Benign ovarian tumours

1. BENIGN OVARIAN TUMOURS DR. SRAVANTHI DR. CHINMOY DR. MINAKSHI

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. 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

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. Differential diagnosis of the adnexal masses varies considerably with the age of the patients . In pre-menarchal girls and post-menopausal women adnexal mass should be considered highly abnormal – requires immediate investigation . In menstruating patients differential diagnosis is varied.

6. DIAGNOSTIC EVALUATION OF THE PATIENT WITH AN ADNEXAL MASS Complete physical examination Pelvic ultrasound examination Computed tomography scan with contrast enhancement or intravenous pyelography Colonoscopy or barium enema study, if symptomatic Laparoscopy , laparotomy

7. FOLLICULAR CYST CORPUS LUTEUM CYST THECA LUTEIN TUBO OVARIAN ABSCESS BENIGN BORDERLINE MALIGNANT ENDOMETRIOMA ENLARGED PCO PAROVARIAN CYST

8. 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

9. 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.

10. Follicular cysts Cystic follicle is defined as Follicular cyst of diameter > 3cm Most common functional cysts. Rarely larger than 8cm. Lined by granulosa cells Found incidentally on pelvic examination Usually resolve within 4 – 8 weeks with expectant management May rupture or torse occasionally causing pain and peritoneal symptoms.

11. Follicular cysts

12. Corpus luteal cyst Less common than follicular cyst. May rupture leading to hemoperitoneum and requiring surgical management( more in patients taking anti coagulants or with bleeding diathesis) Unruptured cysts may cause pain because of bleeding into enclosed ovarian cyst cavity.

13. Corpus luteal cyst

14. Theca lutein cysts Least common Usually bilateral Result from overstimulation of the ovary by β - hCG Do not commonly occur in normal pregnancy Often associated with hydatidiform moles, choriocarcinoma, multiple gestations, use of clomiphene and GnRH analogues. May be quite large (up to 30 cm) , multicystic, and regress spontaneously.

15. Theca lutein cysts

16. Management of functional cysts Expectant Watchful waiting for two or three cycles is appropriate. Combined oral contraceptives appear to be of no benefit. Should cysts persist, surgical management is often indicated. Oral contraceptives for functional ovarian cysts (Review) Cochrane Database of Systematic Reviews 2011

17. Endometriomas Most common site of involvement is the ovary. Endometriomas are pseudocysts formed by invagination of the ovarian cortex, sealed off by adhesions. They may completely replace normal ovarian tissue. Cyst walls are usually thick and fibrotic. USG: anechoic cysts to cysts with diffuse low-level echoes to solid-appearing masses. Fluid–fluid or debris–fluid levels may also be seen. They may be unilocular or multilocular with thin or thick septations Malignant transformation: 0.3% to 0.8% Management: medical and/ or surgical

18. BENIGN OVARIAN NEOPLASMS

19. Benign ovarian tumors Serous cystadenoma Mucinous cystadenoma Dermoid cyst Fibroma Thecoma Brenner’s tumor

20. SEROUS CYSTADENOMA Generally benign Bilateral – 10% Risk of malignancy : 5 – 10 % borderline malignant 20 -25% malignant GROSS : multilocular with papillary components. MICRO : low columnar epithelium with cilia. Characteristic psammoma bodies (end products of degeneration of papillary implants)are found. Associated fibrosis may lead to “ cystadenofibroma ”

21. MUCINOUS CYSTADENOMA Have tendency to become huge masses Round to ovoid masses with smooth capsules that are usually translucent or bluish to whitish gray. Interior divided by discrete septa into loculi containing clear , viscid fluid. Epithelium – tall, pale staining, secretary with basal nuclei and goblet cells 5 – 10% are malignant

22. DERMOID CYST Often bilateral (15 -25%) GROSS: thick, opaque , whitish wall. CONTENTS: hair, bone, cartilage, and a large amount of greasy sebaceous material. MICROSCOPICALLY : all the three germ layers (ectoderm, mesoderm and endoderm) Malignant change occurs in 1-3%. Usually of a squamous type. Risk of torsion is 15% An ovarian cystectomy is almost always possible, even if it appears that only a small amount of ovarian tissue remains

23. FIBROMA Most common benign, solid neoplasms of the ovary. Compose approx 5% of benign ovarian neoplasms and 20% of all solid tumors of the ovary. Frequently seen in middle-aged women. Characterized by their firmness and resemblance to myomas Misdiagnosed as exophytic fibroids or primary ovarian malignancy Not hormonally active Fibromas may be associated with ascites or hydrothorax as a result of increased capillary permeability thought to be a result of VEGF Mieg’s syndrome (ovarian fibromas, ascites and hydrothorax) is uncommon and usually resolves after surgical excision.

