The SCSTs account for approximately 7% of all ovarian tumors
[1, 3, 4]. Although these usually present at younger age group, there is wide age range of presentation and wider morphologic spectrum of these tumors
[3, 5]. The coexistence of two different types of sex-cord stromal tumors is also extremely rare
In Pakistan, little research has been done focusing on epidemiology of ovarian sex cord stromal tumors. In this retrospective analysis, we aimed to report the experience with a large series of these rare tumors in a major tertiary care center in Pakistan.
Most of the characteristics of our study population were similar to those reported in the literature. The commonest symptoms are abdominal pain and distention along with menstrual disturbances. However in our study population, the hormonal changes were not very frequently observed. In our series, just under half of women were below the age of 50 at the time of diagnosis and fertility sparing surgery is often desired among these women. So the nature of specimen listed in Table
3 vary according to the tumor type hence reflecting the median age of patient at the time of diagnosis and the surgical impression of malignancy intra-operatively. Moreover there was little variation in size of tumors among the sub-groups, hence did not correlate significantly with the benign or malignant nature of tumor. In children, the most frequent tumors were JGCTs followed by SST, SLCT and fibrothecomas.
Newer entities were also encountered though less frequently as reported in literature to date. Total 5 mitotically active cellular fibromas were found, exclusive of 7 cellular fibromas.
GCTs are sex-cord-stromal tumors that make up 70% of all such tumors but in our study these tumors comprised of 43.5% of all the sex cord stromal tumors that were diagnosed during the study period. The granulosa cell tumors are divided into adult (95%) and juvenile (5%) types based on specific diagnostic histological findings; however our observation showed that juvenile granulosa cell tumors were around 10% of all GCT which is bit higher than reported in other large series. The JGCT occurred in premenarchal girls and young women
Inhibin was positive in all the granulosa cell tumors. Cytokeratin’s dot positivity was observed in most of the cases of AGCT (76.5%). In JGCTs, Cytokeratin negativity was one of the major helpful features to rule our epithelial malignancy despite greater nuclear pleomorphism and mitotic activity than adult granulosa cell tumor. Molecular analysis is also helpful in diagnosis of AGCT, which was not available in our set-up. Complete follow-up data of only 86 patients was available with mean follow-up duration of 37 months. In our study population, late recurrences with the granulosa cell tumors were not infrequent, encountered in 5 patients, which re-emphasizes the need for long term follow-up of these patients
[12–14]. When the disease could not be completely resected or recurred after surgical resection, prognosis was poorer with 1 patients dying soon after recurrence. Metastasis was observed at the time of presentation in 13 of the cases and subsequent metastasis was observed in 4 of patients.
Addition of Calretinin and WT-1 these two antibodies was found to be quite useful in the diagnosis of ovarian SCSTs in equivocal cases
Among total 98 cases of fibromas, the mean age of patients was in accord with the international data i.e. 42.2 years. Median age was 52, which was just slightly lower than the international published data. The seven Cellular fibromas had mean size of 14.5 cm, which is larger than the previously reported studies. 5 cases of mitotically active cellular fibromas had mean age of 46 years and mean size of 9.7 cm, which is comparable to the past series
[15, 16]. One case of fibroma was associated with carcinoma cervix and interestingly one case each with carcinoma of endometrium and endometrial hyperplasia, once again proving that these tumors are hormonally active as were many thecomas because endometrial pathology was present in 11 out of 26 cases of thecomas.
. Calretinin proved to be more sensitive than inhibin. In addition, we tested few of our subset of fibromas with CD10, because ovarian endometrial stromal sarcomas may have areas that resemble fibroma
. Follow-up of 37 cases was available including 3 cases each of mitotically active cellular fibroma and cellular fibroma. No metastasis was observed complying to the benign nature of tumor, however one case of mitotically active cellular fibroma recurred, 14 months after surgery.
Most of the ovarian sex cord stromal tumors, in which information regarding the FIGO stage was available, presented at Stage I. FIGO staging is the most important, globally accepted, prognostic factor. Most of fibromas and thecomas presented at stage I, in all cases except one in which tumor infiltrated the urinary bladder wall, and only in this case, moderate atypia and significant mitoses (3/10 HPF) were present
[18, 19]. Most common specimen received was unilateral oophorectomy, relating to the clinically and radiologically benign nature of most of the tumors. Predominantly only in granulosa cell tumors and Sertoli Leydig cell tumors among our study population, surgical staging procedures were done. And this number was also very low, but owing to no nodal metastasis in these cases, this might be appropriate. In patients with SLCT where proper surgical staging procedure was done (n = 19), it was found that majority of tumors (n = 11) presented at higher stage i.e. FIGO stage IIA/IIB or higher. Although mostly these tumors present at stage I, the probable explanation for presenting at higher stage in our observation could be the very low number of well-differentiated SLCT.
Total 34 cases of sertoli-leydig cell tumor were found. Mean age 35.2 years. Mean size 15.4 cm. Poorly differentiated were a little more frequent as compared to previous study data but SL tumor with heterologous elements were somewhat less.
SST is a very rare ovarian stromal tumour that was for the first time described by Chalvardjian and Scully. 26 cases of sclerosing stromal tumor were diagnosed with the mean age of 28.7 years, which was comparable to other studies
[23–26]. However age range was slightly wider, 10 to 64 years. In all cases except one, capsule was intact. Analysis of cut surface showed that most of the cases had solid and cystic areas, however 4 cases had entirely solid surface. The spindly cells were stained strongly for both ASMA and desmin along with Inhibin and theca like component stained positive with CD 99 and calretinin. Metastatic signet-ring cells were excluded with the negative staining for keratin and EMA.
Steroid cell tumors were total 10 in number. Mean age was 45.2 years, which was in accord with the previously reported mean age for this tumor
[20, 21]. Most common presentation was virilizing symptoms. Additional Immunohistochemical stain used was Melan A, which was positive in all of cases when applied. WT-1 was also positive in all the cases. Cytokeratins were negative in all the cases.
Sex cord stromal tumor with annular tubules was the diagnosis in 4 cases, with a wide age range of 15 to 57 years. Two of the cases were found to be associated with of Peutz-Jeghers Syndrome. In the other two cases, adequate history was not available. Because of this missing data, the strong association between SCTAT and Peutz-Jeghers Syndrome could not be re-substantiated.
Out of four bilateral cases, two were fibrothecomas, one was AGCT and one was sertoli leydig cell tumor. No two different sex cord stromal tumors occurred bilaterally at same time, however 8 fibrothecoma group tumors and 12 granulosa cell tumors were found to be associated with contralateral ovarian cystadenofibroma.
To our knowledge, this is first kind of study of long duration and large data set, addressing ovarian sex cord stromal tumors in Pakistani population specifically. Also our set-up is one of the largest anatomical pathology and oncology setup with laboratory specimen collection centres all over Pakistan, so representation of all of the parts of country has been done in this study. Although referral/second opinion cases were also included in this study so unusual cases such as AGCT were more commonly observed rather than Fibroma/FT as in many previously done international studies. However in our opinion this might not have affected the results to a larger extent as the other unusual and complex tumor i.e. SLCTs were encountered much less frequently as opposed to international data.
One of the drawbacks and deficiency of our study was unavailability of long term follow up of about half of the patients, which might be required to see the exact recurrence rate and patterns of metastasis of ovarian sex cord stromal tumors in our population