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Gonadoblastoma Clinical Presentation

  • Author: Joseph L Lasky, III, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
Updated: Jun 05, 2014


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  • Any history of abnormal genitourinary anatomy at the time of delivery is most helpful in identifying patients with an intersex disorder who are at risk of developing gonadoblastoma.
  • If the diagnosis is not established in the neonatal period, the most pertinent findings in the medical history are the individual's age, physical examination findings, mental developmental history, and family history.
    • Obtain any history of maternal exposure to androgens, drugs, alcohol, or illness during the first trimester of pregnancy.
    • Additionally, obtain a thorough family history regarding any existence of genital ambiguity, infertility, or amenorrhea because some evidence suggests that a hereditary component has a role in intersex disorders.
    • A family history can also be useful for screening purposes because a number of reports have documented the occurrence of gonadoblastoma and/or dysgerminoma in siblings of patients with male pseudohermaphrodism (46,XY) or in individuals with mixed gonadal dysgenesis (45,X/46,XY).
  • In patient history, a symptom of primary amenorrhea is often the first clue to the diagnosis of an intersex disorder.
  • Additionally, any developmental delay of the genitalia or secondary sexual characteristics should also initiate a prompt search for an intersex abnormality with a karyotype analysis. Troche and Hernandez (1986) found that approximately 10% of patients younger than 10 years with dysgenic gonads already had a gonadoblastoma or a dysgerminoma.[12] The study further underscored the importance of karyotype analysis in patients with primary or secondary amenorrhea and abnormal sexual development.
  • In Turner syndrome, persistence of infantile external genitalia and/or developmental delays can often be elicited from a medical history. Most of these individuals never have menstruated and have primary amenorrhea; however, exceptions are recognized, and, in 10% of women with Turner syndrome, puberty, menarche, and (rarely) pregnancy may occur.


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  • In patients at risk of developing gonadoblastoma, the tumor can frequently be diagnosed at birth by performing a careful physical examination. The unique abnormal physical findings of intersex syndromes are characteristic and can be easily detected by examining the genitalia.
  • However, infants with pure forms of an intersex disorder can appear completely normal on the physical examination, and these disorders are difficult to diagnose in the neonatal period. These individuals are more frequently discovered after puberty when abnormalities become more apparent with subtle developmental delays.
  • In addition to the genitourinary examination, a full physical examination is important to detect any gross abnormalities that can occur when gonadoblastoma transforms into a malignant dysgerminoma/seminoma and metastasizes. For example, a palpable abdominal mass can be found in approximately 50% of patients with metastatic disease.
  • In females with a normal phenotype but with virilizing features (eg, clitoromegaly, abnormal hirsutism) and in all phenotypic males with undescended testis and hypospadiac urethra, obtain a karyotype analysis to exclude an intersex disorder.
  • Other important physical findings include phallic size, the existence of an inguinal hernia, and the presence of a uterus on the bimanual examination. In the first few days of life, the maternal stimulatory effects of placental human chorionic gonadotropin facilitate the search for a uterus.
  • The diagnosis of complete androgen insensitivity/male pseudohermaphroditism (46,XY) can be difficult in the neonate period; sometimes, the only clue to suggest the diagnosis is an inguinal hernia in these females who display a normal phenotype. Newborn girls with inguinal hernias have a 1.6% incidence of being male pseudohermaphrodites (46,XY) and should undergo a prompt karyotype analysis.
  • Gonadoblastoma that is not identified in neonates is not usually diagnosed until after patients begin puberty when they present with primary amenorrhea. These teenagers have normal breast development, but secondary sexual characteristics are abnormal, with a complete absence of genital and axillary hair growth and a short and hypoplastic vagina.
  • Patients with an incomplete or partial form of androgen insensitivity present with numerous variations of genital ambiguity, and, unlike patients with a pure form of androgen insensitivity/male pseudohermaphrodism (46,XY), these individuals receive the diagnosis soon after birth. The initial genitourinary examination reveals obvious abnormalities at birth. The physical examination findings are unpredictable and hard to interpret. A careful examination of the scrotum, labia, or the presence of an inguinal hernia often demonstrates gonadal tissue and leads to a karyotype analysis that establishes the individual's genotype and helps to characterize the intersex disorder.
  • Patients with Turner syndrome (45,XO) typically present with short stature, a short webbed neck, widely spaced nipples, sparse pubic and axillary hair distribution, and infantile genitalia. Their skin is thick from lymphedema, and many nevi are present. The head and neck examination demonstrates a low hairline with low-set ears and hearing that is frequently impaired.
  • The physical examination of patients with mixed gonadal dysgenesis (45,X/46,XY) is noteworthy for ambiguous genitalia with varying degrees of phallic enlargement, undescended testis, and a urogenital sinus with labioscrotal fusion. Nearly all of these patients have a uterus, vagina, and fallopian tubes in addition to an ovary/streak and a contralateral testicle. One half of these patients are short, and one third can appear similar to individuals with Turner syndrome.


