Ovarian classification and Management

MBBS teaching purpose

1. OVARIAN TUMORS INTRODUCTION Dr. Sourav Chowdhury Senior Resident, IQCMC MBBS, DGO

2. NORMAL OVARIES Normal size 5 x 3 x 3cm Variation in dimensions can result from Endogenous hormonal production(varies with age and menstrual cycle) Exogenous substances, including OCs, GnRH agonists, or ovulation-inducing medication, may affect size

3. mesoovarium Ovarian Ligament Free Posterior Border

4. DIFFERENTIAL DIAGNOSIS OF ADNEXAL MASS ORGAN CYSTIC SOLID OVARY Functional cyst, Neoplastic cyst, Benign, Malignant, Endometriosis Neoplasm Benign Malignant FALLOPIAN TUBES Tubo -ovarian abscess Hydrosalpinx Paraovarian cyst Tubo-ovarian abscess Ectopic pregnancy Neoplasm UTERUS Intrauterine pregnancy in a bicornuate uterus Pedunculated or inteligamentous myoma BOWEL Sigmoid or caecum distended with gas or feces Diverticulitis, Ileitis, Appendicitis, Colonic cancer MISCELLANEOUS Distended bladder, Pelvic kidney, Urachal cyst Abdominal wall hematoma or abscess, retroperitoneal neoplasm

5. Lifetime Risk of ovarian neoplasm A woman has 5–10% lifetime risk of undergoing surgery for a suspected ovarian neoplasm and 13–21% of these will be found to be have an ovarian malignancy

6. COMMON OVARIAN TUMOURS Infancy Pre pubertal Adolescent Reproductive Peri menopausal Post Menopausal 1 Functional cyst Functional cyst Functional cyst Functional cyst Epithelial ovarian tumor Neoplastic ovarian tumor 2. Germ cell tumor Germ cell tumor Germ cell tumor Dermoid Functional cyst Functional cyst 3. Epithelial tumor Epithelial tumor Mets

7. Functional ovarian cysts Follicular cysts Corpus luteum cysts Theca lutein cysts Luteomas of pregnancy By far the most common clinically detectable enlargements of the ovary in the reproductive years. All are benign and usually asymptomatic.

8. WHO CLASSIFICATION

9. Common Epithelial Tumors: Serous tumors Mucinous tumors Endometrioid tumors Clear cell tumors Brenner tumors Mixed epithelial tumors Undifferentiated ca. Unclassified epithelial tumors

10. II. Sex cord tumors: Granulosa -stromal cell tumors, theca cell tumors Androblastomas Gynandroblastomas Unclassified

11. III. Lipid cell tumors IV. Germ cell tumors: Dysgerminoma Endodermal sinus tumor Embryonal ca. Polyembryoma Choriocarcinoma Teratoma Mixed

12. V. Gonadoblastomas : Pure Mixed VI. Soft tissue tumors (not specific to ovary) VII. Unclassified tumors VIII. Secondary tumors IX. Tumor-like conditions

13. CLINICAL PRESENTATION Age Parity Symptoms Signs On Examinations Abdominal Inspection Palpation Percussion Pelvic Benign ovarian neoplasms are indistinguishable clinically from malignant counterparts

14. PHYSICAL EXAMINATION Abdominal and vaginal examination and the presence or absence of local lymphadenopathy Assess Laterality Cystic Vs solid Mobile Vs fixed Smooth Vs irregular Ascites Cul-de-sac nodules Rapid growth rate

15. COMPLICATIONS Torsion Intracystic hemorrhage Infection Rupture Pseudomyxoma peritonei Malignancy

16. Full bladder Pregnancy Fibroid Chocolate cyst Encysted peritonitis Ascites Functional cyst of ovary Diferrential Diagnosis

17. Investigation Special

18. Pattern recognition is superior to all other scores. Subjective evaluation of ovarian masses based on pattern recognition can achieve sensitivity of 88% to 100% and specificity of 62% to 96%. Adding doppler does not seem to yield much improvement in the diagnostic precision, but increases the confidence with which a correct diagnosis of benignity or malignancy is made. TVS

19. DOPPLER EVALUATION Hypoxic tissue in tumors recruit low-resistance, high-flow blood vessels Role in evaluating ovarian mass is controversial – as the ranges of values of RI,PI,MSV between benign and malignant masses overlap. PI<1, RI<0.4 To overcome this, vascular sampling of suspicious areas (papillary projections, solid areas, thick septations) using both 3D USG and power doppler both has been evaluated and found effective. “Chaotic” vascular pattern in malignancy

20. OTHER IMAGING MODALITIES CT, MRI, PET not recommended in the initial evaluation CT scan: evaluating LN involvement, Omental mets, peritoneal deposits, hepatic mets, obstructive uropathy or a probable alternate primary site when cancer is suspected based upon TVS MRI : differentiating non adnexal pelvic masses (like leiomyomata), expensive and inconvenient. ACOG GUIDELINES 2007

21. Differences Benign Malignant 1. Age More common in late child-bearing age More common in post-menopausal age 2. Parity No correlation More with nulliparity or family H/O 3. Symptoms Gradual growth Rapid growth 4. Signs General cond. Uneffected Cachexia & pallor, jaundice, LN 5. Per abdomen More or less mobile, commonly cystic, border defined and smooth surface Liver enlarged, firm and nodular. SOL- solid & heterogenous with restricted mobility, irregular surface with probable adhesions Differences

22. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol2008 RCOG 2011 Sonological Difference

