{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:50:30Z","timestamp":1776088230477,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Malignant germ cell tumors (GCTs) are rare but clinically significant neoplasms arising in gonadal and extragonadal sites. Malignant GCTs, divided into seminomatous and non-seminomatous subtypes, show diverse biological behavior. Although molecular studies have advanced understanding of their origins and genetic features, little is known about metastatic patterns due to their rarity and generally favorable outcomes. This study aimed to describe metastatic patterns of malignant GCTs across primary sites and histologic subtypes using population-based database. Materials and Methods: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) program for patients diagnosed with malignant GCTs between 2010 and 2022. Cases were stratified by primary site (testis, ovary, mediastinum), age group (&lt;8 years vs. \u22658 years), and histologic subtype. Metastatic patterns were assessed using both overall and organotropic metastasis rates, and differences between groups were evaluated descriptively using appropriate statistical tests. Results: A total of 32,015 malignant GCTs were identified, comprising 93.0% testicular, 5.6% ovarian, and 1.4% mediastinal tumors. In patients aged \u22658 years, ovarian tumors tended to show generally lower lymph node and distant metastasis rates. In contrast, mediastinal tumors appeared to have the highest distant metastasis rates. Organotropic analysis suggested distinct subtype- and site-specific differences. For seminoma\/dysgerminoma, the organotropic metastasis pattern was generally consistent across different primary sites, whereas the other subtypes showed variable organotropic metastasis rates depending on the primary site. Conclusions: The metastatic patterns of GCTs appear to differ by histologic subtype and primary site. These findings suggest that both subtype and site of origin should be considered when assessing metastatic risk and may provide a framework for improved risk stratification in clinical practice.<\/jats:p>","DOI":"10.3390\/medicina61111990","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T17:06:06Z","timestamp":1762362366000},"page":"1990","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metastatic Patterns of Malignant Germ Cell Tumors Vary by Histologic Subtype and Primary Site"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5972-3516","authenticated-orcid":false,"given":"Hyung Kyu","family":"Park","sequence":"first","affiliation":[{"name":"Department of Pathology, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/s41568-019-0178-9","article-title":"Human Germ Cell Tumours from a Developmental Perspective","volume":"19","author":"Oosterhuis","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Nogales, F.F., and Jimenez, R.E. (2017). Pathology and Biology of Human Germ Cell Tumors, Springer. [1st ed.].","DOI":"10.1007\/978-3-662-53775-6"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4717","DOI":"10.3390\/curroncol29070374","article-title":"Neuroendocrine Tumor Arising within Mature Cystic Teratoma of the Pancreas: Literature Review and Case Report","volume":"29","author":"Djokic","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/ijc.33999","article-title":"Global Patterns in Testicular Cancer Incidence and Mortality in 2020","volume":"151","author":"Znaor","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yildiran Keskin, G.S., Yetginoglu, O., Vurgun, S., Guzel, E.Z., Ozkan, F.E., Yilmaz, M., Soylemez, C.M., Agyol, Y., Akbas, S., and Sagiroglu, M.F. (2025). Survival Outcomes in Metastatic Germ Cell Tumors: A Multicenter Study from Turkey. Medicina, 61.","DOI":"10.3390\/medicina61060951"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jss.2009.03.069","article-title":"A Population-Based Analysis of 1037 Malignant Ovarian Tumors in the Pediatric Population","volume":"156","author":"Brookfield","year":"2009","journal-title":"J. Surg. Res."},{"key":"ref_7","unstructured":"WHO Classification of Tumours Editorial Board (2022). Urinary and Male Genital Tumours, International Agency for Research on Cancer. [5th ed.]."},{"key":"ref_8","unstructured":"WHO Classification of Tumours Editorial Board (2020). Female Genital Tumours, International Agency for Research on Cancer. [5th ed.]."},{"key":"ref_9","unstructured":"WHO Classification of Tumours Editorial Board (2021). Thoracic Tumours, International Agency for Research on Cancer. [5th ed.]."},{"key":"ref_10","first-page":"iv1","article-title":"Non-Epithelial Ovarian Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"29","author":"Morice","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.annonc.2022.01.002","article-title":"Testicular Seminoma and Non-Seminoma: ESMO-EURACAN Clinical Practice Guideline for Diagnosis, Treatment and Follow-Up","volume":"33","author":"Oldenburg","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Garc\u00eda Rojo, E., Giannarini, G., Garc\u00eda G\u00f3mez, B., Feltes Ochoa, J.A., Guerrero Ramos, F., Alonso Isa, M., Brime Menendez, R., Saenz Calzada, D.M., Justo Quintas, J., and Fraile, A. (2023). Organ-Sparing Surgery for Testicular Germ Cell Tumors: A Current Perspective. Medicina, 59.","DOI":"10.3390\/medicina59071249"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/gcc.10244","article-title":"High-Resolution Comparative Genomic Hybridization Detects Extra Chromosome Arm 12p Material in Most Cases of Carcinoma in Situ Adjacent to Overt Germ Cell Tumors, but Not before the Invasive Tumor Development","volume":"38","author":"Ottesen","year":"2003","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tatanis, V., Veroutis, D., Pantelis, P., Theocharous, G., Sarlanis, H., Georgiou, A., Mulita, F., Peteinaris, A., Natsos, A., and Moulavasilis, N. (2024). Cellular Senescence in Germ Cell Neoplasia in Situ (GCNIS) and Other Histological Types of Testicular Cancer. Medicina, 60.","DOI":"10.3390\/medicina60071108"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/nrc1568","article-title":"Testicular Germ-Cell Tumours in a Broader Perspective","volume":"5","author":"Oosterhuis","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1210\/er.2012-1045","article-title":"Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison with Testicular Counterparts: Implications for Pathogenesis","volume":"34","author":"Kraggerud","year":"2013","journal-title":"Endocr. