بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم Ovarian tumours By Dr. Sallama kamel

2. Introduction: • Ovarian cancer is the second most common gynecological malignancy and the major cause of death from a gynecological cancer. • Unfortunately survival from ovarian cancer remain poor (38%) , due in part to the late presentation of the disease. • Prompte identification and appropriate treatment of cancer of the ovary are essential if the survival rates are to be optimal.

3. -Although differentiating malignant from benign disease is critical in optimizing management for the individual case, -Non invasive diagnosis continues to be elusive

4. Histopathology and classification of ovarian tumors: A cyst or amass in the ovary could be: • Functional cysts -Follicular cyst. -corpus Luteal cyst. -Theca lutien cysts -endometriosis cyst • Primary T. -Epithelial cell T. -Germ cell T. -Sex cord T. • Secondary T. - Breast , colon, stomach

5. Epithelial tumours Germ cell T. Sex cord T. -Serous tumours. -Dysgerminoma -Granulosa cell . -Mucinous tumours. -Teratoma(benign and malign) -Thecoma -Endometroid tumours. -Yolk sac tumor -Sertoli- leydig cell. -Clear cell tumours.-Choriocarcinoma -Gynandroblastoma -Brenner tumours. -Embryonal carcinoma -Fibroma -Mixed epithelial tumours. -Undifferentiated tumours

6. Physiological cyst -They are simply large versions of the cysts that forms in the ovary during the normal ovarian cycle. -Most are asymptomatic and found incidentally on pelvic examination or ultrasound. -They are most common in young women. -They may be a complication of induction of ovulation. -They also occur in women with trophoblastic disease.

7. Follicular cysts: it result from the non-rupture of a dominant follicle or the failure of atresia in a non-dominant follicle. They are lined by Granulosa cells and contain clear fluid. It can persist for several menstrual cycles and may achieve a diameter of up to 10cm. Small cysts are more likely to resolve spontaneously but may require intervention if symptoms develop or if they do not resolve after 8-16 weeks. Occasionally they may continue to produce oestrogen, causing menstrual disturbances and endometrial hyperplasia.

8. Simple follicular cyst

9. Luteal cysts: Less common than follicular cyst. Are more likely to present with intra-peritoneal bleeding. They may also rupture. This is usually happens on day 20-26 of the cycle. They should not called Luteal cyst unless they are more than 3cm. In size. Theca-lutein and granulosalutein cysts. -These occurs in association with hydatidiform moles or Choriocarcinoma. -They are caused by high output of gonadotrophin from the chorion,and may reach a size of 10cm -After treatment or removal of the abnormal chorion the cyst resolves. -Similar cysts may formed if excessive doses of gonadotrophins or of clomiphines are given to induce ovulation causing hyper-stimulation syndrome.

10. Epithelial tumours: -These tumours arise from the ovarian surface epithelium. -So they arise from the Coelomic epithelium overlying the embryonic gonadal ridge. Since the epithelial covering of the ovary and the mullerian duct ( from which the tubal, endometrial and cervical epithelium are derived ) are both from coelomic epithelium , comparable metaplastic transformation into different types of epithelium is possible. -So the cells may differentiate to endocervical cells giving rise to mucinous cystadenoma. -Differentiation into endometrial cells give rise to Endometrioid tumour. -Differentiation to tubal epithelium give rise to serous cystadenoma. -Differentiation along uro-epithelium give rise to Brenner tumour. They are most common in women over 40 years old.

11. 1.Serous cystadenoma: -These are the most common epithelial tumours with a range from benign to the highly malignant . -The benign form are called benign serous cyst. -It is unilocular cyst with papilliferous processes on the inner surface and occasionally on the outer surface. -The lining epithelium is cuboidal or columnar and may be ciliated. -The cyst contain thin serous fluid. -They are usually smaller than the mucinous tumour. -They are often bilateral -They occur most commonly in late reproductive and early postmenopausal life.

12. The malignant form called Serous papilliferous carcinoma: -This is the commonest primary ovarian carcinoma. -It is bilateral in 50%. -The growth often penetrates the capsule and project on the external surface with dissemination of the cells into the peritoneal cavity giving multiple seedling metastases and ascites. -The cyst contains many papillary processes which have proliferated so much that they almost fill the cavity and there may be exophytic papillary growth on the surface. -The lining cells are multilayer and may invade normal tissues.

