Testicular germ-cell tumour

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Testicular germ-cell tumours are highly curable seminomatous or non-seminomatous cancers arising mainly in younger men; histology, post-orchidectomy marker decline and anatomical stage create the treatment risk group. Cryptorchidism, impaired spermatogenesis, hypospadias and reduced testicular development are associated with germ-cell neoplasia in situ and later cancer. A contralateral previous germ-cell tumour and first-degree family history increase risk and guide counselling about the remaining testis. Seminoma retains primitive germ-cell morphology, usually spreads predictably and is highly radiosensitive and chemosensitive. Embryonal carcinoma, yolk-sac tumour, choriocarcinoma and teratoma components differ in marker production, tempo and residual-mass behaviour.

Recognition depends on the tempo, host context and anatomical pattern rather than one isolated result. A firm unilateral lump, change in consistency or diffuse enlargement is the common presentation and needs urgent ultrasound. Dull discomfort can occur, but abrupt severe pain and a high-riding testis must trigger torsion management. hCG secretion can cause gynaecomastia, while testicular dysgenesis and tumour may be associated with subfertility. Investigation should answer immediate safety, diagnostic confirmation and extent in that order. Scrotal ultrasound A solid vascular intratesticular mass is malignant until assessed; ultrasound of the contralateral testis documents baseline and additional lesions. AFP, hCG and LDH before orchidectomy AFP elevation excludes pure seminoma regardless of initial label; normal markers do not exclude either seminoma or non-seminomatous cancer. Radical inguinal orchidectomy Control the spermatic cord at the internal ring and avoid trans-scrotal biopsy, which disrupts lymphatic drainage and risks local contamination.

Management is determined by physiological urgency, disease extent, treatment intent and the person's priorities. The pathway moves through use markers and inguinal surgery, then choose surveillance or adjuvant risk reduction, then assign igcccg risk and treat for cure; each transition requires named multidisciplinary ownership. Follow-up must anticipate infertility and hypogonadism, tumour lysis and choriocarcinoma haemorrhage, bleomycin lung injury while measuring function and treatment toxicity.

Key points

Painless intratesticular mass is a pivotal clue in Testicular germ-cell tumour: A firm unilateral lump, change in consistency or diffuse enlargement is the common presentation and needs urgent ultrasound.
Immediate priority in unstable Testicular germ-cell tumour: Use immediate urological exploration for suspected torsion without delaying for tumour markers, and stabilise metastatic emergencies with the germ-cell centre because precipitous chemotherapy can cause tumour lysis or pulmonary haemorrhage in heavy choriocarcinoma burden.
Scrotal ultrasound is used early to distinguish an intratesticular solid lesion from epididymal, cystic or inflammatory pathology. A solid vascular intratesticular mass is malignant until assessed; ultrasound of the contralateral testis documents baseline and additional lesions.
AFP, hCG and LDH before orchidectomy refines the next decision because aFP elevation excludes pure seminoma regardless of initial label; normal markers do not exclude either seminoma or non-seminomatous cancer.
Use markers and inguinal surgery: Take AFP, hCG and LDH before surgery, assess the contralateral testis and arrange urgent referral to the germ-cell pathway.
Choose surveillance or adjuvant risk reduction: For seminoma, consider surveillance or risk-adapted carboplatin; avoid routine radiotherapy where modern pathways favour lower late toxicity.
A major avoidable harm is infertility and hypogonadism; Baseline dysgenesis, orchidectomy, chemotherapy and retroperitoneal surgery can impair sperm, testosterone, sexual health and body image.
A common diagnostic trap is epididymal cyst or spermatocele: A separate fluctuant extratesticular lesion is usually benign, but examination uncertainty warrants ultrasound.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Testicular dysgenesis

Cryptorchidism, impaired spermatogenesis, hypospadias and reduced testicular development are associated with germ-cell neoplasia in situ and later cancer.

