eMedicine Specialties > Pediatrics: General Medicine > Oncology
Gonadoblastoma: Differential Diagnoses & Workup
Updated: Nov 26, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Workup
Laboratory Studies
- Chromosome analysis
- Chromosome analysis is the most important laboratory study in the diagnosis of gonadoblastoma.
- The karyotype at birth is used as a screening test in neonates with abnormal genitalia.
- The karyotype may also be used at a later age to detect patients who have androgen insensitivity/male pseudohermaphroditism (46,XY) and who present with primary amenorrhea.
- The karyotype confirms the diagnosis of Turner syndrome and can differentiate the many other chromosomal abnormalities that have been described.
- The presence of a Y chromosome has clearly been linked to the risk of developing gonadoblastoma in the intersex population. However, because the karyotype is not able to detect the molecular presence of a Y chromosome in patients with Turner syndrome, the absence of a Y chromosome does not exclude the patient from developing gonadoblastoma.
- In patients with Turner syndrome (45,XO), the karyotype analysis lacks the sensitivity to detect the molecular presence of a Y chromosome, which has been confirmed and well documented with the use of the PCR and fluorescence in situ hybridization (FISH).
- Serum electrolyte panel
- In newborns with clitoromegaly, obtain a serum electrolyte panel to exclude life-threatening electrolyte disturbances.
- Elevated serum potassium and low serum sodium are observed in patients with 21-hydroxylase deficiency, and other abnormalities of androgen synthesis are observed in patients with congenital adrenal hyperplasia.
- Endocrinologic evaluation: Concomitant endocrine abnormalities should be delineated, including measurement of luteinizing hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH), testosterone/dihydrotestosterone (after gonadotrophin chorionic hormone [GCH] stimulation), 17-OH progesterone, and cortisol.
Imaging Studies
- Imaging studies are useful in diagnosing features of intersexuality in newborns but have a limited role in the diagnosis gonadoblastoma. All of these studies help to identify patients at risk of developing gonadoblastoma in addition to characterizing the specific intersex disorder of the individual.
- Most patients with ambiguous genitalia usually undergo retrograde genitography to delineate the urogenital anatomy. Often, the bladder, vagina, and any communication between the 2 structures can be identified.
- If a diagnostic surgical procedure is planned, cystourethroscopy and vaginoscopy can be performed to better visualize the anatomy.
- In patients that present later in life, localization studies such as ultrasonography, CT scanning, and MRI may be useful.
- Ultrasonographic evaluation of the gonads and other pelvic organs is frequently used to identify and characterize any persistence of müllerian duct structures.
- Particularly in patients with mixed gonadal dysgenesis, ultrasonography can be helpful in visualizing the uterus, vagina, fallopian tubes, ovary, and a contralateral testicle.
- A flat abdominal radiograph can sometimes reveal gonadal calcification, which is a classic pathologic finding in gonadoblastoma.
Procedures
- The role of exploratory laparotomy and gonadal biopsy is not well defined. More often in the past, it has been used for diagnostic purposes to help identify and characterize the anatomy of patients with mixed intersex disorders. Currently, the diagnosis can be made with the use of karyotype identification and molecular techniques, minimizing the need for a diagnostic biopsy. Today, an exploratory laparotomy is reserved for patients who undergo predominately a therapeutic and not a diagnostic gonadectomy.
Histologic Findings
- Gross evaluation of gonadoblastoma usually reveals a small, slightly lobulated, 1-cm to 3-cm, soft to firm, gray-tan to brown, slightly lobulated tumor. The consistency has been described as gritty on cut sections because of the presence of multifocal calcification. Histologically, the tumor is composed of 2 main cell types. The first type is similar to the large germ cells found in dysgerminoma/seminoma. The second cell type resembles small immature Sertoli cells. Additionally, a third type of cell can frequently be observed in the stroma of the tumor and is nearly identical to the Leydig cells with the exception of having visible Reinke crystals.
- The 2 main cell types form discrete solid aggregates that often contain calcifications. If the germ cells invade the margins of these discrete aggregates, the lesion is no longer considered benign and is termed a dysgerminoma/seminoma. With advanced local growth, the dysgerminoma/seminoma nearly obliterates the architecture that characterizes the benign histologic features of the gonadoblastoma. Approximately 17% of germinomas arising in gonadoblastomas are bilateral.