13. Ovarian carcinoma

14. 2.Mucinous cystadenoma: -The 2nd most common epithelial tumour. -They are large, unilateral , multilocular cysts with smooth inner surface. -The lining epithelium is columnar mucous-secreting cells. -The cyst contain thick glutinous fluid. -A rare complication is pseudomyxoma peritonei, when there is shedding of cells on the surface of the peritoneum and grow there and continue to secrete mucin so the abdominal and pelvic cavities are slowly filled with a gelatinous mass of mucin , causing matting together and consequent obstruction of the bowel loops. -A similar condition may occur after rupture of a mucocele of the appendix and the two may co-exist, raising the possibility of a metastasis from an ovarian primary.

15. Mucinous cystadenoma

16. Malignant mucinous cyst (Mucinous carcinoma): -Constitute 10% of ovarian cancers. -On histological examination, 5% of mucinous cysts found to be malignant. Epithelial tumours of borderline malignancy: - mean that the tumour carry some of the features of malignancy( e.g. multilayering of cells and nuclear atypia). -But there is no stromal invasion. -20% of epithelial tumours are of borderline malignancy. -It is rare for such tumours to be more than stage1, i.e. beyond one or two ovaries , and surgical removal of the pelvic organs usually results in cure.

17. 3.Endometrioid cystadenoma: -These are very similar to ovarian endometriosis. -They may be associated with pelvic pain and dyspareunia due to adhesions. -It may coexist with uterine endometrial adenocarcinoma. 4.Clear cell tumours( mesonephroid): -They arise from serosal cells showing little differentiation, and are only rarely benign. -The typical histological appearance is of clear or hobnail cells( which have scanty cytoplasm and large nuclei) arranged in mixed patterns .

18. 5.Brenner tumours: -These account for only 1-2% of all ovarian tumours. -They are bilateral in 10-15%. -The vast majority is benign but can occasionally be borderline or malignant -Three quarter occurs in women over the age of 40. -The majority is less than 2cm in diameter. -Some secrete oestrogens and abnormal vaginal bleeding is a common presentation. Macroscopically:a Brenner tumour resembles a fibroma, being a solid tumour with a white cut surface. Histologically: -It consists of islands of round transitional-like epithelium in a dense fibrotic stroma giving a solid appearance.

19. Germ cell tumours: •It is among the commonest ovarian tumours seen in women of less than 30years old. ●In women under 20 years ,up to 80% of ovarian malignancies are due to germ cell tumours. •Overall only 2-3 percent are malignant . •These tumours arise from a totipotential germ cell •Thus they contain element of all three germ layer( embryonic differentiation). Differentiation into embryonic tissues result in teratoma (dermoid cyst). •Differentiation into extra-embryonic tissues results in ovarian Choriocarcinoma or endodermal sinus tumour. •When neither embryonic nor extra-embryonic differentiation occurs, dysgerminoma results.

20. Dermoid cyst (mature cystic teratoma) -This is the commonest germ cell tumour and it is benign. -It results from differentiation into embryonic tissues. -It account for about 40% of all ovarian neoplasm. -It is most common in young women and the median age of presentation is 30 years old. -it contain a variety of tissues derived from the two or more of the primary germ layers.. -The dermoid cyst is usually unilocular cyst. -Less than 15cm in diameter -It is often lined by epithelium like the epidermis and contain skin appendages, teeth , sebaceous material , hair and nervous tissues, cartilage bone and thyroid tissues. -The cavity of the cyst contain yellow greasy material.

21. Dermoid cysts

22. -The majority of dermoid cysts (60%) are asymptomatic. -However it may undergo torsion. -Less commonly it may rupture spontaneously, either suddenly causing an acute abdomen and chemical peritonitis, or slowly causing chronic granulomatous peritonitis. -During pregnancy, rupture is more common due to external pressure from expanding gravid uterus or to trauma during delivery. -Some dermoid cysts contain single type of tissues like thyroid tissue and called stroma ovarii and might present with feature of hyperthyroidism. Mature solid teratoma: -These are tumours contain mature tissues just like the dermoid cyst but are solid. -They must be differentiated from immature teratomas which are malignant.

