| Abstract|| |
Gonadoblastomas (GBYs) are rare gonadal tumors almost always arising from a dysgenetic gonad with a Y chromosome. Very rarely, GBYs appear in otherwise normal women with a history of pregnancy. The typical histological appearance of GBY can be altered by extensive deposition of basement membrane material, calcification, or overgrowth by a malignant tumor. Less than 10 cases have been reported with normal 46XX karyotype. Only six cases of GBY have been described in pregnant women. We present a unique case of GBY with dysgerminoma in a genotypically and phenotypically normal woman with a history of normal pregnancy, absence of virilization, and characteristic immunohistomorphological features.
Keywords: Fertile woman, gonadoblastoma with dysgerminoma, gonadoblastoma with normal karyotype
|How to cite this article:|
Kulkarni MM, Sinai Khandeparkar SG, Joshi AR, Bhayekar PV. Unilateral gonadoblastoma with dysgerminoma in normal fertile woman having a child: Extremely rare occurrence with characteristic immunohistomorphology. Indian J Pathol Microbiol 2016;59:527-9
|How to cite this URL:|
Kulkarni MM, Sinai Khandeparkar SG, Joshi AR, Bhayekar PV. Unilateral gonadoblastoma with dysgerminoma in normal fertile woman having a child: Extremely rare occurrence with characteristic immunohistomorphology. Indian J Pathol Microbiol [serial online] 2016 [cited 2020 May 29];59:527-9. Available from: http://www.ijpmonline.org/text.asp?2016/59/4/527/191815
| Introduction|| |
Gonadoblastomas (GBY) are rare gonadal tumors almost always arising from a dysgenetic gonad with a Y chromosome.  Most patients have 46XY karyotype or various forms of mosaicism.  The clinical picture may include a mass and virilization caused by the tumor, as well as clinical manifestations of the underlying gonadal disorder.  Very rarely, GBYs appear in otherwise normal women with a history of pregnancy.  GBYs have a distinct histological appearance which distinguishes them from any other gonadal neoplasm. It was first described by Scully in 1953.  They are composed of germ cells intimately admixed with sex cord derivatives resembling immature Sertoli and granulosa cells.  The typical histological appearance of GBY can be altered by extensive deposition of basement membrane material, calcification, or overgrowth by a malignant tumor. In 80% of cases, malignant tumor is germinoma. Its extent ranges from a focus of microinvasion to massive replacement of the underlying GBY. The differential diagnosis of GBY is pure dysgerminoma and sex cord tumor with annular tubules (SCTAT). SCTAT lacks germ cell component. Less than 10 cases have been reported with normal 46XX karyotype.  Only six cases of GBY have been described in pregnant women. , To the best of our knowledge, this is the seventh case of GBY in a normal fertile woman to be reported.
| Case Report|| |
A 20-year-old female presented to the gynecology outpatient department with pain in abdomen on and off for 1 month. Her last menstrual period was 10 days back. Her menstrual history was normal with regular 28-day cycle. She was G1P1 L1A0. She had a 2-year-old child. On local examination, she had tenderness in the left iliac fossa. On ultrasonography, the left adnexal mass was noted, measuring 7 cm × 6 cm. Right adnexa was normal in appearance. CA125 level was normal. The patient underwent excision of the left adnexal mass with omental biopsy. Grossly, it was measured 8 cm × 6 cm × 6 cm with attached fallopian tube. Externally, it was smooth. On cutting open solid, grayish white, lobular tumor mass was seen [Figure 1]a. On microscopic examination, tumor predominantly composed of dysgerminoma was visualized [Figure 1]b. Furthermore, there were areas of discrete cell nests composed of a mixture of germ cells and smaller epithelial-like cells. These smaller cells were round to oval and had pale nuclei. Within these nests, were seen round eosinophilic hyaline bodies [Figure 1]c. Areas of calcification were noted [inset, [Figure 1]c. Dysgerminoma component was immunoreactive for placental alkaline phosphatase [Figure 1]d. Vimentin showed immunoreactivity only in stromal component [Figure 1]e. Surrounding these nests, stroma showed cells which were immunoreactive for inhibin [Figure 1]f. The section from omentum was free of tumor. The diagnosis of GBY with dysgerminoma was given. XY fluorescence in situ hybridization (FISH) test was done, and female pattern was proved. There was the absence of Y chromosome signal.
