This tumor, as the name implies, usually presents in children before puberty. In spite of its name, it bears little histologic resemblance to the adult granulosa cell tumor. About 80% of these tumors presenting in children result in isosexual precocity. Tumors that present after puberty may have abdominal swelling and pain associated with menstrual irregularities or amenorrhea.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/Immunohistochemistry/Electron Microscopy Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE Rare
5% of all granulosa cell tumors
97% occur within first three decades
Rare after 30 years
DISEASE ASSOCIATIONS CHARACTERIZATION Ollier's disease (Enchondromatosis) Mafucci's syndrome (Enchondromatosis and hemangiomatosis)
GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION General Bilateral in 2%
Ruptured at initial discovery in 10%
Ascites in 10%
Size Average 12.5 cm
Range 3-32 cm
Solid and cystic neoplasm with cysts containing hemorrhagic fluid
Solid is yellow-gray with extensive necrosis or hemorrhage
HISTOLOGICAL TYPES CHARACTERIZATION Classic
Solid cellular neoplasm with focal follicle formation
Solid areas with diffuse cells that may be divided into nodules by fibrous septa
Granulosa and theca cells may be admixed
Follicles vary in size and shape with eosinophilic or basophilic secretions staining positive for mucicarmine in 2/3 of cases
The tumor cells have rounded hyperchromatic nuclei which lack the nuclear grooves seen in the adult variant-there is also frequent abundant luteinized eosinophilic cytoplasm
In general, there is wide variability in nuclear atypia
Mitotic rate varies from 5-7 MF/10 hpf
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Adult granulosa cell tumors Small cell carcinoma of hypercalcemic type Thecoma Malignant germ cell tumor
SPECIAL STAINS/IMMUNOHISTOCHEMISTRY CHARACTERIZATION GENERAL
Ovarian sex cord-stromal tumors: an immunohistochemical study including a comparison of calretinin and inhibin.
Deavers MT, Malpica A, Liu J, Broaddus R, Silva EG.
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Mod Pathol. 2003 Jun;16(6):584-90. Abstract quote
Because ovarian sex cord-stromal tumors (SCST) are morphologically heterogeneous neoplasms that are relatively infrequently encountered, their diagnosis can be difficult. Immunohistochemical staining may be useful for establishing the diagnosis in problematic cases.
We studied 53 ovarian SCSTs to characterize their immunohistochemical staining pattern: 17 adult granulosa cell tumors (AGCTs), 4 juvenile granulosa cell tumors (JGCTs), 3 sex cord tumors with annular tubules (SCTATs), 9 Sertoli-Leydig cell tumors (SLCTs), 10 fibromas, 5 fibrothecomas (FTs), and 5 thecomas. In 8 of the 53 cases, the tissue studied was from a metastatic site. The immunopanel included calretinin, inhibin, WT1, cytokeratin cocktail, epithelial membrane antigen (EMA), and cytokeratin 5/6 (CK5/6). The fibromas and FTs were also tested with CD10. The extent of staining was assessed in a semiquantitative fashion and ranked on a scale of 0 through 4+. All of the tumors, except for 1 metastatic SLCT, were positive for calretinin. Forty-five of the cases (85%) stained for inhibin; 1 metastatic AGCT, 3 fibromas, and 4 FTs were negative. WT1 was present in 39 tumors (74%), with expression most prominent in the SLCTs. The cytokeratin cocktail stained 23 of the 53 tumors (43%), whereas just 1 tumor was positive for EMA (1+ in a JGCT). All tumors were negative for CK5/6, and the 15 fibromas and FTs were negative for CD10.
We conclude that because cytokeratin is frequently expressed by SCSTs, in particular by granulosa cell tumors, SLCTs, and SCTATs, the inclusion of EMA in a panel may help to exclude epithelial neoplasms. In addition, WT1, present in normal granulosa cells, is expressed by a majority of SCSTs. Finally, these results demonstrate that calretinin is at least as sensitive as inhibin for ovarian SCSTs overall and that it is more sensitive than inhibin for fibromas and FTs.
Immunohistochemical staining for calretinin is useful in the diagnosis of ovarian sex cord-stromal tumours.
McCluggage WG, Maxwell P.
Department of Pathology, Royal Group of Hospitals Trust, Belfast and The Queen's University of Belfast, Grosvenor Road, Belfast BT12 6BL, Northern Ireland.
