Four cases of endometrioid borderline ovarian tumour: case reports and literature review

Endometrioid borderline tumours (EBTs) of the ovary are uncommon tumours of low malignant potential. They consist of atypical endometrioid cells lacking destructive stromal invasion. As the prognosis of EBT is excellent, excessive treatment should be avoided and preoperative diagnosis is important. Here we report four cases of ovarian EBTs along with imaging findings and a review of literature. The average patient age was 52 years. They presented with abdominal discomfort or abnormal vaginal bleeding. The final diagnoses for all four cases were EBT Stage IA with endometriosis. Pathologically, one case was an adenofibromatous type tumour, and three cases were intracystic type tumours. Two patients had concurrent endometrial cancer. MRI of the tumours showed enhanced solid components. The intracystic type tumours presented a dendritic structure in the cyst; fine papillary branches surrounded a low-signal trunk on T2 weighted imaging. Positron emission tomography demonstrated marked fluorodeoxyglucose uptake in the solid component. One case with MRI 3 years before diagnosis indicated that the tumour arose in ovarian endometriotic cyst. EBT cases were difficult to distinguish from malignant ovarian tumours preoperatively. Intraoperative frozen section analysis may aid to determine treatment. Prognoses were excellent. Care should be taken for co-existing endometrial cancer.


INTRODUCTION
Endometrioid borderline tumours (EBTs) of the ovary are defined as tumours of borderline malignancy, which consist of atypical endometrioid epithelium but lack destructive stromal invasion. 1 The incidence of EBTs is very low, comprising up to 0.2% of all epithelial ovarian tumours. 2 EBTs are often diagnosed at an early stage with a good prognosis. Here we report four cases of EBTs diagnosed at our institution.

Case 1
The patient was a 47-year-old, gravida 2, para 2 female. She presented with lower right abdominal pain. MRI revealed a complex solid and cystic lesion measuring 9 cm in the right ovary ( Figure 1

Case 2
The patient was a 65-year-old, gravida 2, para 2 postmenopausal female. She presented with vaginal bleeding. She was pointed out a pelvic mass on clinical examination and ultrasound. MRI showed a multiloculated mass measuring 15 cm of mixed high and low signal intensities on T1WI. Within a cyst, irregular shaped papillary projections were observed at the tumour wall on T2WI and were well enhanced indicating solid components (Figure 1 upper right, Figure 4a-c). This lesion showed restricted water diffusion on diffusion weighted imaging (DWI) (Figure 4d). A malignant ovarian tumour was suspected, and laparotomy was performed. A large right ovarian tumour was found extending into the retroperitoneum, strongly adherent to the pelvic wall. Analysis of intraoperative frozen sections revealed EBT. Final pathological diagnosis was EBT, pT1aN0M0. Intracystic papillary proliferation of atypical endometrioid epithelium was observed ( Figure 3, upper right), with coincidental non-atypical endometriosis. A benign endometrial polyp was detected in the uterine endometrium.

Case 3
The patient was a 54-year-old, gravida 2, para 2 post-menopausal female. She presented with lower abdominal discomfort and a right ovarian mass was pointed out by pelvic examination. Endometrial cytology detected adenocarcinoma cells. MRI and CT revealed a complex solid and cystic lesion of 8.4 cm diameter within the right ovary. A papillary lesion was observed on the Reflecting abundant stroma, the components are of low signal intensity, and are of various shapes, including papillary projections on T2WI (Cases 2-4). Together with the high intensity on T 1 WI (data not shown), multicystic portions are assumed to have bloody content, but show variable intensity. The MR images are reminiscent of malignant tumours arising from endometriosis such as endometrioid carcinoma or clear cell carcinoma. T1WI, T 1 weighted image; T2WI, T 2 weighted image.  (Figure 5d,e). Endometrial lesions were indistinct on imaging studies including CT and MRI. Concurrent ovarian and endometrial cancer was suspected, and she underwent surgery. During the surgery, the multiloculated right ovary measuring 8 cm was found to be adherent to the pelvic peritoneum. Blueberry spots, or blue tiny spots on peritoneum were observed in the Douglas pouch, indicating pelvic endometriosis. Intraoperative frozen section analysis suggested EBT. Analysis of FFPE specimens revealed an intracystic proliferation of atypical endometrioid epithelium showing crowded fusing glands ( Figure 3 lower left). The area of confluent glands were smaller than 5 mm, and destructive stromal invasion was absent, justifying the diagnosis of EBT, pT1aN0M0. Coincidental endometrioid carcinoma, Grade 1, pT1aN0M0 was found in the uterine endometrium.