24. THECOMA Solid fibromatous lesions that show varying degrees of yellow or orange discoloration Almost always confined to one ovary Usually >40 years, 65% after menopause May be hormonally active and hence associated with estrogenic or occasionally androgenic effects. Luetinised thecoma – younger, sclerosing peritonitis and ascites Leydeig cell thecoma – ass. with Reinke crystals Rarely malignant

25. BRENNER TUMOR Uncommon tumor grossly identical to fibroma Arise from Walthard cell rests ,also from surface epithelium, rete ovarii and ovarian stroma On microscopy – markedly hyperplastic fibromatous matrix interspersed with nests of epitheloid cells showing coffee bean pattern Considered uniformly benign. But scattered reports of malignant Brenner’s available Endocrinologically inert, but could be ass. with virilization and endometrial hyperplasia

26. GONADOBLASTOMAS Gonadoblastoma is a rare benign tumor that has the potential for malignant transformation and affects a subset of patients with an intersex disorder or disorder of sex development (DSD). Contain both germ cells and sex cord stromal cells. Arise in patients with dysgenetic gonads - 46 XY f/b 45XO/ 46 XY mosaic . Presents usually as phenotypic female <30 years with primary amenorrhea and virilization. Treatment – laparoscopy or laparotomy with removal of b/l dysgenetic gonads. Further treatment depends on malignant germ cell component

27. CLINICAL PRESENTATION Asymptomatic – accidentally discovered on USG Chronic pattern of pain, increasing abdominal girth over months or weeks. Associated with secondary symptoms of anorexia, nausea, vomiting, urinary frequency. Could be associated with primary or secondary amenorrhea, menstrual irregularities, virilization, precocious puberty Become acutely symptomatic if undergoes torsion, rupture or haemorrhage. Benign ovarian neoplasms are indistinguishable clinically from malignant counterparts

28. COMPLICATIONS Torsion Intracystic hemorrhage Infection Rupture Pseudomyxoma peritonei Malignancy

29. MANAGEMENT

30. 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

31. TVS 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.

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

33. 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. “ C haotic ” vascular pattern in malignancy

34. 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

35. TUMOR MARKERS

36. SENSITIVITY SPECIFICITY PPV NPV 61-90% 71-93% 35-91% 67-90% CA125 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%

37. 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

38. 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

39. Operative intervention

40. INDICATIONS FOR SURGERY Any solid ovarian lesion Any ovarian lesion with papillary vegetation on the cyst wall Any adnexal mass >10cm in diameter Palpable adnexal mass in a premenarchal or postmenopausal women Torsion or rupture suspected

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

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

43. CYST ASPIRATION Diagnostic cytology has poor sensitivity to detect malignancy, ranging from 25% to 82% N ot therapeutic , even when a benign mass is aspirated Approx. 25% of cysts will recur within 1 year Aspiration of a malignant mass may induce spillage and seeding of cancer cells into the peritoneal cavity

44. INDICATIONS OF FNAC Predominantly benign masses based on clinical, USG findings and CA125 levels, but a few findings are causing diagnostic dilemma – then FNAC helps to confirm the nature and aid in pre-op planning and counseling. Patients who have clinical and radiographic evidence of advanced ovarian cancer and who are medically unfit to undergo surgery- Malignant cytology will establish a cancer diagnosis, thereby permitting initiation of neo-adjuvant chemotherapy ACOG, 2007

45. OPERATIVE MODALITIES Laparoscopy vs laparotomy – decision based on suspicion of malignancy and technical expertise No RCTs comparing recurrence rates following laparoscopy or laparotomy. The objective is to try cystectomy if possible. Laparoscopic surgery for benign ovarian tumours is associated with less pain, shorter hospital stay, and fewer adverse events than with laparotomy. Cochrane Database of Systematic Reviews 2009

46. The standards for laparoscopy in benign tumours careful examination of the external surface of the tumour and sampling of the peritoneal cavity avoidance of any tumoral rupture protection of the ovarian tumour with an endoscopic bag before removal

47. ROLE OF FROZEN SECTION The diagnostic accuracy of frozen section analysis is high for malignant and benign ovarian tumours, but accuracy is poor in the case of borderline ovarian tumors. Medeiros 2005

48. 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

49. No specific lit. regarding recurrence rate esp. Hence recommendations are at best empirical. Should be followed up with annual USG. In adults follow up with biannual USG is sufficient Tumor markers are not regularly used Post op surveillance in children

50. OVARIAN CYSTS IN POSTMENOPAUSAL WOMEN

51. 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 physician to the possibility of an underlying malignancy.

