• Scarlet fever
• Scrofuloderma
• Seminal vesiculitis
• Sarcoidosis
• Something else entirely?

Seminoma

Definition

Etiology / Risk Factors

1. Germ Cell Neoplasia In Situ (GCNIS)

• Formerly called Intratubular Germ Cell Neoplasia (ITGCN), this is the most important precursor lesion
• Consists of undifferentiated germ cells located basally within seminiferous tubules that morphologically resemble seminoma cells
• Approximately 50% of men with GCNIS will develop a germ cell tumor within 5 years
• Seminoma is thought to arise directly from GCNIS, which also acts as the common precursor for non-seminomatous subtypes - Campbell Walsh Wein Urology

2. Cryptorchidism (Undescended Testis)

• The strongest known risk factor - approximately 7-10% of testicular tumors develop in patients with a history of cryptorchidism
• Seminoma is the most common tumor type arising in cryptorchid testes
• Risk is highest for the intra-abdominal testis (1 in 20) and lower for the inguinal testis (1 in 80)
• Even the contralateral normally descended testis carries a 5-10% risk
• Orchiopexy performed before age 13 significantly lowers the malignancy risk

3. Demographic and Genetic Factors

• Predominantly affects Caucasian males; incidence in African-Americans is ~one-quarter that of Caucasians
• Slightly more common on the right side (paralleling the increased right-sided cryptorchidism rate)
• Higher incidence in Scandinavian countries; lower in Japan
• Higher socioeconomic class doubles the risk compared to lower classes

4. Maternal Estrogen Exposure

• Exogenous estrogen given to the mother during pregnancy is associated with a relative risk of 2.8 to 5.3 for testicular tumors in the fetus

5. Other Factors

• Trauma and infection-related testicular atrophy have been associated, though a causal relationship has not been established
• Bilateral tumors occur in 1-2% of cases; ~50% of these men have a history of cryptorchidism

Histological Subtypes and Pathology

• Positive: CD117, PLAP (placental alkaline phosphatase), OCT3/4
• Negative: CD30, AFP

Gross specimen: Seminoma of the testis showing homogeneous lobulated nodular cut surface - Bailey and Love's

Clinical Features

Typical Presentation

• Age: Most commonly the 4th or 5th decade (older than NSGCTs). Rare in childhood and patients over 70.
• Painless testicular swelling - the classic and most common presentation
• A firm, non-tender scrotal mass that does not transilluminate
• Sensation of heaviness or dragging in the scrotum

Less Common Presentations

• Dull ache or pain in the testis (in ~30-40%)
• Epididymo-orchitis - may mimic infection, delaying diagnosis
• Gynaecomastia - due to syncytiotrophoblast hCG secretion (~15%)
• Hydrocele may coexist and mask the underlying mass

Features of Metastatic Disease

• Seminoma spreads primarily via lymphatics to the para-aortic lymph nodes (near origin of gonadal vessels) - see lymphatic drainage diagram below
• Inguinal lymph nodes are affected only if scrotal skin is involved
• Haematogenous spread is uncommon in pure seminoma
• Symptoms may include: back pain (retroperitoneal LN), respiratory symptoms (lung mets), abdominal mass

Lymphatic drainage of the testes showing para-aortic node drainage - Bailey and Love's

Investigations

1. Ultrasound (First-Line Investigation)

• Scrotal ultrasound is the first and most important investigation
• Reveals a hypoechoic intratesticular mass with increased vascularity on Doppler
• Can detect small tumors with minimal distortion of tunica albuginea
• Sensitivity approaches 100% for intratesticular lesions

Doppler ultrasound of a small seminoma with minimal distortion of tunica albuginea - Bailey and Love's

2. Serum Tumor Markers

Key point: Pure seminoma does NOT produce AFP. Any AFP elevation should prompt reclassification as NSGCT and treatment accordingly.

3. CT Scanning

• CT chest, abdomen, and pelvis is essential for staging
• Identifies retroperitoneal lymphadenopathy, visceral metastases
• CT is also used to diagnose mediastinal seminoma (where tissue biopsy and testicular examination are also required to exclude a gonadal primary)

4. Histological Confirmation

• Radical inguinal orchidectomy - this is both diagnostic and the primary surgical treatment
• The testis is never biopsied via a scrotal approach (risk of altering lymphatic drainage and seeding inguinal nodes)

5. Staging (Royal Marsden / TNM)

Treatment

Step 1: Radical Inguinal Orchidectomy (for all stages)

• First step in both diagnosis and treatment
• Performed via inguinal approach - never scrotal (to preserve lymphatic drainage integrity)
• Provides definitive histology and local disease control

Stage I Seminoma (~80% of cases)

• Most patients with CS I seminoma can be managed with surveillance alone after orchidectomy
• Relapse rate is ~15-20%, but virtually all relapses are salvaged with chemotherapy or radiotherapy
• Avoids toxicity of adjuvant treatment in ~80% who are already cured
• Requires regular CT scans and tumor markers

• Radiation to retroperitoneum and ipsilateral pelvis ("dog-leg" field)
• Dose: 25-35 Gy in 15-20 daily fractions
• Progression-free rate: 95-97%
• Long-term cancer-specific survival approaches 100%
• Risk: Secondary malignant neoplasms (estimated 18% at 25 years), late cardiovascular toxicity, radiation scatter to contralateral testis (oligospermia in ~8%)

• 1-2 cycles of carboplatin (AUC 7)
• Equivalent efficacy to radiotherapy for stage I
• Less neurotoxicity, nephrotoxicity, and ototoxicity than cisplatin
• Long-term cardiovascular and secondary cancer risks still under evaluation

Stage II Seminoma

• IIA/IIB: Radiotherapy remains effective; BEP chemotherapy is an alternative
• IIB/IIC: BEP chemotherapy (Bleomycin + Etoposide + Cisplatin) - standard 3-4 cycles
• Carboplatin-based regimens for stage II are less well-established

Stage III / Metastatic Seminoma

• Standard chemotherapy: BEP (Bleomycin, Etoposide, Cisplatin) - the backbone of treatment
• For mediastinal seminoma: BEP chemotherapy is the standard of care; surgical management is largely limited to biopsy
• Radiotherapy (RT) is reserved for patients with contraindications to chemotherapy (e.g., constrictive pericarditis, valvular disease where bleomycin pulmonary toxicity is a concern)
• Residual masses post-chemotherapy are often necrotic tissue; small residual masses may be followed up radiologically
• 5-year survival with treatment: ~90% - Current Surgical Therapy 14th Ed.

Relapsed Seminoma

• Most relapses after surveillance are salvaged with first-line BEP chemotherapy
• Isolated inguinal relapse may be salvaged with radiotherapy or surgical resection
• High-dose chemotherapy with stem cell rescue may be used in platinum-refractory disease

Summary Table