J Pathol Transl Med.  2018 Sep;52(5):344-348. 10.4132/jptm.2018.06.28.

Ovarian Gynandroblastoma with a Juvenile Granulosa Cell Tumor Component in a Postmenopausal Woman: A Case Report and Literature Review

• Jang NR
• Lee DH
• Jang EJ
• Bae YK
• Baek J
• Jang MH

• KMID: 2422102
• DOI: http://doi.org/10.4132/jptm.2018.06.28

Abstract

Gynandroblastoma is an extremely rare sex cord-stromal tumor with both female (granulosa cell tumor) and male (Sertoli-Leydig cell tumor) elements. Juvenile granulosa cell tumors are also very rare and are so named because they usually occur in children and adolescents. A 71-year-old woman with right upper quadrant abdominal pain visited our hospital. Pelvic computed tomography showed a large multilocular cystic mass, suspected to be of ovarian origin. We performed a total abdominal hysterectomy (total abdominal hysterectomy was performed) with bilateral salpingo-oophorectomy. A 13-cm multilocular cystic mass with serous fluid was observed in her right ovary. Upon microscopic examination, the solid component of the mass showed both Sertoli-Leydig cell and juvenile granulosa cell differentiation, which we diagnosed as gynandroblastoma. Gynandroblastoma with a juvenile granulosa cell tumor component is extremely rare and, until now, only six cases have been reported in the English literature. We report the first gynandroblastoma with a juvenile granulosa cell tumor component diagnosed in an elderly patient, along with a literature review.

Keyword

Ovarian gynandroblastoma; Juvenile granulosa cell tumor; Ovary; Postmenopause

MeSH Terms

Abdominal Pain
Adolescent
Aged
Child
Female
Granulosa Cell Tumor*
Granulosa Cells*
Humans
Hysterectomy
Male
Ovary
Postmenopause
Sex Cord-Gonadal Stromal Tumors*

Figure

• 

  Fig. 1. Pelvic computed tomography (CT) and ultrasonography findings. (A) Pelvic CT reveals a large multilocular cystic mass (arrow) with a solid component. (B) Ultrasonography shows a cystic mass (arrow) of approximately 13 cm arising from the right adnexa.

• 

  Fig. 2. Gross findings. (A) A 13.0×7.5×6.5-cm multilocular cystic and solid mass replaced the entire ovary. (B) The cysts were filled with serosanguinous fluid and approximately 30% of the mass was solid, hard, and yellow.

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  Fig. 3. Microscopic findings. (A) The tumor was composed of a Sertoli-Leydig cell tumor (SLT) and a juvenile granulosa cell tumor (JGCT). (B) The JGCT shows solid and nodular growth patterns with relatively uniform tumor cells. (C) Various sized follicles with mucin-like basophilic secretions are also frequently observed. (D) The tumor cells were rounded and had hyperchromatic nuclei without nuclear grooves, which are the characteristic features of adult granulosa cell tumors. (E) A well-differentiated SLT component is also identified. (F) Sertoli cells formed hollow tubules with delicate fibrous stroma. Small clusters of Leydig cells are observed in the fibrous stroma. (G, H) The immunohistochemical staining results confirms that the tumor was of sex cord-stromal origin. Both components stained positive for calretinin (G, left, SLT; right, JGCT) and inhibin (H, left, SLT; right, JGCT).

Reference

1. Mechler EA, Black WC. Gynandroblastoma of the ovary. Am J Pathol. 1943; 19:633–53.

2. Wilberger A, Yang B. Gynandroblastoma with juvenile granulosa cell tumor and concurrent renal cell carcinoma: a case report and review of literature. Int J Surg Pathol. 2015; 23:393–8.

3. Takeda A, Watanabe K, Hayashi S, Imoto S, Nakamura H. Gynandroblastoma with a juvenile granulosa cell component in an adolescent: case report and literature review. J Pediatr Adolesc Gynecol. 2017; 30:251–5.

4. Chivukula M, Hunt J, Carter G, Kelley J, Patel M, Kanbour-Shakir A. Recurrent gynandroblastoma of ovary: a case report: a molecular and immunohistochemical analysis. Int J Gynecol Pathol. 2007; 26:30–3.

5. Talerman A. Gynandroblastoma with elements of juvenile granulosa cell tumor. Int J Gynecol Pathol. 1998; 17:190.

6. Broshears JR, Roth LM. Gynandroblastoma with elements resembling juvenile granulosa cell tumor. Int J Gynecol Pathol. 1997; 16:387–91.

7. Chan R, Tucker M, Russell P. Ovarian gynandroblastoma with juvenile granulosa cell component and raised alpha fetoprotein. Pathology. 2005; 37:312–5.

8. McCluggage WG, Sloan JM, Murnaghan M, White R. Gynandroblastoma of ovary with juvenile granulosa cell component and heterologous intestinal type glands. Histopathology. 1996; 29:253–7.

9. Zhao C, Vinh TN, McManus K, Dabbs D, Barner R, Vang R. Identification of the most sensitive and robust immunohistochemical markers in different categories of ovarian sex cord-stromal tumors. Am J Surg Pathol. 2009; 33:354–66.

10. Chen L, Yang B. 14-3-3 sigma is a useful immunohistochemical marker for diagnosing ovarian granulosa cell tumors and steroid cell tumors. Int J Gynecol Pathol. 2013; 32:156–62.

11. Oparka R, Cassidy A, Reilly S, Stenhouse A, McCluggage WG, Herrington CS. The C134W (402 C>G) FOXL2 mutation is absent in ovarian gynandroblastoma: insights into the genesis of an unusual tumour. Histopathology. 2012; 60:838–42.

12. Tian W, Wang Y, Zhang H, Liu G, Ma X, Xue F. Androgen insensitivity syndrome with gynandroblastoma and vulvar leiomyoma: case report and literature review. J Low Genit Tract Dis. 2013; 17:335–9.

13. Conlon N, Schultheis AM, Piscuoglio S, et al. A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal tumors. Mod Pathol. 2015; 28:1603–12.

14. Shah SP, Kobel M, Senz J, et al. Mutation of FOXL2 in granulosacell tumors of the ovary. N Engl J Med. 2009; 360:2719–29.

15. D’Angelo E, Mozos A, Nakayama D, et al. Prognostic significance of FOXL2 mutation and mRNA expression in adult and juvenile granulosa cell tumors of the ovary. Mod Pathol. 2011; 24:1360–7.

16. Jamieson S, Butzow R, Andersson N, et al. The FOXL2 C134W mutation is characteristic of adult granulosa cell tumors of the ovary. Mod Pathol. 2010; 23:1477–85.

17. McCluggage WG, Singh N, Kommoss S, Huntsman DG, Gilks CB. Ovarian cellular fibromas lack FOXL2 mutations: a useful diagnostic adjunct in the distinction from diffuse adult granulosa cell tumor. Am J Surg Pathol. 2013; 37:1450–5.

18. Auguste A, Bessière L, Todeschini AL, et al. Molecular analyses of juvenile granulosa cell tumors bearing AKT1 mutations provide insights into tumor biology and therapeutic leads. Hum Mol Genet. 2015; 24:6687–98.

19. Kalfa N, Ecochard A, Patte C, et al. Activating mutations of the stimulatory g protein in juvenile ovarian granulosa cell tumors: a new prognostic factor? J Clin Endocrinol Metab. 2006; 91:1842–7.

20. Heravi-Moussavi A, Anglesio MS, Cheng SW, et al. Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med. 2012; 366:234–42.