How should a suspected germ‑cell tumor in a 15‑35‑year‑old male be evaluated and managed?

Evaluation and Management of Suspected Germ Cell Tumor in Males Aged 15-35 Years

A young male aged 15-35 years with a suspected germ cell tumor requires immediate serum tumor marker assessment (AFP, β-HCG, LDH), testicular ultrasonography with a 7.5 MHz transducer, and radical inguinal orchiectomy followed by risk-stratified treatment based on histology and stage. 1

Initial Diagnostic Workup

Mandatory Serum Tumor Markers

• Measure AFP, β-HCG, and LDH before any therapeutic intervention to determine histologic classification and establish prognostic baseline 1, 2, 3
• AFP elevation always indicates non-seminomatous components, even when histology appears to show "pure seminoma" 4, 3
• β-HCG may be elevated in 15-20% of seminomas and 40% of advanced non-seminomatous tumors 4
• LDH serves as an important prognostic factor and is mandatory for International Germ Cell Cancer Collaborative Group (IGCCCG) risk stratification 1

Essential Imaging Studies

• Testicular ultrasonography using a 7.5 MHz transducer is the primary imaging modality for testicular masses 1
• Chest X-ray for initial pulmonary metastasis screening 1
• CT scan of abdomen and pelvis for retroperitoneal lymph node assessment and staging 1, 2
• Chest CT scan is mandatory for non-seminoma but optional for clinical stage I seminoma 1

Critical Clinical Assessment Points

• Maintain high suspicion in young males presenting with testicular mass, retroperitoneal mass, supraclavicular lymphadenopathy, or mediastinal mass 1
• Document risk factors: cryptorchidism, contralateral testicular tumor, first-degree family history (brothers have 6.3-fold increased risk, fathers/sons 4.4-4.7-fold) 1
• Never delay diagnosis by misclassifying testicular masses as epididymitis 1

Surgical Management

Primary Testicular Tumor

• Radical inguinal orchiectomy is the definitive diagnostic and therapeutic procedure 1, 3, 5
• Trans-scrotal biopsy is contraindicated as it alters lymphatic drainage patterns 1
• Fertility preservation through sperm cryopreservation should be offered before orchiectomy 2

Extragonadal Presentations

• For retroperitoneal or mediastinal masses with elevated tumor markers, testicular ultrasonography remains mandatory because one-third harbor intratubular germ cell neoplasia or "burned-out" testicular primary requiring orchiectomy 1, 2
• When tumor markers are normal, obtain tissue diagnosis via Trucut biopsy or mediastinoscopy before treatment 2
• In dramatic presentations with rapidly rising β-HCG and disseminated disease, chemotherapy may be initiated immediately without awaiting biopsy 4

Histologic Classification and Treatment Implications

Seminoma (50% of testicular GCTs)

• Represents undifferentiated germ cell lineage resembling primordial germ cells 3, 6
• Never produces AFP—any AFP elevation indicates non-seminomatous histology regardless of imaging 3
• May produce β-HCG from syncytiotrophoblast cells 4, 3
• Highly radiosensitive; radiation therapy is an option for stage I disease 3, 6

Non-Seminomatous Germ Cell Tumors (50% of testicular GCTs)

• Include embryonal carcinoma (stem cell component), yolk sac tumor, teratoma, and choriocarcinoma 6, 5
• Show differentiation into embryonic and extra-embryonic tissue types 3, 6
• Less radiosensitive than seminoma but remain chemotherapy-sensitive, except mature teratoma 6

Risk Stratification and Systemic Therapy

Stage I Disease (70-75% at diagnosis)

• Localized to testicle with 99% five-year survival 5
• Options include surveillance with tumor markers and imaging, adjuvant chemotherapy, or radiation (seminoma only) 1, 5

Stage II Disease (20% at diagnosis)

• Retroperitoneal lymph node involvement with 92% five-year survival 5
• Treatment based on histology and nodal burden 1

Stage III Disease (10% at diagnosis)

• Widely metastatic with 85% five-year survival 5
• Cisplatin-based combination chemotherapy (BEP: bleomycin, etoposide, cisplatin) is the cornerstone treatment 2
• Number of cycles (typically 3-4) determined by IGCCCG risk classification 2

Post-Chemotherapy Management

Residual Mass Evaluation

• Surgical resection of residual mediastinal or retroperitoneal masses after chemotherapy with normalized markers independently improves survival 2
• Complete resection achievable in approximately 87% of cases 2
• For seminoma, surgery indicated when residual mass ≥3 cm persists after chemotherapy 2
• PET scanning may identify viable tissue in residual seminoma lesions ≥3 cm when performed ≥4 weeks post-chemotherapy 1

Surveillance and Long-Term Considerations

Follow-Up Protocol

• Tumor marker assays (AFP, β-HCG, LDH) and imaging every 2-3 months during first year 2
• 15-20% may experience relapse, but early detection allows curative salvage therapy 2
• Five percent of men develop contralateral testicular GCT (standardized incidence ratios of 13 for seminoma, 29 for non-seminoma) 1

Survivorship Issues

• Address fertility concerns, hypogonadism risk, cardiovascular disease from chemotherapy, secondary malignancies, and psychosocial effects including anxiety and depression 5
• Consider contralateral testis biopsy in high-risk patients as one-third may harbor testicular intra-epithelial neoplasia 2

Critical Pitfalls to Avoid

• Never assume pure seminoma if AFP is elevated—this automatically indicates non-seminomatous components 3
• Never perform trans-scrotal biopsy or orchiectomy—always use inguinal approach 1
• Never misdiagnose testicular masses as epididymitis in young males aged 15-35 years 1
• Never delay testicular ultrasonography in patients presenting with retroperitoneal or mediastinal masses 1, 2