23. Malignant germ cell tumours: These are rare tumours accounting for only 3% of ovarian cancers. 1.Dysgerminoma: -This is the most common malignant germ cell tumours accounting for about 50%. -Nearly all occur in young women less than 30 years old. -Spread mainly by lymphatics. -They are solid tumours with a smooth or nodular external surface. -The mean diameter is 15cm. -Approximately 10% are bilateral( the only malignant germ cell tumour that can be bilateral ). -Pure Dysgerminoma have a good prognosis as they are normally stage 1 tumours in 75% of cases. -It may occur in cases of gonadal dysgenesis,and it is radiosensitive.

24. 2.Yolk sac tumour ( endodermal sinus tumour). -These are the second most common malignant germ cell tumour of the ovary. -Making 10-15% over all and reaching a higher proportion in children -The tumour is usually well – encapsulated and solid. -It may present as acute abdomen due to rupture of the tumour following necrosis. -It secrete alfa-feto protein (AFP) which can be used as a tumour marker.

25. 3.Immature Solid Teratoma: -These account for approximately 20% of malignant germ cell tumours with a peak incidence in the second decade of life. -They contain embryonic( immature) tissues and they are highly malignant. 4.Non gestational Choriocarcinoma: -These generally arise as a component of a solid teratoma. -They consist of syncytiotrophoblast and cytotrophoblast and secret gonadotrophin, which can be used as a diagnostic marker.

26. sex cord stromal tumours: -These account for only 4% of benign ovarian tumours. -They occur at any age from prepubertal children to elderly, postmenopausal women. -They secrete hormones and present with the results of inappropriate hormone effects. 1.Granulosa cell tumours: -These are all malignant tumours but they are generally confined to the ovary when they present and so have a good prognosis. -They grow very slowly and recurrences are often seen 10-20 years later. -They are solid in most cases. -Some produce oestrogens causing postmenopausal bleeding in older women or precocity in prepubertal girls and -most appear to secrete inhibin which can be used to monitor treatment..

27. 2.Theca cell tumours: -Almost all are benign, solid and unilateral tumours. -They present in the sixth decade of life. -Many produce oestrogens in sufficient quantity to have systemic effects such as precocious puberty, postmenopausal bleeding , endometrial hyperplasia and endometrial cancer.

28. 3.Fibroma: -These unusual tumours are most frequent around 50 years of age. -Most are derived from stromal cells and are similar to thecomas. -They are hard mobile and lobulated with glistening white surface . -Less than 10% are bilateral. -Meig’s syndrome( ascites , pleural effusion in association with a fibroma of the ovary) is seen in only 1% of cases.

29. 4.Sertoli- leydig cell tumours: -These are usually of low grade malignancy. -Most occur around 30 years of age. -They are rare ( only 0.2% of ovarian tumours). -Many produce androgens and signs of virilization are seen in three-quarters of patients

30. Benign ovarian tumours: presentation: -Asymptomatic. -Pain. -Abdominal swelling. -Pressure effects. -Menstrual disturbances. -Hormonal effects. -Abnormal cervical smear.

31. 1.Asymptomatic: Many benign ovarian tumours are found incidentally in the course of investigating another unrelated problem or during a routine examination. 2.Pain: -Acute pain from an ovarian tumour may result from complication e.g. torsion, rupture, haemorrhage or infection. -Torsion give rise to a sharp, constant pain caused by ischaemia of the cyst and areas may become infarcted. -Haemorrhage into the cyst may cause pain as the capsule is stretched. -Rupture of the cyst causes intraperitoneal bleeding mimicking ectopic pregnancy (this happens mostly with a luteal cyst ). -Chronic lower abdominal pain sometimes results from the pressure of a benign ovarian tumour but is more common if endometriosis or infection is present.

