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CASE REPORT
Year : 2020  |  Volume : 13  |  Issue : 1  |  Page : 89-92  

Juvenile granulosa cell tumor of the ovary in a 7-year-old girl: Rare case report


1 Department of Pediatric Surgery, SMS Medical College, Jaipur, Rajasthan, India
2 Department of Pathology, SMS Medical College, Jaipur, Rajasthan, India

Date of Submission19-Mar-2019
Date of Decision26-Jun-2019
Date of Acceptance03-Sep-2019
Date of Web Publication16-Dec-2019

Correspondence Address:
Aditya Pratap Singh
Near The Mali Hostel, Main Bali Road, Falna, Pali, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_86_19

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  Abstract 


Ovarian granulosa cell tumor (GCT) is a rare ovarian neoplasm, which typically occurs in children and young women. More than 90% of the patients are diagnosed in Stage IA, who can be cured by unilateral oophorectomy. Meanwhile, the remaining is diagnosed in more advanced stages, wherein tumors may exhibit aggressive behavior. In this stage, surgery and adjuvant chemotherapy may be required. Isosexual precocious puberty in girls is mostly idiopathic in origin. However, this is a diagnosis of exclusion, and many differential diagnoses have to be thought of in evaluation of precocity in girls. We are presenting here a case of isosexual precocity in a 7-year-old girl due to juvenile GCT of ovary, a rare etiology of precocity.

Keywords: Granulosa cell tumor, juvenile, precocious puberty, salpingo-oophorectomy, surgery


How to cite this article:
Singh AP, Gupta AK, Jindal A, Ansari M. Juvenile granulosa cell tumor of the ovary in a 7-year-old girl: Rare case report. Med J DY Patil Vidyapeeth 2020;13:89-92

How to cite this URL:
Singh AP, Gupta AK, Jindal A, Ansari M. Juvenile granulosa cell tumor of the ovary in a 7-year-old girl: Rare case report. Med J DY Patil Vidyapeeth [serial online] 2020 [cited 2020 Jul 7];13:89-92. Available from: http://www.mjdrdypv.org/text.asp?2020/13/1/89/272891




  Introduction Top


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 hypothalamic–pituitary–gonadal axis, and the latter is due to sexual steroids and is unrelated to gonadotrophins.[1]

Peripheral or gonadotropin-independent precocity constitutes <20% of precocity cases.[2] Causes of isosexual peripheral precocity in girls include ovarian follicular cyst, estrogen-secreting adrenal or ovarian tumors (granulosa cell tumor [GCT], sex cord tumor, and estrogenizing Sertoli–Leydig cell tumors), and environmental exposure to compounds with estrogenic activity, severe untreated primary hypothyroidism, and McCune–Albright syndrome. Functional ovarian follicular cysts are the most frequent cause.[2]


  Case Report Top


A 7-year-old healthy girl presented to us with the complaint of vaginal bleeding with mild lower abdominal pain for the last 1 month. There was no history of meningitis, cranial irradiation, head trauma, seizures, medication intake, headache, visual problem, or behavioral change. There was no evidence of local trauma or sexual abuse. Family history was negative for precocious puberty, endocrine, autoimmune, and malignancy disorders. On physical examination, she looked well, conscious, alert, and oriented. Vital signs and physical examinations were normal. Routine blood investigations were within normal limits including complete blood counts, renal function test, and serum electrolytes. There was a hypogastric region palpable mass in abdominal examination; local genital examination was within normal limits [Figure 1]a. Tumor markers were within normal limits including beta human chorionic gonadotropin and alpha fetoprotein except serum estradiol rose. Ultrasonography abdomen showed heterogeneous lesion measuring 9.7 cm × 5.8 cm × 8.3 cm (vol 248cc) with solid and cystic component in the right adnexa with minimal vascularity. Contrast enhanced computed tomography (CT) showed well-defined complex solid cystic mass lesion seen in the lower abdominal pelvic location measuring approximately 97 mm × 86 mm × 63 mm in size with mild right side hydroureteronephrosis [Figure 2]a and [Figure 2]b. It was suggested of ovarian neoplasm. A diagnosis of precocious pseudopuberty due to estrogen-producing ovarian tumor was reached. She underwent laparotomy, a right salpingo-oophorectomy was done, and the mass was sent for histopathological examination [Figure 1]b. The pathology report showed diffuse proliferation of neoplastic cells with irregular macrofollicles; tumor cell nuclei were large and round without nuclear grooves with rich vascular network. The mitosis was 4–6/hpf with necrosis. All findings were consistent with juvenile GCTs (JGCTs) [Figure 3]a, [Figure 3]b, [Figure 3]c, [Figure 3]d. Immunohistochemistry showed tumor cells were positive for vimentin, calretinin, and reticulin and negative for CK, EMA, CD 99 [Figure 4]a and [Figure 4]b. It was also in favor of JGCT. Inhibin positivity was ambiguous.
Figure 1: (a) Preoperative photo, (b) peroperative photo