Case 4
The patient was a 41-year-old, gravida 0 female. She was diagnosed with a left ovarian endometriotic cyst and uterine myomas when she was 34-years-old. At the age of 36, she was diagnosed with breast cancer and underwent left mastectomy and axillary lymphadenectomy, chemotherapy, and    3-cm left ovarian cyst was adherent to the peritoneum. Intraoperative frozen section analysis demonstrated a seromucinous borderline tumour. In FFPE specimens, a left ovarian cyst was identified, with intracystic proliferation of papillary endometrioid epithelium with cellular and structural atypia (Figure 3, lower right). The case was diagnosed as EBT of the ovary, pT1aN0M0 and endometrioid carcinoma Grade 1 of the uterine endometrium, pT1aN0M0. Table 1 lists patient characteristics, image study findings and pathological findings. Table 2 lists the results of immunohistochemistry for estrogen receptor, p53, and ARID1A. None of the patients underwent adjuvant therapy, but they were all well without recurrence. All patients provided written informed consent. Table 3 lists 122 reported EBT cases in the literature. Case reviews reporting more than 3 cases are included. [2][3][4][5] DISCUSSION Pathologically, EBT is classified into two types: adenofibromatous type, with atypical endometrioid glands proliferating among abundant stroma, and intracystic type with proliferation of atypical endometrioid glands inside a cyst. 1 In the present case report, one adenofibromatous (Case 1) and three intracystic (Cases 2-4) types were described ( Table 1). As both types of EBT show prominent solid growth, the differential diagnosis includes malignant ovarian tumours. For a diagnosis of EBT, confluent gland proliferation must not exceed 5 mm, and destructive stromal invasion must be lacking on histological examination, otherwise it is an obvious malignant tumour. 1 Clinically, EBT is a tumour with excellent prognosis. The majority of the reported cases are confined to a unilateral ovary, and metastasis and recurrence are rare (Table 3). [3][4][5][6] EBT is often associated with endometriosis and endometrial lesions. Among 122 EBT cases, 56 (46%), including 4 cases from our institution, were associated with endometriosis (Table 3). [3][4][5][6] Among 43 patients who underwent hysterectomy, endometrial lesions including endometrial polyps, endometrial hyperplasia, and endometrial cancer were diagnosed in 23 patients (53%) ( Table 3). In the four patients from our institution, one had endometrial polyp and two had early-stage endometrial cancer (Table 1). Case 4, with endometrial cancer, had a history of tamoxifen intake, suggesting a role for tamoxifen in tumorigenesis from orthotopic and ectopic endometrium. 7 Table 1  On a comprehensive search of the literature, there are no reports dedicated to MRI findings for EBT tumour types. MRI visualization of the four cases presented here showed mixed tumours with cystic and solid portions (Figure 1). The solid portions demonstrated enhancement and water diffusion was restricted, indicating malignant tumours. In Case 1, which was pathologically diagnosed as adenofibromatous type EBT, abundant stroma in histological examination might be reflected in low-signal intensity in the solid portion on T 2 WI. In Cases 2-4, which were intracystic type EBTs, showed a thickened stroma corresponding to low-signal intensity on T 2 WI in the center of the solid portion, and at the periphery, fine branch-like structures of low-signal intensity were observed. MRI findings of the intracystic type EBTs were similar to serous borderline tumour (SBT) of the ovary, 8 but reflecting abundant stroma characteristic in EBT histology, low-intensity portion on T 2 WI was thicker than that in SBT. Multicystic portions showed stained-glass patterns with various intensities. Case 4 showed a solid portion in a single cyst. In this case, MRI taken 3 years prior to diagnosis showed endometriotic cyst of the ovary, indicating that the tumour arose in endometriosis tissue. Three patients in the current study underwent PET-CT, and all three showed marked FDG uptake in the solid portion of the tumour ( Intraoperative consultation based on the pathology of frozen sections of tumour may aid in deciding adequate operative procedures for the ovarian tumour. 9 In the four cases presented here, 3 were diagnosed as EBT, and 1 was diagnosed as seromucinous borderline tumour (Case 4). However, in Case 1 the pathologist stated that endometrioid carcinoma could not be excluded. Cross et al reported that in their case series of 22 endometrioid tumours, 19 cases that were diagnosed as borderline tumours by intraoperative frozen section analysis were ultimately diagnosed as malignant tumours. 10 This data suggests that endometrioid tumours tend to be under-diagnosed. Because of the high suspicion for malignant tumours based on preoperative imaging studies we performed staging laparotomy including lymphadenectomy in all four cases. As EBTs are very rare, more research with larger case series is needed to determine the reliability of frozen section analyses.

CONCLUSION
We reported four cases of EBT along with a review of the literature.
Imaging studies of our four cases of EBT presented mixed solid and cystic lesions, often including haemorrhagic cysts, with papillary solid projections demonstrating low signal intensity on T2WI. Enhancement, water restriction, and FDG uptake were observed in the solid components, making the cases almost indistinguishable from malignant ovarian lesions. Intraoperative frozen section analysis may help determine treatment. Concurrent endometrial lesions including endometrial cancer need to be considered and excluded.