The rare condition can easily be confused with hepatocellular carcinoma, but immunohistochemical studies can help accurately diagnose intrahepatic sarcomatoid cholangiocarcinoma.
A report published in Frontiers in Surgery details a case of intrahepatic sarcomatoid cholangiocarcinoma (s-CCC), a very rare malignancy of the hepatobiliary system, in a 32-year-old man who is the youngest reported patient with s-CCC. The case report aims to provide insight into the diagnosis and treatment of the condition, as well as raise awareness to facilitate accurate diagnosis of s-CCC versus other hepatobiliary cancers.
A subtype of intrahepatic cholangiocarcinoma, s-CCC comprises less than 1% of hepatobiliary cancers overall. While its pathogenesis is not well understood, s-CCC can affect various organs, including the urinary tract, uterus, thyroid, breast, skin, pancreas, lung, upper digestive tract, and gall bladder. It is easily confused for hepatocellular carcinoma (HCC) and other liver malignancies, and the most common symptoms are nonspecific, such as fever and abdominal pain. Accurate diagnosis of s-CCC requires immunohistochemical staining to differentiate it from other liver cancers.
The highest risk group for s-CCC mainly encompasses patients older than 40 years, and the case report of a 32-year-old individual represents the youngest recorded s-CCC patient thus far. The patient presented with occasional pain in the upper abdomen and nausea at night, but without other symptoms such as fever or chills. He was seen at a different hospital and found to have an occupancy in segment 5 of his liver 3 days prior. He had a history of chronic hepatitis B spanning more than 20 years and had undergone entecavir treatment, but did not have any notable family history.
A physical examination was uneventful, and alanine aminotransferase (ALT), serum carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), serum total bilirubin, and serum aspartate aminotransferase (AST) were all within normal ranges based on initial lab results. Abnormalities in common serological markers, including CEA and AFP, were previously thought to distinguish s-CCC, but this case and several other studies suggest that these markers are not reliable. CT scans showed a hypodense mass in segment 5 of the patient’s liver, and MRI scans showed a similarly sized mass.
The patient underwent a laparoscopic segmentectomy of segment 5 and cholecystectomy. Recovery was smooth with no bleeding events or biliary fistula, and the patient was discharged after 8 days. Histology reports identified a primary high-grade malignant tumor that showed patchy necrosis and abundant lymphocyte infiltration, but no infiltration into nerves, vessels, or the margin of the hepatectomy.
“Immunohistochemical examinations further showed positive staining for vimentin, CK19, CK7, CD34 (vessels), CD31 (vessels) and PD-L1 while results for AFP, Glypican-3, CK20, PD-L1 and HepPar-1 were negative,” the authors wrote. “The latter, as a marker of hepatocytes, helps to distinguish cholangiocarcinoma and metastatic carcinoma in the liver from HCC and as such, it is of diagnostic value.”
With the s-CCC diagnosis confirmed, the patient was started on adjuvant therapy with albumin-paclitaxel in combination with gemcitabine for 8 cycles. At 17 months post-surgery, there was no recurrence.
Relevant case reports and series were also reviewed by the authors to gain insight into common characteristics of s-CCC, and 76 cases were identified in PubMed. Most patients in the dataset reported their main complaints, and the most common was abdominal pain. This was more common than fever and weight loss. In immunohistochemical analyses, HepPar-1 and AFP were found to be useful diagnostic markers based on data from 50 patients.
“Electron microscopy is also used to diagnose neoplasms of s-CCC and in this case, irrespective of their hepatocyte origin, the tumors are characterized by the presence of microvilli and basement membranes,” the authors wrote. “Hence, based on results from electron microscopy, immunohistochemistry as well as histological examinations, sarcomatoid cholangiocarcinoma can be accurately diagnosed.”
Tumor treatment data was available for 74 patients, 35 (47.3%) of whom underwent surgical intervention. Radiotherapy or chemotherapy was given in 15 (20.3%) cases, and 8 patients (10.8%) received supportive treatment or palliative care. Five patients (6.8%) had surgery plus chemotherapy or radiotherapy, 2 (2.7%) had transcatheter arterial embolization, 1 (1.3%) underwent viscum album treatment, and 1 (1.3%) had transcatheter arterial infusion chemotherapy and surgical treatment. Seven patients (9.5%) were untreated. Of 73 patients with follow-up data available, 44 (60.3%) experienced disease progression leading to death, and 15 (20.5%) survived. Disease recurred in 12 patients (16.4%) and 2 patients (2.7%) were lost to follow-up.
Overall, the report stresses a need for established guidelines in this rare disease, as well as further research on the effectiveness of chemotherapy or radiation therapy for these patients. The progression of s-CCC is still unclear, and surgical resection with or without adjuvant chemotherapy remains the standard treatment route.
Xi LF, Jin Y, Li JT. Intrahepatic sarcomatoid cholangiocarcinoma: A case report of the youngest patient on record and a review of the condition's characteristics. Front Surg. Published online September 1, 2022. doi:10.3389/fsurg.2022.963952