Secondary Hepatocellular Carcinoma Following Hepatic Infiltration of Chronic Lymphocytic Leukemia

Abstract

Purpose: A 75-year-old Hispanic female from Puerto Rico, who presented to our hospital in 2008 for oncology evaluation. She had been diagnosed of chronic lymphocytic leukemia (CLL) 4 months earlier. This was confirmed by a sternal bone marrow aspiration. At that time, she was completely asymptomatic and had no palpable lymphadenopathy. Other pertinent past medical histories were diabetes mellitus, hypertension, hyperlipidemia, and migraine headaches. Laboratory exams were notable for mild lymphocytosis. Flow cytometry showed typical CLL with CD 19+/CD5+ (co-expression), CD20+ (dim), CD23+, CD38- and kappa light chain+ (dim), 0% of ZAP 70 positive. Bone marrow cytogenetics showed normal karyotype. Since her presentation, she had an abnormal elevation in alkaline phosphatase that ranged from 288 U/L to 440 U/L. Hepatitis C antibody and hepatitis B surface antigen were negative. All work-up for chronic liver disease was negative. She underwent a liver biopsy, which showed liver parenchyma with a patchy infiltrate of small lymphocytes expressing CD20, PAX-5, CD5, CD23, CD43, and BCL-2 characteristic of B-small lymphocytic lymphoma/chronic lymphocytic leukemia. Serial CT scans showed progressive intra-abdominal lymph node affectation; however, she did not meet criteria for treatment for her CLL, as her WBC count, as well as other markers of disease activity remained stable. In 2012, as part of the routine evaluation of her progressive intra-abdominal lymphadenopathy, an abdominal CT scan showed an 8-cm liver mass. Though initially asymptomatic, she developed a right upper quadrant pain that was severe, associated with malaise, constipation, and loss of appetite. Physical examination showed submandibular lymphadenopathy and right upper quadrant tenderness. She had no peripheral stigmata of chronic liver disease. The presence of a large liver mass with an underlying history of liver biopsy being positive for CLL/B-lymphocytic lymphoma made a suspicion of a rapidly growing lymphoma likely. Alpha fetoprotein was also normal. She underwent a second liver biopsy that now revealed grade II hepatocellular carcinoma (HCC). Being Child-Pugh stage B, with a huge liver mass and maintaining a good functional status, she only met the Barcelona Clinic Liver Cancer (BCLC) criteria for treatment with sorafenib, which she was started on, but tolerated for only few weeks. Unfortunately, she continued to decline while the tumor increased exponentially. She was eventually placed in a hospice, and died 3 weeks later. There may be a real association between HCC and CLL. Future studies are required to establish evidence and the goals of treatment.