Previous or family tumour

A contralateral previous germ-cell tumour and first-degree family history increase risk and guide counselling about the remaining testis.

Genomic susceptibility

Gain of chromosome 12p is characteristic of invasive postpubertal germ-cell tumours, while inherited common variants create polygenic risk.

Germ-cell neoplasia in situ

Abnormal primordial germ cells persist within seminiferous tubules and can evolve into seminoma or non-seminomatous components after puberty.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Seminoma differentiation
Seminoma retains primitive germ-cell morphology, usually spreads predictably and is highly radiosensitive and chemosensitive. In Testicular germ-cell tumour, this distinction materially changes mechanistic assessment.
2
Non-seminomatous differentiation
Embryonal carcinoma, yolk-sac tumour, choriocarcinoma and teratoma components differ in marker production, tempo and residual-mass behaviour.
3
Marker kinetics
AFP and hCG fall according to biological half-lives after orchidectomy; persistent or rising values indicate occult residual or metastatic disease.
4
Lymphatic spread
Testicular lymphatics drain to retroperitoneal para-aortic nodes, making inguinal nodes unusual unless prior scrotal surgery disrupted drainage.
5
Cisplatin sensitivity
Germ-cell cancers remain exceptionally susceptible to platinum-induced DNA damage, enabling cure even with metastatic disease but creating important late toxicity.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Painless intratesticular mass

A firm unilateral lump, change in consistency or diffuse enlargement is the common presentation and needs urgent ultrasound.

Scrotal heaviness or ache

Dull discomfort can occur, but abrupt severe pain and a high-riding testis must trigger torsion management.

Endocrine features

hCG secretion can cause gynaecomastia, while testicular dysgenesis and tumour may be associated with subfertility.

Retroperitoneal spread

Back or abdominal pain, hydronephrosis and leg oedema can arise from bulky para-aortic nodes.

Thoracic diseaseRed flag

Cough, dyspnoea or haemoptysis suggests lung or mediastinal spread and can become critical with high-volume choriocarcinoma.

Brain or liver metastasis

Headache, focal deficit, jaundice or abdominal pain marks poor-risk visceral disease requiring urgent specialist staging.

Red flags requiring action

A painless firm intratesticular lump or enlarged testis persists despite lack of constitutional symptoms.
Acute testicular pain and swelling could be torsion and requires immediate surgical assessment.
Gynaecomastia, infertility or testicular atrophy accompanies a suspicious lesion.
Back pain, cough, haemoptysis, neck nodes or weight loss suggests retroperitoneal or distant spread.
Very high hCG with lung metastases and haemoptysis raises concern for choriocarcinoma syndrome.
A patient with a solitary testis or future fertility wishes is about to undergo orchidectomy or gonadotoxic chemotherapy.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Scrotal ultrasoundFirst step
Why
Distinguish an intratesticular solid lesion from epididymal, cystic or inflammatory pathology.
Interpretation and limitations
A solid vascular intratesticular mass is malignant until assessed; ultrasound of the contralateral testis documents baseline and additional lesions.
02
AFP, hCG and LDH before orchidectomy
Why
Support diagnosis and provide a kinetic baseline for staging and risk classification.
Interpretation and limitations
AFP elevation excludes pure seminoma regardless of initial label; normal markers do not exclude either seminoma or non-seminomatous cancer.
03
Radical inguinal orchidectomy
Why
Obtain definitive histology and local control through an oncologically safe route.
Interpretation and limitations
Control the spermatic cord at the internal ring and avoid trans-scrotal biopsy, which disrupts lymphatic drainage and risks local contamination.
04
Post-orchidectomy markers
Why
Determine whether marker concentrations decline appropriately and contribute to metastatic risk group.
Interpretation and limitations
Measure at guideline-defined intervals until normal or clearly plateauing; classify from the appropriate post-operative value, not only the preoperative peak.
05
CT chest, abdomen and pelvis
Why
Stage retroperitoneal, mediastinal, pulmonary and visceral disease.
Interpretation and limitations
Use after diagnosis or earlier if unstable bulky disease is suspected; a small residual lesion and teratoma require different interpretation from active marker-positive cancer.
06
Fertility assessment and sperm banking
Why
Preserve reproductive options before orchidectomy in a solitary testis or before gonadotoxic treatment when this causes no unsafe delay.
Interpretation and limitations
Offer semen cryopreservation before chemotherapy and discuss testosterone, fertility, prosthesis and genetic or family implications.
07
Brain MRI
Why
Detect cerebral metastases in neurological symptoms, very high-risk choriocarcinoma or other guideline-defined poor-risk situations.
Interpretation and limitations
Do not use routinely in every stage I tumour; obtain urgently before anticoagulation or treatment if haemorrhagic brain disease is suspected.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Epididymal cyst or spermatocele

