Humpath.com - Human pathology

Home > E. Pathology by systems > Reproductive system > Female genital system > Ovaries (Ovary) > ovarian granulosa cell tumor

ovarian granulosa cell tumor

Tuesday 28 June 2005

Granulosa cell tumors of the ovary; granulosa cell tumors of the ovary.

!WKP!PO!

Definition: Ovarian sex cord stromal tumor showing differentiation towards follicular granulosa cells that can occur in adults (adult-type granulosa cell tumor) and in younger patients (juvenile granulosa cell tumor). See also : granulosa cell tumor

Granulosa cell tumor has sheets of small cells with longitudinal nuclear grooves (“coffee bean nuclei”), and Call-Exner bodies (eosinophilic fluid filled spaces surrounded by granulosa cells). Most tumors cause hyperestrogenism.

Macroscopy

- Granulosa cell tumor with solid cut surface
- Granulosa cell tumor showing admixture of solid and cystic areas
- Predominantly cystic granulosa cell tumor
- Granulosa cell tumor with an entirely cystic gross appearance

Microscopy

Granulosa cell tumor has sheets of small cells with longitudinal nuclear grooves (“ coffee bean nuclei ”), and Call-Exner bodies (eosinophilic fluid filled spaces surrounded by granulosa cells). Most tumors cause hyperestrogenism.

Suspect granulosa cell origin of a metastatic tumor if a combination of microcystic and trabecular formations, especially if also Call–Exner bodies and grooved nuclei.

Digital slides

- NCK1-03 : ovarian juvenile granulosa cell tumor (Flash or ICS-Viewer)
- NCK1-02 : ovarian juvenile granulosa cell tumor (Flash or ICS-Viewer)
- HPC:44 : Ovarian juvenile granulosa cell tumor.
- JRC:373: Ovary Granulosa cell tumor.

Clinical Features

- adult-type granulosa cell tumor

  • Usually childbearing age
    • 75% have hyperestrinism, which may result in:
      • isosexual precocious puberty in children
      • metrorrhagia in adults, including postmenopausal
    • Some cases clinically hormonally inactive
    • A few androgenic
    • Elevated serum inhibin and follicle regulatory proteins

- juvenile granulosa cell tumor

  • more aggressive than adult
  • more likely to produce distant metastases
  • ≈80% during first two decades of life
  • Usually presents with isosexual precocity
  • Occasionally associated with:

Pathogenesis

- Differentiation toward follicular granulosa cells
- Debatable whether arises from:

  • granulosa cells in preexisting follicles
  • specialized ovarian stroma

Types

- juvenile granulosa cell tumor
- adult-type granulosa cell tumor

Subtypes

- ovarian granulosa cell tumors of the ovary, pseudopapillary pattern (18301054)

Video

- https://youtu.be/Cf8VEfJyThM

Open references

- The new molecular biology of granulosa cell tumors of the ovary. Kalfa N, Veitia RA, Benayoun BA, Boizet-Bonhoure B, Sultan C. Genome Med. 2009 Aug 25;1(8):81. PMID: 19725933 [Free]

References

- Granulosa cell tumors of the ovary with a pseudopapillary pattern: a study of 14 cases of an unusual morphologic variant emphasizing their distinction from transitional cell neoplasms and other papillary ovarian tumors. Irving JA, Young RH. Am J Surg Pathol. 2008 Apr;32(4):581-6. PMID: 18301054

- Fuller PJ, Chu S. Signalling pathways in the molecular pathogenesis of ovarian granulosa cell tumours. Trends Endocrinol Metab. 2004 Apr;15(3):122-8. PMID: 15046741

- Lack EE, Perez-Atayde AR, Murthy ASK, Goldstein DP, Crigler JF, Vawter GF. Granulosa theca cell tumors in premenarchal girls. A clinical and pathologic study of ten cases. Cancer. 1981;48:1846–1854.

- Evans AT, Gaffey TA, Malkasian GD, Annegers JF. Clinicopathologic review of 118 granulosa and 82 theca cell tumors. Obstet Gynecol. 1980;55:231–238.

- Castro CY, Malpica A, Hearne RH, Silva EG, Castro CV. Androgenic adult granulosa cell tumor in a 13-year-old prepubertal patient: a case report and review of the literature. Int J Gynecol Pathol. 2000;19:266–271.