23. TUMOR MARKERS

24. SENSITIVITY SPECIFICITY PPV NPV 61-90% 71-93% 35-91% 67-90% CA-125 Most useful when non-mucinous epithelial cancers are present Elevated in 80% of patients with epithelial ovarian Ca but only in 50% of patients with stage I disease Increased sensitivity in post menopausal women esp. when associated with relevant clinical and USG findings Cut-off of 30 u/ml, sensitivity of 81% and specificity of 75%

25. HE4 HE4 is a precursor to the epididymal secretory protein E4 and in normal ovarian tissue, there is minimal gene expression and production of HE4. As a single tumor marker, HE4 had the highest sensitivity for detecting ovarian cancer, especially Stage I disease. Combined CA125 and HE4 is a more accurate predictor of malignancy than either alone or to any other dual combination of markers HE4 levels(>70 pM ) were found to be elevated in over half of the patients with ovarian cancer with normal serum CA125 levels (>35 U/ml) HE4 when studied in the premenopausal group of patients was able to discriminate benign tumors from malignancies Moore et al. / Gynecologic Oncology, 2008

26. NEW SCORES ROMA : Risk of Ovarian Malignancy Algorithm The dual marker algorithm utilizing HE4 and CA125 to calculate a ROMA value In patients with stage I and II disease, ROMA achieved a sensitivity of 85.3% compared with 64.7% for RMI MOORE ET AL, AJOG 2010 OVA 1 : FDA approved. Combination of 5 immunoassays CA 125, transthyrettin , apo lipoprotein A1, transferrin , B2 microglobulin Sensitivity : 93%, specificity: 43% PPV 42% NPV 93% COMMUN ONCOL, 2010

27. Asymptomatic simple cysts <5cms Likely physiological (do not require follow up ) 5-7 cms Yearly USG >7cm Require further imaging/surgical intervention. RCOG 2011

28. Ovarian mass in reproductive age group <5 cms . >/= 5 cms USG USG cystic observation Complex, solid, suspicious Persistence or progression surgery

29. Ovarian mass in childhood: History and physical examination Appr . Imaging studies Simple cyst - Observe and reassess Solid or solid cystic MRI and tumor markers High suspicion of malignancy Low suspicion of malignancy Laparotomy laparoscopy Frozen section Malignant – oophorectomy and staging Benign - cystectomy

30. Ovarian cysts in postmenopausal women: Post menopausal gonad atrophies to a size of 1.5 X 1 X 0.5cm on average Shouldn’t be palpable on pelvic examination. Presence of palpable ovary must alert the possibility of an underlying malignancy.

31. Incidence in asymptomatic post menopausal women – 1.5% by pelvic examination 3.3% to 14.5% by USG. obstet gynecol survey, 2002 Causes -10% functional 90% neoplastic (either benign or malignant )

32. ASSESSMENT It is recommended that ovarian cysts in postmenopausal women should be assessed using CA125 and transvaginal grey scale sonography. There is no routine role yet for Doppler, MRI, CT or PET. RCOG 2010 SENSITIVITY SPECIFICITY TVS 89% 73% CA 125 81% 75%

33. RCOG Simple, unilateral, unilocular ovarian cysts, less than 5 cm in diameter, have a low risk of malignancy. It is recommended that, in the presence of a normal serum CA125 levels, they be managed conservatively. Aspiration is not recommended for the management of ovarian cysts in postmenopausal women. It is recommended that a ‘risk of malignancy index’ should be used to select women for laparoscopic surgery, to be undertaken by a suitably qualified surgeon. It is recommended that laparoscopic management of ovarian cysts in postmenopausal women should involve oophorectomy (usually bilateral) rather than cystectomy.

34. BORDERLINE OVARIAN TUMORS

35. They were not separately classified by the  FIGO and the WHO until the early 1970s. Borderline tumors make up approximately 15 % of all epithelial ovarian tumors. The mean age of occurrence is approximately 10 years younger than that of women with frankly malignant ovarian cancer.

36. Tumour subtypes  2 major histological tumor subtypes Serous(50%) (bilateral in 30%) Could be associated with extraovarian lesion : implants(35%) Mucinous (46%) Mucinous tumors do not have a clearly defined origin. Substantial information indicates that many tumors may actually originate from the appendix ; thus, this organ should be removed at the time of surgery .

37. Histology and Cytology According to Dietel and Hauptmann, the histology of borderline tumors is characterized by the following features: Epithelial multi-layering of more than 4 cell layers Not more than 4 mitoses per 10 high-power field (HPF) Mild nuclear atypia Increase in nuclear/cytoplasmic ratio Slight to complex branching of epithelial papillae and pseudopapillae Epithelial budding and cell detachment into the lumen No destructive stromal invasion - A major component in differentiating malignant from borderline tumors

38. TUMOR STAGING Comprehensive staging : of significant prognostic value and is performed surgically Borderline ovarian tumors are staged according to the FIGO classification of ovarian cancer.

39. International Federation Of Obstetrics And Gynecology (FIGO) staging FIGO stage Definition I Tumor confined to the ovary II Peritoneal implants within the pelvis III Peritoneal implants beyond the pelvis, Positive lymph nodes, or both IV Liver parenchyma involvement , or tumor beyond the peritoneal cavity

40. TREATMENT

41. * No further chemotherapy (in all stages.)

42. Summary Ovarian Mass Reproductive Age <45yrs Peri /Postmenopausal 3-5cm >5-7cm >=7cm Do Nothing Follow-up MRI or Surgery RCOG guidelines-62 &34;2011 & 2010 TVS if not performed & CA-125 Calculate RMI RMI<25 RMI>25-250 RMI>250 Simple U/L <5cm & CA-125 <30 Other cyst F/U with TVS & CA-125 4monthly / 1yr Laraoscopic removal Laparoscopy or laparotomy in Cancer unit Laparotomy in other Sp. Centre