Atypical proliferative endometrioid tumor of ovary: Report of a rare case.

Borderline ovarian tumors represent 10-20% of epithelial ovarian neoplasms that typically have an excellent prognosis. Both the oncological behavior of this group of tumors and also the diagnostic histological criteria are intermediate between the specific criteria of benign and malignant. They usually occur in the third to fourth decade of women's lives and are limited to the ovary in 80% of cases. Atypical proliferative or borderline ovarian tumors constitute a group of epithelial tumors with an excellent prognosis due to the low aggressiveness, microscopic examination is mandatory in order to establish an accurate histological diagnosis in all cases of borderline ovarian tumors and to differentiate from well differentiated adenocarcinoma. We report a case of a 45 year old female who presented with irregular bleeding per vaginum and underwent hysterectomy with bilateral salpingo-oophorectomy. Atypical proliferative endometrioid tumor of the left ovary was an incidental finding, which is a very rare occurrence.

Introduction

Borderline Ovarian tumors, as a distinct category were first recognized by Taylor in 1929 who used terminologies like ‘semi-malignant’ and ‘borderline’ to describe them.[1] Subsequent WHO classifications separated this group from carcinomas and called them as atypical proliferative ovarian tumors or borderline tumors.[2] Another terminology which has also been used is ‘ovarian tumor of low malignant potential’. Borderline ovarian tumors represent 10-20% of epithelial ovarian neoplasms[3] with an incidence of 1.8-4.8 out of 100,000 women per year[4] and typically have an excellent prognosis. Both the oncological behavior of this group of tumors and also the diagnostic histological criteria are intermediate between the specific criteria of benign and malignant. They usually occur in the third to fourth decade of women's lives and are limited to the ovary in 80% of cases. This is reflected in a good overall survival rate of ten years for 90% of patients in the initial stages and 60-70% in the advanced stages[56] Atypical proliferative endometrioid ovarian tumors or borderline endometrioid ovarian tumors constitute a minuscule 0.2% among all ovarian surface epithelial tumors[7] We report a case of a 45 year old female who presented with irregular bleeding per vaginum and underwent hysterectomy with bilateral salpingo-oophorectomy. Atypical proliferative endometrioid tumor of the left ovary was an incidental finding, which is a very rare occurrence.

Case Report

A 45 year old female presented with complaints of irregular bleeding per vaginum off and on since the last two months. The general condition of the patient was stable. Per speculum examination revealed a large, firm mass protruding out from the cervical os. Ultrasound scan of the pelvis showed an enlarged uterus with a well defined heterogenous and hypoechoic mass lesion in the posterior lower uterine wall and extending to the posterior cervix, measuring 96 × 62 mm [Figure 1]. Both ovaries could not be localized because of the large uterus and the overall impression was that of a uterine fibroid. The patient was then taken up for surgery and hysterectomy with bilateral salpingo-oophorectomy was done in view of the enlarged left ovary. Peritoneal washings were also taken.

Figure 1

Ultrasonogram showing large mass posteriorly. Inset shows hypoechoic areas in the mass

A specimen of uterus with cervix and bilateral adnexa was received in the laboratory. Gross examination showed a firm, globular mass which had widened and distorted the cervix. It measured 9 × 6 × 6 cm, cut surface was firm with a whorled appearance and was attached at the isthmus. The endometrial thickness was 4 to 5 mm and no evidence of adenomyosis was seen on gross examination [Figure 2]. The left ovary was enlarged and measured 6 × 4 × 5 cm with a smooth external surface. The cut section was firm with multiple cysts ranging from 1to 3 mm in diameter filled with brownish colored fluid [Figure 2]. The right ovary measured 2 × 2 ×1.3 cm with a smooth external surface and was cystic on cut section. Microscopic examination confirmed the firm, globular mass to be leiomyoma with areas of myxomatous degeneration. Endometrium was in proliferative phase with no evidence of endometrial hyperplasia. No foci of adenomyosis were seen. The right ovary showed a benign follicular cyst with histologically normal fallopian tubes. Peritoneal washings were negative for malignant cells.

Figure 2

Photograph of the gross shows globular mass which distorted the cervix, cut section had a firm whorled appearance. Enlarged left ovary on cut section showed multiple cysts

The enlarged left ovary showed a solid tumor comprising of glands with intervening fibrous stroma. The glands were of varying sizes from small round to large tortuous, serrated and cystically dilated with areas of confluent epithelial proliferation which were less than 5mm in diameter. They were lined by tall columnar cells with coarse nuclear chromatin and nuclear stratification resembling those of proliferative phase endometrium [Figure 3]. Glandular complexity was evident, however no stromal invasion was seen. The intervening stroma was cellular and compact, composed of spindle cells and no associated endometriosis was noted. The tumor was limited to the left ovary and the capsule was intact. The histological diagnosis was Atypical Proliferative Endometrioid Tumor of the ovary, Pathologic Stage IA. The patient has been on regular follow up which was uneventful including serial imaging findings i.e. CT scans, were found to be unremarkable.

