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

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

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

19cm huge thick walled cystic lesion arising from left liver

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

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

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

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

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

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

Biliary cystadenoma/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

Biliary cystadenoma/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

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

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

Imaging – biliary cystadenoma/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

Imaging – biliary cystadenoma/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

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

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

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

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

Definite diagnosis can only be made upon histopathology after excision 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

What should we do?

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

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

The End Thank you!

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

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