Pseudoprecocious puberty due to functional cystic juvenile granulosa cell tumor of the ovary in a 5-year-old girl

Shailaja Prabhala; Jayashankar Erukkambattu; Karthikbabu Perumalla; Annapurna Srirambhatla; Ramamurti Tanikella

doi:10.4103/0971-9903.189530

CASE REPORT

Year : 2016 | Volume : 21 | Issue : 2 | Page : 144-146

Pseudoprecocious puberty due to functional cystic juvenile granulosa cell tumor of the ovary in a 5-year-old girl

Shailaja Prabhala¹, Jayashankar Erukkambattu¹, Karthikbabu Perumalla², Annapurna Srirambhatla³, Ramamurti Tanikella¹
¹ Department of Pathology, Kamineni Academy of Medical Sciences and Research Centre, Hyderabad, Telangana, India
² Department of Pediatric and General Surgery, Kamineni Academy of Medical Sciences and Research Centre, Hyderabad, Telangana, India
³ Department of Radiodiagnosis, Kamineni Academy of Medical Sciences and Research Centre, Hyderabad, Telangana, India

Date of Web Publication

31-Aug-2016

Correspondence Address:
Shailaja Prabhala
H.No. 8-14/1, Street No. 8, Ravindra Nagar Colony, Habsiguda, Hyderabad - 500 007
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/0971-9903.189530

Abstract

A 5-year-old girl child presented with features of pseudoprecocious puberty in the form of bleeding per vaginum and bilateral breast enlargement since 10 days. The radiological imaging showed a right ovarian cyst and the biochemistry revealed elevated estradiol. With a provisional diagnosis of functioning ovarian lesion, a right-sided ovarian cystectomy and ovariotomy was performed, which showed features of cystic juvenile granulosa cell tumor.

Keywords: Functional ovarian cyst, juvenile granulosa cell tumor, pseudoprecocious puberty

How to cite this article:
Prabhala S, Erukkambattu J, Perumalla K, Srirambhatla A, Tanikella R. Pseudoprecocious puberty due to functional cystic juvenile granulosa cell tumor of the ovary in a 5-year-old girl. J Mahatma Gandhi Inst Med Sci 2016;21:144-6

How to cite this URL:
Prabhala S, Erukkambattu J, Perumalla K, Srirambhatla A, Tanikella R. Pseudoprecocious puberty due to functional cystic juvenile granulosa cell tumor of the ovary in a 5-year-old girl. J Mahatma Gandhi Inst Med Sci [serial online] 2016 [cited 2023 Mar 30];21:144-6. Available from: https://www.jmgims.co.in/text.asp?2016/21/2/144/189530

Introduction

Precocious puberty in girls is usually defined as the appearance of secondary sexual characteristics before the age of 8 years and is divided as central and peripheral types. The former is due to premature activation of the hypothalamo-pituitary-gonadal axis, and the latter is due to sexual steroids and is unrelated to gonadotrophins.^[1] One of the most common causes of peripheral pseudoprecocious puberty is functional ovarian follicle cysts,^[1] which overlap with malignant juvenile granulosa cell tumors (JGCTs) in many aspects, but the behavior, treatment and prognosis of these two entities is completely different.

Case Report

Informant: Mother

A 5-year-old girl child presented with complaints of scanty to moderate bleeding per vaginum and bilateral painful enlargement of nipple buds since 10 days. There was no history of dysmenorrhea, galactorrhea, drug intake, vomiting, head injury, or recent growth spurt. Her family history and past history were unremarkable. She was a full term normal vaginal delivery baby with uneventful perinatal period. She had attained milestones normally and was immunized for age.

On examination, the child was afebrile, active, moderately built, weighing 21.5 kg, 113 cm in height and in 97^th percentile.

The breast buds were elevated (Tanner stage 2) with hyperpigmented nipples. Axillary hair was present (Tanner stage 1). The external genitalia appeared normal. There were no café-au-lait spots or bony deformities. The systemic examination was normal. The abdomen was soft, nontender with no organomegaly.

Her surgical profile was within normal limits. CA125-13 U/ml (normal: <35). The alpha-fetoprotein, beta unit of human chorionic gonadotrophin, testosterone, follicle-stimulating hormone, luteinizing hormone and prolactin levels in serum were within normal range. Serum estradiol was elevated to 39 pg/ml (normal: 6–27 pg/ml).

The chest X-ray and magnetic resonance imaging (MRI) brain were normal. X-ray of the wrist showed bone age of 6 to 7 years. The ultrasonography of the abdomen showed an enlarged uterus with a right ovarian cyst 36 mm × 28 mm with few smaller cysts within. The MRI pelvis plain showed a 42 mm × 31 mm × 42 mm cystic lesion with smaller cysts within and no solid component. Impression on MRI was a simple ovarian cyst [Figure 1]a and [Figure 1]b.