Figure 3

Microphotgraph of the left ovary showed a solid tumor comprising of glands of varying sizes, large tortuous, serrated and cystically dilated with areas of confluent epithelial proliferation with intervening fibrous stroma. Inset shows lining tall columnar cells with coarse nuclear chromatin and nuclear stratification

Discussion

Atypical Proliferative Ovarian Tumors or borderline ovarian tumors constitute a heterogenous group of epithelial tumors, which have intermediate clinical and histological features between benign cystadenomas, and high grade malignant surface epithelial ovarian tumors. Broadly speaking, they differ from benign cystadenomas by the presence of cellular atypia and from the high grade malignant tumors by the absence of stromal invasion. In fact, the absence of obvious stromal invasion is a principal diagnostic criterion for borderline ovarian tumors. Limited to ovary in 80% of cases, many of these tumors are often first identified during a routine pelvic examination or when the patient undergoes surgery for some other pathology, as was seen in the present case. An Australian case-control study, which documented the symptoms associated with borderline ovarian cancer, reported that 16% of the women experienced no symptoms before diagnosis. They reported the most common symptom as abdominal pain (44%), abdominal mass (12%) and gynecologic symptoms (12%).[8] In our case, the presenting symptom of menorrhagia was attributed to the large fibroid in the lower uterine wall and the enlarged ovary was not visualized on pre operative imaging. These tumors usually occur during the third to fourth decades of women's lives and have an excellent prognosis due to their low aggressiveness and being limited to the ovaries. In a review of 247 cases of borderline ovarian malignancy, Wong et al. reported an age range of 16 to 89 years with a mean age of 38 years, majority of the cases (92%) being in FIGO Stage I.[9] Our patient was a 45 year old premenopausal female with a recent history of menstrual irregularities, in whom borderline endometrioid ovarian carcinoma, restricted to one ovary was discovered incidentally.

Bell et al. in a study of 56 proliferative endometrioid tumors discussed the clinicopathologic features along with the criteria for invasion and the significance of microinvasion. They described three categories of atypical proliferative endometrioid tumor:

Atypical proliferative tumor

Atypical proliferative tumor with intraepithelial carcinoma (high grade cytology in the epithelium in a tumor lacking stromal invasion)

Atypical proliferative tumor with microinvasion, (less than 5mm in a linear dimension).

The proposed criteria for carcinoma were glandular confluence or destructive stromal invasion.[10] Roth et al. used the less preferred terminology of ovarian tumors of low malignant potential and compared them to well differentiated endometrioid adenocarcinoma.[7] The differentiating features were similar, i.e. the absence of destructive stromal invasion, glandular confluence or stromal disappearance. They defined intraepithelial carcinoma in a low malignant potential tumor as areas showing grade 3 nuclei, sometimes associated with an intracystic villoglandular or cribriform pattern. Microinvasion in an ovarian tumor of low malignant potential was defined as one or more areas of invasion with an area of ≤10 mm2. In both the above series, majority of the borderline endometrioid tumors were limited to the ovary, 41/41 in the study by Bell et al. and 29/30 cases in the study by Roth et al. To the best of our knowledge and after extensive literature search only two series reported by Bell et al. documenting 56 cases of atypical proliferative endometroid tumour of the ovay and Roth et al. 30 cases were found. This stresses on the rarity of such cases.[710] The bilaterality ranged from 2% to about 5% at the time of diagnosis. The predominant growth pattern was adenofibromatous in both the series and this histologic picture was also seen in our case. In addition, we also found glandular and papillary proliferations with a high grade of complexity and severe atypia in the lining epithelial cells. No squamous differentiation was noted and there was no stromal invasion, the growth being limited to only one ovary with the capsule intact. Both the above series of borderline endometrioid ovarian tumors in the long term followup of their cases have shown that neither the presence of intraepithelial carcinoma nor microinvasion have a bearing on the prognosis, which remains excellent in these cases.[710] All patients of borderline endometrioid tumors were found to be free from recurrent disease or metastasis whereas 20% of patients with well-differentiated endometrioid adenocarcinoma followed for >6 months developed recurrent disease.[7] It has been observed that endometrioid tumors of the ovary are usually carcinomas, while borderline forms are very rare; they can arise from endometriosis and can also be associated to endometrial hyperplasia. No foci of endometriosis were found either in the uterus or the ovary in this case and endometrium was also in proliferative phase with no evidence of hyperplasia/adenocarcinoma. In a retrospective cohort study of ovarian endometrioid adenocarcinoma, McMeekin et al. showed that endometriosis associated endometrioid adenocarcinoma was associated with a better prognosis and a longer disease free survival as compared to other endometrioid carcinomas which were not associated with endometriosis.[11] They concluded that these factors may reflect a more favorable biologic behavior of ovarian endometrioid adenocarcinoma when arising in association with endometriosis.

Conclusion

In conclusion, atypical proliferative or borderline ovarian tumors constitute a group of epithelial tumors with an excellent prognosis due to the low aggressiveness and the fact they are usually diagnosed in the early stages. As has already been previously emphasized, extensive sampling of the tumor especially from the solid and papillary areas and meticulous microscopic examination are mandatory in order to establish an accurate histological diagnosis in all cases of borderline ovarian tumors and to differentiate from well differentiated adenocarcinoma.[12] Thus, this case highlights the importance of correctly diagnosing this extremely rare and anecdotal ovarian tumor.

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Conflict of interest

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