بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. MALIGNANT OVARIAN TUMOURS Prof.Osman Donia

3. Malignant epithelial tumours: • Serous adenocarcinoma • Mucinous adenocarcinoma • Endometrioid adenocarcinoma • undifferentiated adenocarcinoma • Malignant germ cell tumours: • Dysgerminoma • Endodermal sinus tumour • Choriocarcinoma • Solid teratoma • Malignant sex cord stromal tumours: • Granulosa cell tumour • Sertoli-Leydig cell tumour

4. I. EPITHELIAL OVARIAN CANCER

5. Incidence: • Primary ovarian epithelial cancer forms 60-70% of all ovarian tumours. • 90% of all ovarian malignancies. • It is the third common malignancy of female genital organs.

6. Aetiology: Possible factors include: • Reproductive factor: Nulliparous or infertile women are more liable to develop it. 2. Hereditary 'Genetic' factor: • 5- 10% of epithelial ovarian cancer occur in women with hereditary predisposition. • A particular feature of familial cancer is that it tends to occur at a younger age. • Hereditary predisposition is due to a defective gene in their families, which is tumour suppression gene BRCA, BRCA2 .i.e. gene mutation.

7. Three types of familial ovarian cancer are identified: • Site specific ovarian cancer syndrome (15%) • Hereditary breast / ovarian cancer syndrome (75%) • Hereditary non polyposis colorectal cancer syndrome with endometrial, breast, or ovarian cancer (10%).

8. Risk factors for epithelial cancer: • Age • Nulliparity & infertility • White race • Prior history of endometrial or breast cancer • Family history of ovarian cancer

9. PATHOLOGY OF PRIMARY EPITHELIAL OVARIAN CANCER Macroscopic appearance: • Usually solid but may be partially cystic partially solid. • Unilateral or bilateral • The size is extremely variable • The substance of the tumour is the seat of extensive haemorrhage and necrosis.

11. Microscopic picture: It is an Adenocarcinoma Which might be either : • Serous cystadenocarcinoma • Mucinous cystadenocarcinoma. • Endometrioid cystadenocarcinoma. Which could be either : a. Well differentiated(Gr I) b. Moderately differentiated(Gr II) c. Undifferentiated (Gr III) N.B. Border line epithelial tumours

12. MALIGNANT GERM CELL TUMOURS

13. The incidence of germ cell tumours is only 20-30% of all ovarian tumours. • Five per cent of germ cell tumours are malignant.

14. Classification of malignant germ cell tumours: • Dysgerminoma • Endodermal sinus tumour (yolk sac tumour) • Choriocarcinoma • Malignant teratoma • Benign cystic teratoma with malignant transformation • Malignant solid teratoma

15. Special Features of Germ Cell Tumours: They differ from epithelial ovarian cancer by the following points: • Lower age incidence • The commonest tumours of abnormal gonads and in sex chromatin negative females. • tend to grow rapidly resulting in pelvic pain and pressure symptoms occurring earlytend to grow rapidly resulting in pelvic pain and pressure symptoms occurring early.

16. Most tumours produce substances in the circulation that can be used as tumour markers; • Dysgerminoma: alkaline phosphatase & lactic acid dehydrogenase. • Endodermal sinus tumour : alpha feto proteins. • Choriocarcinoma :hCG • Radiosensitive, chemotherapy in some of them gives excellent results in stage Ia. • Conservative surgery in the form of salpingoopherectomy is the first line of treatment.

17. Dysgerminoma: • The commonest malignant germ cell tumour accounting for about 30-40% of all malignant germ cell tumours. • Represents 1-3% of all ovarian tumours. • Tends to occur at a younger age (10-20 years). • May secrete alkaline phosphatase and lactic acid dehydrogenase.

18. Pathology: • Solid ovarian tumour, usually of small or moderate size • Bilateral in only 10% of cases. • Greyish with lobulated surface with tendency to haemorrhage and necrosis.

