Abstract
Introduction
Germ cell tumors (GCTs) are uncommon neoplasms predominantly arising in midline tissues. The prognostic significance of histopathology in predicting metastatic GCT behavior is poorly understood.
Methods
Multicenter international cohort study including 29 patients with GCTs metastatic to brain were retrospectively investigated (18 patients from Mayo Clinic and 11 patients from the intracranial germ cell tumor genome analysis consortium in Japan). Clinical characteristics were analyzed using the Chi-square test (two-tailed) for categorical variables and using the log-rank test for survival data.
Results
Median age at treatment was 31 years (range 14–58). Primary disease sites were testis (71%), mediastinum (18%), and female reproductive organs (11%). Median metastatic interval was 223 days (range, 6–6124). Median follow-up was 346 days (range, 1–5356), with 16 deaths (57%) occurring after the median overall survival of 455 days. Actuarial one-year survival was 51%; 12-of-16 deaths (75%) were attributed to intracranial disease. Appearance of the same GCT subtype at the metastatic site as the primary was high for non-seminomatous GCT (NSGCT, 64–100%), but low for seminoma/dysgerminoma and mature teratoma (MT, 14, 17%, respectively). Gain of a new component was seen in 4 (20%)—3 of which included embryonal carcinoma (EC) at the primary site (75%). Incidence of cases without seminoma/dysgerminoma increased significantly after metastasis (p = 0.02). Metastatic interval was shorter in cases with histological change (199 vs 454 days, p = 0.009). Overall survival was associated with MT primary histopathology (p = 0.02).
Conclusion
Histological differentiation at the primary GCT site influences metastatic prognosis. Aggressive behavior is associated with NSGCT, while EC frequently demonstrates multi-directional histological differentiation after brain metastasis, and such histological dynamism is associated with shorter metastatic interval. Most metastases occurred within one year of diagnosis, emphasizing the need for close surveillance in newly diagnosed extra-cranial GCT.
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HT, CSG, AP and DJD have designed the study and analyzed the data. All the authors (HT, CSG, AP, MO, JI, CG, YN, YN, NS, RN, MM, KI and DJD) have contributed to the interpretation of the data, the writing of the manuscript and approved the final version of the manuscript.
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All pertinent aspects of the study were approved by the Institutional Review Boards of all involved facilities and organizing bodies, including provision of an informed consent waiver for what was deemed a minimal-risk retrospective review.
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Takami, H., Graffeo, C.S., Perry, A. et al. Histopathology and prognosis of germ cell tumors metastatic to brain: cohort study. J Neurooncol 154, 121–130 (2021). https://doi.org/10.1007/s11060-021-03810-x
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DOI: https://doi.org/10.1007/s11060-021-03810-x