Could Aberrant Migration Explain Metachronous Germ Cell Tumors?. (7th February 2021)

• Record Type: Journal Article
• Authors: Kubicek, Pierre; Fenouil, Tanguy; Jacquemus, Julien; Chapuis, Olivia; Fléchon, Aude; Dumesnil, Cécile; Faure-Conter, Cécile
• Is Part Of: Cancer investigation. Volume 39:Number 2(2021)
• Page Start: 195
• Page End: 201
• Publication Date: 2021-02-07
• Subjects: Metachronous -- germinoma -- nonseminomatous germ cell tumors -- primordial gonadal cells -- migration; Cancer -- Periodicals; Oncology -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- Periodicals; 616.994
• DOI: 10.1080/07357907.2020.1828447
• Languages: English
• ISSNs: 0735-7907

Abstract

Abstract: Background: Extragonadal germ cell tumors (GCTs) are thought to arise as a result of local transformation of primordial gonadal cells (PGCs) that become misplaced during embryogenesis. With the exception of bilateral testis tumors, metachronous GCT (i.e., occurring at a site classically described for primary GCTs) are rare events. Patients and Methods: The clinical, radiological, and molecular data (if available) of patients with metachronous GCT were analyzed. Results: Three Caucasian males were identified: case 1 presented with a pineal germinoma 19 years after a mediastinal seminoma that had been treated with chemotherapy, case 2 presented with a pineal non-seminomatous GCT (NSGCT) that occurred three years after a mediastinal seminoma treated with chemotherapy, and case 3 presented with a mediastinal seminoma concomitant with a suprasellar germinoma that occurred two years after a stage I testicular NSGCT treated exclusively with surgery. None of these patients had a positive family history or disorder of sex development. Molecular data were available for cases 2 and 3. In case 2, a CHEK2 gene biallelic inactivation in the second tumor suggested chemoresistance to cisplatin. This was further confirmed by tumor progression during second-line treatment. In case 3, the molecular analysis revealed different profiles in the three tumors, thus suggesting distinct tumor cell origins. Conclusion: These rare cases should alert clinicians of the possibility of multiple GCTs that should not be considered to be relapses. The underlying physiopathology is unknown, but multiple PGC mismigrations is a likely cause. Initial treatment with cisplatin may select chemo-resistant clones, thereby making the subsequent treatment more of a challenge.