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Figure 2: (a and b) Contrast-enhanced computed tomography abdomen images

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Figure 3: Histopathology slides' images ([a] follicle, [b] macrofollicular pattern, [c] lacking of coffee bean nuclei of adult granulosa cell tumor, and [d] granulosa cell tumor low power)

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Figure 4: Immunohistochemistry images ([a] calretinin and [b] reticulin)

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  Discussion Top


Ovarian JGCT is an extremely rare sex cord-stromal tumor of the ovary that accounts for 2%–5% of malignant ovarian neoplasms. According to the literature, the mean age of presentation of JGCT is 13 years.[3]

Ovarian tumors are uncommon during childhood and are rare causes of precocity.[1] Ovarian sex cord-stromal tumors are neoplasms containing granulosa cells,  Sertoli cells More Details, theca cells, Leydig cells, and fibroblasts of gonadal stromal origin. GCTs represent about 2% of all ovarian tumors and fall under ovarian sex cord-stromal tumors. There are two types: adult GCT (95% of cases) and JGCT (5% of cases).[4] Adult and JGCT have differences which are illustrated in [Table 1].
Table 1: Differences between the adult and juvenile granulosa cell tumor

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JGCT can present with some other conditions such as tuberous sclerosis, nonhereditary congenital syndromes like Ollier's diseases, and Maffucci syndrome. Bilateral presentation can be seen in Goldenhar and Potter syndrome.

The most frequent presentation in prepubertal girls is precocity.[5] Clinical manifestations may also include hyperandrogenism, pleural effusion, ascites, or surgical emergency.

Secondary amenorrhea, virilization, abdominal pain, or abdominal mass may be the presenting symptoms in postpubertal girls.[6] Peritoneal rupture and recurrence are higher in postpubertal girls. In our case, presentation was abdominal mass with vaginal bleeding.

Isosexual precocity occurs in 70%–80% of prepubertal girls with GCT.[7] However, only 1% of all cases of sexual precocity in prepubertal girls are due to granulosa and theca cell tumors. This hormonally active ovarian neoplasm is an estrogen-producing tumor which may lead to its early detection. Advanced bone age and accelerated height velocity were seen due to tumor-derived estradiol,[8] while in our case, there was no such finding.

The presence of undetectable basal serum follicular-stimulating hormone and luteinizing hormone levels had a specificity of 95% in girls with gonadotropin-independent precocious pseudopuberty.[4] Tumor markers, whether positive or negative, are not conclusive in all cases but useful for postoperative surveillance.

On CT and ultrasonography, they most typically appear as large, multilocular masses, with either thin or thick septations, as well as solid components, predominantly solid or large multisystem mass.[4] Ovarian tumors are usually capsulated, and extracapsular invasion is rare.[4]

Most of prepubertal patients with JGCT present with isosexual precocious pseudopuberty, which may include breast enlargement, development of pubic hair, increased vaginal secretions, vaginal bleeding, advanced somatic development, and other secondary sex characteristics.[8],[9] Serum estradiol concentration is nearly always elevated, but there have been reports of pseudopuberty even with normal or low estradiol concentrations.[8] Hormonal disorders are often associated with other signs: most commonly, abdominal swelling, pain, constipation, and a palpable tumor in the lower abdomen.[9] In our case, there was only vaginal bleeding and lump abdomen. Serum estradiol level was normal in our case.

