A 64-year-old obese male with history of atrial fibrillation, congestive heart failure (CHF) and alcohol use presented with subacute worsening of lower extremity edema, fatigue, and exercise tolerance. Five months prior to presentation, he was admitted to an outside hospital with newly diagnosed atrial fibrillation and CHF. At that time an echocardiogram showed an ejection fraction of 35% and liver ultrasound revealed non-specific steatotic changes. On presentation this admission, mental status was notable for inattentiveness, lethargy and disorientation. Physical examination revealed a normal pulmonary exam, but marked nodular hepatomegaly and 2+ pitting edema to his thighs. It was also noted he had lost 45 lbs between admissions. Labs were notable for hypercalcemia (Ca 13.6 mg/dl), anemia (Hgb 12.6 g/dl), mild transaminitis (AST/ALT 93/15 IU/L), and elevated international normalized ratio (INR 1.37).
Subsequent work-up with abdominal CT revealed a cirrhotic liver with diffuse ill-defined infiltrative hypodensities extending throughout, with a focal region measuring 3.9×4.8 cm, as well as tumor thrombus expanding into the portal vein. Follow-up triple phase CT failed to show the characteristic enhancement and washout pattern seen in hepatocellular carcinoma (HCC); however, the CT findings of an infiltrative mass with an elevated alpha-fetoprotein (210.5 ng/ml) were highly suspicious for HCC. Hypercalcemia work-up revealed suppressed parathyroid hormone (<6.3 pg/ml) and elevated parathyroid hormone-related protein (PTHrP 7.3 pmol/L). In addition, his erythropoietin levels returned highly elevated. The patient was treated for hypercalcemia and hepatic encephalopathy with initial improvement of mental status. He subsequently developed uric acid nephropathy from high cellular turnover and progressed to acute renal failure despite rasburicase treatment. He also deteriorated into progressive liver failure and ultimately passed away.
This case represents a classic demonstration of two paraneoplastic syndromes associated with HCC: hypercalcemia and erythropoiesis. HCC has been shown to be associated with hypercalcemia, usually in the context of osteolytic metastases, but sometimes due to secretion of PTHrP. Infiltrative disease accounts for a minority of HCC cases and can be challenging to diagnose. They often do not show the typical pattern of enhancement and washout on triple phase imaging, and also may not be seen on ultrasound given the lack of discrete lesions. Infiltrative HCC can also be highly aggressive as seen in this patient where high cellular turnover led to uric acid nephropathy as well as the rapid deterioration of liver function.
We report this case to discuss an unusual presentation likely of HCC. This case highlights two important learning points: the recognition of paraneoplastic syndromes associated with HCC and the diagnostic challenges of identifying infiltrative HCC.
To cite this abstract:Caroff, A; Ou, A; Kingsley, T; Lee, MSL . A UNIQUE CASE OF INFILTRATIVE HEPATOCELLULAR CARCINOMA WITH HYPERCALCEMIA AND URIC ACID NEPHROPATHY. Abstract published at Hospital Medicine 2017, May 1-4, 2017; Las Vegas, Nev. Abstract 373. Journal of Hospital Medicine. 2017; 12 (suppl 2). https://www.shmabstracts.com/abstract/a-unique-case-of-infiltrative-hepatocellular-carcinoma-with-hypercalcemia-and-uric-acid-nephropathy/. Accessed January 19, 2020.