The mandatory workup for a scrotal mass suspicious for testicular neoplasm is: history and physical exam; serum tumour markers (AFP, hCG, LDH); and imaging — scrotal ultrasound with Doppler (primary), CT abdomen/pelvis (regional), and CT chest (distant; CXR may substitute for CS I seminoma).
Presentation & Physical Exam
- Most common presentation: a painless scrotal mass. Metastatic symptoms (e.g. dyspnea) are the presenting complaint in 10–20%.
- A firm intratesticular mass is malignant until proven otherwise and warrants scrotal ultrasound.
- Differential for a scrotal mass — painless: testicular neoplasm, paratesticular neoplasm (benign or malignant), hernia, varicocele, spermatocele; painful: torsion, hematoma, epididymo-orchitis.
- Examine for metastatic sites — supraclavicular nodes, and inguinal nodes if prior inguinal/scrotal surgery.
- Gynecomastia occurs in 2% of males with GCT, from elevated hCG, decreased androgen production, and/or increased estrogen.
Tumour Markers
Mnemonic for which tumours secrete which marker — A·YET (AFP: Yolk sac, EC, Teratoma) and B·SEC (β-hCG: Seminoma, EC, Choriocarcinoma).
AFP
- Elevated in 50–70% of low-stage (CS I, IIA, IIB) and 60–80% of advanced (CS IIC, III) NSGCT.
- Produced by yolk sac, EC, and teratoma — not by choriocarcinoma or seminoma. A pure seminoma with elevated serum AFP must be treated as NSGCT.
- Upper limit <11 ng/mL. Although many labs flag AFP >8 ng/mL, some people reach 15–25 ng/mL without pathology — treating on a stable AFP <25 ng/mL alone is discouraged.
- Half-life 5–7 days. Other causes: non-malignant liver disease (infectious, drug/alcohol-induced, autoimmune), HCC, cancers of the stomach/pancreas/biliary tract/lung, ataxic telangiectasia, hereditary tyrosinemia, and hereditary persistence of AFP.
β-hCG
- Elevated in 20–40% of low-stage and 40–60% of advanced NSGCT.
- Produced by seminoma (~15% of cases), EC, and choriocarcinoma. Upper limit <5 mU/mL; levels >10,000 IU/L are usually choriocarcinoma.
- Half-life 24–36 hours (peds literature cites 24–48 h). Other causes: hypogonadism (elevated LH cross-reacts with the hCG assay — supplemental testosterone lowers LH and allows accurate hCG measurement); cancers of the liver, biliary tract, pancreas, stomach, lung, breast, kidney, and bladder; and cannabis use. (Assays target the β subunit because the α subunit is shared with pituitary tumours.)
LDH
- Elevated in ~20% of low-stage and 20–60% of advanced GCT. The least specific and least clinically useful marker; main role is the prognostic S-stage classification.
- Treating on LDH elevation alone with normal AFP/hCG is discouraged. Normal 48–115 IU/L; magnitude correlates with disease bulk. Also elevated by cancers (kidney, lymphoma, GI, breast) and non-cancer conditions (heart failure, anemia, HIV).
Interpreting Markers Around Orchiectomy
- Pre-orchiectomy markers support the diagnosis but must not decide whether to operate (normal AFP/hCG do not exclude GCT) and must not be used for clinical staging/risk stratification (risks over- or under-treatment).
- Post-orchiectomy markers should normalize after 4 half-lives (AFP typically normal 20–28 days after effective therapy). Track whether persistently elevated markers are declining by their half-lives or rising — this drives treatment. For borderline elevations (within 3× ULN), confirm a rising trend before acting (false positives occur). Also used to detect recurrence during surveillance and after therapy.
Imaging
Scrotal Ultrasound
- Scrotal US with Doppler; evaluate both testes (2% bilateral GCT — metachronous is the most common pattern). High-frequency transducers (5–10 MHz) distinguish intratesticular lesions of a few millimetres from extra-testicular pathology. Typical GCT is hypoechoic.
