Abstract
We describe five patients with 46,XY gonadal dysgenesis who developed gonadoblastomas,
dysgerminomas, a mature teratoma, and a testicular intraepithelial neoplasia. The
age of the patients was between 12.2 and 18.5 years. The external genitalia were normal
female in two cases, in three they were intersexual. Four of our patients presented
with slight retardation of puberty followed by stagnation. Most importantly the development
of the breast (Tanner stage 2 - 4) did not correspond with pubic hair stage (Tanner
stage 4). The patients can be classified as virilized phenotypical females. Serum
testosterone was detectable in three, estradiol in two patients. None of the gonadoblastomas
showed immunoreactivity with antibodies against steroid hormone receptors and against
testosterone and estradiol, respectively. Probably the immature cells are able to
produce steroid hormones. Only steroid-like cells with Leydig cell appearance showed
positive cytoplasmatic immunostaining for testosterone in three patients. The findings
in our patients underline that dysgenetic gonads must be removed as early as possible
to prevent development of malignant tumors.
Key words
46,XY gonadal dysgenesis - male pseudohermaphroditism - gonadoblastoma - dysgerminoma
- immunoreactivity
References
- 1
Alikasifoglu A, Kandemir N, Caglar M, Kotiloglu E, Yordam N.
Prepubertal gonadoblastoma in a 46,XY female patient with features of Turner syndrome.
Eur J Pediatr.
1996;
155
653-655
- 2
Barbosa A S, Ferraz-Costa T E, Semer M, Liberman B, Moreira.
Filho CA. XY gonadal dysgenesis and gonadoblastoma: A study in two sisters with a
cryptic deletion of the Y chromosome involving the SRY gene.
Hum Genet.
1995;
95
63-66
- 3
Benini E, Rao S, Daidone M G, Pilotti S, Silvestrini R.
Immunoreactivity to MIB-1 in breast cancer: Methodological assessment and comparison
with other proliferation indices.
Cell Prolif.
1997;
30
107-115
- 4
Berkovitz G D, Fechner P Y, Zacur H W, Rock J A, Snyder H M, Migeon C J, Perlman E J.
Clinical and pathologic spectrum of 46,XY gonadal dysgenesis: Its relevance to the
understanding of sex differentiation.
Medicine.
1991;
70
375-383
- 5
Bosze P, Magyar E, Toth A.
45,X streak gonad syndrome associated with bilateral “burnt out” gonadoblastoma.
Gynecol Obstet Invest.
1989;
28
113-117
- 6
Chen F P, Chu K K, Soong Y K.
46,XY pure gonadal dysgenesis with gonadoblastoma - a case report.
Chang Gung Med J.
1991;
14
264-268
- 7
Dumic M, Jukic S, Batinica S, Ille J, Filipovic-Grcic B.
Bilateral gonadoblastoma in a 9-month-old infant with 46,XY gonadal dysgenesis.
J Endocrinol Invest.
1993;
16
291-293
- 8
Fukamatsu Y, Tsukahara Y, Hayashi S, Yoshikawa F, Fukuta T.
Bilateral gonadoblastoma producing steroid hormones in a patient with 45,X/46,XY gonadal
dysgenesis.
Gynecol Obstet Invest.
1990;
30
189-191
- 9 Greulich W W, Pyle S I. Radiographic Atlas of Skeletal Development of the Hand and
Wrist. 2nd ed. Stanford; Stanford University Press 1959
- 10
Hong J R, Barber M, Scott C I, Guttenberg M, Wolfson P J.
3-year-old phenotypic female with campomelic dysplasia and bilateral gonadoblastoma.
J Pediatr Surg.
1995;
30
1735-1737
- 11
Hussong J, Crussi F G, Chou P M.
Gonadoblastoma: Immunohistochemical localization of Müllerian-inhibiting substance,
inhibin, WT-1, and p53.
Mod Pathol.
1997;
10
1101-1105
- 12
Iezzoni J C, von Kap-Herr C, Golden W L, Gaffay M J.
Gonadoblastomas in 45,X/46,XY Mosaicism. Analysis of Y chromosome distribution by
fluorescence in situ hybridization.
Am J Clin Pathol.
1997;
108
197-201
- 13
Jäger R J, Anvret M, Hall K, Scherer G.
A human XY female with a frame shift mutation in the candidate testis-determining
gene SRY.
Nature.
1990;
348
452-454
- 14
Jorgensen N, Müller J, Jaubert F, Clausen O P, Skakkebaek N E.
Heterogeneity of gonadoblastoma germ cells: Similarities with immature germ cells,
spermatogonia and testicular carcinoma in situ cells.
Histopathology.
1997;
30
177-186
- 15
Kauf E, Hesse V.
Hermaphroditismus mit Gonadoblastomentwicklung im Kindesalter.
Z Klin Med.
1989;
44
1449-1452
- 16
Lange A, Wieacker P, Schweikart H U, Schumann K.
Androgenproduzierendes Gonadoblastom bei reiner XY-Gonadendysgenesie (Swyer-Syndrom).
Zentralbl Gynäkol.
1998;
120
555-558
- 17
Liu Y C, Wei T C, Hsu Y H, Fang J S, Lee M L.
Gonadoblastoma and choriocarcinoma in dysgenetic gonads: Report of a case.
J Formos Med Assoc.
1995;
94
568-571
- 18
Löffler S, Horn L C, Weber W, Spanel-Borowski K.