20. Microscopically: • Consists of gem cells arranged in alveoli or nests separated by fibrous tissue septa heavily infiltrated with lymphocytes. • Cells are round, large, with abundant cytoplasm and a large irregular nucleus. Treatment: • Surgery: • Unilateral salpingoophorectomy, • TAH&BSO • Radiotherapy

21. B) Endodermal Sinus Tumour “EST” • Prevalent ina young age (median age of 16-18 years). • Most EST secrete alpha-fetoproteins that are used as a tumour marker. Pathology: • Small solid tumours which are almost always unilateral.

22. Microscopically: • EST have a characteristic microscopic picture; Shiller-Duval bodies. These are cystic spaces in which projects a glomerulous-like structure with a central vascular core. Treatment: • Surgery: • unilateral salpingoophorectomy • TAH&BSO • Chemotherapy:the tumour is chemosensitive

23. MALIGNANT SEX-CORD STROMAL TUMOURS

24. Sex-cord stromal tumours may arise from non- functioning or functioning stroma of the ovary. • Functioning sex–cord tumours may be: • Estrogenic: as granulosa cell tumour. • Androgenic: as Sertoli-leydig cell tumours • Both estrogenic and androgenic effect (very rare): as in Gynandroblastoma. • Non- functioning stroma may very rarely give rise to fibrosarcoma of the ovary.

25. A) Granulosa Cell Tumours: • Usually unilateral, solid,yellow or yellow-grey in colour. • Some are functioning secreting oestrogen, while most appear to secrete inhibin. • Associated with endometrial carcinoma in 5-10% of cases, and with endometrial hyperplasia in 25-50% of cases. • They may cause irregular bleeding or precocious puberty (before puberty), menstrual irregularities or post menopausal bleeding.

27. Microscopically: • The tumour is formed of granulosa cells arranged in different patterns.Call-Exner bodies are pathognomonic, but are present in only 50% of cases. These are cystic spaces surrounded by granulosa cells arranged in a rosette-like shape. Treatment: • Unilateral salpingoophorectmy: • TAH BSO: • No place for irradiation or chemotherapy

28. B) Sertoli-Leydig Cell Tumours: • They are very rare representing < 0.2% of all ovarian tumours. • They are usually small, unilateral, solid tumours, oflow grade malignancy. • Many are functioning producing androgens. • Treatment:Either unilateral salpingoopherectmy if the patient is young or TAH&BSO.

29. PATTERNS OF SPREAD OF OVARIAN CANCER Primary methods of spread of ovarian cancer are: • Direct extension • Lymphatic spread • Transcoelomic spread • Haematogenous spread

30. Metastatic Ovarian Cancer Metastatic ovarian cancer forms about 5-6% of all ovarian tumours. The primary may be: • Genital tumours: From the endometrium, cervix, tube, and contralateral ovary. • Extragenitaltumours: From the stomach, colon, breast, biliary tract, and thyroid gland.

32. Krukenberg Tumour: • It accounts of 30-40% of metastatic cancer to the ovary. • The primary is usually in the pylorus, less commonly in colon, breast or biliary tract. • They are bilateral solid ovarian tumour retaining the shape of the ovary. • The main interest is in its histogenesis, the most acceptable theory is that malignant cells reached both ovaries by retrograde lymphatic spread.

33. Prognosis: Bad, most patients die within one year because most of the lesions are not discovered until the primary disease is advanced.

34. CLINICAL PICTURE OF PRIMARY MALIGNANT OVARIAN TUMOURS • This is a disease of late decade of life: 55–65 years of age in the majority of cases. • It is more common in industrial countries. SYMPTOMS: • Early stage disease: are mostly asymptomatic. • may be associated with non specific GIT symptoms in the form of dyspepsia, indigestion, and anorexia. Pressure symptoms as urinary frequency, and constipation may be present, with or without pelvic pain.

35. Late stage disease: may present with: • Abdominal pain and cachexia, abdominal swelling. • Abnormal uterine bleeding, and especially postmemnopausal bleeding. • Rarely ascites may be the first clinical presentation.

36. PHYSICAL SIGNS: • The most important physical sign is the palpation of a pelvic mass. • If the patient is lucky this pelvic mass is discovered during routine pelvic examination. • In late cases a pelviabdominal fixed solid mass is felt. • Bilateral solid fixed masses are always suspicious of malignant ovarian tumour.

