α-Fetoprotein (AFP) is the Definitive Marker to Distinguish Nonseminoma from Seminoma
The answer is (d) α-fetoprotein (AFP), as it is the only marker that definitively distinguishes between these two tumor types—seminoma cells do not produce AFP, while nonseminomatous cells do. 1
Why AFP is the Distinguishing Marker
AFP is produced exclusively by nonseminomatous germ cell tumor cells (specifically embryonal carcinoma and yolk-sac tumor components) and is never elevated in pure seminoma. 1 This fundamental biological difference makes AFP the definitive discriminating marker:
- Any elevation of AFP above normal range indicates the presence of nonseminomatous elements, even if the histology appears to be "pure seminoma"—this suggests an undetected focus of nonseminoma is present 1
- Pure seminomas are constantly AFP-negative, making this marker 100% specific for distinguishing tumor type 1, 2
- AFP has a half-life of 5-7 days, allowing for reliable monitoring 1
Why the Other Markers Do NOT Distinguish Between Types
Human Chorionic Gonadotropin (hCG)
- hCG can be elevated in BOTH seminoma and nonseminoma, making it useless for distinguishing between them 1
- Approximately 30% of pure seminomas show elevated hCG levels (typically up to 200 IU/L) due to syncytiotrophoblastic giant cells 3
- While extremely high hCG levels (>200 IU/L) may suggest nonseminomatous elements, moderate elevations occur in both types 3
Lactate Dehydrogenase (LDH)
- LDH is a nonspecific marker that can be elevated in both seminoma and nonseminoma 1, 4
- LDH serves primarily as a prognostic marker rather than a diagnostic discriminator 1, 5
- It reflects tumor burden and tissue destruction but provides no information about histologic subtype 1
Alkaline Phosphatase
- Standard alkaline phosphatase is not a specific tumor marker for germ cell tumors 1
- While placental alkaline phosphatase (PLAP) may be elevated in seminoma, it is not included in standard guideline recommendations and does not distinguish between tumor types 6, 7
Clinical Application
All three standard markers (AFP, hCG, and LDH) should be measured before and after orchiectomy for complete staging, but only AFP provides histologic discrimination 1:
- If AFP is elevated → diagnose and treat as nonseminoma regardless of histology 1
- If AFP is normal with elevated hCG and/or LDH → consistent with either seminoma or nonseminoma (requires histologic confirmation) 1
The correct answer is (d) α-fetoprotein.