VALUE OF MRI IN CHARACTERIZATION OF BORDERLINE OVARIAN TUMOR H. MHALLA(1) , S. MELLITI(1), S.GHARBI DHAOUADI (1), C. MBARK(2), H.OUESLATI (2), S.MEZGHANI(1) (1) Radiology department, Ben Arous Hospital, Ben Arous, Tunisia (2) Gynecological department, Ben Arous Hospital, Ben Arous, Tunisia

INTRODUCTION Borderline ovarian tumours (BTs) are low grade malignant neoplasms and have have a rather good prognosis. Bts account for 10 to 15% of the ovarian tumours (1,2). Serous and mucinous are the common subtypes (3). BTs are staged according to the same principles as malignant tumours. Inaccurate preoperative diagnosis of a BT could result in patiens being undertreated for an ovarian neoplasm. Correct preoperative diagnosis may allow the option of fertility preserving ovarian surgery in selected cases.

OBJECTIVES The aim of this study is to describe the range of magnetic resonance imaging (MRI) appearances of Borderline ovarian tumor (BT) and to assess the importance of preoperative diagnosis of BT for management strategies.

MATERIALS AND METHODS 5 women were referred to our department. All underwent ultrasonography (US) and MRI. For each tumor, site, size, ultrasound features and MRI characteristics were recorded. Laparoscopic was performed for all of the patients. Anathomopathologic exam confirmed the diagnosis.

RESULTS Clinical parameters Case Gravidity/Parity Age Complains Exam CA125 levels N°1 G6P6 42 Pelvic pain Painful pelvic mass (20 cm) CA 125 : 9 UI /ml (NV : 0-35UI/ml) N°2 G0P0 31 Chronic pelvic pain (5 months) __ _ N°3 G7P6 51 Pelvic pain and pelvic mass (1month) Abdominal and pelvic mass (40cm) N°4 G3P3 Pelvic pain and pelvic mass (4months) Abdominal and pelvic mass (30 cm) CA 125 : 34 UI/ml N°5 33

Controlateral ovarian RESULTS Ultrasonography morphologic analysis Case Size description Doppler Controlateral ovarian Ascites N°1 17 cm Cystic mass with thin septations and intracystic papillary projections - Normal +/- N°2 7 cm Cystic mass with solid component, thick septations, intracystic and exophytic papillary projections + Not seen N°3 >30 cm Cystic mass with solid component, thin septations without papillary projections N°4 >20 cm Cystic mass with solid component, thin septations and intracystic papillary projections N°5 6 cm Cystic mass with thin septations with intracytic and exophytic papillary projections

Abdominal and pelvic cystic mass with thin septations and papillary projections Ultrasonography morphologic analysis of adnexal masses was accurate for identifying ovarian site, suspecting epithelial tumor and to confirm its neoplastic nature.

MRI PROTOCOL Use of a pelvic multicoil Sagittal inversion recovery localizer sequence axial and FSE T2 weighted sequence axial T1 weighted sequence and an optional axial Tl-weighted sequence with fat saturation if a high signal in T1 weighted images is identified ( for differentiating lipid-containing masses from hemorrhagic adnexal lesions) Typical parameters for the FSE T2-weighted sequence : TR, 5,000 to 7,000 milliseconds; effective TE, 90 to 130 milliseconds; FOV, 20 to 24 cm; section thickness, 4 to 5mm; intersection spacing, 1.0 to 2.0 ram, numberof signal averages (NSA)2 to 4, ETL, 16; matrix of 512 • 256. The phase encoding direction : anterior to posterior, Using a20-cm FOV and a 512 x 256 matrix, in-plane resolution is 0.4 mm (frequency) by 0.8 mm(phase) . Axial and sagittal T1 weighted fat saturated sequences following the administration of gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) contrast agent.

