AFP

**Basics:** AFP is a fetal albumin-like glycoprotein. It is produced first by the yolk sac, then by the fetal liver and GI tract. Levels fall sharply after birth, and adult levels are normally very low. It is measured in maternal serum (and sometimes amniotic fluid) during prenatal screening, and in adult serum as a tumor marker.

**Prenatal screening (Step 1 and Step 2 CK):** - Maternal serum AFP is measured at 15–20 weeks as part of the "quad screen" (AFP, hCG, estriol, inhibin A). - **Elevated AFP (or elevated amniotic fluid AFP and acetylcholinesterase):** - Open neural tube defects (spina bifida, anencephaly) - Abdominal wall defects (gastroschisis, omphalocele) - Multiple gestation - Incorrect dating (the most common cause of an abnormal result) - Fetal demise - Other causes: placental abnormalities, congenital nephrosis - **Decreased AFP:** - Down syndrome (trisomy 21), which also shows ↓ estriol, ↑ hCG, and ↑ inhibin A - Edwards syndrome (trisomy 18), which shows ↓ AFP, ↓ hCG, and ↓ estriol - Incorrect dating - **Workup of an abnormal result:** Confirm gestational age with ultrasound first. Then do a detailed anatomic ultrasound, with amniocentesis if needed. - **Prevention:** Folic acid supplementation before conception and in early pregnancy reduces neural tube defect risk. The dose is 0.4 mg/day for average-risk women and 4 mg/day for women with a prior affected pregnancy.

**Tumor marker in adults:** - **Hepatocellular carcinoma (HCC):** - Risk factors are cirrhosis, hepatitis B and C, hemochromatosis, aflatoxin (Aspergillus), and alcohol. - Screen high-risk patients with ultrasound ± AFP every 6 months. - AFP is used for surveillance and for monitoring response to treatment and recurrence. It is not specific, because levels may also rise with cirrhosis and hepatitis flares. - **Yolk sac (endodermal sinus) tumor:** - It is a nonseminomatous germ cell tumor of the testis or ovary. - It has Schiller-Duval bodies, which resemble glomeruli, on histology. - It is the most common testicular tumor in infants and young children. - AFP is elevated. - **Mixed germ cell tumors:** Embryonal carcinoma and mixed tumors may also have elevated AFP. - **Pure seminoma/dysgerminoma:** AFP is *not* elevated. An elevated AFP in a "seminoma" means a nonseminomatous component is present. Seminomas may have a mildly elevated β-hCG. - **Other:** AFP may be elevated in hepatoblastoma, ataxia-telangiectasia (the AFP rise is a clue, along with IgA deficiency), and some gastric and pancreatic cancers.

**High-yield pearls:** - Do not confuse AFP with CEA (colorectal, pancreatic), CA-125 (ovarian epithelial), CA 19-9 (pancreatic), and β-hCG (choriocarcinoma, hydatidiform mole). - Elevated AFP with a hepatic mass in a cirrhotic patient points to HCC. - Elevated AFP in a young child with a testicular or sacrococcygeal mass points to yolk sac tumor.