37. CLINICAL FEATURES SUGGESTING MALIGNANCY INOVARIAN TUMOURS A) History: • Age, especially extremes of age (before puberty, or > 40-60 years). • Rapid growth of the tumour. • Pain and loss of weight are always late symptoms. • Post menopausal bleeding and symptoms of virilisation, are suspicious.

38. B) General examination: • Malignant Cachexia (with marked and rapid weight loss and dehydration) • Palpable supraclavicular lymph nodes especially on the left side, (Virchows glands). • Pleural effusion, however it may be present in Meig’s syndrome. • Associated breast mass, on breast examination • Unilateral leg & edema (unilateral pressure by tumour with venous and lymphatic obstruction).

39. C) Abdominal Examination: • Inspection:Abdominal enlargement, over lying skin showing peau d’orange. • Palpation:Tumour which is solid (or partially solid), fixedespecially if bilateral. • Percussion: Presence of ascites (except with ovarian fibroma in Meig’s syndrome).

40. D) Pelvic examination: • Nodules in Douglas pouch in the presence of a non tender adnexal mass. • Bilateral, especially if solid adnexal masses are very presumptive. • Fixed pelvic masses especially if amalgamated with pelvic organs (frozen pelvis).

41. At Laparotomy: • Ascites, especially if altered blood stained ascites. • Bilaterality, fixation, and invasion of the capsule. • Extracystic papillae, and adhesions to surrounding structures. • Peritoneal nodules or secondary deposits in omentum, intestine or liver • Variable consistency with a cut section of the tumour shows haemorrhage and necrosis.

42. SPECIAL INVESTIGATIONS FOR OVARIAN CANCER • Pelvic ultrasound • Endometrial curettage • Chest X-Ray • Plain X-Ray abdomen • Barium meal and/or enema • Upper and/or lower G.I. Endoscopy • I.V.P. • Paracentesis. • CT & MRI.

43. Tumour markers: • CA 125 (n < 35 u/ml): • This the most important marker used. • However it may be elevated in some benign conditions; as endometriosis and chocolate cysts. • It can be used also to monitor response to chemotherapy (decreasing levels denote good response). • Other markers include; serum B-hCG (choriocarcinoma), alpha fetoprotein (EST), serum alkaline phosphatase, and lactic acid dehydrogenase (dysgerminoma).

44. SCREENING for Ovarian Cancer: • Routine yearly pelvic examination in premenopausal and postmenopausal women. • Periodic TVS coupled with a serum CA-125 in those with an enlarged ovary

45. DIFFERENTIAL DIAGNOSIS of ovarian masses • Pelvic masses: as • adnexal masses. • uterine enlargement (myomata & pregnancy). • colonic masses. • retroperitoneal masses (pelvic kidney, retroperitoneal sarcoma, ...) • Abdominal masses as • liver or pancreatic tumour. • tense ascites.

46. EXPLORATORY LAPAROTOMY IN OVARIAN CANCER The final diagnosis of ovarian cancer can only be made at exploratory laparotomy, which will serve not only for diagnosis but also for surgical staging and primary surgical treatment.

47. STAGING OF OVARIAN CANCER Clinical staging For a malignant ovarian tumour will always be short of important items that will affect the prognosis and line of treatment, surgical staging is therefore the only standard method.

48. Surgical staging of primary ovarian cancer: entails a mid line subumbilical suprapubic exploratory laparotomy in which the following is performed: • Exploration of the pelvic and peritoneal cavity • Aspiration of any fluid in cul de sac (ascites), or perform peritoneal washings for Cytology. • Performing an infracolic omentectomy. • Pelvic and paraaortic lymph node sampling • Resection of any visible enlarged nodules or masses.

50. The complete procedure will then be a TAH BSO (or debulking of the malignant tumour), omentectomy, lymph node sampling or resection, removal of any pelvic or extrapelvic tumour masses >2.0 cm, and cytology to peritoneal fluid.