Hepatic Adenoma 2005.Incidence of HCC in adenomas-8 to 14% “The surgeon is tempted to operate. However in most uncomplicated cases of adenoma it is advisable to be conservative.” Sheila Sherlock. D of Liver & Biliary System “Malignant progression of adenomas have been reported, but it is rare” International Working Party on classification of nodular hepatocellular lesions. Hepatology 1997.”The author cannot find a single report of definite malignant transformation during follow up of an unresected adenoma” John Foster.Surgery of the Liver. Ed LH Blumgart.

Hepatic Adenoma What is the truth?

Hepatic adenoma Zucman-Rossi et al. Hepatology 43;515: 2006 Retrospective, multicentre, pathological study 96 tumors from13 French university hospitals over 12 years = < 1 tumor/ hospital /year =rare! Inclusion criteria=definite (87) or possible (9) diagnosis of adenoma (HA) from hepatectomy! (95) or Tx (1 ) Final Diagnosis by Panel of 22 pathologists:-  HA……...68  HA/HCC..11(14%)  HA/FNH…14  HCC……….1

Hepatic Adenoma Zucman-Rossi (2006).”hepatic adenomas may bleed, and rarely undergo malignant transformation! What is going on?

Hepatic Adenoma 85 female:11male 61 females on OC 18 hepatic adenomatosis 27multiple adenomata <10 (? Forme fruste hepatic adenomatosis) Hemorrhage ( 55 micro and 32 macro) 87 cases 60 rest of liver normal 36 abnormal liver-F2/F3 fibrosis(4);sinusoidal dilatation(5);steatosis (23);iron(2);polycystic(2)

Hepatic Adenoma In order to clarify and try and classify the tumors the authors used mutations of 2 genes HNF1  and  -catenin Non-HNF1  tumors-size of tumor  hemorrhage; NB.Bleed, mean 8cm v no bleed 5cm diameter. NB.  -catenin mutation was significantly associated with malignancy. Of the 11 cases, 5cases were male. All but one of the women were on OC The authors did not describe any association between size and malignancy

Hepatic Adenoma My conclusions from Zucman-Rossi 2006 (State of the Art?) Clinicians, radiologists and pathologists are not great at diagnosing liver adenomas The size of the adenoma may only be important as a predictor of bleeding In general malignant transformation of single adenomas may indeed be rare However there appears to be a subgroup, especially in men in which associated malignancy is more common The finding of adenoma and HCC in the same tumor, even with the same genetic mutation, may indicate an association, and not necessarily transformation. i.e. both may be primary neoplastic growths due to the same mutation

Hepatic Adenoma Recommendations in patients diagnosed as adenoma:- Try and confirm diagnosis in any way possible; history ( female on OC), radiographically, biochemically (eg AFP, sensitivity 20%, specificity 96%) Increase suspicion of HCC in males Increase suspicion in multiple adenomas

Hepatic Adenoma Should you perform a biopsy? Higher risk of bleeding Pathologists have difficulty differentiating adenoma from well differentiated HCC

Hepatic Adenoma What about surgery? Resect all single adenomas in men, because of a higher risk of malignancy? Resect all adenomas >8cm (very high risk of bleeding)? Resect all adenomas >5cm ( risk of clinical bleeding 20-40%)? Resect all adenomas with history of pain over the liver and/or evidence of previous bleed?

Hepatic adenoma What about surgery? 1970’s mortality rate 9% 1980’s mortality rate 4% >1990 mortality rate 1% How would we feel if a young mother with an asymptomatic 5cm adenoma died post- operatively?

Hepatic Adenoma My conclusion-we should have a good indication for resecting an asymptomatic adenoma