32. Twisted ovarian cyst

33. 3.Abdominal swelling: -Patients seldom note abdominal swelling until the tumour is very large . -A benign mucinous cyst may occasionally fill the entire abdominal cavity. 4.Miscellaneous : pressure effects. -Gastro-intestinal or urinary symptoms may result from pressure of large tumour. -In extreme cases, oedema of the legs, varicose veins and haemorrhoids may result. -menstrual disturbances: • Occasionally the patient will complain of menstrual disturbances but this may coincidence rather than due to the tumour. -hormonal effects : rarely Sex cord tumours may present with oestrogens effects such as precocious puberty, menorrhagia and glandular hyperplasia, breast enlargement and postmenopausal bleeding. -Secretion of androgens may cause hirsutism and acne initially progressing to frank virilism with deepening of the voice or clitoral hypertrophy.

34. Diagnosis: 1.Full history: -Details of the presenting symptoms and a full gynaecological history should be obtained with particular reference to the date of the last menstrual period , the regularity of the cycle, any previous pregnancies , contraception, medication and family history ( particularly of ovarian, breast and bowel cancer ). 2.Examination ( abdominal and pelvic examination): -If the patient presented with acute abdomen look for evidence of hypovolaemia. -The neck , axilla and groins should be examined for lymphadenopathy. A malignant ovarian tumour may cause a pleural effusion. -This is much less commonly found with benign tumour. -Also some patient may have ankle oedema. -The abdomen should be inspected for distension by fluid or by the tumour itself. -A male distribution of hair may suggest a rare androgen-producing tumour.

35. Bimanual examination: -This is an essential part of assessment. -To palpate the mass , its mobility, consistency. -Presence of nodules in the pouch of Douglas and the degree of tenderness. -A cystic mobile mass is mostly benign, while a hard, irregular fixed mass is likely to be malignant.

36. Investigations: . Ultrasound -Trans-abdominal and trans-vaginal ultrasound can demonstrate the presence of an ovarian mass with reasonable sensitivity and specificity. -However it can not distinguish reliably between benign and malignant tumours but solid masses are more likely to be malignant than the purely cystic mass. -The use of colour- flow Doppler may increase the reliability of ultrasound. -MRI may have a role in differentiating benign and malignant ovarian tumours.

37. Radiological investigations: -A chest X- ray is essential to detect metastatic disease in the lungs or a pleural effusion . -Occasionally an abdominal X-ray may show calcification, suggesting the possibility of a benign teratoma. -A barium enema is indicated only if the mass is irregular or fixed, or if there are bowel symptoms. Blood test and serum markers: -Elevated WBCcount may indicate infection. -Ca125 Raised serum Ca125 is strongly suggestive of ovarian carcinoma, especially in postmenopausal women.

38. -Women with extensive endometriosis also have elevated levels but the concentration is usually not as high as that seen with malignant disease. - B-HCGlevel is elevated in women with choriocarcinoma. -Oestradiollevels may be elevated in some women with physiological follicular cysts and sex cord stromal tumours. -Androgensare increased with Sertoli-lydig tumours. -Raised alpha-fetoproteinlevels suggest a yolk sac tumour.

39. Management of benign ovarian tumours: This will depend upon the -Severity of the symptoms. -Age of the patient . -The risk of malignancy. -Her desire for future pregnancy. The asymptomatic women: The older women: Women over 50 years of age are more likely to have a malignancy so surgery is usually indicated. -but for a simple cyst less than 6cm in diameter with a normal Ca 125 and normal vascular resistance pattern are likely to be benign and may safely be managed conservatively.

40. -So a 2nd ultrasound should be made after 12 weeks if there is no change in the cyst happened, follow up with six- Monthly ultrasound and Ca125 estimation is safe. Most would resolve in 3 years but some do persist for up to 7 years. In pre-menopausal women: -Young women of less than 35 years are both more likely to wish to have further children and are less likely to have malignant epithelial tumour. 1-A normal follicular cyst up to 3 cm in diameter requires no further investigation. 2-A clear unilocular cyst of 3-10 cm identified by ultrasound should be re- examined after 12 weeks for evidence of diminution in size .

41. - If the cysts persists, such women may be followed with a six-monthly ultrasound and Ca125 estimations. -The use of combined oral contraceptive pills is unlikely to accelerate the resolution of a functional cyst. -If the cyst does enlarge , laparoscopy or laparotomy may be indicated. 3.A cyst of more than 10 cm is unlikely to be physiological or to resolve spontaneously and operation indicated. The patient with symptoms: If the patient present with severe acute pain or signs of intraperitoneal bleeding an emergency laparoscopy or laparotomy will be required.