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pinto, M.T., Eiras Martins, G., Vieira, A.G.S., Galv\u00e3o, J.M.S., de P\u00e1dua Souza, C., Macedo, C.R.P.D., and Lopes, L.F. (2023). Molecular Biology of Pediatric and Adult Ovarian Germ Cell Tumors: A Review. Cancers, 15.","DOI":"10.3390\/cancers15112990"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/gcc.10053","article-title":"Genetic Analysis of Mediastinal Nonseminomatous Germ Cell Tumors in Children and Adolescents: Analysis of Mediastinal Germ Cell Tumors","volume":"34","author":"Schneider","year":"2002","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1093\/biolre\/ioab052","article-title":"Whole-Exome Sequencing Reveals Potential Germline and Somatic Mutations in 60 Malignant Ovarian Germ Cell Tumors","volume":"105","author":"Chen","year":"2021","journal-title":"Biol. Reprod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/modpathol.3800596","article-title":"Analysis of Ovarian Teratomas for Isochromosome 12p: Evidence Supporting a Dual Histogenetic Pathway for Teratomatous Elements","volume":"19","author":"Poulos","year":"2006","journal-title":"Mod. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gille, R., Allignet, B., Izarn, F., Peyrat, P., Boyle, H., and Fl\u00e9chon, A. (2024). Bone Metastases in Non-Seminomatous Germ Cell Tumors: A 20-Year Retrospective Analysis. J. Clin. Med., 13.","DOI":"10.3390\/jcm13113280"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/joim.13778","article-title":"Malignant Ovarian and Testicular Germ Cell Tumors: Common Characteristics but Different Prognoses","volume":"295","author":"Jansson","year":"2024","journal-title":"J. Intern. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1038\/sj.bjc.6603014","article-title":"Late Recurrences of Germ Cell Malignancies: A Population-Based Experience over Three Decades","volume":"94","author":"Oldenburg","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_24","unstructured":"Surveillance Research Program, National Cancer Institute (2025, August 05). SEER*Stat Software, Version 9.0.41.4, Available online: www.seer.cancer.gov\/seerstat."},{"key":"ref_25","unstructured":"Surveillance, Epidemiology, and End Results (SEER) Program (2025, August 16). SEER*Stat Database: Incidence\u2014SEER Research Data, 17 Registries, Nov 2024 Sub (2000\u20132022), National Cancer Institute, DCCPS, Surveillance Research Program, Released April 2025, Based on the November 2024 Submission, Available online: www.seer.cancer.gov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1034\/j.1600-0463.2003.1110119_1.x","article-title":"Germ Cell Tumours in Neonates and Infants: A Distinct Subgroup?","volume":"111","author":"Veltman","year":"2003","journal-title":"APMIS"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Park, H.K. (2023). The Metastasis Pattern of Renal Cell Carcinoma Is Influenced by Histologic Subtype, Grade, and Sarcomatoid Differentiation. Medicina, 59.","DOI":"10.3390\/medicina59101845"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9078","DOI":"10.3390\/curroncol30100656","article-title":"Do Histology and Primary Tumor Location Influence Metastatic Patterns in Bladder Cancer?","volume":"30","author":"Park","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ygyno.2008.04.022","article-title":"The Prevalence and Prognostic Impact of Lymph Node Metastasis in Malignant Germ Cell Tumors of the Ovary","volume":"110","author":"Kumar","year":"2008","journal-title":"Gynecol. Oncol."},{"key":"ref_30","first-page":"4458","article-title":"Clinical Outcome of Lymphadenectomy in Malignant Ovarian Germ Cell Tumors: A Systematic Review and Meta-Analysis","volume":"12","author":"Han","year":"2022","journal-title":"Am. J. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"International Germ Cell Cancer Collaborative Group (1997). International Germ Cell Consensus Classification: A Prognostic Factor-Based Staging System for Metastatic Germ Cell Cancers. J. Clin. Oncol., 15, 594\u2013603.","DOI":"10.1200\/JCO.1997.15.2.594"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101670","DOI":"10.1016\/j.ijgc.2025.101670","article-title":"Controversies in Malignant Ovarian Germ Cell Tumors","volume":"35","author":"Seckl","year":"2025","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/bjc.2011.267","article-title":"Prognostic Impact of Lymphadenectomy in Clinically Early Stage Malignant Germ Cell Tumour of the Ovary","volume":"105","author":"Mahdi","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.3802\/jgo.2025.36.e108","article-title":"Malignant Germ Cells Tumor of the Ovary","volume":"36","author":"Amant","year":"2025","journal-title":"J. Gynecol. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1097\/IGC.0b013e3182236582","article-title":"Outcome and Risk Factors for Recurrence in Malignant Ovarian Germ Cell Tumors: A MITO-9 Retrospective Study","volume":"21","author":"Mangili","year":"2011","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ygyno.2022.12.022","article-title":"Predicting Outcomes in Female Germ Cell Tumors Using a Modified International Germ Cell Cancer Collaborative Group Classification System to Guide Management","volume":"170","author":"Liu","year":"2023","journal-title":"Gynecol. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1200\/JCO.2007.10.8738","article-title":"Management of Ovarian Germ Cell Tumors","volume":"25","author":"Gershenson","year":"2007","journal-title":"J. Clin. Oncol."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/11\/1990\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T05:32:07Z","timestamp":1762493527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/11\/1990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,5]]},"references-count":37,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["medicina61111990"],"URL":"https:\/\/doi.org\/10.3390\/medicina61111990","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,5]]}}}