Benign ovarian tumours

Benign ovarian masses include functional cysts and tumors; most are asymptomatic.Most functional cysts and benign tumors are asymptomatic. Sometimes they cause menstrual abnormalities. Hemorrhagic corpus luteum cysts may cause pain or signs of peritonitis, particularly when they rupture. Occasionally, severe abdominal pain results from adnexal torsion of a cyst or mass, usually > 4 cm. Treatment varies depending on the patient's reproductive status.

1. BENIGN OVARIAN TUMOURS Dr. NIRANJAN CHAVAN Professor & Unit Chief LTMMC & LTMGH Hospital , Sion, Mumbai -22 Chairperson, FOGSI Oncology & TT Committee.(2012-2014) Convener & Chair, FOGSI –Violence against Doctor Cell (2015-2016) Member, Oncology Committee AOFOG (2013-2015) Managing Committee Member ,AFG & IAGE Editor-AFG Times Newsletter Director, Chavan Maternity & Nursing hOME J.P. Road, Andheri West, Mumbai 53

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. Benign Ovarian Tumours Epidemiology Embryology E tiology Risk factors WHO classification Pathology of ovarian tumours Management (diagnosis & management) Surgery

4. Embryology of the ovary Primitive gonads appear around the 5 th week of IUL as the gonadal ridge from the coelomic epithelium on the medial aspect of the urogenital ridge. In the xx embryo , the cortex develop as the ovary and the medulla regress to a small area. The ovarian serosa is the direct descent of the coelomic epithelium and it give rises to endocervical,endometrial,endosalphinx and the epithelium of the urogenital system. The undifferentiated serosal cells can undergo neoplastic changes and lead to tumours of the above tissues.

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

6. (I) Functional (II) Inflammatory (III) Others (IV) Neoplastic (1) Germ cell (2) Epithelial (3)Sex cord stromal (a) Follicular cyst (b) Corpus Luteal cyst (c) Theca Luteal cyst Tubo -ovarian abscess ( a) Endometrioma Ovary (a) Benign teratoma / Dermoid Cyst (a) Serous cyst adenoma (b ) Mucinous cyst adenoma (c) Brenner tumour (d) Fibroma Thecoma (a) Granulosa cell , Sertoli - leydig cell CAUSES OF BENIGN OVARIAN CYSTS

7. OVARIAN TUMOUR SCREENING MULTI MODEL C a 125 and Ultrasound scanning Ca 125 >30 u\ml is abnormal Ca 125 is an antigen found in the foetal amniotic and coelomic epithelium.in adults it is found in mesothelial cells of pleura Pericardium and tubal, endometrial, endocervical and the ovary. The surface epithelium of normal foetal and adult ovaries does not express the antigen , except in inclusion cysts, papillae or metaplasia An elevated level is found in 50% of stage 1 and >90% in women with advanced disease. Sensitivity is 97% Specificity is 96% False positive in ca endometrium ,ca colon, endometriosis, fibroid, PID, pregnancy and menstruation

8. Classification of ovarian mass 1. Simple cyst 2. Hemorrhagic cyst 3. Hyperstimulation in women who have undergone fertility treatment 4. Luteoma of Pregnancy 5. Endometrioma 6. Brenners tumour 7. Epithelial tumours Serous and mucinous , endometroid and clear cell tumours . 8. Sex cord and Mesenchymal tumours Fibrothecomas , granulosa cell , sclerosing stromal and sertoli-leydig cell tumours . 9. Germ cell tumours Mature and immature teratomas , dysgerminomas , endodermal sinus tumours , embryonal carcinomas.

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. 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.

12. Corpus luteal cyst

13. 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.

14. Theca lutein cysts

15. 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

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

17. (I) Functional  (II) Inflammatory (III) Others (IV) Neoplastic (1) Germ cell (2) Epithelial (3)Sex cord stromal (a) Follicular cyst (b) Corpus Luteal cyst (c) Theca Luteal cyst  (a) Tubo -ovarian abscess Endometrioma Ovary (a) Benign teratoma / Dermoid Cyst (a) Serous cyst adenoma (b ) Mucinous cyst adenoma (c) Brenner tumour (d) Fibroma Thecoma (a) Granulosa cell , Sertoli - leydig cell CAUSES OF BENIGN OVARIAN CYSTS

18. (a) Inflammatory ovarian cysts Tubo-ovarian abscess Are present in 14-38% of patients hospitalized with pelvic inflammatory disease (PID) . Commonly seen in patients with poor access to routine gynecologic care .

