Klinefelter syndrome and germ cell tumors: review of the literature

Kimberley Bonouvrie; Jutte van der Werff Ten Bosch; Machiel van den Akker

doi:10.1186/s13633-020-00088-0

Klinefelter syndrome and germ cell tumors: review of the literature

Int J Pediatr Endocrinol. 2020:2020:18. doi: 10.1186/s13633-020-00088-0. Epub 2020 Sep 30.

Authors

Kimberley Bonouvrie^{1

2}, Jutte van der Werff Ten Bosch^{2

3}, Machiel van den Akker^{2

3}

Affiliations

¹ Department of Pediatrics, Maxima Medisch Centrum, Veldhoven, The Netherlands.
² Department of Pediatrics, ZNA Queen Paola Children's Hospital, Lindendreef 1, 2020 Antwerp, Belgium.
³ Department of Pediatric Hematology and Oncology, University Hospital Brussel, Brussels, Belgium.

Abstract

Objective: The most common presentation of Klinefelter syndrome (KS) is infertility and features of hypogonadism. Currently no consensus exists on the risk of malignancy in this syndrome. Several case reports show an incidence of extragonadal germ cells tumors (eGCT) of 1.5 per 1000 KS patients (OR 50 against healthy population). Malignant germ cell tumors are rare in children. They account for 3% of all children cancers. Young patients with a germ cell tumor are not routinely tested for Klinefelter syndrome. This can therefore result in underdiagnosing. Literature data suggest a correlation between eGCT and KS. To the best of our knowledge there is no precise description of the primary locations of germ cell tumors in KS patients. The purpose of this study is to evaluate age groups and primary locations of extragonadal germ cell tumors in Klinefelter patients. With this data we investigate whether it is necessary to perform a cytogenetic analysis for KS in every eGCT patient.

Study design: This study is based on case report publications in PubMed/Medline published until march 2020 that described "Klinefelter Syndrome (MeSH) AND/OR extragonadal germ cell tumors". Publications were included when patients age, location and histology of the germ cell tumor was known. Two double blinded reviewers selected the studies.Results: 141 KS patients with eGCTs were identified. Mean age at presentation was 17.3 years (StDev + - 10.2). In contrast to the extragonadal germ cell tumors in adults, most eGCT in children were mediastinal or in the central nervous system (respectively 90/141; 64% and 23/141; 16% of all tumors). Distribution of histologic subtypes showed that the largest fraction represented a teratoma, mixed-type-non-seminomateus GCT and germinoma, respectively 34/141; 24%, 26/141; 18% and 20/141; 14% of all tumors.

Conclusion: These data suggest a correlation between primary extragonadal germ cell tumors and Klinefelter syndrome. There appears to be an indication for screening on KS in young patients with an eGCT in the mediastinum. A low threshold for radiologic examinations should be considered to discover eGCT. We emphasize the need for genetic analysis in all cases of a male with a mediastinal germ cell tumor for the underdiagnosed Klinefelter syndrome.

Keywords: Extragonadal germ cell tumor malignancy; Incidence analysis; Klinefelter syndrome.

Publication types

Review