42. The pregnant patient: -An ovarian cyst in pregnant women may undergo torsion or may bleed. -The pregnant women with an ovarian cyst is a special case because of the risk of surgery to the fetus. -Thus if the patient present with acute pain due to torsion or haemorrhage into an ovarian cyst or if appendicitis is a possibility, the correct course is to undertake a laparotomy regardless the stage of the pregnancy. -The operation should be covered with by tocolytic drugs and performed in a center with intensive neonatal care. -If asymptomatic cyst is discovered during the 1st trimester, it is prudent to wait until after 14 weeks’ gestation before removing it.

43. -This avoids the risk of removing a corpus luteal cyst upon which the pregnancy might still be dependent. -In the 2nd and 3rd trimesters , the management of an asymptomatic ovarian cyst may be either conservative or surgical. -Cysts < 10cm , which have simple appearance on U/S , are unlikely to be malignant or to result in cyst accident and may therefore be followed by U/S. -Many may resolve spontaneously . If the cyst unresolved 6 weeks postpartum , surgery indicated.

44. -Malignancy is uncommon in pregnancy occurring in less than 3% of the cysts. -However a cyst with a features suggestive of malignancy on U/S , or one that is growing, should be removed surgically. -The tumour marker C 125 is not useful in pregnancy since it may be elevated in normal pregnancies. Prepubertal girl: -Ovarian cysts are uncommon and often benign. -Teratoma and follicular cysts are the most common. -Presentation may be abdominal pain, distension or precocious puberty. -Management depends on: -relief of symptoms. -exclusion of malignancy and -conservation of maximum ovarian tissue without depressing fertility.

45. Types of surgery for apparently benign ovarian tumours: For young women less than 35 years: 1.Cystectomy ( removal of the cyst only). 2.Oophorectomy( removal of the ovary). For woman more than 45 yearswith ovarian cyst more than 6cm in diameter it is advisable to do total abdominal hysterectomy and bilateral salpingo-oopgorectomy.

46. Malignant disease of the ovary: -Most ovarian tumours are of epithelial origin. -They are rare before the age of 35 years, but the incidence increases with age to a peak in the 50-70 years. -Most epithelial tumours are not discovered until they have spread widely. -Surgery and chemotherapy forms the main stay of treatment. The results are poor. -The 5 year survival is around 38%. -Only 3 % of ovarian cancers are seen in women younger than 35 years and most are non-epithelial cancers such as germ cell tumours.

47. 1.-Epithelial tumours account for 60-65% of all ovarian tumours and approximately 90% of those that are malignant (it is the most common). -It is a disease of late reproductive and postmenopausal women (average presentation at 64 years). 2.Germ cell tumours, derived from the germ cells and account for 30% of ovarian tumours. Although they represent only 1-3% of all ovarian malignancies, they are commonest tumours encountered in children and adolescent (more than 60% of ovarian cancers in this age group. 3.sex cord stromal tumours are derived from sex cord and stroma of the ovary and account for approximately 8% of all ovarian tumours (least common).

48. Incidence: -The lifetime risk of developing ovarian cancer on the general population is 1.4 % (one in 70). -Ovarian cancers are more prevalent in developed nations. -There are variations in incidence with ethnicity, Caucasian women have the highest incidence (14 per 100 000) whereas Asian women have a lower incidence (10 per 100 000). -There is a significant genetic aspect to ovarian cancer with earlier presentation at 54 years.

49. Aetiology and risk factors: Epithelial ovarian cancer(EOC) is due to malignant transformation of the ovarian epithelium. There are two main theories regarding this malignant transformation: 1.Incessant ovulation theory Continuous ovulation causing repeated trauma to the ovarian epithelium leading to genetic mutation and development of cancer. -This theory is supported by an increased incidence of EOC in nulliparous women, women with early menarche or late menopause . -reduced incidence in multiparous women and women used oral contraceptive pills

50. 2.Excess gonadotrophin secretion: This promotes higher levels of oestrogen which in turn leads to epithelial proliferation and malignant transformation of the ovarian epithelium.