An Unusual Case of Intrahepatic Stone Masquerading as Cholangiocarcinoma

ABSTRACT

A cancer of the biliary tree, cholangiocarcinoma (CCA) often presents with painless jaundice, right upper quadrant abdominal pain, and unintended weight loss. Serologic testing to include cancer antigen 19-9 (CA 19-9) is elevated in CCA but can also be elevated in inflammatory processes in the biliary system. Diagnosis is difficult and even with advanced imaging techniques false-positives may occur. We present a case of a patient with elevated CA 19-9 and biliary stricture concerning for CCA but was due to hepatic stone. It demonstrates the challenge of correctly diagnosing CCA and an instance of nonmalignant elevation of CA 19-9.

INTRODUCTION

Cholangiocarcinoma (CCA) is a malignancy stemming from biliary epithelial cells, and the incidence is increasing in the United States.¹ It often presents with right upper quadrant (RUQ) abdominal pain accompanied by unintended weight loss, though intrahepatic CCA is less likely to cause pain. Workup begins with laboratory testing, with emphasis on cancer antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) levels.² However, its sensitivity and specificity are not sufficiently high for diagnosis.³ Magnetic resonance cholangiopancreatography (MRCP) is often used, and tissue must be collected to make the diagnosis.^4,5 We present a case with elevated CA 19-9 and stricture of hepatic duct on multiple MRCPs but with negative biopsies for CCA that was due to hepatic stone confirmed on cholangioscopy.

CASE REPORT

A 53-year-old Latino man with a history of choledocholithiasis status post endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and laparoscopic cholecystectomy for common bile duct retained stone presented for acute RUQ abdominal pain. He was afebrile, and examination was significant for tenderness to palpation at the RUQ, but no jaundice. MRCP showed a 7 mm stricture of the anterior branch of the left hepatic duct with ill-defined peribiliary enhancement concerning for intrahepatic CCA with subsequent upstream intrahepatic biliary ductal dilation involving segment four A (Figure 1). Laboratory studies showed alanine transaminase 30 U/L, aspartate aminotransferase 24 U/L, direct bilirubin 0.4 mg/dL, alkaline phosphatase 83 U/L, immunoglobulin G4 27, CA 19-9 843 U/mL, and CEA 2.9 ng/mL. A positron emission tomography scan was overall unremarkable. ERCP cholangiogram did not demonstrate an evident stricture with associated dilation. Subsequent cholangioscopy demonstrated a stone in the second order left hepatic duct (Figure 2). It was unable to be traversed with wire to guide therapeutic maneuvers due to angulation. A cytobrush was also unable to cannulate segment IVA. Targeted biopsies around the stone were performed with microforceps through the cholangioscope. On the pathologist review, biopsies of the duct wall showed benign inflamed biliary mucosa. Later, there was spontaneous passage of the stone with resolution of symptoms.

Figure 1.

Maximum intensity projection image of the biliary system, showing a 7 mm stricture of the anterior branch of the left hepatic duct with an arrow pointing to the area of interest.

Figure 2.

Segment IVA hepatic duct stone on cholangioscopy.

Subsequent laboratory results showed alkaline phosphatase, aspartate aminotransferase, and alanine transaminase above normal limits (1.2×, 3×, 2×, respectively), but CA 19-9 normalized to 10 U/mL. MRCP 3 months later showed the segment IVA dilation resolved. Repeat liver enzyme testing and CA 19-9 showed normal levels.

DISCUSSION

CCA is a diverse group of malignancies arising from the biliary epithelial cells. East Asian populations are most affected, but the incidence of CCA is increasing in the United States.¹

Diagnosis of CCA begins with laboratory and imaging techniques. CA 19-9 levels are usually elevated in CCA and have been shown to correlate to its presence.² However, sensitivity and specificity of CA 19-9 is low for diagnosing intrahepatic CCA.³ This is one reason why CA 19-9 is measured with CEA and cross-sectional imaging as part of the workup for CCA. In one study, combining CA 19-9 with CEA to diagnose CCA yielded sensitivity of 100% with a reported specificity of 78.4%.⁶ Chemical studies are paired with imaging, specifically MRCP, to aid in increasing the likelihood of diagnosing intrahepatic CCA.⁷

Sensitivity and specificity of MRCP detection of CCA is high,⁴ but, in our patient, even repeated MRCPs were insufficient to confirm the presence of CCA and tissue is needed to confirm CCA. Cytologic brushings during ERCP of biliary strictures show sensitivities of 30%–83%.⁵ In our patient, even with elevated CA 19-9, CEA, and MRCP findings consistent with possible CCA, tissue diagnosis refuted the presumed diagnosis (Figure 3).

Figure 3.

Normal biliary duct architecture with chronic inflammation.

The prognosis of hepatic stones with concomitant CCA is poor.⁶ This is important because CA 19-9 is relied on to help diagnose CCA, and the consequences of missing CCA are dire. Mirizzi syndrome can also cause release of CA 19-9, further complicating the diagnosis. In a prior reported case of Mirizzi syndrome, extremely high CA 19-9 levels in a patient with findings seemingly indicative of CCA ended up being a biliary stone blocking the cystic duct, compressing the common hepatic duct.⁸ The same findings present in a patient with obstructing biliary stone may, therefore, be caused by biliary malignancy. Choledocholithiasis can also cause distension of the intrahepatic bile ducts and mask CCA by hiding biliary strictures, even after repeated ERCPs and cholangiograms.⁹

We underscore the difficulty in distinguishing CCA from its differential diagnoses, even with advanced imaging and endoscopy, and a potential pitfall using CA 19-9 as a diagnostic marker of CCA. Our case demonstrated an intrahepatic stone mimicking malignancy. It is therefore vital to delineate the cause of biliary inflammation, repeating imaging, and diagnostic studies as needed, and to continue to search for confirmation when considering CCA as a diagnosis.

DISCLOSURES

Author contributions: All authors made substantial contributions to the conception or design of the work; acquisition, analysis, or interpretation of data; drafting or reviewing it critically for important intellectual content; and gave final approval for the version to be submitted. S. Liu is the article guarantor.

Financial disclosure: None to report.

Disclaimer: Some of the listed authors are military service members or employees of the US Government. This work was prepared as part of our official duties. Title 17, U.S.C. §105 provides that copyright protection under this title is not available for any work of the US Government. Title 17, U.S.C. §101 defines a US Government work as work prepared by a military service member or employee of the US Government as part of that person's official duties. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the US Government.

Informed consent was obtained for this case report.