- The pathologic diagnosis of gonadoblastoma can be challenging. Gonadoblastoma is often misdiagnosed as a nonseminomatous germ cell tumor. Only a few cases of nonseminomatous germ cell tumors (eg, yolk sac, embryonal cell carcinoma, teratoma, mucinous adenoma) have been reported in patients with gonadoblastoma.
- In patients with Turner syndrome, the gonads are streaks, made up of fibrous stroma arranged in whorls similar to those in ovarian stroma but lacking primordial follicles.
Staging
- Gonadoblastoma is not staged because it is not a malignant tumor. However, not removed early, at least 30% of these lesions develop into a higher grade malignancy, usually dysgerminoma or seminoma. These, of course, need to be appropriately staged depending on their histology.
More on Gonadoblastoma |
| Overview: Gonadoblastoma |
 Differential Diagnoses & Workup: Gonadoblastoma |
| Treatment & Medication: Gonadoblastoma |
| Follow-up: Gonadoblastoma |
| References |
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References
Scully RE. Gonadoblastoma. A review of 74 cases. Cancer. Jun 1970;25(6):1340-56. [Medline].
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. Sep 2000;85(9):3199-202. [Medline]. [Full Text].
Troche V, Hernandez E. Neoplasia arising in dysgenetic gonads. Obstet Gynecol Surv. Feb 1986;41(2):74-9. [Medline].
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].
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. Jun 30 2008;[Medline].
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. Oct 1 2008;123(7):1573-85. [Medline].
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].
Brant WO, Rajimwale A, Lovell MA, et al. Gonadoblastoma and Turner syndrome. J Urol. May 2006;175(5):1858-60. [Medline].
Chen MJ, Yang JH, Mao TL, et al. Successful pregnancy in a gonadectomized woman with 46,XY gonadal dysgenesis and gonadoblastoma. Fertil Steril. Jul 2005;84(1):217. [Medline].
Frias JL, Davenport ML. Health supervision for children with Turner syndrome. Pediatrics. Mar 2003;111(3):692-702. [Medline].
Gourlay WA, Johnson HW, Pantzar JT, et al. Gonadal tumors in disorders of sexual differentiation. Urology. Apr 1994;43(4):537-40. [Medline].
Kido T, Lau YF. A Cre gene directed by a human TSPY promoter is specific for germ cells and neurons. Genesis. Aug 2005;42(4):263-75. [Medline].
Lau YF. Gonadoblastoma, testicular and prostate cancers, and the TSPY gene. Am J Hum Genet. Apr 1999;64(4):921-7. [Medline].
Levin HS. Tumors of the testis in intersex syndromes. Urol Clin North Am. Aug 2000;27(3):543-51, x. [Medline].
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). Jan 1999;50(1):19-26. [Medline].
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. Mar 2005;18(3):439-45. [Medline].
Rutgers JL, Scully RE. Pathology of the testis in intersex syndromes. Semin Diagn Pathol. Nov 1987;4(4):275-91. [Medline].
Sultana R, Myerson D, Disteche CM. In situ hybridization analysis of the Y chromosome in gonadoblastoma. Genes Chromosomes Cancer. Aug 1995;13(4):257-62. [Medline].
Tewari K, Cappuccini F, Disaia PJ, et al. Malignant germ cell tumors of the ovary. Obstet Gynecol. Jan 2000;95(1):128-33. [Medline].
Vlasak I, Plochl E, Kronberger G, et al. Screening of patients with Turner syndrome for "hidden" Y-mosaicism. Klin Padiatr. Jan-Feb 1999;211(1):30-4. [Medline].
Further Reading
Keywords
gonadoblastoma, intersex disorders, germinoma, seminoma, gonadal dysgenesis, complete androgen insensitivity, male pseudohermaphrodites, male pseudohermaphroditism, male pseudohermaphrodism, mixed gonadal dysgenesis, Turner syndrome, Turner's syndrome, germ cell tumors, testicular seminoma, amenorrhea, clitoromegaly, abnormal hirsutism, inguinal hernias, hypoplastic vagina
