Schaapherder AF. Management of ruptured hepatocellular adenoma. Dig Surg 2010;27: Noels JE, van Aalten SM, van der Windt DJ, Kok NF, de Man RA, Terkivatan T, et al. Management of hepatocellular adenoma during pregnancy. J Hepatol 2011;54:

29 TEXT

30 LIVER LESION IN NORMAL LIVER TAKE TO HOME MESSAGES Focal liver lesion rising Conservative management OK Most die with FLL than from FLL Know the differential diagnosis Make the diagnosis Risk of biopsy and NOT biopsy Multidisciplinary team

31 MUCHAS GRACIAS TE ESPERAMOS ESPERAMOS VOCÊS WE LL BE WAITING FOR YOU