Advanced Intrahepatic Cholangiocarcinoma Presenting as a Bilobar Liver Mass
In our emerge ncy department, a 70 year old male presented with fever, night sweats and diffuse abdominal pain in the right upper quadrant, which had been ongoing for four weeks. He reported a weight loss of 10kg and a loss of appetite. Until four weeks he felt well. The medical history included coronary artery disease and diabetes mellitus type 2. There was no family history of malignant diseases. The daily medication consisted of 100mg aspirin.On examination the patient’s temperature was 37.0°C, the pulse 90 beats per minute, and the blood pressure 125/75 mm Hg; the oxygen saturation was 95% while the patient was breathing ambient air. The lung was clear on auscultation, cardiovascular examination was unremarkable, there was abdominal pain and tenderness in the right upper quadrant, the liver was enlarged. No enlarged lymph nodes were palpated.The laboratory results showed a mild anemia (12.6g/ dl), the coagulation tests were impaired (INR 1.4) and the c-reactive-protein was elevated (10.5mg/dl, normal < 0.5mg/ dl). Electrolytes, liver function tests, bilirubin and creatinine were in the normal range.
The ultrasound examination revealed a diffuse echopoor infiltration of the enlarged left liver lobe (figure 1) and multiple echopoor focal liver lesions in the right lobe. Enlarged lymph nodes in the liver hilum were noted. There was a small around of free fluid around the liver and in the douglas space. The gallbladder showed no abnormalities. After administration of an ultrasound contrast agent (1,2ml SonoVue®, Bracco)
Figure 1. Ultrasound examination of the liver shows a diffuse infiltration of the left liver lobe.multiple arterial hypoenhancing nodules were seen in both liver lobes with washout in the late phase (figure 2).A MRI of the liver confirmed the diffuse infiltration of the liver (figure 3). There were no signs of extrahepatic biliary obstruction.
Additionally a mass around the major duodenal papilla was suspected. In consideration of a possible ampullary carcinoma with secondary metastases we performed a gastroscopy with
Figure 3. MRI T1 VIBE: mutiple hypointense nodules, partially convergating in the left lobe.
a duodenoscope and conducted an endoscopic ultrasound examination which showed a normal papilla (figure 4) and periampullary area, a normal distal ductus hepatocholedochus and multiple lymph nodes up to 4cm in the liver hilum (figure 5). A colonoscopy and a CT scan of the thorax were unremarkable.
In summary we suspected a multifocal intrahepatic cholangiocarcinoma. A percutaneous ultrasound-guided liver biopsy was performed. The histologic specimen revealed a moderately to poorly differentiated adenocarcinoma (G2-G3). The immunohistochemical staining was positive for CK-7, Ca19.9. CK-20, PSAP and TTF-1 were negative, consistent with the suspected cholangiocarcinoma.
Figure 5. Endoscopic Ultrasound – liver hilum: enlarged (38mm) echopoor lymphnode (inside markers).
The patient was discussed in our multidisciplinary tumor board and due to advanced features like involvement of both liver lobes and ascites, palliative chemotherapy was recommended.
Because of the rapid clinical deterioration the patient showed within four weeks we had several differential diagnoses in mind. Beside infections we early considered a malignant disease, especially poorly differentiated neoplasms like high grade lymphoma or neuroendocrine carcinoma. Surprisingly a G2-G3 cholangiocarcinoma was responsible for the severe symptoms.
Intrahepatic cholangiocarcinomas (ICC) are the second most common primary liver malignancies with an increasing incidence over the last decades. The clinical presentation is nonspecific and remains asymptomatic in the early phase .The ICC presents normally with a mass in the non-cirrhotic liver, the main differential diagnosis is hepatocellular carcinoma (HCC) or metastatic adenocarcinoma.Imaging studies can help differentiate between ICC and HCC. A contrast enhanced ultrasound (CEUS) shows an early wash out with a variety of patterns in the arterial phase of an ICC (mainly peripheral rim-like enhancement or sometimes diffuse hypoenhancement like in our case), while a HCC presents with hyperenhancement in the arterial phase with a chaotic vascular pattern and a later wash out [2,3].
Secondary metastases are more common than ICCs, so an accurate evaluation has to be performed including cross sectional imaging of the chest and abdomen, a gastroscopy and colonoscopy and a gynecologic or urologic evaluation where appropriate .
A multi-disciplinary discussion, ideally in the form of a tumor board is necessary to guide further treatment. Resectability has to be evaluated by an experienced liver surgeon. Extrahepatic disease, multiple bilobar or multicentric tumours are formal contraindications to resection .
In the palliative setting, a liver biopsy is indicated. Percutaneous ultrasound-guided liver biopsy is a safe procedure with very rare bleeding complications . In case of impaired coagulation an INR up to 1.5 is accepted. Our patients INR was measured 1.4 and there were no complications noted despite additional medication with aspirin.
The histologic appearance of an ICC can be similar to metastatic adenocarcinoma, so an immunohistochemical evaluation is required (positive: CK7, CK20, Ca19.9; negative: TTF1 (lung), CDX2 (colon), DPC4 (pancreas)) .
Intrahepatic cholangiocarcinoma often becomes symptomatic at advanced stages where only palliative chemotherapy like the combination of cisplatin / oxaliplatin and gemcitabine can be offered despite a poor prognosis under chemotherapie (progression free survival at 4-5 month) .
In conclusion our case presents the diagnostic workup for intrahepatic cholangiocarcinoma presenting as a diffuse infiltrating bilobar liver mass presenting initially with a rapid clinical deterioration over a short period of time. This case report emphasizes the diagnostic value of different imaging modalities with consideration of the differential diagnoses.
2.Claudon M, Dietrich CF, Choi BI, Cosgrove DO, Kudo M et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver–update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultrasound Med Biol. 2013, 39(2): 187-210.
5.Strobel D, Mueller T, Blank W, Will U, Reichel A et al. Incidence of bleeding in 8172 percutaneous ultrasound-guided intraabdominal diagnostic and therapeutic interventions – results of the prospective multicenter DEGUM interventional ultrasound study (PIUS study). Ultraschall Med. 2015, 36(2): 122-131.