Which tumors produce human chorionic gonadotropin (hCG)?

hCG-Producing Tumors

The primary tumors that produce hCG are gestational trophoblastic neoplasias (choriocarcinoma, invasive mole, PSTT, ETT) and germ cell tumors (choriocarcinoma, embryonal carcinoma, mixed germ cell tumors, and some dysgerminomas/seminomas), with choriocarcinoma producing the highest levels often exceeding 50,000 IU/L. 1

Gestational Trophoblastic Tumors

High hCG Producers

• Choriocarcinoma is the most potent hCG producer, characterized by abnormal trophoblastic hyperplasia and anaplasia with marked hCG production, often reaching levels greater than 100,000 IU/L and sometimes millions of mIU/mL 2, 1
• Choriocarcinoma develops from villous trophoblast and can occur after hydatidiform mole (50%), term/preterm gestation (25%), or tubal pregnancy/abortion (25%) 2
• Invasive mole produces elevated hCG, with persistent elevation after molar evacuation being the most common diagnostic finding 2

Lower hCG Producers

• Placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT) secrete hCG but at significantly lower levels compared to other gestational trophoblastic neoplasias 2
• These intermediate trophoblastic tumors make hCG a less reliable tumor marker for monitoring disease course 2

Germ Cell Tumors

In Males

• Choriocarcinoma produces the highest β-hCG levels of any tumor type, often exceeding 50,000 IU/L according to the National Comprehensive Cancer Network 1
• Embryonal carcinoma produces moderate β-hCG elevations 1
• Mixed germ cell tumors containing choriocarcinoma elements produce β-hCG proportional to the choriocarcinoma component 1
• Pure seminomas can produce elevated β-hCG levels, though typically lower than choriocarcinoma 1
• β-hCG levels >50,000 IU/L define poor-prognosis nonseminoma in the IGCCCG classification 1

In Females

• Yolk sac tumors, embryonal carcinomas, and polyembryomas produce alpha-fetoprotein and can produce hCG 2
• Choriocarcinomas produce hCG, while dysgerminomas may produce low levels 2
• Intracranial germ cell tumors show virtually universal hCG expression, with the highest levels in tumors harboring choriocarcinoma or syncytiotrophoblastic giant cell components 3

Non-Germ Cell Malignancies

Epithelial Tumors

• Colon carcinoma can produce hCG through a distinct hCG-producing cell subpopulation, representing biochemical heterogeneity within the tumor 4
• This hCG-producing subpopulation in epithelial carcinomas may demonstrate chemosensitivity to agents typically effective against germ cell tumors 4
• hCG has been detected by immunohistochemical techniques in various extragonadal malignancies, though at lower levels than trophoblastic or germ cell tumors 5

Clinical Significance

hCG measurement is essential for diagnosis, risk stratification, and monitoring treatment response in these tumors. The level of hCG elevation helps distinguish tumor types and predict prognosis, with levels >50,000 IU/L indicating poor prognosis in nonseminomatous germ cell tumors 1. However, β-hCG should not be used alone to distinguish seminoma from nonseminoma, as both can have elevated levels 1.