Figure 1: (a) Ultrasonography image – simple cyst in right ovary with multiple daughter cysts along the wall. (b and c) Magnetic resonance imaging image-A T1-weighted hypointense and T2-weighted hyperintense cystic lesion 42 mm × 31 mm × 42 mm with smaller daughter cysts within are present. No solid components seen. Normal right ovary not visualized, likely to be compressed. The uterus is enlarged 64 mm × 19 mm × 24 mm

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Cystectomy and right ovariotomy was done under general anesthesia. Ten milliliters of clear fluid were aspirated intraoperatively from the cyst. Its cytocentrifuge smears showed clusters and follicles of round to oval cells having round, hyperchromatic nuclei without any grooving. Possibility of JGCT was suggested [Figure 2]a.

Figure 2: (a) The cyst is thin walled, containing smaller cysts within. No solid areas seen. (b) Smear shows clusters of small cells with round, hyperchromatic nuclei. (H and E, ×100) (c) Smear shows small sheets of round cells with dark nuclei. No nuclear grooving seen (Giemsa stain, ×400)

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The gross specimen was a smooth, thin-walled, greyish, cystic mass, 20 g and 4 cm × 3 cm × 2.7 cm containing thin, clear, colorless fluid and few tiny cysts 0.5–0.8 cm within it [Figure 2]b. Compressed ovarian tissue was present on one side (0.4 cm × 0.8 cm). Histopathology showed multiple cystic areas lined by round to oval tumor cells showing the stratification (2–10 cell thick) with round hyperchromatic nuclei and eosinophilic cytoplasm. No nuclear grooving was evident. Mitotic activity was 6–8/10 high power field, (hpf). Some of the cysts showed eosinophilic granular secretions. Normal ovarian parenchyma was seen at the periphery. Immunohistochemistry (IHC) with calretinin showed 100% positivity and epithelial membrane antigen (EMA) was negative. IHC for inhibin was advised but could not be done. It was reported as JGCT of the right ovary [Figure 3]a,[Figure 3]b,[Figure 3]c,[Figure 3]d.

Figure 3: (a) Section shows a multilayered macrofollicle with central eosinophilic secretions. (H and E, ×100) (b) Section shows multilayered granulosa cells having dark, round nuclei and mitotic figures. (H and E, ×400) (c) Section shows 100% positivity with intense staining for calretinin. (Immunohistochemistry [IHC] for calretinin, ×100) (d) Section shows negative staining for epithelial membrane antigen (IHC for epithelial membrane antigen, ×100)

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Discussion

The first description of granulosa cell tumor of ovary was given by Rokitansky in 1855 as chronicled by Chew et al.^[2]

Histologically, the granulosa cell tumors are divided as an adult form accounting for almost 95% cases and a juvenile type accounting for 5% cases.^[3] Most of the cases of JGCT in prepubertal patients present with isosexual pseudoprecocity that is due to excessive estrogen production.^[3] The patients' age ranges from 6 months to 56 years (median age 17 years).^[4] Our case was also a 5-year-old child who presented with features of excessive estrogen secretion resulting in thelarche, bleeding per vaginum and increased bone age. They are sometimes associated with the McCune Albright syndrome, which have typical café-au-lait spots, endocrinopathies and fibrous dysplasias,^[5] but our case had none of these findings. Sometimes JGCTs may secrete androgens as reported by Nomelini et al.^[6] Usually, JGCT are solid and cystic, but they can be completely cystic as reported by Sahin et al.^[7] Our case also had a completely cystic presentation, with estrogenic manifestations. JGCT vary in size from 2.5 cm to 30 cm in diameter with an average of 12 cm.^[8] Our patient also had a cystic tumor of 4.5 cm diameter. The closest differential diagnosis would be a functional follicular cyst as they too secrete estrogen and have a similar presentation.^[1] However, JGCT is a malignant tumor, whereas, simple, functional cysts are completely benign and self-limiting with spontaneous resolution in some.^[1] The correct diagnosis in our case was ascertained only on histopathology. The JGCT show mixture of cysts and solid areas having macrofollicles containing secretions and are lined by one or more layers of granulosa cells with or without a rim of theca cells. The tumor nuclei are large, round, hyperchromatic and the mitoses is about 6/10 hpf. Nuclear grooving and Call–Exner bodies are absent.^[8],[9] Our case also showed good mitotic activity (6–8/10 hpf) and nuclear atypia and hence, despite the small size of the lesion, a diagnosis of JGCT was entertained. IHC for calretinin and EMA showed results as expected for JGCT.^[8]

The prognosis for stage 1 tumors (confined to the ovary) is excellent and treated adequately by a unilateral salpingo-oophorectomy. However, late recurrences are known to occur, so a long term follow-up is a must. Our patient was lost to follow-up.

Conclusion

Pseudoprecocious puberty in young girls is most often due to functional ovarian follicular cysts. However, cystic JGCTs form an important differential diagnosis. Attention has to be paid to the histopathological features and IHC study is helpful. As JGCT is known for metastatic potential and late recurrences, long-term follow-up is essential.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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