Mediastinal yolk sac tumors or yolk sac tumors of the mediastinum are malignant non-seminomatous germ cell tumors primarily growing in the mediastinum.
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Terminology
The term ‘endodermal sinus tumor’ is not recommended.
Epidemiology
Mediastinal yolk sac tumors are rare mediastinal tumors. 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 tumors being less common than mediastinal seminomas, mixed germ cell tumors or mediastinal teratomas 1,2. In children, they are the most common malignant germ cell tumors 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 tumors (2021 - blue book) 1:
- various histological patterns representing the yolk sac, allantois and extraembryonic mesenchyme
- usually multiple different growth patterns within a single tumor
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 tumor.
Clinical presentation
Clinical signs and symptoms are frequently chest-related and include dyspnea, chest pain and cough, systemic symptoms include weight loss, fever and hemoptysis 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 tumors 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 tumors are non-seminomatous malignant germ cell tumors usually featuring different yolk sac specific histological patterns within a single tumor 1.
Pathogenesis
Primary mediastinal yolk sac tumors are associated with genetic alterations different in patients with mediastinal yolk sac tumors before or after the age of eight years 1.
Location
Mediastinal yolk sac tumors are usually located in the anterior or rarely in the posterior mediastinum 1.
Macroscopic appearance
Macroscopically, mediastinal yolk sac tumors have a pale white to grey color with a mucoid to gelatinous appearance. Areas of necrosis and hemorrhage might be seen after neoadjuvant therapy 1,3.
Microscopic appearance
Microscopically mediastinal yolk sac tumors 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 tumors 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 tumors 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 tumor
- 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 tumor mass excision 2,5.
In adults and adolescents older than 15 years non-seminomatous germ cell tumors have a poor prognosis with a 5-year overall survival rate of approximately 50% 1. Absence of distant metastasis, complete tumor necrosis after chemotherapy, low preoperative β-hCG, complete tumor resection and postoperative normalization of tumor markers are beneficial prognostic factors 1. Children younger than 15 years with non-seminomatous germ cell tumors 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 tumors that might mimic the appearance of mediastinal yolk sac tumors include 1:
- lymphoma
- thymoma
- thymic carcinoma
- teratoma
- other germ cell tumors
- seminoma (typically positive for OCT4 and D2-40)
- embryonal carcinoma (typically positive for OCT4 and SOX2)
- choriocarcinoma
- metastatic carcinoma
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