Fat chance? Macroscopic fatty mediastinal lymphadenopathy from metastatic hepatocellular carcinoma

A 60-year-old man with recurrent hepatocellular carcinoma (HCC) following orthotopic liver transplantation and managed with stereotactic body radiation therapy (SBRT) presented for routine surveillance in 2022 (Figure 1). Imaging revealed stable pulmonary metastases but enlarging mediastinal lymph nodes, prompting bronchoscopy with lymph node biopsy that confirmed extrahepatic HCC lymphadenopathy (Figure 2). Repeat imaging prompted by pleural effusion in 2025 incidentally showed new fat-containing right paratracheal and hilar lymph node enlargement consistent with rare HCC metastases (Figure 3). HCC is the most common primary hepatic malignancy, with frequent extrahepatic metastases present on diagnosis.1 However, extrahepatic lymph node involvement is uncommon. Studies document lymph node involvement in approximately 12% of cases, of which only 4.7% were mediastinal lymph nodes.2,3 While HCC can exhibit intracellular fat, metastatic fatty transformation is exceptionally rare, and reported cases of fat-containing HCC lesions are primarily intrahepatic.4 To our knowledge, no reports to date detail fat-containing HCC metastases in mediastinal lymph nodes. Generally, the differential diagnosis of fatty mediastinal lesions includes lipomas, thymolipomas, liposarcomas, and germ cell neoplasms.5 This case highlights the potential for HCC fat transformation in extrahepatic lymph nodes, expanding the potential differential for fatty mediastinal lymphadenopathy, which could warrant biopsy or short-term follow-up.