Extragonadal germ cell tumours

Key points

Pathophysiology

Germ cells: Haploid - 23 chromosomes

Somatic cells: 46 chromosomes

Germ cells originate from yolk sac and migrate from the caudal end to the primitive gonads, where they will eventually form gametes.

Errors in migration result in some cells being left at site along normal migration tract e.g. Sacrococcygeal teratoma, retroperitoneal, mediastinal, pineal glands

Germ cell tumours can occur at any of these sites, as well as in the gonads.

Categorisation of Germ cell tumours (GCT):

Teratomas:

Mature/Immature

Malignant GCT:

Seminomatous Germ Cell Tumours:

• Seminoma: Testicular

• Dysgerminoma: Ovarian

• Germinoma: Extragonadal

Nonseminomatous Germ Cell Tumours:

• Yolk sac tumour (endodermal sinus tumour): Extragonadal, Ovarian, Testicular

• Choriocarcinoma: Extragonadal, Ovarian, Testicular

• Embryonal carcinoma: Extragonadal, Testicular

• Gonadoblastoma: Associated with gonads in DSD

Mixed Germ Cell Tumours:

• Extragonadal, Ovarian, Testicular

Patients with chromosomal abnormalities e.g. DSD, Klinefelters are at increased risk

Standard scenario

Patient with extragonadal GCT

History

Onset of symptoms

Presence of syndrome

Family history

Examination

Mass

Gonads

Abdomen

Signs of virilisation/feminisation

Dysmorphic features

Investigations

Investigations and management as per CCLG extracranial GCT guideline

Bloods and tumour markers

aFP - produced by Yolk sac tumours

B HCG - βHCG by choriocarcinomas, some germinomas and embryonal carcinomas

Ultrasound of primary site

Chest X-Ray (CXR)

CT scan lungs

MRI/CT abdomen/pelvis

Bone scan if:

o Extensive metastatic disease

o Clinical concerns e.g. bone pain

o Choriocarcinoma

If mediastinal or ovarian primary, do constitutional chromosome analysis

Bone marrow (BM) aspirate if evidence of marrow involvement e.g. BM suppresion

CT/MRI brain if indicated by symptoms/signs or if HCG > 50,000 IU

Differentiate retroperitoneal tumours from Neuroblastomas

Management

Should always resect prior to chemotherapy unless unresectable

Biopsy if near vital structures to look for elements that are responsive to chemotherapy

Neoadjuvant chemotherapy if malignant features on biopsy - may ease resection

Growing teratoma syndrome - benign elements continue to enlarge during chemo

Aim for complete resection - even if organ resection needed

Mature/Immature (as long as benign) teratomas can be treated with resection and observation only

COG + CCLG staging - post op

I - Complete resection

II - Microscopic residual + LN negative

III - Gross residual

IV - Metastases

For all GCT including gonadal:

Low risk:

Stage 1 tumours with tumour markers that normalise

If tumour marker increase - then standard risk

Standard risk:

Stage 2-4 AND <11 years

4-6 cycles of Carboplatin, etoposide and bleomycin (JEB)

If age >11 years AND non-germinoma/seminoma - BEP (Cisplatin instead of carboplatin)

Outcome

Relapse free survival - 56% with incomplete resection, 96% with complete

Age >11 is independent risk factor for long term disease free survival

71% survival - mediastinal

87% 6 year survival - retroperitoneal

Special scenario - Cervical GCT

Pathophysiology

Thyroid has all 3 germ cell layers

Tumour arises from thyroid anlage

37% tumours contain thyroid tissue, can surround like pseudo capsule

Can involve thymus too

Exclusive to neonates

Immature or mature teratomas

20% malignant

Cervical mass detected on antenatal scan

Solid and cystic features are typical

Get MRI

Polyhydramnios - indicates airway obstruction - needs EXIT procedure

Hydrops - may need early delivery or foetal surgery

Foetal surgery has worse outcomes compared to neonatal

Look for pulmonary hypoplasia - seen in 25%

Differentials

• Lymphatic malformations

• Branchial cysts, thyroglossal cyst

• Haemangiomas

• Congenital goitre

Post natal investigations

aFP, BHCG, Thyroid function (most thyroid function will be normal)

Biopsy not necessary - diagnosis on imaging and bloods

USS + CT

Contrast swallow for oesophageal involvement

Management

If polyhydramnios = obstruction, likely will need EXIT procedure

Escalation at exit: Intubate - if not possible > Tracheostomy - if not possible > Resect at EXIT

Deliver early if hydrops

Operation:

Joint with experienced surgeon e.g. ENT

Tumour is deep to strap muscles

Preserve vital structures

May need hemithyroidectomy

Usually no need for adjuvant chemotherapy

Complications

Tracheomalacia

Follow up

Need thyroid function, calcium levels for 1 month

aFP + B HCG every 3-6 months for 2 years

Outcome

Usually good prognosis

Presence of Yolk Sac tumour elements has largest impact on recurrence and survival

Special scenario - Retroperitoneal mass

Differentials:

1. Neuroblastoma

2. Germ cell tumour

3. Rhabdomyosarcoma

History and examination for systemic features of above

Investigations

Tumour markers

Catecholamines

CT/MRI

Oncology MDT decision - likely biopsy

Management

GCT + RMS in the retroperitoneum will likely require neoadjuvant chemotherapy as opposed to usual upfront resection

Resection with experienced surgeon

Delineate Aorta and IVC first

References

CCLG Interim Guidelines for the Treatment of Extracranial Germ Cell Tumours in Children and Adolescents

June 2018

Naik-Mathuria, Bindi, et al. "Mediastinal Germ Cell Tumors." Pediatric Surgery NaT, American Pediatric Surgical Association, 2023. Pediatric Surgery Library, www.pedsurglibrary.com/apsa/view/Pediatric-Surgery-NaT/829790/all/Mediastinal_Germ_Cell_Tumors.

Dicken, Bryan J, et al. "Cervical Germ Cell Tumors." Pediatric Surgery NaT, American Pediatric Surgical Association, 2023. Pediatric Surgery Library, www.pedsurglibrary.com/apsa/view/Pediatric-Surgery-NaT/829791/all/Cervical_Germ_Cell_Tumors.

PDQ Pediatric Treatment Editorial Board. Childhood Extracranial Germ Cell Tumors Treatment (PDQ®): Health Professional Version. 2024 Apr 3. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002–. PMID: 26389316.