RESULTS MRI findings Case description Enhancement Peritoneal signs N°1 Loculated cystic mass with thin septations and intracystic papillary projections Not enhanced small amount of asites- N°2 Multi loculated cystic mass with solid component,thick septations, intracystic and exophytic papillary projections Enhanced solid component, papillary projections septations and wall Moderate ascites and peritoneal implant N°3 Multiloculated cystic mass with solid component, thin septations without papillary projections Enhanced solid component and wall Peritoneal implants N°4 Multiloculated cystic mass with solid component, thin septations and intracystic papillary projections Enhanced solid component, papillary projections, septations and wall Small amount of ascites N°5 Multiloculated cystic mass with thin septations without intracytic and exophytic pseudocystic multiloculated papillary projections Enhanced septations and wall Moderate acites

FIG 1a FIG 1b FIG 1d FIG 1c Figure 1: A 42-year-old female patient with a mucinous ovarian BT. Sagital and axial T2-weighted MRI image (a, b), axial T1 without and following intravenous contrast ( c, d) illustrates a large cystic mass with one septa, a solid component both not enhanced. Normal right ovarian. FIG 1d FIG 1c

FIG 2a FIG 2b FIG 2c FIG 2f FIG 2e FIG 2d Figure 2: A 31-year-old woman with a mucinous BT. Axial, sagital, T2-weighted, MRI image ( a, b).Axial T1 ©, Axial, sagital T1+C ( e, f), axial T1 +C FS (d). A cystic lesion is present with numerous irregular septa and intra-cystic frond-like papillary projections involving both the wall and septa enhanced following contrast. Exophytic papillary projections are also present extending from the posterior and inferior surface of the cyst (head arrow) and are delineated by ascites. We notice cystic containing loculi with different signal intensity ( high T1 signal of hemorrhage) FIG 2f FIG 2e FIG 2d

FIG 3a FIG 3b FIG 3c FIG 3f FIG 3e FIG 3d Figure 3: A 51-year-old woman with a mucinous BT. Sagital, coronal T2-weighted, MRI image ( a, b). Axial T1 ©,sagital, coronal and axial T1+C ( e, f,d). Multiloculated cystic lesion is present with numerous thin septa enhanced following contrast. FIG 3f FIG 3e FIG 3d

FIG 4a FIG 4b FIG 4c Figure 4: A 42-year-old woman with a mucinous BT. Sagital, coronal and axial T2-weighted, MRI image ( a, b ,c) Multiloculated cystic lesion is present with thin septa and intracystic papillary projections. MRI confirmed the ovarian site especially when considering voluminous tumor. Signal intensity characteristics allowed better analysis of cystic and solid components.

FIG 5 FIG 5 a FIG 5 b FIG 5 c FIG 5 d FIG 5 e Unialteral right ovarian mucinous borderline epilthelioma Axial and sagittal T2-weighted , MRI demonstrates a cyctic lesion with intracystic and exophytic pseudocystic multiseptate papillary projections; the exophytic part of the tumor is extented from the unterrumpted posterior surface of the cyst and is delineated by ascites.; notify the normal appearing of the ipsilateral ovarian stroma (arrow) FIG 5 a FIG 5 b FIG 5 c FIG 5 d FIG 5 e

RESULTS Treatment Case description Histological type Peritoneal implants N°1 Hysterectomy. Bilateral annexectomy. Omentectomy. Apendicectomy Mucinous BTs No N°2 Not invasive N°3 N°4 N°5 Right annexectomy. Apendicectomy

DISCUSSION Definition: Borderline ovarian tumours (BTs) are an intermediate category of epithelial ovarian tumour, which histologically demonstrate cellular proliferation and moderate nuclear atypia but without stromal invasion. Described by Taylor in 1929 (4), and recognized by the International Federation of Gynaecology and Obstetrics and World Health Organization in the early 1970s (5), they occur in all types of epithelial ovarian tumours but are most common in serous and mucinous subtypes.