Histopathology 2001 May;38(5):403-8 Abstract quote
AIMS: Ovarian sex cord-stromal tumours are a heterogeneous group of neoplasms which may be confused morphologically with a wide variety of tumours. Calretinin positivity has previously been demonstrated in a small number of ovarian sex cord-stromal tumours. The aim of this study was to investigate calretinin staining in a series of these tumours and their histological mimics in order to determine the value of calretinin staining in a diagnostic setting.
METHODS AND RESULTS: Seventy-two neoplasms, including 37 ovarian sex cord-stromal tumours and 35 miscellaneous neoplasms which may enter into the differential diagnosis, were stained with a commercially available polyclonal antibody against calretinin. All sex cord-stromal tumours exhibited positivity except for a single fibrothecoma. In this group of tumours staining was generally diffuse and strong. Small numbers of the miscellaneous group of neoplasms exhibited positivity but this tended to be focal and weak, although this was not always the case. There was consistent strong positive staining of granulosa cells in follicular cysts and corpora lutea. There was also positive staining of luteinized stromal cells in two cases of ovarian stromal hyperplasia and hyperthecosis.
CONCLUSIONS: Calretinin is a sensitive immunohistochemical marker of ovarian sex cord-stromal tumours and may be useful in a diagnostic setting. However, the value is somewhat limited since occasional neoplasms which enter into the morphological differential diagnosis may be positive. Be that as it may, calretinin positivity may be of value in the diagnosis of an ovarian sex cord-stromal tumour and its differentiation from other neoplasms. In this regard, calretinin should always be used as part of a larger panel.
Inhibin immunohistochemical staining: a practical approach for the surgical pathologist in the diagnoses of ovarian sex cord-stromal tumors.
Zheng W, Senturk BZ, Parkash V.
Adv Anat Pathol 2003 Jan;10(1):27-38 Abstract quote
Through a brief introduction of inhibin history, characteristics of the antibody against inhibin, and normal tissue distribution of alpha-inhibin expression, this comprehensive review focuses on a practical approach to using alpha-inhibin in the differential diagnosis of ovarian sex cord-stromal tumors (SCSTs). Alpha-inhibin has become a most useful immunohistochemical marker of gonadal SCST, regardless if the tumors are primary, recurrent, or metastatic. However, pathologic diagnosis of individual SCST is still based largely on morphologic criteria.
Alpha-inhibin immunohistochemical (IHC) staining should be used only when a difficult morphologic diagnosis is encountered. In this perspective, alpha-inhibin and other properly selected markers should be ordered at the same time. This is simply because alpha-inhibin is not specific for SCSTs.
Caution should be exercised in the interpretation of alpha-inhibin-positive cells, because a wide variety of primary and metastatic ovarian tumors may contain significant numbers of alpha-inhibin-positive stromal cells. As with other immunohistochemical stains, a panel of stains and comparison with the corresponding hematoxylin and eosin (H&E) slides is necessary, especially when staining patterns and cellular localization are in question. The antibody will not help to differentiate tumors within the category of SCST. The pattern or the intensity of staining in SCSTs does not predict tumor behavior, although there is a tendency of loss of alpha-inhibin expression in poorly differentiated Sertoli or Sertoli-Leydig cell tumors.
In cases where metastatic granulosa or Sertoli-Leydig cell tumors are a concern, positive alpha-inhibin staining is diagnostic, but a negative result does not rule out metastatic disease. Calretinin has been recently recognized as a more sensitive, but less specific marker for SCSTs and it may be used to recognize an inhibin-negative SCST.
In this review, we have listed nine of the most commonly encountered clinical scenarios where alpha-inhibin and other markers could be used in diagnostic surgical pathology of ovarian tumors.
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors
Rupture has no adverse prognostic effect
Confined to ovary has excellent prognosis
General correlation with increased mitotic figures and nuclear atypia but no correlation in stage I tumors
5 Year Survival Overall high cure rate Metastasis
2/80 stage I tumors were clinically malignant
2/10 stage IC tumors were malignant
3/3 stage II tumors were fatal
Treatment Stage IA tumors may be treated with unilateral salpingo-oophorectomy
Blaustein's Pathology of the Female Genital Tract-Fourth Edition. Springer-Verlag. 1994.
Adult granulosa cell tumor
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