Gonadal and Germ Cell Neoplasms in Pediatric Age
Gonadal and Germ Cell Neoplasms in Pediatric Age
Gonadal and germ cell neoplasms are a diverse group of tumors that arise from primordial germ cells. These tumors can occur in both gonadal (ovaries and testes) and extragonadal sites. In children, they account for approximately 3% of all malignancies. This comprehensive overview covers key aspects of these neoplasms, essential for pediatricians and medical students.
Epidemiology
- Incidence: 2.4 cases per million children per year
- Age distribution: Bimodal, with peaks in early childhood (0-4 years) and adolescence (15-19 years)
- Sex predilection: Slight male predominance (M:F ratio 1.1:1)
- Geographical variation: Higher incidence in Asian and Hispanic populations
- Risk factors: Cryptorchidism (for testicular tumors), family history, genetic syndromes (e.g., Klinefelter syndrome, Turner syndrome)
Classification
Germ cell tumors are classified based on their histology and location:
- Germinomas
- Seminomas (in testes)
- Dysgerminomas (in ovaries)
- Teratomas
- Mature teratomas
- Immature teratomas
- Yolk sac tumors (endodermal sinus tumors)
- Embryonal carcinomas
- Choriocarcinomas
- Mixed germ cell tumors
Location-based classification:
- Gonadal: Testicular or ovarian
- Extragonadal: Sacrococcygeal, mediastinal, retroperitoneal, central nervous system
Pathophysiology
Germ cell tumors arise from primordial germ cells that fail to undergo normal differentiation during embryonic development. Key aspects of their pathophysiology include:
- Genetic alterations: Isochromosome 12p is a characteristic finding in many germ cell tumors
- Developmental origin: Arise from totipotent primordial germ cells, explaining their diverse histological appearances
- Malignant transformation: Can occur in previously benign teratomas
- Hormone production: Some tumors produce hormones (e.g., hCG, AFP) that can be used as tumor markers
- Metastasis: Occurs via lymphatic and hematogenous routes, with patterns varying by primary site
Clinical Presentation
Symptoms vary depending on the tumor's location and type:
- Testicular tumors:
- Painless testicular mass
- Scrotal swelling or heaviness
- Acute pain (in case of torsion)
- Ovarian tumors:
- Abdominal pain or distension
- Palpable abdominal mass
- Precocious puberty (in hormone-producing tumors)
- Extragonadal tumors:
- Sacrococcygeal: Visible mass in the sacral area
- Mediastinal: Respiratory symptoms, superior vena cava syndrome
- Intracranial: Headache, visual disturbances, endocrine abnormalities
- Constitutional symptoms: Weight loss, fatigue, fever (in advanced cases)
Diagnosis
Diagnostic approach includes:
- Physical examination
- Imaging studies:
- Ultrasound: First-line for gonadal tumors
- CT scan: For staging and evaluation of metastases
- MRI: Particularly useful for CNS tumors
- Tumor markers:
- Alpha-fetoprotein (AFP)
- Beta-human chorionic gonadotropin (β-hCG)
- Lactate dehydrogenase (LDH)
- Biopsy: Often necessary for definitive diagnosis
- Genetic testing: For associated syndromes and prognostic information
Treatment
Treatment is multimodal and depends on the tumor type, stage, and location:
- Surgery:
- Primary treatment for most germ cell tumors
- Radical inguinal orchiectomy for testicular tumors
- Fertility-sparing surgery when possible for ovarian tumors
- Chemotherapy:
- BEP regimen (Bleomycin, Etoposide, Cisplatin) is standard
- Used for advanced-stage disease or as adjuvant therapy
- Radiation therapy:
- Limited use in pediatric germ cell tumors
- May be used for certain CNS germ cell tumors
- Stem cell transplantation: Considered for high-risk or relapsed cases
- Clinical trials: For refractory or relapsed disease
Prognosis
Prognosis varies depending on several factors:
- Overall survival rates:
- Gonadal germ cell tumors: >90% 5-year survival
- Extragonadal germ cell tumors: 70-80% 5-year survival
- Prognostic factors:
- Tumor histology: Seminomas and dysgerminomas have better prognosis
- Stage at diagnosis: Early-stage disease has better outcomes
- Tumor markers: Rapid decline post-treatment is favorable
- Age: Younger children often have better outcomes
- Location: Gonadal tumors generally have better prognosis than extragonadal
- Long-term considerations:
- Fertility preservation
- Risk of secondary malignancies
- Endocrine dysfunction
- Psychosocial impact
Gonadal and Germ Cell Neoplasms in Pediatric Age
- What is the most common malignant germ cell tumor in children?
