Histopathology and prognosis of germ cell tumors metastatic to brain: cohort study
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...
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| Veröffentlicht in: | Journal of neuro-oncology 2021-08, Vol.154 (1), p.121-130 |
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| creator | Takami, Hirokazu Graffeo, Christopher S. Perry, Avital Ohno, Makoto Ishida, Joji Giannini, Caterina Narita, Yoshitaka Nakazato, Yoichi Saito, Nobuhito Nishikawa, Ryo Matsutani, Masao Ichimura, Koichi Daniels, David J. |
| description | 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. |
| doi_str_mv | 10.1007/s11060-021-03810-x |
| format | Article |
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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.</description><identifier>ISSN: 0167-594X</identifier><identifier>EISSN: 1573-7373</identifier><identifier>DOI: 10.1007/s11060-021-03810-x</identifier><identifier>PMID: 34272633</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adolescent ; Adult ; Brain cancer ; Brain Neoplasms - secondary ; Brain tumors ; Clinical Study ; Cohort analysis ; Cohort Studies ; Female ; Genomes ; Histopathology ; Humans ; Male ; Mediastinum ; Medical prognosis ; Medicine ; Medicine & Public Health ; Metastases ; Metastasis ; Middle Aged ; Neoplasia ; Neoplasms, Germ Cell and Embryonal - pathology ; Neurology ; Oncology ; Patients ; Prognosis ; Reproductive organs ; Seminoma ; Teratoma ; Tumors ; Young Adult</subject><ispartof>Journal of neuro-oncology, 2021-08, Vol.154 (1), p.121-130</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-6bb91425492168eda0fff78d995f36fab1dee13adea994e6298093cc3b0c394b3</citedby><cites>FETCH-LOGICAL-c441t-6bb91425492168eda0fff78d995f36fab1dee13adea994e6298093cc3b0c394b3</cites><orcidid>0000-0001-9742-7462</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11060-021-03810-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11060-021-03810-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34272633$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takami, Hirokazu</creatorcontrib><creatorcontrib>Graffeo, Christopher S.</creatorcontrib><creatorcontrib>Perry, Avital</creatorcontrib><creatorcontrib>Ohno, Makoto</creatorcontrib><creatorcontrib>Ishida, Joji</creatorcontrib><creatorcontrib>Giannini, Caterina</creatorcontrib><creatorcontrib>Narita, Yoshitaka</creatorcontrib><creatorcontrib>Nakazato, Yoichi</creatorcontrib><creatorcontrib>Saito, Nobuhito</creatorcontrib><creatorcontrib>Nishikawa, Ryo</creatorcontrib><creatorcontrib>Matsutani, Masao</creatorcontrib><creatorcontrib>Ichimura, Koichi</creatorcontrib><creatorcontrib>Daniels, David J.</creatorcontrib><title>Histopathology and prognosis of germ cell tumors metastatic to brain: cohort study</title><title>Journal of neuro-oncology</title><addtitle>J Neurooncol</addtitle><addtitle>J Neurooncol</addtitle><description>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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - secondary</subject><subject>Brain tumors</subject><subject>Clinical Study</subject><subject>Cohort analysis</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Genomes</subject><subject>Histopathology</subject><subject>Humans</subject><subject>Male</subject><subject>Mediastinum</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Neoplasia</subject><subject>Neoplasms, Germ Cell and Embryonal - pathology</subject><subject>Neurology</subject><subject>Oncology</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Reproductive organs</subject><subject>Seminoma</subject><subject>Teratoma</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>0167-594X</issn><issn>1573-7373</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kE1LwzAYx4Mobk6_gAcJeI4mTZo03mSoEwaCKHgLaZtsHW0zkxS2b2-0vtw8PYfn__I8PwDOCb4iGIvrQAjmGOGMIEwLgtHuAExJLigSVNBDMMWEC5RL9jYBJyFsMMZMUHIMJpRlIuOUTsHzognRbXVcu9at9lD3Ndx6t-pdaAJ0Fq6M72Bl2hbGoXM-wM5EHaKOTQWjg6XXTX8DK7d2PsIQh3p_Co6sboM5-54z8Hp_9zJfoOXTw-P8dokqxkhEvCwlYVnOZEZ4YWqNrbWiqKXMLeVWl6Q2hlBdGy0lMzyTBZa0qmiJKypZSWfgcsxN974PJkS1cYPvU6XKcp5eF0TQpMpGVeVdCN5YtfVNp_1eEaw-MaoRo0oY1RdGtUumi-_ooexM_Wv54ZYEdBSEtOoTo7_uf2I_AA9Hft8</recordid><startdate>20210801</startdate><enddate>20210801</enddate><creator>Takami, Hirokazu</creator><creator>Graffeo, Christopher S.