Primary mediastinal germ cell tumours: an immunohistochemical and molecular diagnostic approach

Aims Primary mediastinal germ cell tumours (PMGCTs) are rare mediastinal neoplasms and their diagnosis can be challenging due to small biopsy samples. The aim of this study was to elaborate a diagnostic algorithm using immunohistochemical stainings with focus on novel markers and molecular analysis of isochromosome 12p [i(12p)]. Methods and results Paraffin-embedded tissues of 32 mediastinal tumours were analysed using immunohistochemical stainings for SALL4, LIN28, OCT3/4, D2-40, CD117, SOX17, SOX2, CD30, s-hCG, GATA3, FOXA2, GPC3, AFP, TdT, NUT and pan-cytokeratin. Quantitative real-time polymerase chain reaction (qPCR) was performed to investigate i(12p) status. Fifteen seminomas, seven teratomas, one yolk sac tumour, one choriocarcinoma and seven mixed PMGCT were diagnosed. Each entity had different immunohistochemical staining patterns which helped to distinguish them: seminoma (OCT3/4, D2-40, CD117, TdT), embryonal carcinoma (OCT3/4, SOX2), yolk sac tumour (FOXA2, GPC3, AFP) and choriocarcinoma (s-hCG, GATA3). Mature teratomas stained positive for pan-cytokeratin in epithelial components and focally for SALL4, SOX2, GATA3, D2-40 and FOXA2. Furthermore, a NUT carcinoma mimicking a PMGCT was diagnosed showing a strong nuclear SOX2 and speckled nuclear NUT staining. i(12p) was detected in 24 out of 27 PMGCTs [89%]. Conclusion A diagnostic algorithm is of great importance for a reliable diagnosis of PMGCTs in the usually small tissue biopsy samples. Therefore, a combination of three to four antibodies to identify the correct histological subtype is usually necessary in addition to morphological features. The i(12p) status serves as an additional option to underline germ cell origin in selected cases.