S5957 Paraneoplastic Leukemoid Reaction in a Patient With Poorly Differentiated Hepatocellular Carcinoma: A Rare and Aggressive Presentation

Introduction: Paraneoplastic leukemoid reaction (PLR) is a rare but serious complication of solid tumors, characterized by extreme leukocytosis in the absence of infection or hematologic malignancy. It is associated with cytokine secretion by the tumor and signifies poor prognosis. PLR in hepatocellular carcinoma (HCC) is infrequently reported. Case Description/Methods: A 72-year-old man with a history of hypertension, hydrocele, and a biventricular pacemaker presented with progressive weight loss, anorexia, and episodic nausea. Imaging revealed liver cirrhosis with a right hepatic mass and extensive retroperitoneal lymphadenopathy. Triple-phase computed tomography and biopsy confirmed poorly differentiated hepatocellular carcinoma. Serum alpha-fetoprotein was markedly elevated (>1000 ng/mL). During hospitalization, the patient developed progressive leukocytosis, with WBC counts rising from 29.3 × 10⁹/L to >94 × 10⁹/L and neutrophilic predominance (91.9%) without evidence of infection or myeloproliferative disease. Inflammatory markers were negative, and peripheral smear revealed mature neutrophilia with rare immature cells. These findings were consistent with a paraneoplastic leukemoid reaction, likely mediated by tumor-derived granulocyte colony-stimulating factor (G-cerebrospinal fluid). Despite preserved liver function and acceptable performance status, imaging demonstrated rapid disease progression with new psoas infiltration and worsening adenopathy. The patient was not a candidate for curative or locoregional therapy and was initiated on systemic immunotherapy. Palliative care was engaged for symptom management and goals of care discussions. Discussion: This case highlights paraneoplastic leukemoid reaction as a rare and aggressive manifestation of advanced HCC. Early recognition is critical, as it often indicates poor prognosis and may mimic infectious processes. Clinicians should maintain a high index of suspicion in patients with rapidly rising neutrophilic leukocytosis and advanced malignancy.