Rare Combined Liver Cancer Highlights Challenges in Diagnosis and Treatment
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June 24, 2026“Its mixed hepatocytic and cholangiocytic features pose major diagnostic challenges, and the absence of standardized treatment guidelines limits effective management.”
BUFFALO, NY — June 24, 2026 — A new case report was published in Volume 13 of Oncoscience on May 19, 2026, titled “Combined hepatocellular-cholangiocarcinoma: A rare and challenging diagnostic entity- A case report.”
The study was led by first and corresponding author Faten Limaiem from the Hospital Mongi Slim La Marsa in Marsa, Tunisia.
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare and aggressive form of primary liver cancer that exhibits characteristics of both hepatocellular carcinoma and cholangiocarcinoma within the same tumor. Representing only a small percentage of primary liver malignancies, cHCC-CCA is often difficult to diagnose because its clinical, radiological, and pathological features can resemble those of other liver cancers.
In this report, the researchers describe the case of a 61-year-old man with a history of chronic hepatitis B, type 2 diabetes, and hypertension who presented with persistent right upper abdominal pain. Imaging studies revealed a heterogeneous liver mass accompanied by capsular retraction and enlarged hilar lymph nodes. Laboratory testing showed elevated alpha-fetoprotein levels, a finding commonly associated with hepatocellular carcinoma.
Based on imaging and a CT-guided liver biopsy, the patient was initially diagnosed with hepatocellular carcinoma. However, after surgical removal of the tumor, comprehensive pathological examination revealed a more complex diagnosis. The resected tumor consisted of approximately 20% hepatocellular carcinoma and 80% cholangiocarcinoma, leading to a final diagnosis of combined hepatocellular-cholangiocarcinoma.
The case illustrates one of the major challenges associated with cHCC-CCA. Because different regions of the tumor can contain distinct cellular components, small biopsy samples may capture only part of the lesion and fail to reveal its mixed nature. As a result, preoperative diagnosis can be difficult even when advanced imaging and pathology techniques are used.
The investigators performed detailed histopathological and immunohistochemical analyses to confirm the diagnosis. The hepatocellular component expressed markers including Glypican-3, HepPar1, and alpha-fetoprotein, while the cholangiocarcinoma component showed strong positivity for CK7 and CK19, confirming the presence of both tumor lineages.
The authors also note that imaging findings often reflect the dominant component of the tumor. In this case, radiological features suggested a cholangiocarcinoma-predominant lesion, which was later confirmed by pathological examination showing that most of the tumor consisted of cholangiocarcinoma tissue.
Although surgical resection remains the primary potentially curative treatment for cHCC-CCA, there are currently no standardized treatment guidelines for this rare malignancy. The biological diversity of these tumors continues to complicate both diagnosis and therapeutic decision-making.
“cHCC-CCA poses a significant diagnostic and therapeutic challenge. Recognizing this mixed phenotype in complex liver masses is crucial.”
According to the authors, accurate diagnosis requires careful integration of clinical findings, imaging studies, histopathology, and immunohistochemistry. They emphasize that detailed case reports remain important for improving understanding of this uncommon cancer and for helping guide future diagnostic and treatment strategies.
Overall, this case highlights the diagnostic complexity of combined hepatocellular-cholangiocarcinoma and the limitations of preoperative biopsy in highly heterogeneous tumors. The findings underscore the importance of thorough pathological evaluation and multidisciplinary management when confronting unusual liver masses.
DOI: https://doi.org/10.18632/oncoscience.658
Correspondence to: Faten Limaiem – faten.limaiem@fmt.utm.tn
Keywords: liver cancer, combined hepatocellular-cholangiocarcinoma, pathology, immunohistochemistry, case report
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