(28) Malig Ov Tumours

‫بسم ال الرحمن‬ ‫الرحيم‬

MALIGNANT OVARIAN TUMOURS

• 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

 

I. EPITHELIAL OVARIAN CANCER

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.

Aetiology: Possible factors include: 3. 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.

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%).

Risk factors for epithelial cancer: – – – –

Age Nulliparity & infertility White race Prior history of endometrial or breast cancer – Family history of ovarian cancer

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.

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

MALIGNANT GERM CELL TUMOURS

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

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

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 early tend to grow rapidly resulting in pelvic pain and pressure symptoms occurring early.

1.

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

2. Radiosensitive, chemotherapy in some of them gives excellent results in stage Ia. 3. Conservative surgery in the form of salpingoopherectomy is the first line of treatment.

• •

• • •

Dysgerminoma: The commonest malignant germ cell tumour accounting for about 3040% 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

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.

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

B) Endodermal Sinus Tumour “EST” • Prevalent in a 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.

Microscopically: • EST have a characteristic microscopic picture; Shiller-Duval bodies. These are cystic spaces in which projects a glomerulouslike structure with a central vascular core.

Treatment: • Surgery :

– unilateral salpingoophorectomy – TAH&BSO

• Chemotherapy: the tumour is chemosensitive

MALIGNANT SEX-CORD STROMAL TUMOURS

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.

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 510% 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.

Microscopically: • The tumour is formed of granulosa cells arranged in different patterns. CallExner bodies are pathognomonic, but are present in only 50% of cases. These are cystic spaces surrounded by granulosa cells arranged in a rosettelike shape. Treatment: • Unilateral salpingoophorectmy: • TAH BSO:

• No place for irradiation or

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

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

Metastatic Ovarian Cancer

Metastatic ovarian cancer forms about 56% of all ovarian tumours. The primary may be: – Genital tumours: From the endometrium, cervix, tube, and contralateral ovary. – Extragenital tumours: From the stomach, colon, breast, biliary tract, and thyroid gland.

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.

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

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.

• • • •

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.

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.

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.

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

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

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).

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.

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.

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).

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

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.

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.

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.

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.

• 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.

FIGO surgical staging for primary epithelial ovarian carcinoma

Stage

FIGO definition (simplified)

Stage Growth limited to ovaries I Ia Growth limited to one ovary No ascites; No tumour on external surfaces; capsule intact Ib Growth limited to both ovaries No ascites; no tumour on external surfaces; capsule intact

FIGO surgical staging for primary epithelial ovarian carcinoma (ctd) Ic

 Growth involving one or both ovaries with pelvic extension to Uterus and tubes Other pelvic tissues Stages IIa, or IIb with tumour on surface of one or both ovaries, capsule ruptured, or presence of ascites containing malignant cells or +ve peritoneal washings

FIGO surgical staging for primary epithelial ovarian carcinoma (ctd) Stage Growth involving one or both II ovaries with pelvic extension to IIa

uterus and tubes

IIb IIc

other pelvic tissues stages IIa, or IIb with tumour on surface of one or both ovaries, capsule ruptured, or presence of ascites containing malignant cells or +ve peritoneal washings

FIGO surgical staging for primary epithelial ovarian carcinoma (ctd)

Stage III IIIa

 Growth involving one or both ovaries with peritoneal implants outside the pelvis or positive retroperitoneal or inguinal nodes tumour grossly limited to the true pelvis with –ve nodes

IIIb

tumour with implants < 2.0 cm on abdominal peritoneal surface. Nodes are -ve

IIIc

tumour with implants > 2.0 cm or Nodes are +ve N.B.; superficial liver metastases is included in stage III c.

FIGO surgical staging for primary epithelial ovarian carcinoma (ctd) Stage IV

Growth involving one or both ovaries with distant metastases. •If pleural effusion is present there must be +ve cytology to allot a case to stage IV. •Parenchymal liver metastasis equals stage IV.

SURGICAL TREATMENT OF OVARIAN CANCER A) Early stage Ovarian Cancer: • TAH BSO and infracolic omentectomy is the standard treatment for patients with disease limited to the ovary (no gross evidence for extension beyond the ovaries Stage I-IIa). Surgical staging is completed via peritoneal wash, and lymph node sampling, for microscopic assessment of the extent of the disease.

• Occasionally, unilateral salpingooophorectomy may be done in selected cases of stage Ia disease (tumour confined to one ovary, with capsule intact, and –ve peritoneal cytology), only when the patient is young and fertility is desired. Such conditions are mostly met with in some early epithelial tumours (border line tumours), but more commonly with malignant germ cell tumours (dysgerminoma and EST), and malignant sex cord stromal tumours (granulosa and Sertoli Leydig cell tumours).

B) Advanced stage Ovarian Cancer: • Primary Cytoreductive surgery (initial Debulking) • Interval Debulking • Radical oophorectomy

Second-look Surgery in ovarian cancer: • Second look laparotomy or laparoscopy, have been advocated to asses residual tumour within the abdominal cavity after primary surgery and chemotherapy, to decide on further adjuvant therapy needed. Nowadays modern imaging technique, as • spiral CT & MRI, together with serum CA125 tests have largely nullified the need for second look surgery. At the present state its only place is when a tumour marker is rising apart from negative imaging for tumour residues.

CHEMOTHERAPY IN OVARIAN CANCER Chemotherapy whether single or multiple agents has a major role in the management of ovarian cancer especially in advanced disease, and mostly with epithelial ovarian cancer: • Early stage disease: It has a limited place only with poor prognostic factors as Poorly differentiated tumours, ruptured capsule, or +ve peritoneal wash (even in

•

Advanced stage disease: Chemotherapy is indicated in all cases of stage II-IV disease. a) All cases after primary cytoreductive debulking surgery b) Palliative therapy in patients with irresectable tumours, or patients with recurrent disease.

Types of chemotherapy used: • Chemotherapy is usually recommended as soon as possible after surgery, and is given for five or six cycles at 3-4 weekly intervals. • The most frequently used chemotherapeutic agents include: Cisplatin or Carboplatin alone or in combination with Paclitaxel (Taxol).

Toxicity from chemotherapy: Chemotherapeutic agents are • highly toxic at therapeutic doses, and therefore need close monitoring during treatment cycles. Toxicity includes; nausea, vomiting, myalgia and arthralgia. In severe cases renal damage, peripheral neuropathy, hearing loss, dehydration and electrolyte imbalance may occur.

RADIATION THERAPY IN OVARIAN CANCER Radiation therapy has little place in epithelial ovarian cancer. It may be used as an adjuvant therapy following cytoreductive surgery in patients who refuse or are not good candidate for chemotherapy. Two main forms are used:

PROGNOSIS IN OVARIAN CANCER The prognosis depends upon: • Histopathological type of ovarian cancer (epithelial or non epithelial ovarian cancer) • Stage of ovarian malignancy: the best prognosis is in stage Ia • Optimal versus Suboptimal surgery (TAH BSO + omentectomy, versus debulking) • Histology and grading of the tumour. Well differentiated tumours carry best prognosis, while poorly differentiated and clear cell carcinomas carry the worst prognosis. • Response of the tumour to adjuvant therapy (chemotherapy – irradiation).

• The 5-year survival rate in epithelial ovarian cancer is as follows: • In stage I 85-90% • In stage II 80% • In stage III 15-20% • In stage IV 5%

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