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Histopathology and prognosis of germ cell tumors metastatic to brain: cohort study

  • Clinical Study
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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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Data availability

All data pertaining to this research article are included within the manuscript and the table as written.

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Authors and Affiliations

  1. Department of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA

    Hirokazu Takami, Christopher S. Graffeo, Avital Perry & David J. Daniels

  2. Laboratory Medicine and Pathology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA

    Caterina Giannini

  3. Division of Brain Tumor Translational Research, National Cancer Center, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Hirokazu Takami & Koichi Ichimura

  4. Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Hirokazu Takami & Nobuhito Saito

  5. Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Makoto Ohno & Yoshitaka Narita

  6. Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan

    Joji Ishida

  7. Department of Pathology, Hidaka Hospital, 886, Nakaomachi, Takasaki-shi, Gunma, 370-0001, Japan

    Yoichi Nakazato

  8. Department of Neuro-Oncology/Neurosurgery, Saitama Medical University Internationanl Medical Center, 1397-1, Yamane, Hidaka-shi, Saitama, 350-1298, Japan

    Ryo Nishikawa & Masao Matsutani

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  1. Hirokazu Takami
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  2. Christopher S. Graffeo
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  7. Yoshitaka Narita
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  13. David J. Daniels
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Contributions

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.

Corresponding authors

Correspondence to Hirokazu Takami or David J. Daniels.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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

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