Virchows Archiv

, Volume 443, Issue 4, pp 549–560

Ovarian sex cord–stromal tumors—a clinicopathological study of 72 cases from the Kiel Pediatric Tumor Registry

  • Dominik T. Schneider
  • Ute Jänig
  • Gabriele Calaminus
  • Ulrich Göbel
  • Dieter Harms
Original Article

Abstract

We analyzed 72 patients with ovarian sex cord–stromal tumors (OSCST) registered at the German Pediatric Tumor Registry in Kiel over a 20-year period. Juvenile granulosa cell tumors (JGCT, n=48) were the most frequent histological subtype. In addition, there were 14 Sertoli-Leydig cell tumors, 5 sclerosing stromal tumors, 2 sex cord tumors with annular tubules, 2 thecomas and 1 steroid cell tumor. Stage according to FIGO (International Federation of Gynecologists and Obstetricians) was Ia in 39 patients, Ic in 17 patients, II in 3 patients and III in 1 patient (60 patients with complete data). Compared with adult granulosa cell tumors, JGCT showed pronounced mitotic activity [mean 9.8 mitoses/10 high power field (HPF)], which was significantly higher than in other histological subtypes (2.7/10 HPF, P=0.001). Immunohistochemical analysis revealed frequent coexpression of vimentin (positive in 52/52 examined tumors), cytokeratin (27/33), and inhibin (19/20). Of patients, 12 with Ic or higher stage tumors received adjuvant cisplatinum-based chemotherapy. Event-free survival at 10 years was 0.88±0.05 (38/43 patients with follow-up data). Outcome significantly correlated with stage and mitotic activity (<20 versus ≥20 mitoses/10 HPF: event-free survival 1.0 versus 0.48±0.05, P=0.0001). In conclusion, this analysis confirms that the majority of patients with OSCST present at low tumor stage and that prognosis in these patients is excellent. Refractory tumors are characterized by high proliferative activity. Therefore, histopathological evaluation substantially contributes to risk assessment in patients with OSCST and might be useful for therapy stratification in prospective therapeutic protocols.

