Could aberrant migration explain metachronous germ cell tumors?

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.

the clinical, radiological, and molecular data (if available) of patients with metachronous GCT were analyzed.

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.

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.

Cancer investigation. 2020 Oct 05 [Epub ahead of print]

Pierre Kubicek, Tanguy Fenouil, Julien Jacquemus, Olivia Chapuis, Aude Fléchon, Cécile Dumesnil, Cécile Faure-Conter

Institut d'Hématologie et d'Oncologie Pédiatrique, 69008 Lyon, France., Hospices Civils de Lyon, Department of Pathology, Lyon, France., Centre Léon Bérard, 69008 Lyon, France., Department of Pathology, Mont-Blanc Pathologie, 74370 Argonay, France., Centre Hospitalier Universitaire, Department of Pediatric Oncology, 76000 Rouen, France.

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