The select DSDs associated with a clear risk of developing gonadoblastoma include the following:

  • Complete androgen insensitivity (46,XY)
  • Pure gonadal dysgenesis or Swyer syndrome (46,XY)[13]
  • Mixed gonadal dysgenesis (45,X/46,XY)
  • A subset of patients with Turner syndrome (45,XO usually with evidence of XY mosaicism)
  • Frasier syndrome (a rare 46,XY DSD caused by a mutation in the Wilms tumor 1 gene [WT1])[14]
  • Denys-Drash syndrome (associated with disorder of sexual development, nephropathy, and Wilms tumor development, also caused by WT1 mutations)[15]
  • 9p Partial monosomy (syndrome with trigonocephaly, minor anomalies, and intellectual disability)[16]

The 2 essential findings that predispose these abnormal gonads to undergo neoplastic transformation into gonadoblastoma are (1) the karyotype has either macroscopic or molecular evidence of a Y chromosome (or a small piece) and (2) the gonads are nearly always located intra-abdominally. However, a limited number of cases of gonadoblastoma have been reported in patients with a 46,XX karyotype, suggesting that other molecular events besides the existence of a Y-chromosome remnant may lead to gonadoblastoma.[17] To the author's knowledge no environmental or dietary exposures predispose to gonadoblastoma development.

Contributor Information and Disclosures

Joseph L Lasky, III, MD Clinical Associate Professor of Pediatrics and Neurosurgery, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Pediatric Hematology/Oncology, Harbor-UCLA Medical Center

Joseph L Lasky, III, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, Society for Neuro-Oncology, American Society of Clinical Oncology

Disclosure: Received grant/research funds from Novo-Nordisk for site pi; Received grant/research funds from Emmaus for site pi; Received consulting fee from Octapharma for consulting; Received consulting fee from CSL Behring for consulting; Received grant/research funds from Novartis for site pi.


Kathleen M Sakamoto, MD, PhD Shelagh Galligan Professor, Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine

Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Nejd F Alsikafi, MD Clinical Assistant Professor, Department of Urology, Loyola University, Chicago Stritch School of Medicine

Nejd F Alsikafi, MD is a member of the following medical societies: American Urological Association, Endourological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Timothy P Cripe, MD, PhD, FAAP Chief, Division of Hematology/Oncology/BMT, Gordon Teter Endowed Chair in Pediatric Cancer, Nationwide Children's Hospital; Professor of Pediatrics, Ohio State University College of Medicine

Timothy P Cripe, MD, PhD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Association for Cancer Research, American Pediatric Society, American Society of Gene and Cell Therapy, American Society of Pediatric Hematology/Oncology, Connective Tissue Oncology Society, Society for Pediatric Research, Children's Oncology Group

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Stephan A Grupp, MD, PhD Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania School of Medicine

Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, Society for Pediatric Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.


William J Cromie, MD, MBA President and Chief Executive Officer, Health Care, Capital District Physicians' Health Plan

William J Cromie, MD, MBA is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, American Medical Association, American Urological Association, Medical Society of the State of New York, Société Internationale d'Urologie (International Society of Urology), Society for Pediatric Urology, Society of University Urologists, and Society of Uroradiology

Disclosure: Nothing to disclose.

Dimitri Kuznetsov, MD Staff Physician, Department of Surgery, Section of Urology, University of Chicago

Dimitri Kuznetsov, MD is a member of the following medical societies: American Urological Association and Endourological Society

Disclosure: Nothing to disclose.

  1. Scully RE. Gonadoblastoma. A review of 74 cases. Cancer. 1970 Jun. 25(6):1340-56. [Medline].

  2. SCULLY RE. Gonadoblastoma; a gonadal tumor related to the dysgerminoma (seminoma) and capable of sex-hormone production. Cancer. 1953 May. 6(3):455-63. [Medline].

  3. Page DC. Hypothesis: a Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads. Development. 1987. 101 Suppl:151-5. [Medline].

  4. Tsuchiya K, Reijo R, Page DC, Disteche CM. Gonadoblastoma: molecular definition of the susceptibility region on the Y chromosome. Am J Hum Genet. 1995. 57(6):1400-7. [Medline].

  5. Li Y, Lau YF. TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities. Oncogene. 2008 Jun 30. [Medline].

  6. Kido T, Lau YF. The human Y-encoded testis-specific protein interacts functionally with eukaryotic translation elongation factor eEF1A, a putative oncoprotein. Int J Cancer. 2008 Oct 1. 123(7):1573-85. [Medline].

  7. Lau YF, Li Y, Kido T. Gonadoblastoma locus and the TSPY gene on the human Y chromosome. Birth Defects Res C Embryo Today. 2009 Mar. 87(1):114-22. [Medline].

  8. Kido T, Lau YF. A Cre gene directed by a human TSPY promoter is specific for germ cells and neurons. Genesis. 2005 Aug. 42(4):263-75. [Medline].

  9. Brant WO, Rajimwale A, Lovell MA, et al. Gonadoblastoma and Turner syndrome. J Urol. 2006 May. 175(5):1858-60. [Medline].