Keywords

Children Adolescents Sertoli-Leydig tumors Granulosa cell tumors Ovary 

References

  1. 1.
    Benedet JL, Bender H, Jones H, III, Ngan HY, Pecorelli S (2000) FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet 70:209–262PubMedGoogle Scholar
  2. 2.
    Benjamin E, Law S, Bobrow LG (1987) Intermediate filaments cytokeratin and vimentin in ovarian sex cord–stromal tumours with correlative studies in adult and fetal ovaries. J Pathol 152:253–263PubMedGoogle Scholar
  3. 3.
    Calaminus G, Wessalowski R, Harms D, Göbel U (1997) Juvenile granulosa cell tumors of the ovary in children and adolescents: results from 33 patients registered in a prospective cooperative study. Gynecol Oncol 65:447–452CrossRefPubMedGoogle Scholar
  4. 4.
    Cronje HS, Niemand I, Bam RH, Woodruff JD (1998) Granulosa and theca cell tumors in children: a report of 17 cases and literature review. Obstet Gynecol Surv 53:240–247CrossRefPubMedGoogle Scholar
  5. 5.
    Czernobilsky B, Moll R, Levy R, Franke WW (1985) Co-expression of cytokeratin and vimentin filaments in mesothelial, granulosa and rete ovarii cells of the human ovary. Eur J Cell Biol 37:175–190PubMedGoogle Scholar
  6. 6.
    Fujimoto T, Sakuragi N, Okuyama K, Fujino T, Yamashita K, Yamashiro S, Shimizu M, Fujimoto S (2001) Histopathological prognostic factors of adult granulosa cell tumors of the ovary. Acta Obstet Gynecol Scand 80:1069–1074CrossRefPubMedGoogle Scholar
  7. 7.
    Gershenson DM, Morris M, Burke TW, Levenback C, Matthews CM, Wharton JT (1996) Treatment of poor-prognosis sex cord–stromal tumors of the ovary with the combination of bleomycin, etoposide, and cisplatin. Obstet Gynecol 87:527–531CrossRefPubMedGoogle Scholar
  8. 8.
    Groisman GM, Dische MR, Fine EM, Unger PD (1993) Juvenile granulosa cell tumor of the testis: a comparative immunohistochemical study with normal infantile gonads. Pediatr Pathol 13:389–400PubMedGoogle Scholar
  9. 9.
    Harms D, Kock LR (1997) Testicular juvenile granulosa cell and Sertoli cell tumours: a clinicopathological study of 29 cases from the Kiel Paediatric Tumour Registry. Virchows Arch 430:301–309PubMedGoogle Scholar
  10. 10.
    Hussong J, Crussi FG, Chou PM (1997) Gonadoblastoma: immunohistochemical localization of Mullerian-inhibiting substance, inhibin, WT-1, and p53. Mod Pathol 10:1101–1105PubMedGoogle Scholar
  11. 11.
    Juric G, Zarkovic N, Nola M, Tillian M, Jukic S (2001) The value of cell proliferation and angiogenesis in the prognostic assessment of ovarian granulosa cell tumors. Tumori 87:47–53PubMedGoogle Scholar
  12. 12.
    Kudelka AP, Vasuratna A, Edwards CL, Augustine K, Benjapibal M, Verschraegen CF, Kavanagh JJ (1998) Gemcitabine after bone marrow transplantation for refractory juvenile granulosa cell tumor. Anticancer Drugs 9:621–623PubMedGoogle Scholar
  13. 13.
    Miller BE, Barron BA, Wan JY, Delmore JE, Silva EG, Gershenson DM (1997) Prognostic factors in adult granulosa cell tumor of the ovary. Cancer 79:1951–1955CrossRefPubMedGoogle Scholar
  14. 14.
    Plantaz D, Flamant F, Vassal G, Chappuis JP, Baranzelli MC, Bouffet E, Dyon JF, Armari C, Bost M (1992) Granulosa cell tumors of the ovary in children and adolescents. Multicenter retrospective study in 40 patients aged 7 months to 22 years. Arch Fr Pediatr 49:793–798PubMedGoogle Scholar
  15. 15.
    Powell JL, Otis CN (1997) Management of advanced juvenile granulosa cell tumor of the ovary. Gynecol Oncol 64:282–284CrossRefPubMedGoogle Scholar
  16. 16.
    Powell JL, Johnson NA, Bailey CL, Otis CN (1993) Management of advanced juvenile granulosa cell tumor of the ovary. Gynecol Oncol 48:119–123CrossRefPubMedGoogle Scholar
  17. 17.
    Powell JL, Connor GP, Henderson GS (2001) Management of recurrent juvenile granulosa cell tumor of the ovary. Gynecol Oncol 81:113–116CrossRefPubMedGoogle Scholar
  18. 18.
    Riopel MA, Perlman EJ, Seidman JD, Kurman RJ, Sherman ME (1998) Inhibin and epithelial membrane antigen immunohistochemistry assist in the diagnosis of sex cord–stromal tumors and provide clues to the histogenesis of hypercalcemic small cell carcinomas. Int J Gynecol Pathol 17:46–53PubMedGoogle Scholar
  19. 19.
    Rogatsch H, Jezek D, Hittmair A, Mikuz G, Feichtinger H (1996) Expression of vimentin, cytokeratin, and desmin in Sertoli cells of human fetal, cryptorchid, and tumour-adjacent testicular tissue. Virchows Arch. 427:497–502Google Scholar
  20. 20.
    Russell P, Robboy SJ, Anderson MC (2002) Ovarian tumors: classification and clinical perspectives. In: Robboy et al. S.J. (eds) Pathology of the female reproductive tract. Churchill Livingstone, London, pp 527–538Google Scholar
  21. 21.
    Schneider DT, Calaminus G, Wessalowski R, Pathmanathan R, Harms D, Göbel U (2002) Therapy of advanced ovarian juvenile granulosa cell tumors. Klin Pädiatr 214:173–178Google Scholar
  22. 22.
    Scully RE (1977) Sex cord–stromal tumors. In: Blaustein A (ed) Pathology of the female genital tract. Springer, Berlin Heidelberg New YorkGoogle Scholar
  23. 23.
    Scully RE (2002) Histological typing of ovarian tumours. Springer, Berlin Heidelberg New YorkGoogle Scholar
  24. 24.
    Stratakis CA, Kirschner LS, Carney JA (2001) Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab 86:4041–4046PubMedGoogle Scholar
  25. 25.
    Teilum G (1971) Special tumors of ovary and testis. Munksgaard, CopenhagenGoogle Scholar
  26. 26.
    Vassal G, Flamant F, Caillaud JM, Demeocq F, Nihoul-Fekete C, Lemerle J (1988) Juvenile granulosa cell tumor of the ovary in children: a clinical study of 15 cases. J Clin Oncol 6:990–995PubMedGoogle Scholar
  27. 27.
    Wessalowski R, Spaar HJ, Pape H, Willers R, Harms D, Göbel U (1995) Successful liver treatment of a juvenile granulosa cell tumor in a 4-year-old child by regional deep hyperthermia, systemic chemotherapy, and irradiation. Gynecol Oncol 57:417–422CrossRefPubMedGoogle Scholar
  28. 28.
    Westerman AM, Wilson JH (1999) Peutz-Jeghers syndrome: risks of a hereditary condition. Scand J Gastroenterol Suppl 230:64–70CrossRefPubMedGoogle Scholar
  29. 29.
    Yamashita K, Yamoto M, Shikone T, Minami S, Imai M, Nishimori K, Nakano R (1997) Production of inhibin A and inhibin B in human ovarian sex cord stromal tumors. Am J Obstet Gynecol 177:1450–1457PubMedGoogle Scholar
  30. 30.
    Young RH, Dickersin GR, Scully RE (1984) Juvenile granulosa cell tumor of the ovary. A clinicopathological analysis of 125 cases. Am J Surg Pathol 8:575–596PubMedGoogle Scholar
  31. 31.
    Young RH, Scully RE (1985) Ovarian Sertoli-Leydig cell tumors. A clinicopathological analysis of 207 cases. Am J Surg Pathol 9:543–569PubMedGoogle Scholar
  32. 32.
    Young RH, Lawrence WD, Scully RE (1985) Juvenile granulosa cell tumor--another neoplasm associated with abnormal chromosomes and ambiguous genitalia. A report of three cases. Am J Surg Pathol 9:737–743PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Dominik T. Schneider
    • 1
  • Ute Jänig
    • 2
  • Gabriele Calaminus
    • 1
  • Ulrich Göbel
    • 1
  • Dieter Harms
    • 2
  1. 1.Clinic of Pediatric Oncology, Hematology and Immunology, Children's HospitalUniversity Hospital Düsseldorf, Heinrich-Heine-UniversityDüsseldorfGermany
  2. 2.Institute of Pediatric PathologyChristian-Albrechts-UniversityKielGermany

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