Synchronous primary tumors of the endometrium and ovary

Background: Primary synchronous cancer of the female genital tract is a relatively uncommon. Simultaneously detected endometrial and ovarian malignancies constitute the commonest occurrence. A set of pathological criteria has been described to differentiate synchronous primaries from metastatic tumors. The purpose of this study was to characterize patients with synchronous primary endometrial and ovarian tumors. Materials and Methods: This was a retrospective study done in Department of Pathology, Tribhuwan University Teaching Hospital from September 2006 to August 2011. The datas were retrieved from computer database. Results: There were totally of 10 cases of simultaneously detected endometrial and ovarian cancers. Out of 10 cases, 7 cases were synchronous primary endometrial and ovarian cancers while three were metastatic. Median age at presentation was 47.4 years. Six (85.8%) of these patients presenting with dual primary tumors were premenopausal. Grade 1 histology was seen in 57% of endometrial and 42% of ovarian tumors. Atypical endometrial hyperplasia was found in 42.8% of cases while none of the cases showed endometriosis. Conclusion: Though limited by relatively small number of cases, younger and premenopausal women were predisposed to developing synchronous primary tumors of the endometrium and ovary. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6019 JPN 2012; 2(3): 189-192


INTRODUCTION
Primary synchronous cancers of the female genital tract are a relatively uncommon comprising 1-6% of all genital neoplasms.Amongst these, simultaneously detected endometrial and ovarian malignancies constitute the commonest occurrence. 1 Synchronous tumors can be classified into three groups 2 1. Endometrial cancer with metastasis to the adnexa.2. Ovarian cancer with metastasis to the endometrium.3. Synchronous primary tumors.Karki S 1 , Chapagain U 1 1

Department of pathology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal
A set of pathological criteria was devised by Ulbright and Roth for distinguishing metastatic tumors from synchronous primary tumors. 36][7] Currently, differentiating a single primary with metastasis from dual primary cancer involves clinicopathological correlation.But in some cases establishing the relation between co-existing ovarian and endometrial cancers with certainty may still be a diagnostic challenge. 8he purpose of this study was to characterize patients with synchronous primary endometrial and ovarian tumors.

MATERIALS AND METHODS
This was a retrospective study in which 10 cases of simultaneously detected endometrial and ovarian cancers from September 2006 to August 2011, in the Department of Pathology, Tribhuvan University Teaching Hospital were included for study.
Diagnosis of endometrial and ovarian tumors was made on the basis of WHO criteria. 4Pathologic characteristics such as histology of primaries, depth of myometrial invasion, grades, lymphovascular invasion, presence of endometrial hyperplasia or endometriosis for endometrial and ovarian tumors, were collected from computer database.Datas were analyzed by using software SPSS 10.0 version.

RESULTS
There were 10 (0.03%) cases of simultaneously detected endometrial and ovarian cancers.Out of 10 cases, 7 cases were synchronous primary endometrial and ovarian cancers while 3 were metastatatic cancers.Age ranged from 37-51 years with a median age of 47.4 years for synchronous primary tumors.Six of these patients presenting with dual primary tumors were premenopausal.In the metastatic group, the median age at presentation was 59.4 years and all 3 patients were postmenopausal.The macroscopic and histopathologic features of endometrial and ovarian tumors are summarized in Table 4 and Table 5. Comparisons of coexisting tumors are shown in Table 6.

DISCUSSION
The occurrence of coexisting primary malignancies of the female genital tract and their distinction from metastatic disease is a challenging subject in gynecologic oncology as it has associated prognostic and therapeutic significance.In the present study, the age range of patients with synchronous primary cancers was 37-51 years with a median age of 47.4 years, whereas in the metastatic group it was 59.4 years.
Other studies have demonstrated median age ranging from 41-54 years. 2,5,9It is worth mentioning that 6 (85.8%) of the patients with synchronous primaries were premenopausal while all patients with metastasis were post menopausal.In a similar study, it was found that 16/30 cases (53%) with synchronous primary tumors were premenopausal. 10e presence of precancerous histological features generates a strong evidence of in situ genesis rather than metastasis in endometrium and ovaries.Presence of atypical endometrial hyperplasia or endometriosis suggests de novo development of cancers in endometrium and ovary respectively. 1,11In this study atypical endometrial hyperplasia was found in 3 cases while none of the cases showed endometriosis.In a similar study 14/30 cases had histological evidence of endometrial hyperplasia and 8/30 had endometriosis. 10l 7 cases of synchronous primaries were of endometrioid cell type (fig. 1) and all of the tumors were concordant in  both sites.In another study 90% of the dual primaries were endometrioid cell type and the cell type was concordant in both sites in 93% of the cases. 1 This is about the expected frequency of adenocarcinoma arising in the endometrium while serous carcinoma is the commonest cell type of carcinoma arising in the ovary in isolation. 1st of the tumors were histological Grade 1 in both the endometrium (57%) and ovary (42%) This distribution of histological grade is similar to the study of Zaino et al 1 and Eifel et al. 5 It has been found in other studies that well differentiated tumors were associated with lower probability of recurrence but the cell type did not contribute significantly to the prediction of recurrence. 1 According to the criteria of Ulbright and Roth 3 , features favoring metastasis like multinodular configuration of ovary, ovarian size <5 cm, bilateral ovarian involvement, vascular invasion and tubal involvement were rare.Furthermore, endometrial hyperplasia and superficial myometrial invasion which are commonly seen in carcinoma arising in the endometrium were frequently observed in the uteri whereas vascular invasion was rare.All these observations suggest that these cases represent simultaneous development of carcinomas in both the endometrium and ovary.Similar results were obtained in a study carried out by Chen et al. 12 Synchronous primary cancers of the endometrium and ovary in this series presented at an earlier stage.In several other studies also presentation of these dual primary cancers at an earlier stage was seen. 10,12Typically it is noted that isolated ovarian cancers are usually diagnosed at advanced stages due to the non specific symptoms of the disease. 135][16] Only 53% concordance rate between genetic and histopathologic diagnosis for synchronous primary tumors was seen in a study based on loss of heterozygosity pattern. 17though a variety of clinical and pathologic characteristics have been proposed for the determination of the origin of such dual primaries, it is not certain whether all these features are always able to distinguish synchronous primaries from metastasis from one site to another.In such cases, it seems that genetic studies and molecular analysis will further help in characterizing and favoring the diagnosis of synchronous primary tumor over metastasis.

CONCLUSION
Overall survival and progression free survival of synchronous primary cancers in patients with endometrial cancer is better than those with ovarian metastasis.Metastasis represents an advance stage cancer with requirement of more aggressive therapy.Thus the diagnosis given will influence the patients' treatment and outcome.Hence, it is recommended to categorize patients with synchronous primary tumors of the endometrium and ovary.

Table 3 : Endometrioid tumors of the ovary and endome- trium 4
Absence of other evidence of spread of ovarian tumor 10.Ovarian endometriosis present 11.Different ploidy of DNA indices, if aneuploid, of the tumorsa 12. Dissimilar molecular genetic or karyotypic abnormalities in the tumors

Table 6 : Coexisting endometrial and ovarian cancers
E: endometroid type