A separate fluctuant extratesticular lesion is usually benign, but examination uncertainty warrants ultrasound. In Testicular germ-cell tumour, this distinction materially changes diagnostic assessment.

Epididymo-orchitis

Pain, urinary infection and hyperaemia support inflammation; a persistent focal intratesticular mass after treatment needs repeat imaging.

Testicular torsion

Sudden pain, high lie and absent cremasteric reflex is a time-critical surgical diagnosis; cancer work-up must not delay exploration.

Testicular lymphoma

In an older man, bilateral or infiltrative disease may represent lymphoma and can alter the need for systemic biopsy planning.

Adrenal-rest or benign stromal tumour

Endocrine context and imaging can suggest a benign mimic, but tissue route remains inguinal when malignancy cannot be excluded.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01MassUse markers and inguinal surgeryFirst stepExamination or ultrasound identifies a suspicious solid intratesticular lesion.

1Take AFP, hCG and LDH before surgery, assess the contralateral testis and arrange urgent referral to the germ-cell pathway.
2Offer sperm banking before orchidectomy when a solitary testis or fertility context makes this important and delay is safe.
3Perform radical inguinal orchidectomy without trans-scrotal biopsy, then obtain expert pathology including all germ-cell components and local stage.

02Stage IChoose surveillance or adjuvant risk reductionPost-orchidectomy imaging and marker kinetics show no metastatic disease.

1Explain the relapse pattern, cure rate, radiation burden and adherence requirements of active surveillance.
2For seminoma, consider surveillance or risk-adapted carboplatin; avoid routine radiotherapy where modern pathways favour lower late toxicity.
3For non-seminoma, use vascular invasion and other pathology to discuss surveillance, adjuvant BEP or selected retroperitoneal surgery in expert centres.

03MetastaticAssign IGCCCG risk and treat for cureMarkers or imaging demonstrate metastatic germ-cell tumour.

1Classify histology, primary site, metastatic distribution and correctly timed AFP, hCG and LDH into the international risk group.
2Use 3 cycles of BEP for good-risk or 4 cycles for intermediate- or poor-risk disease, substituting EP where bleomycin is contraindicated through the specialist protocol.
3Manage tumour-lysis, infection, thrombosis, pulmonary and fertility risks proactively and avoid dose delay or reduction without germ-cell specialist review.

04ResidualInterpret post-treatment masses by histologyMarkers normalise or plateau and imaging shows residual disease after chemotherapy.

1In non-seminoma, refer residual retroperitoneal masses for expert surgical resection because teratoma or viable cancer may remain despite normal markers.
2In seminoma, observe small residual masses and use delayed FDG PET selectively for larger masses according to timing and guideline criteria.
3For rising markers or viable cancer, use salvage chemotherapy and high-volume centre review rather than routine surveillance.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Curative first-line treatment for good-risk metastatic germ-cell tumour; 4 cycles are used for intermediate- or poor-risk disease under specialist protocols.

BEP chemotherapy

A standard 21-day good-risk regimen gives bleomycin 30,000 international units IV on days 1, 8 and 15, etoposide 100 mg/m² IV on days 1–5 and cisplatin 20 mg/m² IV on days 1–5 for 3 cycles.