- Nakashima N, Young RH, Scully RE. Androgenic granulosa cell tumors of the ovary. A clinicopathologic analysis of 17 cases and review of the literature. Arch Pathol Lab Med. 1984;108:786–791.

- Tamimi HK, Bolen JW. Enchondromatosis (Ollier’s disease) and ovarian juvenile granulosa cell tumor. A case report and review of the literature. Cancer. 1984;53:1605–1608.

- Tanaka Y, Sasaki Y, Nishihira H, Izawa T, Nishi T. Ovarian juvenile granulosa cell tumor associated with Maffucci’s syndrome. Am J Clin Pathol. 1992;97:523–527.

vNorris HJ, Taylor HB. Virilization associated with cystic granulosa tumors. Obstet Gynecol. 1969;34:629–635.

- Scully RE. Ovarian tumors. A review. Am J Pathol. 1977;87:686–720.

- Young RH, Oliva E, Scully RE. Luteinized adult granulosa cell tumors of the ovary. A report of four cases. Int J Gynecol Pathol. 1994;13:302–310.

- Young RH, Dudley AG, Scully RE. Granulosa cell, Sertoli-Leydig cell, and unclassified sex cord-stromal tumors associated with pregnancy. A clinico-pathological analysis of thirty-six cases. Gynecol Oncol. 1984;18:181–205.

- Ahmed E, Young RH, Scully RE. Adult granulosa cell tumor of the ovary with foci of hepatic cell differentiation: a report of four cases and comparison with two cases of granulosa cell tumor with Leydig cells. Am J Surg Pathol. 1999;23:1089–1093.

- Nogales FF, Concha A, Plata C, Ruiz-Avila I. Granulosa cell tumor of the ovary with diffuse true hepatic differentation simulating stromal luteinization. Am J Surg Pathol. 1993;17:85–90.

- Norris HJ, Taylor HB. Prognosis of granulosa-theca tumors of the ovary. Cancer. 1968;21:255–263.

- Young RH, Scully RE. Ovarian sex cord-stromal tumors with bizarre nuclei. A clinicopathologic analysis of 17 cases. Int J-Gynecol Pathol. 1983;1:325–335.

- Czernobilsky B, Moll R, Leppien G, Schweikhart G, Franke WW. Desmosomal plaque-associated vimentin filaments in human ovarian granulosa cell tumors of various histologic patterns. Am J Pathol. 1987;126:476–486.

- Roth LM, Nicholas TR, Ehrlich CE. Juvenile granulosa cell tumor. A clinicopathologic study of three cases with ultrastructural observations. Cancer. 1979;44:2194–2205.

- Young RH, Dickersin GR, Scully RE. Juvenile granulosa cell tumor of the ovary. A clinicopathologic analysis of 125 cases. Am J Surg Pathol. 1984;8:575–596.

- Zaloudek C, Norris HJ. Granulosa tumors of the ovary in children. A clinical and pathologic study of 32 cases. Am J Surg Pathol. 1982;6:513–522.

- Kurman RJ, Goebelsmann U, Taylor CR. Steroid localization in granulosatheca tumors of the ovary. Cancer. 1979;43:2377–2384.

- Flemming P, Wellmann A, Maschjek H, Lang H, Georgii A. Monoclonal antibodies against inhibin represent key markers of adult granulosa cell tumors of the ovary even in their metastases. A report of three cases with late metastasis, being previously misinterpreted as hemangiopericytoma. Am J Surg Pathol. 1995;19:927–933.

- Loo KT, Leung AKF, Chan JKC. Immunohistochemical staining of ovarian granulosa cell tumours with MIC2 antibody. Histopathology. 1995;27:388–390.

- McCluggage WG, Maxwell P, Sloan JM. Immunohistochemical staining of ovarian granulosa cell tumors with monoclonal antibody against inhibin. Hum Pathol. 1997;28:1034–1038.

- Miettinen M, Wahlstrom T, Virtanen I, Talerman A, Astengo-Osuna C. 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.

- Rodgers KE, Marks JF, Ellefson DD, Yanagihara DL, Tonetta SA, Vasilev SA, et al. Follicle regulatory protein. A novel marker for granulosa cell cancer patients. Gynecol Oncol. 1990;37:381–387.

