Seminoma

Definition and Overview

• Peak incidence: 4th-5th decade of life (older average age than NSGCT)
• Seldom occurs in childhood, young adults, or patients over 70

Gross & Histological Features

• Soft, tan-to-white, diffuse or multinodular mass
• Homogeneous, pinkish-cream cut surface
• Necrosis may be present but is usually focal (less prominent than other GCTs)

Figure: Gross specimen - seminoma of the testis (Bailey & Love, 28th ed.)

• Sheets of polygonal cells with clear cytoplasm and large, rounded nuclei with prominent acidophilic nucleoli
• Cells divided into nests by fibrovascular septae containing lymphocytes
• Active lymphocytic infiltration suggests good host response and better prognosis
• Syncytiotrophoblasts (hCG-positive) present in ~15% of cases - no clear prognostic significance
• Lymphocytic infiltrates and granulomatous reactions are often seen; associated with increased incidence of sarcoidosis

Subtypes

1. Classic Seminoma (85%)

• Most common subtype; 4th decade
• Coalescing gray nodules grossly
• Monotonous sheets of large cells with clear cytoplasm and densely staining nuclei
• ~15% have syncytiotrophoblastic elements (with corresponding mild hCG elevation)

2. Anaplastic Seminoma (5-10%)

• Requires ≥3 mitoses per high-power field
• Higher degree of nuclear pleomorphism
• Tends to present at a higher stage
• No worse prognosis when stage is controlled for - no longer considered a distinct biologic entity

3. Spermatocytic Seminoma / Spermatocytic Tumor (1%)

• Renamed "spermatocytic tumor" in 2016 WHO classification - now considered a distinct entity, NOT a true seminoma
• Does NOT arise from GCNIS; not associated with cryptorchidism or bilaterality; no i(12p)
• Peak incidence: 6th decade
• Three cell types: small lymphocyte-like cells, medium cells with dense eosinophilic cytoplasm, large mono/multinucleated cells
• Virtually benign - only 3 documented cases of metastasis; cured by orchiectomy alone

Tumor Markers

Key rule: An elevated AFP in a patient with apparent seminoma means the tumor must be treated as an NSGCT, regardless of histology.

Staging (TNM / AJCC)

• CS I: ~80-85% of cases
• CS II: ~10%
• CS III: ~5%

Metastatic Spread

• Spreads primarily via lymphatics to para-aortic lymph nodes near the origin of the gonadal vessels
• Contralateral para-aortic nodes may also be involved
• Inguinal nodes only affected if scrotal skin is involved
• Haematogenous spread is uncommon (vs. NSGCT)
• Lower incidence of occult retroperitoneal metastasis in CS I: 10-15% (vs. 25-35% for NSGCT)

Figure: Ultrasound of a small seminoma with minimal distortion of the tunica albuginea (Bailey & Love)

Seminoma vs. NSGCT - Key Differences

Management

Initial Step - All Testicular Tumors

Clinical Stage I Seminoma

• ~80% are cured by orchiectomy alone
• Surveillance duration: up to 10 years (slow growth rate)
• Schedule: H&P + tumor markers every 3-6 months (year 1) → every 6-12 months (years 2-3) → annually to year 10
• Imaging: abdominal/pelvic CT each visit + CXR as indicated
• Preferred to avoid long-term toxicity of RT/chemo

• Retroperitoneal ± ipsilateral pelvic ("dog-leg" configuration)
• Dose: 25-35 Gy in 15-20 fractions
• Long-term cancer-specific survival approaches 100%
• PFS 95-97%
• In-field recurrence <1%
• Most common relapse sites: thorax and left supraclavicular fossa
• Risks: SMN (secondary malignant neoplasm) risk ~18% at 25 years; late GI toxicity; oligospermia in 8%

• Less neurotoxicity, ototoxicity, and nephrotoxicity than cisplatin
• Long-term SMN and cardiovascular risk not fully characterized
• Non-inferior to radiotherapy in randomized trials for disease control

Clinical Stage IIA-IIB Seminoma

• Radiotherapy or chemotherapy
• Low-volume retroperitoneal disease: retroperitoneal irradiation, 5-year survival ~87%

High-Stage / Bulky Seminoma (CS IIC-III)

• Good-risk: 3 cycles BEP (bleomycin + etoposide + cisplatin) or 4 cycles EP
• Intermediate-risk: 4 cycles BEP
• No "poor risk" IGCCCG category exists for seminoma - >90% of advanced seminoma is classified as good risk

• Residual masses <3 cm → usually fibrosis (~90%); observation
• Residual masses >3 cm well-circumscribed → ~40% harbor residual seminoma → FDG-PET scan
  • PET positive → consider PC-RPLND (post-chemotherapy retroperitoneal lymph node dissection)
  • PET negative → observation

Relapsed Seminoma

• Chemo-naive relapse (after surveillance or primary RT): cisplatin-based chemotherapy; salvage approaches 100% for bulky/systemic relapse
• Post-chemotherapy relapse: VeIP x4 (vinblastine, ifosfamide, cisplatin) → 83% complete response; ~53% durable remission; high-dose chemotherapy (HDCT) also evaluated

Key Points Summary

1. Seminoma = most common testicular GCT; arises from GCNIS; AFP always negative
2. Histology: clear cytoplasm, fibrovascular septae with lymphocytes; PLAP+ / CD117+ / CD30-
3. Three subtypes - classic (85%), anaplastic (5-10%), spermatocytic tumor (now distinct entity, benign)
4. Spreads via lymphatics to para-aortic nodes; haematogenous spread uncommon
5. Exquisitely radiosensitive; very chemosensitive (platin-based)
6. CS I (85% at diagnosis) - surveillance preferred; RT and carboplatin are alternatives
7. Advanced disease: BEP chemotherapy; post-chemo masses >3 cm need PET then consider PC-RPLND
8. No IGCCCG poor-risk category; >90% of metastatic seminoma is good-risk
9. Risk of NSGCT transformation (~10-15% at relapse sites) must always be considered