Assess lungs, renal function, hearing, neuropathy and fertility; provide hydration, antiemesis and neutropenic-sepsis advice, and avoid compromising curative dose intensity without germ-cell expert input.

Maintains curative platinum treatment while avoiding bleomycin pulmonary exposure in an appropriate risk group.

EP chemotherapy when bleomycin is unsuitable

For good-risk metastatic disease when bleomycin is contraindicated, a standard alternative is etoposide 100 mg/m² IV and cisplatin 20 mg/m² IV on days 1–5 every 21 days for 4 cycles.

Requires full renal, marrow, hearing, neurological, antiemetic and hydration support; it is a specialist substitution, not a reason to omit a whole treatment component casually.

Reduces relapse risk after orchidectomy for selected stage I seminoma, while surveillance remains an important option.

Carboplatin for selected stage I seminoma

Use a single adjuvant dose calculated at area under the curve 7 by the Calvert formula after accurate glomerular filtration assessment, when adjuvant treatment is chosen over surveillance.

Use measured or accurately estimated GFR, monitor marrow and infection, and explain that adjuvant therapy does not eliminate the need for follow-up or guarantee no relapse.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Infertility and hypogonadism

Baseline dysgenesis, orchidectomy, chemotherapy and retroperitoneal surgery can impair sperm, testosterone, sexual health and body image.

Tumour lysis and choriocarcinoma haemorrhage

Highly responsive bulky disease can cause metabolic collapse, while vascular metastases may bleed catastrophically after treatment begins.

Bleomycin lung injury

Cumulative exposure can cause pneumonitis and fibrosis; oxygen, renal clearance, age and lung disease modify risk.

Cisplatin late effects

Survivors face neuropathy, hearing loss, renal impairment, metabolic and cardiovascular risk and a small secondary-malignancy risk.

Residual teratoma

A post-chemotherapy mass can contain mature teratoma that is marker-negative but grows or transforms and requires specialist resection.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Follow AFP and hCG to expected normalisation after orchidectomy and use a plateau or rise as evidence requiring metastatic review.
During BEP or EP, check count, renal function, magnesium, hearing, neuropathy, infection and treatment timing before each component.
Ask about cough and breathlessness before every bleomycin dose and investigate suspected pneumonitis promptly rather than relying on one baseline test.
Use stage- and histology-specific marker, clinical and imaging surveillance while actively minimising unnecessary radiation exposure in young survivors.
Review testosterone, fertility, sexual function, prosthesis, renal, hearing, cardiovascular and metabolic late effects after cure.
Track post-chemotherapy residual masses to a germ-cell surgical decision; normal markers alone do not exclude teratoma.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Never biopsy through the scrotum

The inguinal route preserves oncological planes and normal lymphatic staging; trans-scrotal access can contaminate skin and alter drainage.

AFP changes the label

Pure seminoma does not produce AFP, so a raised AFP means manage as non-seminomatous germ-cell tumour unless another cause is proven.

Markers need kinetics

The post-orchidectomy rate of decline distinguishes removed local disease from persistent cancer more reliably than one isolated value.

Dose intensity cures

Unplanned delay or reduction can compromise an otherwise curable metastatic cancer and needs high-volume germ-cell advice.

A normal marker mass can matter

Residual non-seminomatous teratoma is often marker-negative and requires surgical assessment rather than reassurance.

11Common pitfallsFrequent interpretation and management errors.

01
Performing trans-scrotal biopsy of a suspicious intratesticular mass.
02
Omitting pre-orchidectomy AFP, hCG and LDH.
03
Calling a tumour pure seminoma despite raised AFP.
04
Reducing curative cisplatin dose without germ-cell specialist review.
05
Ignoring fertility and sperm banking before chemotherapy.
06
Observing a post-chemotherapy non-seminoma mass because markers are normal.