Germ Cell Tumors In Children

Neoplasms arise from the human embryo's primordial germ cells. It comprises only about 2-3% of all childhood malignancies.  

Types: Gonadal or extragonadal. 

• Gonadal GCTs > Extragonadal GCTs. 
• Extragonadal GCTs
  • The most common site is Sacrococcygeal Region (42%). 
  • Other sites include Mediastinum, Pineal Region, Retroperitoneum, and Neck.

Histological Subtypes of GCTs

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Risk factors in GCTs

Increased risk of mediastinal GCTs: Klinefelter syndrome. Increased risk of testicular germ cell tumors. 

• Down syndrome. 
• Undescended testis. If orchidopexy is done before 13 years of age, the risk for testicular germ cell tumors is significantly reduced, but it does not become zero.
• Testicular atrophy
• Testicular microlithiasis
• Infertility
• Inguinal hernia
• Testicular dysgenesis syndrome
• Monozygotic twins and first-degree relatives of testicular GCTs.

Clinical Features

Clinical presentation depends on the type and location of the tumor. Mostly present with palpable mass or mass-related effects. For example, compression. CNS germ cell tumors can have anterior and posterior pituitary hormonal defects.

Diagnosis

History and physical examinations. A panel of tumor markers. Imaging studies can be needed, such as chest x-rays and ultrasound abdome.

In suspected gonadal masses, pelvic CT or MRI.  Strong suspicion of malignancy. Additionally, a CT chest and bone scan. Retroperitoneal lymph node sampling for older patients with testicular masses. For ovarian masses, lymph nodes, and peritoneal washings for cytologic analysis. 

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Tumor Markers in GCTs 

Alpha-Fetoprotein (AFP) 

The highest rise is seen in yolk sac tumors. An intermediate rise is seen in embryonal carcinoma. Not elevated in seminomas and choriocarcinomas. 

Alpha-fetoprotein is not specific for germ cell tumors. It can be elevated in hepatoblastoma and even non-malignant conditions like hepatitis and maternal alpha-fetoprotein levels elevated in open types of neural tube defects.

Beta-HCG

Embryonal protein. The highest rise is seen in gestational trophoblastic neoplasm, known as choriocarcinoma.  Raised in embryonal carcinoma and malignant teratomas. 15% of seminomas will show modest elevation. Not elevated in yolk sac tumors. Beta HCG will be elevated in pregnancy and elevated in a tissue-injured state. 

Staging of GCTs

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Treatment of GCTs

Surgery: Complete excision is standard, except for intracranial tumors where chemotherapy and radiotherapy are combined. 

Testicular tumors: inguinal approach with complete resection of the spermatic cord; preoperative chemotherapy if excision is not possible. 

Ovarian tumors: Fertility-sparing surgery unless both ovaries are involved. 

Teratomas: Surgery alone is sufficient. 

Non-resectable GCTs: Cisplatin-based chemotherapy is curative, even in metastasis cases. 

Sex cord-stromal tumors: Often resistant to chemotherapy.

Prognosis

Cure rate > 80%. Histology has minimal impact; age is a key factor, with older age (>12 years) linked to poor outcomes. Non-resected extragonadal GCTs have a slightly worse prognosis.

Associations of GCTs 

Teratoma: linked to musculoskeletal anomalies, rectal stenosis, and congenital heart disease. 

Ovarian postpubertal dysgerminoma: Associated with amenorrhea and menorrhagia. 

Ovarian embryonal carcinoma: Linked to precocious puberty, amenorrhea, and hirsutism.

Gonadoblastoma 

Type of non-invasive germ cell neoplasia. can occur in the testis or ovary. It is commonly seen in the age group of 5–10 years. It can be bilateral in about 30% of cases. 

Associations 

Gonadal Dysgenesis. Mosaic Turner syndrome has a genotype of 45 XO / 46 XY. The presence of an aberrant extra Y chromosome mosaic is associated with an increased risk of developing gonadoblastoma. 