The transient disappearance of cytokeratine in human fetal and adult ovaries.
Anat Embryol.
2000;
201
207-215
- 19
Lukusa T, Fryns J P, Kleczkowska A, van den Berghe H.
Role of gonadal dysgenesis in gonadoblastoma induction in 46,XY individuals.
Genetic Counseling.
1991;
2
9-16
- 20
Mackay A M, Pettigrew N, Symington T, Neville A M.
Tumors of dysgenetic gonads (gonadoblastoma): Ultrastructural and steroidogenic aspects.
Cancer.
1974;
34
1108-1125
- 21
Matias-Guiu X, Pons C, Prat J.
Müllerian inhibiting substance, alpha-inhibin and CD 99 expression in sex cord-stromal
tumors and endometrioid ovarian carcinomas resembling sex cord-stromal tumors.
Hum Pathol.
1998;
29
840-845
- 22
McDonald M T, Fleijter W, Sheldon S, Putzi M J, Gorski J L.
XY sex reversal and gonadal dysgenesis due to 9 p24 monosomy.
Am J Med Genet.
1997;
73
321-326
- 23
Miettinen M, Talerman A, Wahlstrom T, Astengo-Osuna C, Virtanan I.
Cellular differentiation in ovarian sex-cord-stromal and germ-cell tumors studied
with antibodies to intermediate-filament proteins.
Am J Surg Pathol.
1985;
9
640-651
- 24
Müller J, Visfeldt J, Philip J, Skakkebaek N E.
Carcinoma in situ, gonadoblastoma, and early invasive neoplasia in a nine-year-old
girl with 46,XY gonadal dysgenesis.
APMIS.
1992;
100
170-174
- 25
Obata N H, Nakashima N, Kawai M, Kikkawa F, Mamba S, Tomoda Y.
Gonadoblastoma with dysgerminoma in one ovary and gonadoblastoma with dysgerminoma
and yolk sac tumor in the contralateral ovary in a girl with 46XX karyotype.
Gynecol Oncol.
1995;
58
124-128
- 26
Pelkey T J, Frierson H F, Mills S E. et al .
The diagnostic utility of inhibin staining in ovarian neoplasms.
Int J Gynecol Pathol.
1998;
17
97-105
- 27
Petersen L, Kock K, Jacobsen B B.
Germ cell neoplasms in three intersex patients with 46,XY karyotype.
Intern Urol Nephrol.
1992;
24
633-639
- 28
Prader A.
Der Genitalbefund beim Pseudohermaphroditismus femininus des kongenitalen adrenogenitalen
Syndroms.
Helv Paediatr Acta.
1954;
9
231-248
- 29
Quigley M M, Vaughn T C, Hammond C B, Haney A F.
Production of testosterone and estrogen in vitro by gonadal tissue from a 46,XY true
hermaphrodite with gonadal failure and gonadoblastoma.
Obstet Gynecol.
1981;
58
253-259
- 30
Ramani P, Yeung C K, Habeebu S SM.
Testicular intratubular germ cell neoplasia in children and adolescents with intersex.
Am J Surg Pathol.
1993;
17
1124-1133
- 31
Roth L M, Eglen D E.
Gonadoblastoma: Immunohistochemical and ultrastructural observations.
Int J Gynecol Pathol.
1989;
8
72-81
- 32
Rutgers J L.
Advances in the pathology of intersex conditions.
Hum Pathol.
1991;
22
884-891
- 33
Sadi A M, Toda T, Kiyuna M, Miyagi H.
Mixed gonadal dysgenesis with gonadoblastoma in a female with Y chromosome: Case report.
J Obstet Gynaecol Res.
1996;
22
25-30
- 34
Schellas H F.
Malignant potential of dysgenetic gonad. Part II.
Obstet Gynecol.
1974;
44
455-462
- 35
Scully R E.
Gonadoblastoma: A gonadal tumor related to the dysgerminoma (seminoma) and capable
of sex hormone production.
Cancer.
1953;
6
455-463
- 36
Scully R E.
Gonadoblastoma: A review of 74 cases.
Cancer.
1970;
25
1340-1356
- 37
Scully R E.
Neoplasia associated with anomalous sexual development and abnormal sex chromosomes.
Pediatr Adolesc Endocrinol.
1981;
8
203-217
- 38
Slowikowska-Hilczer J, Szarras-Czapnik M, Kula K.
Testicular pathology in 46,XY dysgenetic male pseudohermaphroditism: An approach to
pathogenesis of testis cancer.
J Androl.
2001;
22
781-792
- 39
Slowikowska-Hilczer J, Romer T E, Kula K.
Neoplastic potential of germ cells in relation to disturbances of gonadal organogenesis
and changes in karyotype.
J Androl.
2003;
24
270-278
- 40 Tanner J M. Growth at Adolescence. 2nd ed. Oxford, Edinburgh; Blackwell 1962
- 41 Thamm B.
Direct non-isotopic sequencing of PCR products or standards. Köhler T, Lassner D, Rost AK, Thamm B, Pustoweit B, Remke H Quantitation of mRNA
by Polymerase Chain Reaction. Berlin, Heidelberg, New York; Springer 1995: 39-51
Dr. med. W. Hoepffner
Children's Hospital of the University of Leipzig
Oststraße 21 - 25
04317 Leipzig
Germany
Phone: + 493419726148
Fax: + 49 34 19 72 61 49
Email: Ruth.Gausche@medizin.uni-leipzig.de