- Indications: a scrotal mass; suspected metastatic GCT with a normal testis exam (a small impalpable scar/calcification suggests a "burned-out" primary — a discrete nodule, stellate scar, or coarse calcification warrants orchiectomy, as GCNIS and residual teratoma are common); and suspected primary extra-gonadal GCT (advanced GCT with normal testes on exam and US). With normal markers and indeterminate findings, repeat imaging in 6–8 weeks.
- Testicular microlithiasis has unclear significance — with no GCT history, risk rises only if another established risk factor is present; with a GCT history, contralateral microlithiasis is associated with increased ITGCN risk. No further evaluation if incidental; if a risk factor coexists, counsel on self-examination and follow-up.
- MRI is an adjunct for lesions suspected to be benign but must not delay orchiectomy when malignancy is suspected.
Regional Staging (CT Abdomen/Pelvis)
- CT abdomen/pelvis with oral and IV contrast is the most effective modality for regional staging (MRI is an alternative). Regional nodes: inter-aortocaval, para-aortic, para-caval, pre-aortic, pre-caval, retro-aortic, retro-caval.
- Lymphatic drainage runs right → left: right-testis tumours drain first to the inter-aortocaval nodes (below the renal vessels), then paracaval/para-aortic; left-testis tumours drain first to the para-aortic nodes, then inter-aortocaval.
- Nodes 5–9 mm in the primary landing zone are suspicious, especially if anterior to the great vessels.
- Accuracy limits: understaging — 25–35% of CS I NSGCT with a "normal" CT have positive nodes at RPLND; overstaging — 12–40% of CS IIA/IIB have negative nodes at RPLND.
Chest & Other Imaging
- Chest imaging completes staging but must not delay orchiectomy. CXR is preferred for suspected CS I seminoma (with normal markers, thoracic skip metastasis is ~0%). CT chest is indicated for NSGCT (skip metastases more common), elevated/rising post-orchiectomy markers, or any metastasis on abdominal/pelvic imaging, CXR, or exam.
- Bone scan and CT brain have no routine role; obtain for CNS/bone symptoms, poor-prognosis disease, or highly elevated hCG (>10,000 mU/mL, associated with choriocarcinoma and brain metastases).
- FDG-PET has no role in routine staging of NSGCT or seminoma at diagnosis.
Scrotal Violation
Percutaneous testicular biopsy is contraindicated. Scrotal violation (trans-scrotal orchiectomy, open biopsy, FNA) increases the risk of pelvic/inguinal nodal metastasis (altered lymphatic drainage) and local recurrence. A systematic review (Capelouto, 1995) found local recurrence in 2.5% after scrotal violation vs 0% after radical inguinal orchiectomy, with viable GCT in 9% of excised scrotal scars, though no difference in metastatic disease or all-cause mortality.
Self-Test
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Which tumours secrete AFP, and which secrete β-hCG? AFP — yolk sac, EC, teratoma (A·YET). β-hCG — seminoma (~15%), EC, choriocarcinoma (B·SEC). Choriocarcinoma and seminoma do not produce AFP.
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A pure seminoma on orchiectomy has an elevated serum AFP. How is it managed? As NSGCT — an elevated AFP indicates non-seminomatous elements regardless of the reported histology.
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What are the serum half-lives of AFP and β-hCG? AFP 5–7 days; β-hCG 24–36 hours. Markers should normalize after ~4 half-lives.
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Why should pre-orchiectomy markers not be used for staging? They can be falsely elevated/normal and would risk over- or under-treatment; staging/risk stratification uses post-orchiectomy markers interpreted against their half-lives.
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When is CXR (rather than CT chest) acceptable for staging? Suspected CS I seminoma with normal markers — thoracic skip metastasis is near 0%, so CXR is preferred.