DISCUSSION Classification: I Only Ovaries a One ovary. Ascites (-). Papillary projection (-). No capsular rupture b Bilaterality. Ascites (-). Papillary projection (-). No capsular rupture c Unilaterality or bilaterality. Ascites (+) or positive cytology. Papillary projection or capsular rupture. II Pelvic extension a Uterus without positive ascites b Bladder or rectum without positive ascites c IIa or IIb with ascites or positive cytology or papillary projection or capsular rupture III Abdominal and pelvic peritoneal extension or lymph node metastases a Peritoneal or omental microscopic extension N- b Peritoneal implants < 2 cm, N- c Peritoneal implants > 2 cm and/or pelvic, para aortic or inguinal N+ IV Pleural effusion / Parenchymal metastases

DISCUSSION Histology (1,3,6,7) Numerous subtypes are described; serous, mucinous, endometrioid, clear cells, transitional cells and mixed tumours. Serous BT’s: Cystic mass with intracystic papillary projections or both intracystic and exophytic papillary projection, exclusie exophytic papillary projections are rare. Mucinous BT’: Intestinal: Voluminous multilocular cystic mass without papillary projections. Extension: peritoneal pseudomyxoma. Bilaterality++ mucocele++ Mullerian: Unilocular or cystic mass with intracystic papillary projections. Extension: bilaterality. Peritoneal implants

DISCUSSION Clinical features: Prognosis: Younger age at presentation. Normal or midely elevated CA125 Prognosis: Surgical factors, response to therapy and histological criteria are important for predicting the prognosis of patients with BTs. Newer techniques such as morphometry, DNA cytometry, immunological and immunopathological techniques may help to define prognostic factors even more accurately (8).

DISCUSSION Ultrasonography features: Ultrasonography morphologic analysis of adnexal masses is accurate for identifying ovarian site, suspecting epithelial tumor and to confirm its neoplastic nature. However its specifity remains limited.

DISCUSSION MRI features: MRI signal and morphologic characteristics: Some authors interpreted high signal on T1 weighted images as diagnostic of the presence of mucinous material suggesting an underlying diagnosis of a mucinous BT (9) which is in contradiction with more recent studies in which high signal on T1 weighted images is indicative of haemorrhage or mucinous material without correlation with histological subtype of BT (10). In our study, we described a haemorrhagic component in a mucinous BT. For some authors, the presence of multilocular cystic mass containing loculi of different signal intensities, numerous irregular septas are suggestive of mucinous BT which is in agreement with our findings.

DISCUSSION Size of lesion: Mean maximal diameter and volume of lesion demonstrated the greatest difference between the serous and mucinous subtypes (10). Mean maximal diameter of our mucinous tumours series is 16,2 cm. Ipsilateral adnexal findings: In Literature, presence of normal ipsilateral ovarian stroma was identified in MRI (10). In our study we noticed this finding in the smallest tumor of our series.

DISCUSSION Controlateral adnexal findings: Published literature noticed an important negative findings in which synchronous bilateral BTs occurred only in the serous subset (11) which is in agreement with our series consisting in mucinous borderline tumours since imaging demonstrated unilateral disease in both US and MRI. Ascites Literature did not found correlation between pathological volume of free fluid and histological subtype (12). But the relationship between the presence of a pathological volume of free fluid and exophytic projections was established and supports the increased risk of peritoneal disease (10). In our study 2 patients demonstrated exophytic papillary projections which was associated both to ascites and non invasive peritoneal implants in one case. DISCUSSION

DISCUSSION Some authors categorized MRI appearance of BT’s into 4 broad morphologic groups (10) : Unilocular cysts Minimally septate cysts with papillary projections Markedly septate lesions with plaque-like excrescence Predominant solid lesion with exophytic papillary projections In our present series MRI appearances can be categorized as one case in the second category, one case in the third category and 3 cases in the fourth category.

