MALIGNANT OVARIAN TUMOUR

By: Dr. Johara Al-Mutawa Assistant Professor & Consultant

INTRODUCTION:
* It is common gynaecological tumour continue to kill more women than all other gynaecological cancer * In England the incidents of ovarian cancer 1.4 higher than cervical and endometrial cancer but lower than breast cancer 7.1% * Eventually 80 to 85% of women with ovarian cancer die * Most ovarian cancer as epithelial in origin and incidence increase risk with age.

Germ cell tumour rare and occur mainly in children and young women. * Survival rater 5 years in 60% of stage I disease ovarian malignancy. Histopathology and Classification of ovarian mass. * Ovarian mass Physiological Neoplastic Benign Malignant

* WHO provide international classification that has been universally accepted

Histological classification of ovarian Tumour Epithelial Tumour Serous Tumour Mucinous Tumour Endometrial Tumour Clear Tumour Mixed Tumour Undifferentiated and Unclassified Tumour

* * * * * *

Sex-Cord Stromal tumours

* * * * * Granulosa stromal cell tumours Sertoli stromal cell tumours Gynandroblastoma Sex cord tumour with annular tubules Unclassified sex-cord tumoursSteroid cell tumours

Ovarian germ-cell tumours

* Dysgerminoma * Teratoma (immature, mature and monodermal) * Yolk sac tumour (endodermal sinus tumour) * Embryonal carcinoma * Polyembryoma * Choriocarcinoma * Mixed germ-cell tumour

Epithelial Tumour Arise from surface epithelium of ovary account from 60-65 % of ovarian tumour and approximately 90% are malignant. Benign border line malignant Sex cord stromal tumour Derived from sex cord & Stroma of ovary Account approximately 8% of all ovarian tumour

Germ Cell Tumour = - Arise from germ cells - Account from 30% of ovarian tumour in the form of mature cyst tertoma (Dermoid Cysts) and 1 3 % of ovarian malignancy and represent 60% of ovarian cancer in children and adolescents.

Epithelial ovarian tumour *common bilateral *Serous most common 40 50%. *Mucinous 10% large size associated with pseudomyxoma ovari

* Endometrial ovarian cancer: account for 20% of epithelial tumour. 10% associated with endometrial cancer. * Brenner tumour very small proportion - 99% Benign * Clear Cell cancer Account from 5 10% 10% - Worse prognosis * Mixed epethilium ovarian tumour

Borderline ovarian tumour:

* Account approximately 15% of epithelial ovarian cancer. * They are low malignant potential. * Affecting young women and may present in pregnancy * Microscopically they show malignant features but no stromal invasion. * They have good prognosis.

Sex cord stromal tumours: * They are composed of granuloza, theca

and serotoli cells. * Granuloza cell tumour produce oestrogen and serotoli-stromal produce androgen. * Most of them are benign and most clinically malignant are granuloza cell T. * Meig syyndrome - fibroma + ascites and

Germ Cell Tumour:

* Account approximately 30% of ovarian tumour. * Commonest in the first two decade of life. * Sysgerminoma is the commonest 75% present in stage I disease 10-15% Bilateral 5-10% occur in female with abnormal gonads

Teratomas: drived from 2 -3 embroyonic layers

Mature (Dermoid Cysts) Commonest ovarian tumour Benign Unilateral (10-15% Bilateral) Leading to torsion. Contain teeth and hair in the cyst. Malignant transformation 2%

Immature Teratoma:
* 2nd commonest germ cell malignancy. * Account for 20% ovarian cancer in female under 20 years of age. * Unilateral * classified according to differentiation and quantity of immature tissue.

Embryonic Markers:
* Yolk sac tumour AFP - (rare tumor)

* Ovarian choriocarcinoma secret BHCG (rare tumour) * Normal level does not exclude diagnosis. * Teratoma & dysgemenoma does not secret this tumor marker.

Secondary ovarian malignancy:

* Account up to 10%. * Metastases form Colon Stomach Breast Female genital tract

Krukenberg Tumour: Bilateral enlarged ovaries * Ovarian metastatic tumour from gastric or colon cancer. * Microscopic assessment signet ring cells.

* CEA marker increase

Eitology:
* Environmental Factors: Unknown High fat diet Perineal dusting with talcum powder Risk of caffeine intake and radiation unclean. - Role of certain viral infection (Mumps, rubella, influenza) inconclusive results.

Reproductive and Hormonal factors:

* Contraceptive pill * Pregnancy * Breast feeding * Tubal ligation and Hysterectomy

- early menarche - late menopause - nulliparity

This suggest continous ovulation is important factor. * Using of ovulatory stimulants and subsequent development of epithelial ovarian cancer is currently lacking. * Heriditary factors not more than 10% of all ovarian cancer. * BRCAI responsible for 5% of ovarian cancer in young women < 40 years.

Screening of ovarian cancer:

* No role of ovarian screening in asymptomatic population. * Women at risk of developing ovarian cancer based on family history 10% offered screening. * Women risk vague pelvic abdominal symptoms warrant complete history and examination including vaginal and rectal examination.

Risk of Malignancy index (RMI)

Serum Ca 12.5 USS Score (0-3) calculated by: multilocular cysts Solid area Bilateral lession Metastasis Ascites Menopausal status 1 for premenopausal 3 for post menopausal

This RMI to identify cases for referral to Gynaecology Oncologist

Symptoms: * Early stage Pressure symptom * Late stage metastatic effect to bowel mesentery and ascites. - Vaginal bleeding less common.

