An Unusual Mass in a Cirrhotic Liver

Question: A 61-year-old man presented in the gastroenterological outpatient clinic with a 6-month history of episodic, right-sided upper abdominal pain. Pain episodes occurred every third day on average and lasted for a few minutes at a time. His medical history included a histologically proven ethylic cirrhosis, metabolic syndrome, and hypothyreosis. Physical examination showed mild tenderness on the right upper abdomen, induration of the liver, and splenomegaly. Ultrasonography and magnetic resonance tomography revealed a solid, 4-cm mass in the liver segment VII and furthermore typical signs of cirrhosis and splenomegaly (MR; Figure A, circle). Blood tests, including liver function and alpha-fetoprotein were unremarkable. A liver wedge resection was performed (Figure B, arrows). Gross examination showed a firm, white, well-demarcated tumor measuring 4.8 cm in diameter that protruded slightly from the liver surface (Figure C, arrows). The cut section was solid and glistening. Microscopic examination revealed a tubulocystic and for the most part lobulated proliferation with central sclerosis and focally, the periphery of the tumor featured cellular atypia and infiltrative behavior (Figure D). The postoperative course was uneventful. The patient is doing well with no recurrence 6 months after surgery. What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Further histologic workup demonstrated a biphasic proliferation composed of tubular and cystic spaces lined by regular columnar and cuboidal epithelium of the bile duct type (immunohistochemically positive for cytokeratins 7, 8, 18, 19, EMA, and CA19-9), which was embedded in a myofibroblastic spindle-cell stroma (positive for smooth muscle actin and Vimentin). Peripheral foci showed marked cellular atypia with infiltration into the surrounding cirrhotic liver parenchyma. Notably, approximately 30% of the atypical cells showed p53-accumulation. Overall, the ki67-labelling index was low (<5%), but the infiltrative areas showed “hot spots” of up to 20%. Biliary adenofibromas (BAFs) are rare benign primary biliary tumors that bear resemblance to biliary hamartomas (so-called von Meyenburg complexes) and bile duct adenomas. Only 7 cases of BAFs have been reported in the literature and progression to cholangiocellular carcinoma has only been described twice.1Gurrera A. Alaggio R. Leone G. et al.Biliary adenofibroma of the liver: report of a case and review of the literature.Patholog Res Int. 2010; 2010: 504-584Google Scholar, 2Haberal A.N. Bilezikçi B. Demirhan B. et al.Malignant transformation of biliary adenofibroma: a case report.Turkish Journal of Gastroenterology. 2001; 12: 149-153Google Scholar BAFs generally present as large (≤20 cm) subcapsular nodules that may arise in cirrhotic or noncirrhotic liver of adults. Because radiologic images are nonspecific, the diagnosis of BAF is always based on histologic examination.1Gurrera A. Alaggio R. Leone G. et al.Biliary adenofibroma of the liver: report of a case and review of the literature.Patholog Res Int. 2010; 2010: 504-584Google Scholar The histogenesis of BAF is not known. As they are histomorphologically very similar, the main criterion for distinguishing a BAF from von Meyenburg complexes and a bile duct adenoma is its larger size, which may indicate a similar suggested “hamartomatous” origin.3Tsui W.M. Loo K.T. Chow L.T. et al.Biliary adenofibroma A heretofore unrecognized benign biliary tumor of the liver.Am J Surg Pathol. 1993; 17: 186-192Crossref PubMed Scopus (46) Google Scholar However, some authors have shown that a benign BAF may undergo malignant transformation of the epithelial component and even metastasize. Evidence in favor of premalignant change is nuclear accumulation of p53 and elevated mitotic activity. In our case we observed clear-cut, infiltrative behavior at the tumor margins in addition to p53-positivity and elevated mitotic count and ki67-labelling index, which in our opinion warrants the diagnosis of a cholangiocellular carcinoma arising from a BAF.