- Costa MJ, De Rose PB, Roth LM, Brescia RJ, Zaloudek CJ, Cohen C. Immunohistochemical phenotype of ovarian granulosa cell tumors. Absence of epithelial membrane antigen has diagnostic value. Hum Pathol. 1994;25:60–66.

- Otis CN, Powell JL, Barbuto D, Carcangiu ML. Intermediate filamentous proteins in adult granulosa cell tumors. An immunohistochemical study of 25 cases. Am J Surg Pathol. 1992;16:962–968.

- Santini D, Ceccarelli C, Leone O, Pasquinelli G, Piana S, Marabini A, et al. Smooth muscle differentiation in normal human ovaries, ovarian stromal hyperplasia and ovarian granulosa-stromal cells tumors. Mod Pathol. 1995;8:25–30.

- Young RH, Scully RE. Ovarian sex cord-stromal tumors. Problems in differential diagnosis. Pathol Annu. 1988;23(Pt 1):237–296.

- Clement PB, Young RH, Scully RE. Ovarian granulosa cell proliferations of pregnancy. A report of nine cases. Hum Pathol. 1988;19:657–662.

- Fletcher JA, Gibas Z, Donovan K, Perez-Atayde A, Genest D, Morton CC, et al. Ovarian granulosa-stromal cell tumors are characterized by trisomy 12. Am J Pathol. 1991;138:515–520.

- Halperin D, Visscher DW, Wallis T, Lawrence WD. Evaluation of chromosome 12 copy number in ovarian granulosa cell tumors using interphase cytogenetics. Int J Gynecol Pathol. 1995;14:319–323.

- Gaffey MJ, Frierson HF, Iezzoni JC, Mills SE, Clement PB, Gersell DJ, et al. Ovarian granulosa cell tumors with bizarre nuclei: an immunohistochemical analysis with fluorescence in situ hybridization documenting trisomy 12 in bizarre component. Mod Pathol. 1996;9:308–315.

- Mayr D, Kaltz-Wittman C, Arbogast S, Amann G, Aust DE, Diebold J. Characteristic pattern of genetic aberrations in ovarian granulosa cell tumors. Mod Pathol. 2002;15:951–957.

- Chadha S, Cornelisse CJ, Schaberg A. Flow cytometric DNA ploidy analysis of ovarian granulosa cell tumors. Gynecol Oncol. 1990;36:240–245.

- Evans MP, Webb MJ, Gaffey TA, Katzmann JA, Suman VJ, Hu TC. DNA ploidy of ovarian granulosa cell tumors. Lack of correlation between DNA index or proliferative index and outcome in 40 patients. Cancer. 1995;75:2295–2298.

- Hitchcock CL, Norris HJ, Khalifa MA, Wargotz ES. Flow cytometric analysis of granulosa tumors. Cancer. 1989;64:2127–2132.

- Suh KS, Silverberg SG, Rhame JG, Wilkinson DS. Granulosa cell tumor of the ovary. Histopathologic and flow cytometric analysis with clinical correlation. Arch Pathol Lab Med. 1990;114:496–501.

- Schofield DE, Fletcher JA. Trisomy 12 in pediatric granulosa-stromal cell tumors. Demonstration by a modified method of fluorescence in situ hybridization on paraffin-embedded material. Am J Pathol. 1992;141:1265–1269.

- Jacoby AF, Young RH, Colvin RB, Flotte TJ, Preffer F, Scully RE, et al. DNA content in juvenile granulosa cell tumors of the ovary. A study of early-and advanced-stage disease. Gynecol Oncol. 1992;46:97–103.

- Swanson SA, Norris HJ, Kelsten ML, Wheeler JE. DNA content of juvenile granulosa tumors determined by flow cytometry. Int J Gynecol Pathol. 1990;9:101–109.

- Miller BE, Barron BA, Wan JY, Delmore JE, Silva EG. Prognostic factors in adult granulosa cell tumor of the ovary. Cancer. 1997;79:1951–1955.

- Young RH, Scully RE. Ovarian sex cord-stromal tumors. Recent progress. Int J Gynecol Pathol. 1982;1:101–123.

- Bjorkholm E, Silfversward C. Prognostic factors in granulosa-cell tumors. Gynecol Oncol. 1981;11:261–274.

- Fox H, Agrawal K, Langley FA. A clinicopathologic study of 92 cases of granulosa cell tumor of the ovary with special reference to the factors influencing prognosis. Cancer. 1975;35:231–241.