JGCT of ovaries are characterized by the presence of solid and follicular structures. Follicles have irregular size and shape. Neoplastic cells have ample eosinophilic cytoplasm, polymorphic nuclei, and mitotic figures. Cytologic atypia varies from mild to severe, and mitotic figures are abundant.[10] The correct diagnosis in our case was ascertained only on histopathology. The JGCT shows 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, and hyperchromatic, and the mitoses is about 6/10 hpf. Nuclear grooving and Call–Exner bodies are absent.[11]

A positive immunohistochemical stain for inhibin is also diagnostic. Pathologic and immunohistochemical parameters may not decide the prognosis. Inhibin B and anti-Mullerian hormone are useful serum markers.[12] Immunohistochemistry is a useful adjunct for an accurate diagnosis. Tumor cells are characteristically immunoreactive for inhibin and/or calretinin.[10]

Unilateral oophorectomy is the first choice of therapy. Early diagnosis of JGCT is important, as adjuvant treatment may not be necessary if the tumor is localized to ovaries.[4],[7] Tumor staging is by International Federation of Gynecology and Obstetrics (FIGO) system. Most tumors at FIGO Stage IA have a favorable prognosis, whereas those at higher stages have a less favorable outcome.[4] Five-year survival rates are 90%–95% for FIGO Stage I tumors and 25%–50% for advanced stages.[4] Recurrences occur during the first 3 years after diagnosis. Stage I JGCTs are less likely to recur after surgery, although late recurrences can occur even in Stage I patients, necessitating long-term follow-up.


  Conclusion Top


Ovarian masses, although rare in children, must be included in the differential diagnosis of all girls who present with abdominal pain, swelling, or precocious puberty. The prognosis of the JGCT is excellent after salpingo-oophorectomy in patients who have only ovarian involvement.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

We would like to thank Dr. Neelam Dogra, Senior Professor, Department of Anaesthesia, SMS Medical College, Jaipur, Rajasthan, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Mitrović K, Zdravković D, Milenković T, Sedlecki K, Stanković Z. Ovarian cysts and tumors as the cause of isosexual pseudoprecocious puberty. Srp Arh Celok Lek 2006;134:305-9.  Back to cited text no. 1
    
2.
Lee CT, Tung YC, Tsai WY. Etiology and clinical features of isosexual precocious puberty in Taiwanese girls: Twenty-three years' experience in national Taiwan university hospital. J Pediatr Endocrinol Metab 2009;22:947-53.  Back to cited text no. 2
    
3.
Heo SH, Kim JW, Shin SS, Jeong SI, Lim HS, Choi YD, et al. Review of ovarian tumors in children and adolescents: Radiologic-pathologic correlation. Radiographics 2014;34:2039-55.  Back to cited text no. 3
    
4.
Cartault A, Caula-Legriel S, Baunin C, Le Mandat A, Lemasson F, Galinier P, et al. Ovarian masses in adolescent girls. Endocr Dev 2012;22:194-207.  Back to cited text no. 4
    
5.
Kalfa N, Méduri G, Philibert P, Patte C, Boizet-Bonhoure B, Thibaut E, et al. Unusual virilization in girls with juvenile granulosa cell tumors of the ovary is related to intratumoral aromatase deficiency. Horm Res Paediatr 2010;74:83-91.  Back to cited text no. 5
    
6.
Patel SS, Carrick KS, Carr BR. Virilization persists in a woman with an androgen-secreting granulosa cell tumor. Fertil Steril 2009;91:933.e13-5.  Back to cited text no. 6
    
7.
Dogra S, Yadav YK, Sharma U, Gupta K. Juvenile granulosa cell tumor with an unusual immunoprofile, presenting as precocious puberty. South Asian J Cancer 2013;2:150.  Back to cited text no. 7
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8.
Merras-Salmio L, Vettenranta K, Möttönen M, Heikinheimo M. Ovarian granulosa cell tumors in childhood. Pediatr Hematol Oncol 2002;19:145-56.  Back to cited text no. 8
    
9.
Bouffet E, Basset T, Chetail N, Dijoud F, Mollard P, Brunat-Mentigny M, et al. Juvenile granulosa cell tumor of the ovary in infants: A clinicopathologic study of three cases and review of the literature. J Pediatr Surg 1997;32:762-5.  Back to cited text no. 9
    
10.
Deavers MT, Oliva E, Nucci MR. Sex cord-stromal tumors of the ovary. In: Nucci MR, Oliva E, editors. Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series. Elsevier Churchill Livingstone; 2009. p. 445-500.  Back to cited text no. 10
    
11.
Zaloudek CF. Tumors of the female genital tract. In: Fletcher CD, editor. Diagnostic Histopathology of Tumors. 3rd ed.. China: Elsevier Ltd.; 2007. p. 592-3.  Back to cited text no. 11
    
12.
Geerts I, Vergote I, Neven P, Billen J. The role of inhibins B and antimüllerian hormone for diagnosis and follow-up of granulosa cell tumors. Int J Gynecol Cancer 2009;19:847-55.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1]



 

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