Clinical Signs:
* Supraclavicular, axillary, inguinal lymph nodes. * * * * Breast examination Chest examination pleural effusion Abdominal examination liver size Pelvic & rectal examination Irregular solid mass suggestive of malignancy.

INVESTIGATIONS
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For blood count Urea and electrolyte Liver function test Tumor marker Ca 125 AFP & B-HCG CEA U/S for pelvis, kidney and liver MIR CT Scan Endometrial biopsy Endoscopy

Staging of primary ovarian cancer:

Stage (%) I Ia Ib Ic II IIa IIb IIc Confined to one/both ovaries Limited to a single ovary, no ascites; capsule intact with no surface tumour Limited to both ovaries, no ascites; capsule intact with no surface tumour One or both ovaries have ruptured capsule or surface tumour, malignant ascites or positive peritoneal washings Extension to pelvic structures Extension to uterus or fallopian tubes Extension to other pelvic tissues As for IIA or IIB but one or both ovaries have ruptured capsule or surface tumour; malignant ascites or positive peritoneal washings Description 5 year survival

89.9 84.7 80

69.9 63.7 66.5

III IIIa

58.5

As for stage I/II but also with peritoneal Implants outside pelvis or with positive retroperitoneal lymph nodes Histologically confirmed microscopic seeding of abdominal peritoneal surfaces and negative retroperitoneal lymph nodes Histologically confirmed implants of abdominal peritoneal surfaces <2cm and negative retroperitoneal lymph nodes Histologically confirmed implants of abdominal peritoneal surfaces <2 cm or positive retroperitoneal lymph nodes Distant metastases (including liver parenchyma/positive pleural fluid cytology)

IIIb

39.9

IIIc

28.7

IV 16.8

Metastatic ovarian spread: * Direct tubes uterus - bladder * Trascoelmic along peritoneal surface. * Lymphatic spread pelvic and para aortic lymph nodes. * Haematogenous spread - liver - lung

Technique for Surgical Staging: * Midline incision adequate access for surgical staging and full inspections. 1. Sending ascites or peritoneal washing 2. Performing total hystrectomy and bilateral salpingo ophorectomy. 3. Omentectomy 4. Peritoneal biopsy all suspicious area. 5. Diaphragmatic biopsy or scraping. 6. Sampling of pelvic and a paraaortic lymph nodes.

Surgical Management of Ovarian Cancer:

* Primary surgery in early epithelial ovarian cancer. In young patient fertility is important: * Laparotomy is gold, standard for diagnosis and staging * Frozen section is useful. * Delaying procedure until histopathology is available regardin further surgical management to be made in consultation with patient and cancer team.

Primary surgery in advanced epithelium ovarian cancer.

* Primary cytoreductive surgery followed by chemotherapy is current gold standard. * Cytoreductive surgery remove all primary cancer and if possible metastatic disease to tumor load to achieve optimal status.

Chemotherapy:

Additional therapy in early stage disease with high risk factor.

* Standard adjuvant depending involve IV chemotherapy single agent active in epithelial ovarian cancer. Include: Alkalizing agent (cyclophosophomide) - platinuim compound (cisplatin) - taxanes (paclitaxel) - paclitaxel and platinum became new standard of care in advanced ovarian cancer. - pallative surgery bowel obstruction involve bowel resection and intestinal bypass.

Germ cell tumour:

* Adequate surgical staging. * Cytoreduction and adjuvant chemotherapy is the standard therapy. * Usually occur in young patient so conservative of contralateral ovary and uterus is appropriate. * In dysgeminoma and Immature tertoma stage I ovarian cancer further therapy. From all after patient 2-3 cycles of combination therapy. * Tumor marker useful in monitoring disease and planning management.

Sex cord stromal tumour: Surgery is the gold standard but early stage can be managed by unilateral oophorectomy and endometrial biopsy when fertility is important.

Treatment of ovarian Cancer

The principle of Treatment 1. Surgical staging Laparotomy to classify the growth to its extent of spread. 2. Surgical removal of as much malignant tissue as possible( surgical debulking; cytoreductive treatment), may involve partial resection of bladder and bowel. 3. Follow up with intensive chemotherapy using various combination of drugs Toxanes with platinium are first choice of treatment. 4. Second look laparatomy or laparoscopy to determine effectiveness of chemotherapy only performed for clinical trails.

- Cooperation with general surgeon and experience in field of chemotherapy and radiotherapy. - Treatment by radiotherapy only for pallation. - CA 125 is usually raised in advanced ovarian cancer and used to assess response to chemotherapy.

Chemotherapy:
- Act by inhibiting cell deviation * Alkalyting agent preventing replication of DNA - cyclophosphoamide - Chloraambucil

*Antimitotic antibiotic Prevent DNA protein synthesis actinomycin D Antimetabolites: Preventing the synthesis of nucleoprotein Methotrexate: Other Non Alkylating agent * Cisplatin -Carboplatin * Taxanes Paclitaxel

Toxicity: Bone marrow depression gastrointestinal neurotoxic nephrotoxic alopecia candiatoxic liver failure regular check up for marrow and liver function

Prognosis for epithelial ovarian cancer Stage I II III IV 5 years survival 60 70% 40 - 50% 5 - 10% nil

Borderline epithelial Tumour - has excellent prognosis

5 years 90 95% 15 years survival 70-85%- For serous tumour 5-10% for mucinous Chemotherapy is effective in the in frequent germ cell tumour

Thank you and Good Luck!