title: Leydig cell tumor in a patient with 49,XXXXY karyotype: a review of literature.
abstract: 49,XXXXY pentasomy or Fraccaro's syndrome is the most severe variant of Klinefelter's syndrome (KS) affecting about 1/85000 male births. The classical presentation is the triad: mental retardation, hypergonadotropic hypogonadism and radio ulnar synostosis. Indeed, the reproductive function of Fraccaro's syndrome is distinguished from KS. Besides, Leydig cell tumors are described in cases of KS, but never documented in the Klinefelter variants.We describe a young adult of 22 years old who presented with hyper gonadotropic hypogonadism, delayed puberty and bilateral micro-cryptorchidism. Chromosomal pentasomy was confirmed since infancy. Bilateral orchidectomy revealed a unilateral well-circumscribed Leydig cell tumor associated with bilateral Leydig cell hyperplasia.Inspired from reporting the first case of Leydig cell tumor in a 49,XXXXY patient, we summarize the particularities of testicular function in 49,XXXXY from one side, and the risk and mechanisms of Leydig cell tumorigenesis in Klinefelter variants on the other side. The histological destructions in 49,XXXXY testes and hypogonadism are more profound than in Klinefelter patients, with early Sertoli, Leydig and germ cell destruction. Furthermore, the risk of Leydigioma development in KS and its variants remains a dilemma. We believe that the risk of Leydigioma is much higher in KS than the general population. By contrast, the risk could be lower in the Klinefelter variants with more than 3 supplementary X chromosomes, owing to an earlier and more profound destruction of Leydig cells rendering them irresponsive to chronic Luteinizing hormone (LH) stimulation.
authors.affiliation: Service d'endocrinologie, diabétologie et maladies métaboliques, CHU Clermont-Ferrand, F-63003, Clermont-Ferrand, France. smaqdasy@chu-clermontferrand.fr.|UMR CNRS 6293, INSERM U1103, Université Clermont-Auvergne, Génétique Reproduction et Développement, BP 10448, 63177, Aubiere, France. smaqdasy@chu-clermontferrand.fr.|Service de Médecine Nucléaire, Centre Jean Perrin, 58 rue Montalembert, F-63011, Clermont-Ferrand, France. smaqdasy@chu-clermontferrand.fr.
authors.forename: Salwan
authors.initials: S
authors.lastname: Maqdasy
authors.affiliation: Service d'endocrinologie, diabétologie et maladies métaboliques, CHU Clermont-Ferrand, F-63003, Clermont-Ferrand, France. laura.bogenmann@hotmail.fr.
authors.forename: Laura
authors.initials: L
authors.lastname: Bogenmann
authors.affiliation: Service d'endocrinologie, diabétologie et maladies métaboliques, CHU Clermont-Ferrand, F-63003, Clermont-Ferrand, France. mbatisse@chu-clermontferrand.fr.|UMR CNRS 6293, INSERM U1103, Université Clermont-Auvergne, Génétique Reproduction et Développement, BP 10448, 63177, Aubiere, France. mbatisse@chu-clermontferrand.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Batisse-Lignier
authors.affiliation: Service d'endocrinologie, diabétologie et maladies métaboliques, CHU Clermont-Ferrand, F-63003, Clermont-Ferrand, France. b__roche@chu-clermontferrand.fr.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Roche
authors.affiliation: SIPATH Clermont-Ferrand, F-63003, Clermont-Ferrand, France. frederic.franck@wanadoo.fr.
authors.forename: Fréderic
authors.initials: F
authors.lastname: Franck
authors.affiliation: Service d'endocrinologie, diabétologie et maladies métaboliques, CHU Clermont-Ferrand, F-63003, Clermont-Ferrand, France. fdesbiez@chu-clermontferrand.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Desbiez
authors.affiliation: Service d'endocrinologie, diabétologie et maladies métaboliques, CHU Clermont-Ferrand, F-63003, Clermont-Ferrand, France. itauveron@chu-clermontferrand.fr.|UMR CNRS 6293, INSERM U1103, Université Clermont-Auvergne, Génétique Reproduction et Développement, BP 10448, 63177, Aubiere, France. itauveron@chu-clermontferrand.fr.
authors.forename: Igor
authors.initials: I
authors.lastname: Tauveron
mesh_terms: D006801:Humans; D007621:Karyotyping; D007713:Klinefelter Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D007984:Leydig Cell Tumor / Q000150:complications / Q000235:genetics* / Q000473:pathology; D007985:Leydig Cells / Q000473:pathology; D008297:Male; D013736:Testicular Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D013737:Testis / Q000473:pathology; D055815:Young Adult