S5962 Primary Hepatic Squamous Cell Carcinoma: Diagnostic Dilemmas and Therapeutic Strategies in a Rare Liver Malignancy

Introduction: Primary squamous cell carcinoma (SCC) of the liver is extremely rare, with few cases reported. It is often associated with hepatic cysts or hepatolithiasis, and unlike hepatocellular carcinoma, lacks specific markers or imaging features. Diagnosis requires histopathology and exclusion of metastasis. No standardized treatment exists; options include surgery, chemotherapy, and immunotherapy, but prognosis is poor. This study presents a case of Liver primary SCC in a 64-year-old woman, including imaging and genetic findings. Case Description/Methods: A 64-year-old woman with coronary artery disease status post coronary artery bypass graft surgery, chronic kidney disease, and tobacco use presented with right upper quadrant (RUQ) pain, fever, and 50-pound weight loss. Computed tomography (CT) imaging revealed a large hepatic lesion and a smaller satellite lesion. Labs showed leukocytosis but normal liver enzymes and tumor markers (AFP, CEA). A liver biopsy confirmed squamous cell carcinoma (SCC). Immunohistochemistry ruled out metastases from other primaries. PET scan showed an 8 cm liver mass; endoscopies were negative. Genomic testing showed PD-L1 positivity without targetable mutations. Given poor functional status, she was not a candidate for chemotherapy. Palliative immunotherapy was initiated, but she eventually succumbed to the disease within 4 months of presentation. Discussion: Primary hepatic squamous cell carcinoma (SCC) is an exceptionally rare malignancy with unclear pathogenesis. Proposed mechanisms include chronic bile duct inflammation, hepatic cysts, and squamous metaplasia secondary to prolonged irritation. Most patients, like ours, lack typical risk factors such as viral hepatitis or cirrhosis. Symptoms are nonspecific—commonly RUQ pain, jaundice, and weight loss—often mimicking liver abscess, as in our case. Tumor markers such as AFP, CEA, and CA 19-9 are typically normal, and liver enzymes may also be within the normal range. Diagnosis relies on histopathology and immunohistochemistry, with positive staining for p40, p63, and CKs, and exclusion of other primary SCC sites through imaging and endoscopy. CT imaging usually shows a heterogeneous liver mass without characteristic features. PD-L1 expression may guide immunotherapy, as reported in some cases. However, in our case there were no targetable mutations. Because diagnosis is one of exclusion and no standard treatment exists, a multidisciplinary approach is essential. Prognosis remains poor, with limited survival even with intervention.