Problems Include

Contains malignant GCT elements. Produce abnormal amounts of estrogen. 

Treatment: bilateral gonadectomy. Potential MCQ scenario-based  Prophylactic gonadectomy should be done in patients with mosaic turners with 45 XO, or 46, XY. Even if gonadoblastoma is detected unilaterally, most have elements of gonadal dysgenesis, so bilateral gonadectomy is indicated.

Also read: High-Yield NEET SS Pediatric Oncology Questions

Teratomas 

Histological types of teratoma Histologically, they are categorized into three forms. Immature teratoma, in which the tissue is derived from all 3 germ layers. 

• Grade 1 immaturity with absent neuroepithelium or limited to 1 low magnification field. 
• Grade 2 immaturity with neuroepithelium seen in 1-3 low magnification fields. 
• Grade 3 immaturity with prominent neuroepithelium seen in ≥ 4 low-power magnification fields. 
• Prognosis is inversely related to grade. 
• Surgical resection alone is sufficient. 

Mature Teratoma

Mature tissue is derived from three germ layers. Contain elements: hair, bone, teeth, neuronal tissue, mucosal glands, etc. Requires only surgical resection. 

Teratoma with malignant germ cell elements. Contain foci of frankly malignant tissue like embryonal carcinoma, yolk sac tumor, or choriocarcinoma. need surgery with multimodal chemotherapy.

Sacrococcygeal Teratomas 

Most common teratoma, most common fetal tumor. Most common germ cell tumor in childhood. Females are affected more than males; most cases are present in infancy.

Clinical Presentation 

Mostly present as a large exophytic mass. Some may show associated congenital anomalies—musculoskeletal and central nervous systems. Massive tumors with CCF and hydrops fetalis due to AV shunting. 

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Staging And Grading of Sacrococcygeal Teratoma 

Surgical staging or Altman classification 

Categorizes teratoma into 4 types.

• In type 1, the external element is greater, with a small internal pelvic element. 
• In type 2, one large external element and an internal element extend into the pelvis, which is almost equal in size. 
• In type 3, teratoma's external and internal elements are present, but the internal or pelvic element is more massive than the external element. 
• In type 4, there is no external element. Only the internal pelvic element is present. 

Histologic Grading 

• In grade 1, all mature tissue, whereas no embryonal tissue. 
• In grade 2, rare foci of embryonal tissue up to 1 low-power magnification field (LPF). 
• In grade 3, moderate embryonic tissue and some atypia up to 3 LPF. 
• In grade 4, immature tissue >3 LPF with abundant mitoses and cellular atypia. 

The malignancy rate is < 10% in children below 2 months of age and > 50% in children older than 4 months. If the malignant elements are seen, they are almost always of Yolk Sac Tumour Type. 

AFP is not elevated in most benign lesions. Rise in AFP points to the development of malignancy.  Treatment of Sacrococcygeal teratoma—surgical excision—the entire coccyx is removed. The overall cure rate is 75–90%. In histologic grade 3 or elevated FP, postoperative chemotherapy is needed.

Also read: DM Medical Oncology Preparation for NEET SS 2023

Gonadal Non-Germ Line Tumours 

Very rare in pediatric patients; mostly ovarian>testicular. Arise from coelomic epithelium.

Types 

Non-GCTs of the ovary—epithelial (serous, mucinous) or sex cord-stromal tumors. Non-GCTs of the testes—sex cord-stromal tumors (Leydig and Sertoli cell). 

Clinical Manifestations

They produce a mass. They may associate with the production of hormones and thus often produce virilization, feminization, or precocious puberty. Usually, it has been found that the Sertoli cells will produce estrogen. Thus, feminization is happening, life Leydig cells are present, and testosterone is produced, leading to virilization. If both are present, then eventual results will depend on which is dominant. 

The treatment: surgical resection.

Hope you found this blog helpful for your NEET SS Pediatrics Oncology preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.