Monday, December 29, 2025

Seminoma: Epidemiology, Etiology, Pathogenesis, Histopathology, Types, Symptoms, Diagnosis, Staging, Treatment and Prevention

Seminoma

~Introduction


Seminoma is a malignant germ cell tumor of the testis and represents one of the most common and highly curable cancers in young adult males. It arises from primordial germ cells and belongs to the group of testicular germ cell tumors (TGCTs). Seminomas are characterized by slow growth, radiosensitivity, and excellent prognosis, especially when detected early.

Testicular cancers account for about 1–2% of all male malignancies, but they are the most common solid tumors in men aged 15–40 years. Among these, seminoma constitutes approximately 50–60% of cases. Due to advances in diagnosis, imaging, chemotherapy, and radiotherapy, the survival rate for seminoma exceeds 95%, making it one of the most treatable cancers.

~Definition

Seminoma is a malignant germ cell tumor composed of uniform cells resembling primordial germ cells, typically arising in the testis, and less commonly in extragonadal sites such as the mediastinum or retroperitoneum.

~Epidemiology

  • Accounts for 50–60% of testicular germ cell tumors

  • Most common age group: 30–45 years

  • Rare before puberty

  • Higher incidence in Caucasian males

  • Incidence has been increasing globally

  • Bilateral involvement is rare (1–2%)

~Etiology and Risk Factors

The exact cause of seminoma is unknown, but several risk factors have been identified.

1. Cryptorchidism

  • Undescended testis increases risk by 3–10 times

  • Risk persists even after orchiopexy

2. Genetic Factors

  • Family history of testicular cancer

  • Mutations involving KIT gene

  • Isochromosome i(12p) is characteristic

3. Gonadal Dysgenesis

  • Klinefelter syndrome

  • Testicular atrophy

4. Environmental Factors

  • Prenatal estrogen exposure

  • Endocrine-disrupting chemicals

5. Previous Testicular Cancer

  • Increased risk of contralateral seminoma

~Pathogenesis

Seminoma develops from germ cell neoplasia in situ (GCNIS), formerly known as carcinoma in situ. Under the influence of hormonal and genetic alterations, these precursor cells transform into malignant seminoma cells.

Key molecular features include:

  • Overexpression of KIT receptor

  • Gain of chromosome 12p

  • Expression of placental alkaline phosphatase (PLAP)

~Gross Pathology

  • Testis is enlarged and firm

  • Tumor appears homogeneous, gray-white, and lobulated

  • Lacks hemorrhage and necrosis (unlike non-seminomatous tumors)

  • Tunica albuginea may be stretched but usually intact

~Microscopic (Histopathological) Features

Classic histological features include:

  • Sheets or nests of large uniform cells

  • Cells have:

    • Clear or pale cytoplasm (glycogen-rich)

    • Large central nuclei

    • Prominent nucleoli

  • Tumor cells separated by fibrous septa

  • Septa infiltrated by lymphocytes

  • Occasional granulomas

  • Minimal pleomorphism

Immunohistochemistry

  • Positive for:

    • PLAP

    • OCT3/4

    • KIT (CD117)

  • Negative for AFP

~Types of Seminoma

1. Classical Seminoma

  • Most common type

  • Occurs in adults

  • Typical histological appearance

2. Spermatocytic Tumor (formerly spermatocytic seminoma)

  • Occurs in older men (>50 years)

  • Slow growing

  • Rarely metastasizes

  • Better prognosis

~Clinical Features

Primary Symptoms

  • Painless testicular swelling or mass

  • Heaviness in the scrotum

Associated Symptoms

  • Dull ache in groin or lower abdomen

  • Back pain (due to retroperitoneal lymph node involvement)

  • Gynecomastia (rare, due to hCG secretion)

Advanced Disease Symptoms

  • Weight loss

  • Cough or dyspnea (lung metastasis)

  • Bone pain (rare)

~Tumor Markers

Tumor markers play a crucial role in diagnosis, staging, and follow-up.

MarkerRole in Seminoma
β-hCGMildly elevated in ~15–30%
AFPAlways normal (if elevated → non-seminoma)
LDHReflects tumor burden

~Diagnosis

1. Clinical Examination

  • Palpation of firm, non-tender testicular mass

2. Scrotal Ultrasound

  • First-line investigation

  • Hypoechoic, homogeneous lesion

3. Serum Tumor Markers

  • β-hCG, AFP, LDH

4. Radical Inguinal Orchiectomy

  • Diagnostic and therapeutic

  • Trans-scrotal biopsy contraindicated

5. Imaging for Staging

  • CT scan of abdomen and pelvis

  • Chest X-ray or CT chest

~Staging (TNM Classification)

Stage I

  • Tumor confined to testis

Stage II

  • Spread to retroperitoneal lymph nodes

Stage III

  • Distant metastasis (lungs, liver, brain)

~Treatment of Seminoma

Seminoma is highly radiosensitive and chemosensitive.

1. Radical Inguinal Orchiectomy

  • Standard initial treatment

  • Removes primary tumor

2. Management by Stage

Stage I Seminoma

Options include:

  • Active surveillance

  • Adjuvant radiotherapy

  • Single-agent chemotherapy (Carboplatin)

Preferred: Surveillance in compliant patients

Stage II Seminoma

  • Stage IIA/IIB: Radiotherapy or chemotherapy

  • Stage IIC: Combination chemotherapy

Stage III Seminoma

  • Combination chemotherapy (BEP regimen):

    • Bleomycin

    • Etoposide

    • Cisplatin

~Radiotherapy

  • Seminoma is extremely radiosensitive

  • Target areas:

    • Para-aortic lymph nodes

  • Used mainly in early stages

  • Long-term risks: secondary malignancies, cardiovascular disease

~Chemotherapy

  • Platinum-based regimens

  • Highly effective even in advanced disease

  • Side effects:

    • Nephrotoxicity

    • Ototoxicity

    • Pulmonary toxicity (Bleomycin)

~Prognosis

Seminoma has one of the best prognoses among all cancers.

Stage5-Year Survival
Stage I>99%
Stage II95–98%
Stage III85–90%

Prognosis depends on:

  • Stage at diagnosis

  • Tumor marker levels

  • Response to therapy

~Complications

Disease-Related

  • Metastasis to lymph nodes, lungs

  • Infertility

Treatment-Related

  • Secondary malignancies

  • Cardiovascular disease

  • Pulmonary fibrosis

  • Hormonal imbalance

~Prevention and Screening

  • Testicular self-examination

  • Early evaluation of scrotal swelling

  • Early orchiopexy for cryptorchidism

  • Long-term follow-up of high-risk individuals

~Follow-Up and Surveillance

Regular follow-up includes:

  • Physical examination

  • Tumor markers

  • Imaging studies

  • Monitoring fertility and hormonal status

Follow-up is essential due to risk of:

  • Late relapse

  • Second primary tumors

~Conclusion

Seminoma is a highly curable malignant germ cell tumor of the testis, predominantly affecting young adult males. Early diagnosis, accurate staging, and appropriate treatment result in excellent survival outcomes. Advances in imaging, chemotherapy, and surveillance strategies have reduced treatment-related morbidity while maintaining high cure rates. Awareness, early detection, and long-term follow-up remain key components in the effective management of seminoma.


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