19. The traditional criteria for the diagnosis of PID include subjective bilateral abdominal pain per patient report and positive physical examination findings for bilateral adnexal tenderness at palpation and cervical motion tenderness. A hydrosalpinx is generally anechoic, whereas a pyosalpinx may have increased echoes within the fluid.

20. (I) Functional (II) Inflammatory  (III) Others (IV) Neoplastic (1) Germ cell (2) Epithelial (3)Sex cord stromal (a) Follicular cyst (b) Corpus Luteal cyst (c) Theca Luteal cyst Tubo -ovarian abscess  (a) Endometrioma Ovary (a) Benign teratoma / Dermoid Cyst (a) Serous cyst adenoma (b ) Mucinous cyst adenoma (c) Brenner tumour (d) Fibroma Thecoma (a) Granulosa cell , Sertoli - leydig cell CAUSES OF BENIGN OVARIAN CYSTS

21. (A) Endometrioma of ovary 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.

22. 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

23. Chocolate cyst of Ovary on cut section Ovarian Endometrioma

24. (I) Functional (II) Inflammatory (III) Others  (IV) Neoplastic (1) Germ cell (2) Epithelial (3)Sex cord stromal (a) Follicular cyst (b) Corpus Luteal cyst (c) Theca Luteal cyst Tubo -ovarian abscess (a) Endometrioma Ovary (a) Benign teratoma / Dermoid Cyst (a) Serous cyst adenoma (b ) Mucinous cyst adenoma (c) Brenner tumour (d) Fibroma Thecoma (a) Granulosa cell , Sertoli - leydig cell CAUSES OF BENIGN OVARIAN CYSTS

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

26. (A) 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 ”

27. On USG Serous Cystadenoma Gross appearance Gross appearance Cut section appearance Cut section appearance

28. On MRI Serous Cystadenoma On USG Serous Cystadenoma

29. (B) MUCINOUS CYSTADENOMA Have tendency to become huge masses Gross : 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. Microscopy : Epithelium – tall, pale staining, secretary with basal nuclei and goblet cells 5 – 10% are malignant

30. Epithelium – tall, pale staining, secretary with basal nuclei and goblet cells

31. On MRI Mucinous cystadenoma.

32. DERMOID CYST/ Benign cystic teratoma 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

33. Dermoid Cyst ( Benign Cystic Teratoma )

34. 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.

35. OVARIAN FIBROMA Microscopy .. Gross appearance

36. On MRI Ovarian F ibroma .

37. 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 – associated with Reinke crystals Rarely malignant

38. BRENNER TUMOR It is named for Fritz Brenner, who characterized it in 1907. The term "Brenner tumor " was first used by Robert Meyer, in 1932. Uncommon tumor grossly identical to fibroma . Arise from Walthard cell rests ,also from surface epithelium, rete ovarii and ovarian stroma . Brenner tumors are usually found incidentally at pathologic evaluation, often in conjunction with a mucinous cystadenoma or dermoid cyst. They are relatively rare tumors and are most common in the fifth to sixth decades of life.

39. 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 Cut section Microscopy

40. Ovarian Gonadal Sex Cord Stromal Tumours Granulose theca cell tumours Sertoli-Leydig cell tumours

41. Found in all age groups and associated with the pseudo precocious puberty. Early breast development , menstrual disorders, postmenopausal vaginal bleeding make up the characteristic symptom. Laboratories studies demonstrate an increase in the number of mature epithelial cells in the vaginal cytologic specimen, elevated urinary and serum estrogen levels and varirant degree of endometrial proliferation. Microscopy : The characteristic cell is the round or slightly ovoid granulosa cell with its dark nucleus. Mitosis are common and the ovumlike “Call Exner bodies “ are classic. Granulosa stromal Sex cord tumours

42. Sertoli Leydig cell Tumours Also called as Androblastoma Often affect females beneath the ages of 40yrs Usually be luteinised, simulating the classic pattern of the testes and producing steroids Generally benign, may produce the masculinisation.

