{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T03:13:14Z","timestamp":1787800394503,"version":"build-2784847793"},"reference-count":20,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background and case: An adolescent male presented with a second mediastinal tumor 1.5 years after treatment of a proven malignant germ-cell tumor in that location. The differential diagnosis included a recurrent germ-cell tumor or a non-germ cell malignancy. Serum tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) were negative. The first biopsy was not informative, and the second biopsy gave a broad differential diagnosis including secondary non-germ cell malignancy using histology and immunohistochemistry. DNA methylation profiling, RNA sequencing, and targeted microRNA371a-3p profiling was subsequently performed, without a supportive result. After resection of the tumor the definitive diagnosis yielded two secondary non-germ cell malignancies in the form of a leiomyosarcoma and a solitary neuro endocrine carcinoma (NEC). In spite of the differences between the molecular profiles of the initial germ-cell tumor, the leiomyosarcoma and large-cell NEC are clonally related, as determined by the presence of identical chromosomal breakpoints. The copy number profiles suggest an initial polyploidization step, followed by various independent chromosomal gains and losses. This case demonstrates that germ-cell tumors must be evaluated carefully, including molecularly, in which the non-germ cell malignancy is negative for miR-371a-3p, both in tissue as well as in serum, in contrast to the primary tumor. We conclude that the patient presented with a primary type II mediastinal GCT and, a year and a half later, followed by a leiomyosarcoma and a large-cell NEC presenting as two secondary somatic-type malignancies clonally related to the original GCT. Conclusions: Malignant germ-cell tumors are known to recur as a somatic-type malignancy in very rare cases. This case report illustrates the challenges faced in defining the nature and clonality of the secondary somatic-type malignancies.<\/jats:p>","DOI":"10.3390\/ijms22179310","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T09:53:23Z","timestamp":1630058003000},"page":"9310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Recurrence of a Mediastinal Germ-Cell Tumor as a Somatic-Type Malignancy: A Complex Case Report"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7497-9501","authenticated-orcid":false,"given":"Caroline C. C.","family":"Hulsker","sequence":"first","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00ebtte E. G.","family":"Kranendonk","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands"},{"name":"Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8580-4822","authenticated-orcid":false,"given":"Thomas F.","family":"Eleveld","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad J. M.","family":"Gillis","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis P.","family":"van de Ven","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0526-3737","authenticated-orcid":false,"given":"Natasha K. 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