Abstract
Tumor markers (TM) are biological substances that, depending on their specificity and sensitivity, can be used for cancer screening, diagnosis, monitoring of disease activity, and assessment of treatment response. Human chorionic gonadotropin (hCG), initially employed in pregnancy tests, is a hormone with diverse physiological functions that also serves as a TM, particularly in trophoblastic and germ cell tumors (GCT), where it contributes to cancer progression. We report a rare case of rapidly progressing and fatal stage IV colorectal cancer (CRC) based on radiological data in a 41-year-old woman, in whom the typical TM were only slightly elevated or within normal limits. However, serum levels of the free β-subunit of hCG (β‑hCG) and alpha-fetoprotein (AFP) - markers usually associated with GCT - were elevated. Initially, a pregnancy of unknown location (PUL) was suspected, despite a history of definitive contraception and the absence of ultrasound (US) findings suggestive of pregnancy. Up to 20% of CRCs can secrete β-hCG, usually at low levels, predominantly in tumors located in the rectosigmoid region. β-hCG is physiologically secreted by placental syncytiotrophoblasts during embryo implantation to facilitate trophoblast invasion; analogously, β-hCG-secreting CRC tend to exhibit poor histological differentiation, increased local invasion, and early metastasis, resulting in worse prognosis. In this case, carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) were only slightly elevated, and CA 72-4 levels were within the normal range, which is atypical for most CRC. CRC with serum AFP ≥ 200 ng/mL are more likely to present as stage IV disease; however, in this patient, these features were observed at diagnosis despite lower AFP levels. In women of reproductive age, elevated β‑hCG levels can be misleading, as they often suggest pregnancy and may delay accurate diagnosis. This case highlights a rare presentation of CRC co-expressing β-hCG and AFP. Elevated β-hCG in women of reproductive age can delay recognition of non-gestational malignancies, underscoring the need for careful interpretation in atypical clinical contexts. Co-expression of β-hCG and AFP may indicate a more aggressive tumor phenotype and poorer prognosis. Further studies are warranted to evaluate the potential role of these markers in the diagnosis, monitoring, and prognostication of CRC, particularly in early-onset cases.