43. TREATMENT OF NEOPLASTIC TUMOURS In most instances, simple excision of the solid tumors is adequate therapy, particularly for women of reproductive age.

44. 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

45. Age : late child bearing age dermoid , mucinous adenoma common in reproductive age dermoid common in pregnancy Symptoms Asymptomatic , detected accidently during routine abdominal or gynecological examinations or during laporoscopic or laparotomy . Nonspecific symptoms like Feeling of abdominal distension and vague discomfort. Features of dyspepsia such as flatulence and eructations . Gradually more pronounced symptoms appear like Abdominal swelling which may be rapid Dull abdominal pain Respiratory distress which may be mechanical due to ascites /pleural effusion. Menstrual abnormalities in functioning ovarian tumours. For other ovarian tumours symptoms may differ eg . Androblastoma - Hirsutism . Signs General condition usually remains unaffected. The patient may be cachectic due to protein loss in huge mucinous cyst adenoma. CLINICAL PRESENTATION

46. On abdominal examination Inspection Bulge of lower abdomen over which abdominal wall moves freely with respiration. The mass may fill the entire abdominal cavity everting the umbilicus with visible veins under the skin.the flanks remain flat. Mass is cystic or solid. Palpation Surface is smooth ,non tender and freely mobile from side to side but restricted from above downwards unless pedicle is long. upper and latearal borders are well defined bt the lower pole is difficult to reach. Percussion dull in centre and resonants in the flanks. A fluid thrill may be elicited when the wall are thin and the content is watery. A friction rub may be present over the tumour. Bimanual Pelvic examination Uterus seperate from the mass groove present between uterus and the mass movement of the mass p/a fails to move the cervix lower pole of the cyst felt through the fornix absence of pulsation of uterine vessels through the fornix

47. COMPLICATIONS Of Benign ovarian tumours Torsion : Commonly seen in Dermoid cyst, serous cystadenoma . Intracystic hemorrhage : serous Cystadenoma , venous congestion. Infection : Following torsion. Rupture : Big and tense type,following trauma. Pseudomyxoma peritonei : Seen in Mucinous Cystadenoma Intestinal Obstruction Malignancy : Rare .

48. MANAGEMENT

49. TransVaginal ultraSound 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.

50. simple ultrasound-based rules for the diagnosis of ovarian cancer. ultrasound obstetgynecol2008 RCOG 2011

51. 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.

52. 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

53. TUMOR MARKERS CA125 CEA CA 19-9 HE4

54. 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%

55. Levels higher than 5 mg/ Lare seen in 85-90% of mucinous tumours but only in 30% of other epithelial cancers. CEA It is elevated in mucinous ovarian malignancy. CA 19.9

56. 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. HE4 when studied in the premenopausal group of patients was able to discriminate benign tumors from malignancies 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) Moore et al. / Gynecologic Oncology, 2008

57. Benign Ovarian tumour Malignant Ovarian tumour Common in middle age group Painless unless compicated No edema No varicosities Generally unilateral Unilocular Thin walled Thin septae if present No papillae or solid contents Normal or decreased vascularity on doppler No metastasis Slow growing Smooth, cystic Freely mobile No ascites or if present clear fluid on paracentesis Seen at extremes of ages May be painful Edema maybe present Varicosities may be present May be bilateral Multilocular Thick walled Thick septae Mixed echogenicity High vascularity , low pulsatility index and low resistance index Metastasis in advanced disease Rapidly growing Solid, nodular, irregularly shaped Fixed Ascites present and on paracentesis the fluid may be blood stained.

58. Treatment

59. 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

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

61. CYST ASPIRATION Diagnostic cytology has poor sensitivity to detect malignancy, ranging from 25% to 82% Not 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.

62. 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

63. SURGERY Young women : Ovarian cystectomy Oophorectomy ( salpingo ophorectomy ) Parous women : Total Abdominal Hysterectomy with Bilateral ophorectomy Others : Individualisation

64. 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

65. 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

66. Conclusion Ovarian masses are very commomly seen in general population.Most of the times these are simple functional tumours which resolve spontaneously within six to eight weeks.However an indepth understanding of the ovarian masses is needed as th the grave consequences that may follow if there is a wrong diagnosis.Imaging studies especially ultrasound is a prime tool in diagnosing ovarian tumours. Careful consideration to woman’s need should be addresses before selecting any method of treatment .