Mediastinal yolk sac tumours or yolk sac tumours of the mediastinum are malignant non-seminomatous germ cell tumours primarily growing in the mediastinum.
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Terminology
The term ‘endodermal sinus tumour’ is not recommended.
Epidemiology
Mediastinal yolk sac tumours are rare mediastinal tumours. In adults, they are almost only found in men with a peak incidence between 20 and 30 years of age and account for up to one-tenth of mediastinal germ cell tumours being less common than mediastinal seminomas, mixed germ cell tumours or mediastinal teratomas 1,2. In children, they are the most common malignant germ cell tumours almost ten times more common than in adults and mostly found in baby girls with a peak incidence at one year of age. They are rare after the age of six years 1.
Risk factors
Klinefelter syndrome is a considered risk factor 1,3.
Diagnosis
The final diagnosis is based on histology and immunohistochemistry 1.
Diagnostic criteria
Diagnostic criteria according to the WHO classification of thoracic tumours (2021 - blue book) 1:
- various histological patterns representing the yolk sac, allantois and extraembryonic mesenchyme
- usually multiple different growth patterns within a single tumour
Further desirable criteria are the following 1:
- Schiller-Duval bodies (might be absent)
- markedly elevated serum AFP
- coexpression of cytokeratins, SALL4, GPC3 and possibly AFP
- negative GATA3 and OCT4
Diagnostic clues
A large heterogeneous mediastinal mass with lung metastases on imaging in young men or children in the setting of rapid symptom onset and elevated serum AFP might indicate a non-seminomatous germ cell tumour.
Clinical presentation
Clinical signs and symptoms are frequently chest-related and include dyspnoea, chest pain and cough, systemic symptoms include weight loss, fever and haemoptysis 1-3. They might also present with superior vena cava syndrome or might be found incidentally on imaging studies 1. AFP is most commonly elevated 1. Β-hCG might be elevated 2.
Complications
Mediastinal yolk sac tumours might cause the following complications 1,2:
- superior vena cava obstruction
- infiltration of adjacent structures
- pericardial effusion
- pleural effusion
- nodal and distant metastases
Pathology
Mediastinal yolk sac tumours are non-seminomatous malignant germ cell tumours usually featuring different yolk sac specific histological patterns within a single tumour 1.
Pathogenesis
Primary mediastinal yolk sac tumours are associated with genetic alterations different in patients with mediastinal yolk sac tumours before or after the age of eight years 1.
Location
Mediastinal yolk sac tumours are usually located in the anterior or rarely in the posterior mediastinum 1.
Macroscopic appearance
Macroscopically, mediastinal yolk sac tumours have a pale white to grey colour with a mucoid to gelatinous appearance. Areas of necrosis and haemorrhage might be seen after neoadjuvant therapy 1,3.
Microscopic appearance
Microscopically mediastinal yolk sac tumours show different histological features and patterns 1,5:
- microcystic/reticular: cystic spaces lined by cuboidal, flat or columnar epithelium
- macrocytic
- glandular-alveolar
- endodermal sinus/pseudopapillary: Schiller-Duval bodies resembling primitive glomeruli
- myxomatous
- hepatoid
- enteric
- polyvesicular-vitelline
- solid
- spindle
Immunophenotype
Immunohistochemistry stains of mediastinal yolk sac tumours are usually positive for cytokeratins such as AE1 and/or AE3, GPC3 and SALL4 but usually do not express OCT4, SOX2 and D2-40 1. They variably express AFP, PLAP and KIT/CD117.
Radiographic features
Imaging features of mediastinal yolk sac tumours are unspecific mediastinal masses that might displace or infiltrate the adjacent structures or vessels 3-5.
CT
On thoracic CT mediastinal yolk sac have been described as lobulated, poorly marginated and heterogeneous masses 2.
Nuclear medicine
PET-CT displays high uptake of FDG and might be used to monitor therapy.
Radiology report
The radiological report should include a description of the following:
- location and extent of the tumour
- relation to the heart and great vessels
- associated complications (e.g. superior vena cava obstruction)
- nodal disease
- distant metastases
Treatment and prognosis
Management consists of chemotherapy with subsequent residual tumour mass excision 2,5.
In adults and adolescents older than 15 years non-seminomatous germ cell tumours have a poor prognosis with a 5-year overall survival rate of approximately 50% 1. Absence of distant metastasis, complete tumour necrosis after chemotherapy, low preoperative β-hCG, complete tumour resection and postoperative normalisation of tumour markers are beneficial prognostic factors 1. Children younger than 15 years with non-seminomatous germ cell tumours have a better prognosis with overall survival rates of up to 87%. Completeness of excision is the most important prognostic factor there and primary brain metastases in children carry a poor prognosis 1.
Differential diagnosis
Condition or tumours that might mimic the appearance of mediastinal yolk sac tumours include 1:
- lymphoma
- thymoma
- thymic carcinoma
- teratoma
- other germ cell tumours
- seminoma (typically positive for OCT4 and D2-40)
- embryonal carcinoma (typically positive for OCT4 and SOX2)
- choriocarcinoma
- metastatic carcinoma
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