</creator><creator>Perry, Avital</creator><creator>Ohno, Makoto</creator><creator>Ishida, Joji</creator><creator>Giannini, Caterina</creator><creator>Narita, Yoshitaka</creator><creator>Nakazato, Yoichi</creator><creator>Saito, Nobuhito</creator><creator>Nishikawa, Ryo</creator><creator>Matsutani, Masao</creator><creator>Ichimura, Koichi</creator><creator>Daniels, David J.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><orcidid>https://orcid.org/0000-0001-9742-7462</orcidid></search><sort><creationdate>20210801</creationdate><title>Histopathology and prognosis of germ cell tumors metastatic to brain: cohort study</title><author>Takami, Hirokazu ; Graffeo, Christopher S. ; Perry, Avital ; Ohno, Makoto ; Ishida, Joji ; Giannini, Caterina ; Narita, Yoshitaka ; Nakazato, Yoichi ; Saito, Nobuhito ; Nishikawa, Ryo ; Matsutani, Masao ; Ichimura, Koichi ; Daniels, David J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-6bb91425492168eda0fff78d995f36fab1dee13adea994e6298093cc3b0c394b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - secondary</topic><topic>Brain tumors</topic><topic>Clinical Study</topic><topic>Cohort analysis</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>Genomes</topic><topic>Histopathology</topic><topic>Humans</topic><topic>Male</topic><topic>Mediastinum</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Neoplasia</topic><topic>Neoplasms, Germ Cell and Embryonal - pathology</topic><topic>Neurology</topic><topic>Oncology</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Reproductive organs</topic><topic>Seminoma</topic><topic>Teratoma</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takami, Hirokazu</creatorcontrib><creatorcontrib>Graffeo, Christopher S.</creatorcontrib><creatorcontrib>Perry, Avital</creatorcontrib><creatorcontrib>Ohno, Makoto</creatorcontrib><creatorcontrib>Ishida, Joji</creatorcontrib><creatorcontrib>Giannini, Caterina</creatorcontrib><creatorcontrib>Narita, Yoshitaka</creatorcontrib><creatorcontrib>Nakazato, Yoichi</creatorcontrib><creatorcontrib>Saito, Nobuhito</creatorcontrib><creatorcontrib>Nishikawa, Ryo</creatorcontrib><creatorcontrib>Matsutani, Masao</creatorcontrib><creatorcontrib>Ichimura, Koichi</creatorcontrib><creatorcontrib>Daniels, David J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Journal of neuro-oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takami, Hirokazu</au><au>Graffeo, Christopher S.</au><au>Perry, Avital</au><au>Ohno, Makoto</au><au>Ishida, Joji</au><au>Giannini, Caterina</au><au>Narita, Yoshitaka</au><au>Nakazato, Yoichi</au><au>Saito, Nobuhito</au><au>Nishikawa, Ryo</au><au>Matsutani, Masao</au><au>Ichimura, Koichi</au><au>Daniels, David J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Histopathology and prognosis of germ cell tumors metastatic to brain: cohort study</atitle><jtitle>Journal of neuro-oncology</jtitle><stitle>J Neurooncol</stitle><addtitle>J Neurooncol</addtitle><date>2021-08-01</date><risdate>2021</risdate><volume>154</volume><issue>1</issue><spage>121</spage><epage>130</epage><pages>121-130</pages><issn>0167-594X</issn><eissn>1573-7373</eissn><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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>34272633</pmid><doi>10.1007/s11060-021-03810-x</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-9742-7462</orcidid></addata></record> |
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| subjects | Adolescent Adult Brain cancer Brain Neoplasms - secondary Brain tumors Clinical Study Cohort analysis Cohort Studies Female Genomes Histopathology Humans Male Mediastinum Medical prognosis Medicine Medicine & Public Health Metastases Metastasis Middle Aged Neoplasia Neoplasms, Germ Cell and Embryonal - pathology Neurology Oncology Patients Prognosis Reproductive organs Seminoma Teratoma Tumors Young Adult |
| title | Histopathology and prognosis of germ cell tumors metastatic to brain: cohort study |
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