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The unusual first sign of presentation of hepatocellular carcinoma: a rare case report

Rocco Morra, Anna Nappi, N. Zanaletti, Mauro Piccirillo and 5 more

Frontiers in Oncology | Aug 26, 2026

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Despite its rarity, the differential diagnosis of a paranasal sinus lesion should include the possibility of metastasis from HCC, particularly in patients with underlying chronic liver disease, particularly in patients with underlying chronic liver disease.

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Background Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, characterized by aggressive biological behavior and a high propensity for extrahepatic spread. The most common sites of metastasis are the lungs, regional lymph nodes, bones, adrenal glands, and peritoneum. In contrast, the paranasal sinuses are an unusual site for metastatic HCC, and involvement of the sphenoid sinus represents an even rarer event. Case description We report the case of a 67-year-old male patient who presented with transient diplopia, left eyelid ptosis, and refractory epistaxis as the initial clinical manifestations of a previously undetected HCC. Histopathological evaluation of the sinus mass and subsequent imaging confirmed a metastatic lesion from a silent primary liver tumor. The patient was managed using a multidisciplinary approach, undergoing radiation therapy to the sphenoid sinus for pain control and endovascular embolization of the sphenopalatine arteries for refractory epistaxis. In March 2026, a contrast-enhanced computed tomography (CT) scan revealed new osteolytic lesions, consistent with bone metastases, involving the proximal third of the left clavicle and the T9 vertebral body. The patient subsequently received further palliative radiotherapy to the left clavicle and T7-T9, and initiated first-line systemic therapy with atezolizumab plus bevacizumab, completing four cycles. Due to disease progression at multiple skeletal sites and in the sphenoid region, as revealed by a CT scan in June 2026, second-line treatment with lenvatinib was initiated and is ongoing at the latest follow-up. Conclusions Despite its rarity, the differential diagnosis of a paranasal sinus lesion should include the possibility of metastasis from HCC, particularly in patients with underlying chronic liver disease. Histopathological confirmation and a multidisciplinary approach are critical for optimizing therapeutic planning in this challenging clinical scenario.

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Rocco Morra

first | Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Anna Nappi

middle | Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

N. Zanaletti

middle | Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" | ORCID 0000-0002-2675-2396

Mauro Piccirillo

middle | Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Luca Tarotto

middle | Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" | ORCID 0000-0001-8953-716X

Salvatore Stilo

middle | Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" | ORCID 0009-0006-3295-840X

Francesco Fiore

middle | Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" | ORCID 0000-0002-2212-5811

Francesco Izzo

middle | Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" | ORCID 0000-0003-3093-5408

Antonio Avallone

last | Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" | ORCID 0000-0001-6188-5664

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BibTeX

@article{Morra2026unusual,
  title = {The unusual first sign of presentation of hepatocellular carcinoma: a rare case report},
  author = {Rocco Morra and Anna Nappi and N. Zanaletti and Mauro Piccirillo and Luca Tarotto and Salvatore Stilo and Francesco Fiore and Francesco Izzo and Antonio Avallone},
  journal = {Frontiers in Oncology},
  year = {2026},
  doi = {10.3389/fonc.2026.1907582},
  url = {https://doi.org/10.3389/fonc.2026.1907582}
}

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