ovarian juvenile granulosa cell tumor

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

Images

 Juvenile granulosa cell tumor

• https://twitter.com/Levelsx5/status/718901217020289026

Digital slides

 Case 2 (HPC:2) : Ovarian juvenile granulosa cell tumor
 Case 44 (HPC:44): Ovarian juvenile granulosa cell tumor

Juvenile granulosa cell tumors comprise only 5% of ovarian tumors of childhood or adolescence.

Typically, they present as sexual precocity in prepubertal girls due to excessive estrogen production, although androgens may rarely be produced.

Rarely, they are associated with an abnormal karyotype and ambiguous genitalia. Older patients may present with nonspecific abdominal swelling and pain.

Clinical synopsis

 ≈80% during first two decades of life
 Usually presents with isosexual precocity

Predisposition

 especially if bilateral
 enchondromatosis (Ollier disease)
 Maffucci syndrome
 Goldenhar syndrome

Macroscopy

 Grossly, these tumors are partially solid and cystic.
 Hemorrhage or necrosis may be present.
 Macroscopical variants

• cystic juvenile granulosa cell tumor
• solid juvenile granulosa cell tumor

Microscopy

This tumor is composed of macrofollicles with eosinophilic secretions, and intervening tumor cells with abundant eosinophilic cytoplasm, round/oval hyperchromatic nuclei with small nucleoli, and mildly irregular nuclear contours. There are rare nuclear grooves. Other features often present include high mitotic activity, nuclear atypia and occasionally hobnail-like cells.

 nodular or diffuse growth of granulosa cells
 prominent cyst / follicle formation
 no classical Call–Exner bodies
 diffuse or macrofollicular patterns of growth (former predominating)
 mucin-positive intrafollicular secretion
 cystic areas surrounded by granulosa type cells
 solid areas composed of bland ovoid granulosa cells with eosinophilic cytoplasm.
 larger tumor cells with extensive luteinization
 granulosa cells

• bland
• ovoid
• eosinophilic cytoplasm
• no nuclear grooves
• mitoses common
• inhibin+ and CD99+
   paucity of nuclear grooves
   thecal component
   nuclear atypia
   variable but often high mitotic activity
   follicle-like spaces on low-power examination
   On high power the tumor cells lack the coffee-bean nuclei seen in the adult type.

 Juvenile granulosa cell tumor shows round-to-oval follicles that contain eosinophilic secretion.

• The follicles are separated by luteinized granulosa cells.
• Round-to-oval follicles that contain eosinophilic secretion.
• The follicles are separated by luteinized granulosa cells.
• Follicles of varying sizes and shapes are separated by cellular areas.

 Tumor cells

• abundant eosinophilic cytoplasm
• nuclei
  • hyperchromatic
  • lack grooves

Digitalized slides

 NEM1-2: juvenile granulosa cell tumor (or ICS-Viewer)

Immunochemistry

 Juvenile granulosa cell tumor demonstrates strong staining for inhibin.
 Positive immunostains include inhibin and calretinin.

• They are not usually needed for diagnosis, but may be helpful in excluding germ cell tumors or melanoma.

Genetics

 Consistent trisomy 12
 Greater percentage of aneuploidy than in adult variety.

Differential diagnosis

 adult-type granulosa cell tumor

• Adult granulosa cell tumors have more regularly shaped follicles that contain basement membrane material.
• Tumor cells have prominent nuclear grooves and less hyperchromasia.
   thecoma
• Thecomas almost never occur in patients 30 years or younger, and usually lack mitotic activity.
• Thecomas also lack follicles, which are usually found in juvenile granulosa cell tumors with thorough sampling.
   clear cell carcinoma.
• Patients with clear cell carcinoma are typically older.
• Clear cell carcinomas lack follicles or areas of typical juvenile granulosa type cells.

Although hobnail-type cells may be seen in juvenile granulosa cell tumors, they are typically focal.

Treatment and prognosis

Excision is usually adequate therapy for limited disease, although late recurrence may occur.

See also

 granulosa cell tumor

• juvenile granulosa cell tumor*

Links

 Case #59, pathologyoutlines.com

References

 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.

 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.

 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.

 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.

 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.

 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.