52. 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 )

53. 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%

54. Calculation of RMI (Risk malignancy index): It is an effective way of triaging patients into low , moderate, high risk for malignancy, according to which the referral to a higher centre and management protocol will differ . RCOG 2010

55. It is recommended that a ‘risk of malignancy index’ should be used to select those women who require primary surgery in a cancer centre by a gynecological oncologist. RCOG Guideline No. 34 October 2003 Using a cut off point of 250, a sensitivity of 70% and specificity of 90% can be achieved.

56. 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.

57. It is recommended that laparoscopic management of ovarian cysts in postmenopausal women should involve oophorectomy (usually bilateral) rather than cystectomy.

58. BORDERLINE OVARIAN TUMORS

59. T hey 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.

60. 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 .

61. 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

62. 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.

63. INACCURATE STAGING Pathologic diagnosis is difficult to confirm by frozen section. The diagnosis of borderline ovarian cancer is based on surgical staging . There is no accurate way to predict the final pathology of ovarian tumors from laboratory or imaging studies alone .

64. PROGNOSIS Excellent overall prognosis 60% chance of having stage I disease when diagnosed. 95% of borderline ovarian tumors have diploid deoxyribonucleic acid (DNA) If the tumor is aneuploid, the recurrence rate is high Although  TP  53 positivity and  HER2  over expression in invasive cancer have been associated with a worse prognosis, the same gene profile has conferred a survival advantage in borderline tumors. Invasive implants

65. Recurrence and Survival Stage I disease confirmed by comprehensive staging have a recurrence rate of approximately 15%. The 5-year survival rate for such patients approaches 100%.  With stage II-IV disease, the prognosis is different; an increased stage is associated with a worse prognosis and only age at diagnosis and the presence of invasive implants are shown to influence prognosis .

66. IMAGING - USG Intratumoral blood flow in borderline tumors (90%) is similar to that of malignant neoplasms (92%). The resistance and pulsatility indexes are also significantly reduce

67. IMAGING - CT Preoperatively to identify possible foci of metastasis . CT scanning can For follow up of the patient in the future.  However,no distinguishing characteristics that clearly identify a borderline ovarian tumor .

68. IMAGING - MRI In a retrospective study looking at MRI characteristics of known borderline tumors, Bent et al the investigators were not able to identify any key imaging characteristics that would distinguish borderline tumors from other ovarian tumors. MRI appearances of borderline ovarian tumours.  Clin Radiol . Apr 2009;64(4):430-8. 

69. BIOMARKERS CA-125 levels are not shown to aid in the diagnosis or follow-up care I n mucinous borderline ovarian tumors serum CA 19-9 probably is a more accurate marker than CA 125 for the early detection of recurrence

70. TREATMENT

71. Treatment Most important factors in deciding treatment options is stage of the disease . Proper staging consists of a thorough exploration of the entire abdominal cavity with peritoneal washings, infracolic omentectomy, removal of all macroscopic suspicious peritoneal lesions, and multiple peritoneal biopsies.

72.   No consensus concerning treatment of patients with stage II-IV disease The postoperative management protocol is far from clear. To date, no medical therapy has been shown to clearly improve outcomes An increased stage is associated with a worse prognosis Stage (II vs III vs IV), type of surgery, postoperative treatment, postoperative platinum-based chemotherapy, and even the number of noninvasive implants have no effect on progression-free survival.  Only age at diagnosis and the presence of invasive implants are shown to influence prognosis.

73. Owing to the high association between surface proliferations and peritoneal implants, exploration of the peritoneum should be extensive and thorough. If possible, carefully evaluate and remove the implants. The type of implant ( ie , invasive, noninvasive) should be noted by pathology, as it has significant prognostic value . “ Lymphadenectomy can be omitted for BOTs, even for the advanced disease, because there is no difference in recurrence or survival rate .” Gynecol Oncol 98:390-395, 2005

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

75. CHEMOTHERAPY  Evidence is insufficient to determine exactly which therapy is indicated for borderline ovarian tumors.   Platinum-based agents used, but with varying results Borderline tumors with noninvasive implants do not require any further therapy and should be observed.

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