DISCUSSION Malignant criteria Bilaterality Tumour size greater than 4 cm Predominantly solid mass Cystic tumours with vegetations Contrast enhancement Criteria suggesting borderline ovarian tumours At least one imaging feature to suggest malignancy Predominantly cystic appearing lesion Regular thin wall Presence of normal ipsilateral ovarian stroma Lack of ascites Lack of enlarged lymph nodes Lack of peritoneal and omental disease. DISCUSSION

DISCUSSION Criteria suggesting borderline ovarian tumours At least one imaging feature to suggest malignancy Predominantly cystic appearing lesion Regular thin wall Presence of normal ipsilateral ovarian stroma Lack of ascites Lack of enlarged lymph nodes Lack of peritoneal and omental disease.

DISCUSSION Treatment Fertility sparing surgery for patient with borderline ovarian tumor is safe and can permit future pregnancy suggesting that such surgery should be considered for young patients who wish to preserve fertility (13). Radical surgery including bilateral annexectomy, omentectomy hysterectomy, peritoneal cytology with numerous biopsies remind the typical procedure . (14, 15)

CONCLUSION In young women with normal or moderately raised CA125 levels and a complex adnexal mass, the possibility of borderline ovarian tumor should be considered. MRI showed a wide array of BT’s appearances. Each lesion was associated at least to one criteria of malignancy. Accurate preoperative characterization present a special diagnosis challenge since it influences surgical planning and even allows the possibility of fertility preservation.

REFERENCES 1-Hart WR. Borderline epithelial tumors of the ovary. Modern Pathology 2005;18:S33-50 2- Skírnisdóttir I, Garmo H, Wilander E, Holmberg L. Borderline ovarian tumors in Sweden 1960-2005: Trends in incidence and age at diagnosis compared to ovarian cancer. Int J Cancer 2008; 123:1897-901 3- Duvillard P. Tumeurs ovariennes à la limite de la malignité. Ann Pathol 1996;16:396-405 1- Taylor Jr HC and al. Malignant and semi malignant tumour of the ovary. Surg Gynecol 1929;48:204-30. 4- Taylor Jr HC and al. Malignant and semi malignant tumour of the ovary. Surg Gynecol 1929;48:204-30. 5- International Federation of Gynecology and Obstetrics. Classification and staging of malignant tumours in the female pelvis. Acta Obstet Gynecol Scand 1971;50:1-7 6- JPA. Baak and al. Prognstic factors in Bordeline and invasive ovarian tumors of the common epithelial type. Pathology-Research and practice, Volume 182, Issue 6 December 1987, Pages 755-774. 7-Elias D, Sabourin JC. Pseudomyxome péritonéal. Revue de la littérature. J Chir 1999;136:341-7.  8- Trimble CL, Kosary C, Trimble E. Long-term survival and patterns of care in women with ovarian tumors of low malignat potential. Gynecol Oncol 2002;86:34-7. 9- Bekiesiska-Figatowska M and al. Magnetic Resonance Imaging as a diagnostic tool for ovarian masses in girls and young women. Med Sci Monit 2007;13:116-20 10- C.L Bent and al. MRI appearences of borderline ovarian tumour. Clinical radiology (2009)64,430-438. 11- Barakat RR and al. Borderline Tumor of ovary. Obstet Gynecol Clin North Am 1994;21:93-105. 12-Sgal.GH and al. Ovarian Serous tumours of low malignant potentiel (serous borderline tumours) The relationship of exophytic surface tumor to peritoneal implants. Am J Surg Pathol 1992; 16:577-83. 13- Jeong-Yeal Park. Surgical management of borderline ovarian tumours: the role of fertility-sparing surgey. Gynecologic Oncology Volume 113, Issue 1, April 2009, Pages 75-82. 14- Morice P, Camatte S, Wicart-Poque F, Atallah D, Rouzier R, Pautier P, et al. Results of conservative management of epithelial malignant and borderline ovarian tumours. Human Reproduction Update 2003;9:185-92.  15- Morice P, Camatte S, Rey A, Atallah D, Lhommé C, Pautier P, et al. Prognostic factors for patients with advanced stage serous borderline tumours of the ovary. Ann Oncol 2003; 14:592-8