Joint Hospital Surgical Grand Round

1. A simple liver cyst or a biliarycystadenoma? The diagnostic challenge Joint Hospital Surgical Grand Round Dr Violet Yee-Kei Tsoi Department of Surgery Prince of Wales Hospital

2. Case illustration • A 54 years old gentleman presented with epigastric distension and discomfort for 2 months • Ultrasound abdomen performed in private showed a huge liver cystic mass measuring 17cm arising from left lobe of liver • Physical examination: • No pallor or jaundice • No palpable neck lymph nodes • Abdomen: gross hepatomegaly, smooth surface

3. Blood tests • Bilirubin 16, ALP 133 • CEA 0.5, AFP 3 • HBsAg and anti- HCV : Negative • CT abdomen with contrast was performed

4. 19cm huge thick walled cystic lesion arising from left liver

6. Would it be a biliary cystadenoma? What should be done next? Keep observe?

8. Progress • Laparoscopy findings: • No obvious peritoneal nodule • 21 cm thick wall cystic lesion arising from left lobe of liver • Laparotomy and left hepatectomy of segment 2/3 and part of segment 4 was performed

10. Thickness of wall around 1 cm, unilocular cyst 2.4 L turbid yellowish fluid inside cystic lesion

12. Final Pathology • Benign inflammed liver cyst • No evidence of malignancy • Mixed inflammatory infiltrate • No ovarian type of stroma

13. Introduction • Cystic lesions of the liver consist of a heterogenous group of disorders that present diagnostic and therapeutic challenge • In patients presenting with large solitary liver cystic lesion, it is important to distinguish biliary cystadenoma and cystadenocarcinoma from the benign condition of a simple liver cyst • Inappropriate management may lead to recurrence or even malignant change

14. Simple liver cyst • Benign developmental lesion • Lined by simple cuboidal epithelieum • Surrounding mesenchyme is hypocellular and fibrous • Present in ~ 2.5%- 5% of the population

15. Biliarycystadenoma/cystadenocarcinoma • Malignant counterpart of cystadenoma is biliary cystadenocarcinoma • Biliary cystadenoma and cystadenocarcinoma accounts for 5% of all solitary cystic lesions of the liver • Lined by mucus secreting cuboidal or columnar epithelium with densely cellular “ovarian-like” stroma • Cystic content: mucinous (predominant) or serous type

16. Biliarycystadenoma/cystadenocarcinoma • Female predominant • Median age of 50 years old • Malignant transformation of cystadenoma ~ 25-30% • Evidenced by histopathology finding that areas of pre-existing benign cystadenoma were found in cystadenocarcinoma Hepatobiliary cystadenoma and cystadenocarcinoma. A light microscopic and immunohistochemical study of 70 patients. The American Journal of surgical pathology 18(11): 1078-1091, 1994

17. Clinical Presentation • Similar clinical presentations in liver cyst as well as cystadenoma • Most are asymptomatic • Symptoms: • Abdominal pain ( most common) • Abdominal distension • Palpable mass • Jaundice

18. Imaging – Simple liver cyst • USG • anechoic with posterior acoustic enhancement • CT • Appeared homogenous on non-enhanced CT • No enhancement of its wall or content after contrast injection • MRI • Homogenous low signal intensity in T1 • Very high signal density on T2

19. Imaging – biliarycystadenoma/cystadenocarcinoma • USG • septated, thick-walled, mural nodules • Contrast enhanced USG • hyper-enhancement of the cystic wall in the arterial phase and washed out progressively in portal and late phase may indicate the possibility of underlying malignant nature Diagnosis of biliary cystadenocarcinoma. World J Gastroenterol 2010 Jan 7 ; 16(1): 131-135

20. Imaging – biliarycystadenoma/cystadenocarcinoma • CT • Thick fibrous wall, mural nodules, internal septa, capsular calcifications, papillary projections, contrast enhancement of cystic wall • MRI • Homogenous low signal intensity on T1 • Signal intensity on T2 depends on cyst content, mostly have high signal

21. Pitfalls • Not all cystadenomas or cystadenocarcinoma showed the above radiological features • Diagnostic accuracy varies from 30%-95% • Inflammation or hemorrhage into simple hepatic cyst may have misleading radiological features mimicking biliary cystadenoma Hemorrhagic hepatic cysts mimicking biliary cystadenoma. World J Gastroenterol 2009 Sept 28; 15 (36): 4601-4603

22. Biochemical investigations • Liver function tests • usually normal • Serum tumor markers • CEA and CA 19-9 are usually within normal range • Not diagnostic • Differential Diagnosis for intrahepatic biliary cystadenoma and hepatic simple cyst. Significance of cystic fluid analysis and radiological findings. J Clini Gastroenterol 2010; 44 :289-293 • Intrahepatic biliary cystadenoma: role of cyst fluid analysis and surgical management in the laparoscopic era. Surgery 2004; 136:926-936

23. Cystic fluid analysis • Cystic fluid analysis for tumor markers • CEA and CA 19-9 • Koffron et al reported all 22 patients with biliary cystadenoma exhibited elevation in cystic fluid CA 19-9 • Few subsequent studies showed no significant difference between two groups of patients in both CEA and CA 19-9 • Not diagnostic

24. Cystic fluid analysis • Fluid cytology • Presence of atypical cells may suggest malignant lesion of cystadenocarcinoma • Majority of the cytology results are negative • Possibility of disease dissemination by fine needle aspiration

25. Histopathology • Intra-operative frozen section • Not reliable Definite diagnosis can only be made upon histopathology after excision -Management and long-term follow up of hepatic cysts. Am J Surg 2001;181: 404410 -Cystadenoma and laparoscopic surgery for hepatic cyst disease: a need for laparotomy? Surg Endosc 2005; 19:1077-1081 -Intrahepatic biliary cystadenoma: a need for radical resection. Eur J of Gastroen & Hepatology 2008, 20:10-14

26. What should we do?

27. Management • Complete excision with enucleation, wedge resection, or hepatectomy should be offered if there is any suspicion of biliary cystadenoma or cystadenocarcinoma • If biliary cystadenoma is misdiagnosed and is treated as an simple hepatic cyst, it is associated with risks of malignant transformation and high local recurrence rate with some literature even reported 100% recurrence Management and long-term follow-up of hepatic cysts. The American Journal of Surgery 181 (2001) 404-410

28. Conclusion • Biliary cystadenoma and cystadenocarcinoma is rare • However, no reliable laboratory or radiologic methods can accurately diagnosis it from simple hepatic cyst • Complete excision for any suspicious lesion remains the best method of diagnosis and treatment

29. The End Thank you!

30. Prognosis • Depends on pathology • Cystadenoma: good, low recurrence • Cystadenocarcinoma • Those arising from pre-existing cystadenoma with mesenchymal stroma carried a better prognosis after complete excision Hepatobiliary cystadenoma and cystadenocarcinoma. A light microscopic and immunohistochemical study of 70 patients. The American Journal of surgical pathology 18(11): 1078-1091, 1994

31. Differential Diagnosis for intrahepatic biliary cystadenoma and hepatic simple cyst. Significance of cystic fluid analysis and radiological findings. J Clini Gastroenterol 2010; 44 :289-293