|Figure 1: (a) Gross photograph showing well-circumscribed, lobular solid tumor mass. (b) Photomicrograph showing dysgerminoma component (H and E, ×400). (c) Photomicrograph showing gonadoblastoma component, intimate admixture of germ cells and stromal cells (H and E, ×100). Inset showing area of calcification (H and E, ×400). (d) Photomicrograph showing placental alkaline phosphatase immunoreactivity in dysgerminoma cells (×100). (e) Photomicrograph showing vimentin immunoreactivity in sex cord stromal cells and absent in germ cells of gonadoblastoma nest (×400). (f) Photomicrograph showing inhibin immunoreactivity in the luteinized stromal cells surrounding gonadoblastoma nest (×400)|
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| Discussion|| |
GBYs are found in 25%-30% of patients with XY gonadal dysgenesis and in 15%-20% of 45X/46XY individuals.  Only a small proportion of GBYs develops in 46XX females with no evidence of Y chromosome. The GBY locus is the only oncogenic locus on the human Y chromosome. The recent studies establish the testis-specific protein, Y-encoded (TSPY) gene to be the putative gene for GBY. TSPY serves normal functions in male stem germ cell proliferation and differentiation but is ectopically expressed in early and late stages of GBYs. Ectopic expression and actions of Y-located TSPY gene in incompatible germ cells, such as those in dysgenetic or ovarian environments and dysfunctional testis, disrupt normal cell cycle regulation and predispose the host cells to tumorigenesis.  Cytogenetically normal patients who have GBY may have the GBY gene on the X chromosome or the autosomes.  About 10 cases of GBY have been reported in normal XX karyotype.  Esin et al., in their literature search from PubMed, reported seven cases of GBY in women with normal karyotype from 1990 to 2007 including their case. All cases were in young females, the youngest being 10 years old and the oldest 27 years. All had coexisting germ cell tumor, GBY being common.  The incidence of GBY in fertile women continues to be extremely rare. 
Our patient had a normal menstrual history. She did not show any sign of virilization. It has been reported that dysgerminomas grow rapidly during pregnancy.  In our case, most of the tumors were composed of pure dysgerminoma. The foci of GBY showed all the characteristics defined by Scully. Prognosis of pure GBY and when associated with dysgerminoma is excellent. The presence of other germ cells tumors such as yolk sac tumors makes the prognosis unfavorable. Chemotherapy may be needed after surgery in cases of GBY associated with the other malignant germ cell tumor.  For patients with dysgenetic gonads, bilateral oophorectomy and hysterectomy are recommended. In cases with 46XX karyotype, the necessity of bilateral gonadectomy is less clear, and rareness of the situation makes it difficult to decide the appropriate treatment.  A wedge biopsy of other ovary can be done to see the presence of the tumor. This may be helpful in young women to conserve fertility. FISH or polymerase chain reaction in peripheral blood or from excised tumor could be done to detect low-grade mosaicism.  This was not done in our case due to the lack of facility.
The occurrence of GBY in abnormal gonads may not be an absolute rule.  More case studies can help to understand the pathogenesis of the development of GBY. Multiple sections and careful histopathological examination are the key to correctly diagnose underlying component of GBY in a case of dysgerminoma. This is a unique case of GBY with dysgerminoma in normal women with a history of normal pregnancy and absence of virilization.
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Maithili Mandar Kulkarni
Department of Pathology, Shrimati Kashibai Navale Medical College and General Hospital, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None