Case presentation: We report a rare case of SCC of the gallbladder. A 50-year-old man with no medical history presented with fever, right hypochondrial pain, and general decline over the past month. Physical examination, revealed tenderness in the right upper quadrant. No palpable mass was detected on the abdominal examination. Laboratory tests revealed anemia, elevated white blood cell count, high C-Reactive Protein, and cholestasis. Abdominal CT scan identified a large mass (10 cm) involving the gallbladder and infiltrating liver segments IV and V, with additional nodular lesions throughout the liver. Histopathological examination confirmed the diagnosis of SCC. The liver biopsy of a hepatic metastasis revealed nests, trabeculae, and dyskeratotic cell clusters. Immunohistochemistry showed intense nuclear positivity for anti-p40 and moderate positivity for anti-cytokeratin 7, while anti-cytokeratin 20 was negative. In our patient, there is no squamous cell carcinoma at another site. The diagnosis of SCC of the gallbladder with hepatic metastasis was hence confirmed. As the tumor was unresectable, palliative chemotherapy with Gemcitabine-Cisplatin was recommended but was not administered due to the patient’s rapid deterioration. 

Conclusions: SCC of the gallbladder is a rare and aggressive tumor with poor prognosis. Its management includes surgical resection in localized cases and palliative chemotherapy for unresectable tumors. Further research is needed to enhance understanding and treatment of this rare malignancy.