Yolk sac tumor - Which tumor marker is characteristically elevated in yolk sac tumors?
Alpha-fetoprotein (AFP) - What is the most common testicular tumor in prepubertal boys?
Teratoma - Which chromosome is commonly involved in the isochromosome seen in male germ cell tumors?
Chromosome 12 (i12p) - What is the most common ovarian germ cell tumor in girls under 10 years old?
Mature teratoma - Which tumor marker is elevated in choriocarcinoma?
Beta-human chorionic gonadotropin (β-hCG) - What is the name of the benign testicular tumor composed of Leydig cells?
Leydig cell tumor - Which imaging modality is preferred for initial evaluation of suspected ovarian masses?
Ultrasound - What is the most common malignant ovarian germ cell tumor in adolescent girls?
Dysgerminoma - Which genetic syndrome is associated with an increased risk of gonadoblastoma?
Turner syndrome - What is the characteristic histological feature of seminoma/dysgerminoma?
Sheets of uniform cells with clear cytoplasm - Which chemotherapy regimen is commonly used for malignant germ cell tumors?
BEP (Bleomycin, Etoposide, Cisplatin) - What is the name of the ovarian tumor that can cause precocious puberty?
Juvenile granulosa cell tumor - Which tumor marker is elevated in Sertoli-Leydig cell tumors?
Inhibin - What is the most common presenting symptom of ovarian tumors in girls?
Abdominal pain - Which germ cell tumor is associated with the highest risk of malignant transformation?
Mature cystic teratoma - What is the name of the rare ovarian tumor associated with hypercalcemia?
Small cell carcinoma of the ovary, hypercalcemic type - Which molecular pathway is commonly activated in pediatric germ cell tumors?
KIT/RAS pathway - What is the most common site of extragonadal germ cell tumors in children?
Sacrococcygeal region - Which tumor suppressor gene is commonly mutated in malignant ovarian germ cell tumors?
p53 - What is the characteristic radiological finding in ovarian teratomas?
Fat-fluid levels - Which surgical approach is preferred for suspected malignant ovarian tumors in girls?
Unilateral salpingo-oophorectomy - What is the name of the benign ovarian tumor composed of granulosa and theca cells?
Fibroma-thecoma - Which tumor marker is elevated in embryonal carcinoma?
Both AFP and β-hCG - What is the most common cause of precocious puberty in boys with testicular tumors?
Leydig cell tumor - Which imaging modality is used for staging of malignant germ cell tumors?
CT scan of chest, abdomen, and pelvis - What is the name of the ovarian tumor associated with Peutz-Jeghers syndrome?
Sex cord tumor with annular tubules (SCTAT) - Which chromosome abnormality is associated with gonadoblastoma in patients with disorders of sex development?
Presence of Y chromosome material - What is the typical age of presentation for juvenile granulosa cell tumors?
First decade of life - Which tumor marker is used for monitoring treatment response in dysgerminoma?
Lactate dehydrogenase (LDH)
Disclaimer
The notes provided on Pediatime are generated from online resources and AI sources and have been carefully checked for accuracy. However, these notes are not intended to replace standard textbooks. They are designed to serve as a quick review and revision tool for medical students and professionals, and to aid in theory exam preparation. For comprehensive learning, please refer to recommended textbooks and guidelines.