  10. Scully RE. Ovarian tumors. A review. Am J Pathol. 1977 Jun. 87(3):686-720. [Medline].

  11. Gravholt CH, Fedder J, Naeraa RW, Muller J. Occurrence of gonadoblastoma in females with Turner syndrome and Y chromosome material: a population study. J Clin Endocrinol Metab. 2000 Sep. 85(9):3199-202. [Medline]. [Full Text].

  12. Troche V, Hernandez E. Neoplasia arising in dysgenetic gonads. Obstet Gynecol Surv. 1986 Feb. 41(2):74-9. [Medline].

  13. Michala L, Goswami D, Creighton SM, Conway GS. Swyer syndrome: presentation and outcomes. BJOG. 2008 May. 115(6):737-41. [Medline].

  14. Subbiah V, Huff V, Wolff JE, Ketonen L, Lang FF Jr, Stewart J, et al. Bilateral gonadoblastoma with dysgerminoma and pilocytic astrocytoma with WT1 GT-IVS9 mutation: A 46 XY phenotypic female with Frasier syndrome. Pediatr Blood Cancer. 2009 Dec 15. 53(7):1349-51. [Medline].

  15. Patel PR, Pappas J, Arva NC, Franklin B, Brar PC. Early presentation of bilateral gonadoblastomas in a Denys-Drash syndrome patient: a cautionary tale for prophylactic gonadectomy. J Pediatr Endocrinol Metab. 2013. 26(9-10):971-4. [Medline].

  16. Quinonez SC, Park JM, Rabah R, Owens KM, Yashar BM, Glover TW. 9p partial monosomy and disorders of sex development: review and postulation of a pathogenetic mechanism. Am J Med Genet A. 2013 Aug. 161A(8):1882-96. [Medline].

  17. Esin S, Baser E, Kucukozkan T, Magden HA. Ovarian gonadoblastoma with dysgerminoma in a 15-year-old girl with 46, XX karyotype: case report and review of the literature. Arch Gynecol Obstet. 2012 Feb. 285(2):447-51. [Medline].

  18. Verp MS, Simpson JL. Abnormal sexual differentiation and neoplasia. Cancer Genet Cytogenet. 1987 Apr. 25(2):191-218. [Medline].

  19. Hersmus R, Stoop H, White SJ, Drop SL, Oosterhuis JW, Incrocci L. Delayed Recognition of Disorders of Sex Development (DSD): A Missed Opportunity for Early Diagnosis of Malignant Germ Cell Tumors. Int J Endocrinol. 2012. 2012:671209. [Medline].

  20. Rutgers JL, Scully RE. The androgen insensitivity syndrome (testicular feminization): a clinicopathologic study of 43 cases. Int J Gynecol Pathol. 1991. 10(2):126-44. [Medline].

  21. Chen MJ, Yang JH, Mao TL, et al. Successful pregnancy in a gonadectomized woman with 46,XY gonadal dysgenesis and gonadoblastoma. Fertil Steril. 2005 Jul. 84(1):217. [Medline].

  22. Frias JL, Davenport ML. Health supervision for children with Turner syndrome. Pediatrics. 2003 Mar. 111(3):692-702. [Medline].

  23. Gourlay WA, Johnson HW, Pantzar JT, et al. Gonadal tumors in disorders of sexual differentiation. Urology. 1994 Apr. 43(4):537-40. [Medline].

  24. Lau YF. Gonadoblastoma, testicular and prostate cancers, and the TSPY gene. Am J Hum Genet. 1999 Apr. 64(4):921-7. [Medline].

  25. Levin HS. Tumors of the testis in intersex syndromes. Urol Clin North Am. 2000 Aug. 27(3):543-51, x. [Medline].

  26. Mendes JR, Strufaldi MW, Delcelo R, et al. Y-chromosome identification by PCR and gonadal histopathology in Turner's syndrome without overt Y-mosaicism. Clin Endocrinol (Oxf). 1999 Jan. 50(1):19-26. [Medline].

  27. Pena-Alonso R, Nieto K, Alvarez R, et al. Distribution of Y-chromosome-bearing cells in gonadoblastoma and dysgenetic testis in 45,X/46,XY infants. Mod Pathol. 2005 Mar. 18(3):439-45. [Medline].

  28. Rutgers JL, Scully RE. Pathology of the testis in intersex syndromes. Semin Diagn Pathol. 1987 Nov. 4(4):275-91. [Medline].

  29. Sultana R, Myerson D, Disteche CM. In situ hybridization analysis of the Y chromosome in gonadoblastoma. Genes Chromosomes Cancer. 1995 Aug. 13(4):257-62. [Medline].

  30. Tewari K, Cappuccini F, Disaia PJ, et al. Malignant germ cell tumors of the ovary. Obstet Gynecol. 2000 Jan. 95(1):128-33. [Medline].

  31. Vlasak I, Plochl E, Kronberger G, et al. Screening of patients with Turner syndrome for "hidden" Y-mosaicism. Klin Padiatr. 1999 Jan-Feb. 211(1):30-4. [Medline].

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