A 50-year-old man comes to the office due to a few weeks of fatigue and back pain. The patient has a history of hypertension and major depressive disorder. He does not use alcohol or intravenous drugs. The patient emigrated from Vietnam with his family when he was a child. BMI is 21 kg/m². Vital signs are within normal limits. Physical examination reveals temporal wasting. Cardiopulmonary examination is normal, and no abdominal masses or tenderness is present. Spine palpation reveals significant pain over a mid-lumbar spinous process. There are no palpable testicular lesions, and digital rectal examination reveals a smooth, normal-sized prostate. Laboratory results are as follows: Spine imaging shows osseous blastic and lytic lesions in multiple vertebral bodies. Which of the following is the most likely diagnosis?

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This patient's back pain, cachexia, elevated alkaline phosphatase, and multiple osteoblastic/osteolytic vertebral lesions likely indicate metastatic cancer of the spine. Although a wide range of cancers metastasize to the spine, the presence of elevated alpha-fetoprotein (AFP), a glycoprotein produced by the fetal liver and yolk sac, raises strong suspicion for primary testicular (yolk sac) or liver (hepatocellular carcinoma [HCC]) cancer. This patient's normal testicular examination, older age, and emigration from Vietnam make HCC most likely. HCC usually arises in the setting of chronic liver inflammation due to alcohol abuse, environmental toxins (eg, aflatoxin, betel nut chewing), or viral hepatitis (eg, hepatitis B virus [HBV], hepatitis C virus [HCV]). Incidence is greatest in Asia (eg, Vietnam), Africa, and the Middle East due to high rates of underlying HBV/HCV infection. In these regions, viral transmission often occurs via the maternal-to-child route, leading lifelong viral hepatitis in the newborn (and increased risk of cirrhosis/HCC later in life). Patients with HCC often develop systemic (eg, weight loss, fatigue), abdominal (eg, right upper quadrant pain, early satiety), or metastatic (eg, bone pain) manifestations. Liver function tests may be normal or elevated; alkaline phosphatase is occasionally dramatically elevated due to osteoblastic bone metastases (as in this case). Significant elevation in alpha-fetoprotein raises strong suspicion for HCC but is present only in ~50% of cases. (Choice A) Cholangiocarcinoma, a tumor of the bile duct epithelium, often causes elevated alkaline phosphatase (from biliary obstruction). However, this tumor is associated with CA 19-9 and CEA elevations, not alpha-fetoprotein elevation. (Choices C and E) Although multiple myeloma and renal cell cancer often spread to the spine, they usually cause purely osteolytic (not mixed osteolytic/osteoblastic) lesions. Therefore, alkaline phosphatase is usually normal (serum concentrations of this enzyme elevate in the setting of osteogenesis, not osteolysis). AFP elevations are rare. This patient's elevated creatinine is most likely from chronic hypertension rather than renal cell cancer or multiple myeloma. osteolytic (Choice D) Although prostate cancer often causes elevated alkaline phosphatase (due to osteoblastic bone metastases), most cases are marked by a prostatic nodule on digital rectal examination and/or elevated prostate-specific antigen. (Choice F) Although nonseminomatous germ cell tumors (that contain yolk sac cells) are often associated with elevated AFP and frequently spread to bone, most testicular cancers occur in males age 15-35 and are marked by unilateral testicular swelling or nodules. Educational objective: Hepatocellular carcinoma usually arises due to chronic liver inflammation from viral hepatitis, alcoholism, or environmental toxins. Incidence is greatest in regions that have high rates of hepatitis B and C virus infection, such as Asia, Africa, and the Middle East. Approximately 50% of HCC cases are associated with dramatic elevations in alpha-fetoprotein. References: Frequency, morbidity, and mortality of bone metastases in advanced hepatocellular carcinoma. (http://www.ncbi.nlm.nih.gov/pubmed/29295881) Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. (http://www.ncbi.nlm.nih.gov/pubmed/26231459) Performance of seruma-fetoprotein levels in the diagnosis of hepatocellular carcinoma in patients with a hepatic mass. (http://www.ncbi.nlm.nih.gov/pubmed/23980880) Radiographic characteristics of bone metastases from hepatocellular carcinoma. (http://www.ncbi.nlm.nih.gov/pubmed/23788922)

A 50-Year-Old Man Comes to the Office Due to a Few