OVARIAN MALIGNANCY Ovarian cancers are a clinical challenge

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OVARIAN MALIGNANCY

OVARIAN MALIGNANCY

 Ovarian cancers are a clinical challenge because the majority are asymptomatic until late

Ovarian cancers are a clinical challenge because the majority are asymptomatic until late in the disease process. So 70% women will present with an advanced stage at diagnosis. It has the highest mortality among all the gynecological malignancies.

 About 30% of ovarian tumors in postmenopausal women are malignant. Whereas only 7%

About 30% of ovarian tumors in postmenopausal women are malignant. Whereas only 7% in premenopausal women are malignant.

WHO (Scully 1999) • Epithelial tumors (benign, borderline or malignant) – Serous – Mucinous

WHO (Scully 1999) • Epithelial tumors (benign, borderline or malignant) – Serous – Mucinous – Endometroid – Clear cell (mesonephroid) – Brenner – Mixed epithelial – Undifferentiated – Unclassified

 • Sex cord stromal tumours – Granulosa stromal cell tumour – Androblastoma or

• Sex cord stromal tumours – Granulosa stromal cell tumour – Androblastoma or Sertoli-Leydig cell tumour – Gynandroblastoma – Unclassified • Lipid cell tumors

 Germ cell tumours Dysgerminoma Endodermal sinus tumour Embryonal cell tumour Polyembryoma Choriocarcinoma Teratoma

Germ cell tumours Dysgerminoma Endodermal sinus tumour Embryonal cell tumour Polyembryoma Choriocarcinoma Teratoma Mixed tumours

 Gonadoblastoma Soft tissue tumours not specific to ovary Unclassified tumours Metastatic tumours

Gonadoblastoma Soft tissue tumours not specific to ovary Unclassified tumours Metastatic tumours

Incessant ovulation : Nulliparity Early menarche Late menopause Infertility Regarding the relation with infertility,

Incessant ovulation : Nulliparity Early menarche Late menopause Infertility Regarding the relation with infertility, ovulationinducing drugs are supposed to be a risk factor by resulting in multiple ovulation, but the evidence is still not clear.

GENETIC FACTORS Inheritance has a very important role : BRCA 1 and BRCA 2

GENETIC FACTORS Inheritance has a very important role : BRCA 1 and BRCA 2 genes are implicated 50% risk of ovarian cancer. the other familial syndrome is hereditary Nonpolyposis Colon cancer (HNPCC) or Lynch II syndrome It includes multiple adenocarcinomas, colon cancer, ovarian, endometrial and breast cancers.

PATHOLOGY Most common epithelial tumours 50 -60% of all ovarian tumours Malignant epithelial tumours

PATHOLOGY Most common epithelial tumours 50 -60% of all ovarian tumours Malignant epithelial tumours comprise 90% of all ovarian tumours. Epithelial tumours can be Benign, Borderline malignant Serous tumours commonest – 75% Mucinous 20% Endometroid, clear cell, and transitional

SEROUS TUMOURS Serous tumours resemble the glandular epithelium of the fallopian tubes. They are

SEROUS TUMOURS Serous tumours resemble the glandular epithelium of the fallopian tubes. They are cystic Psammoma bodies are characteristic Papillary ingrowths may be present Mucinous tumours

PAPILLARY SEROUS CYST ADENO CARCINOMA

PAPILLARY SEROUS CYST ADENO CARCINOMA

MUSCINOUS CYST ADENOMA

MUSCINOUS CYST ADENOMA

 Multilocular thin-walled cysts Contain mucinous fluid They are the largest ovarian tumours Cells

Multilocular thin-walled cysts Contain mucinous fluid They are the largest ovarian tumours Cells lining may resemble endo cervical cells 10% bilateral

 • • • Pseudomyxoma peritonei is a term used to describe the presence

• • • Pseudomyxoma peritonei is a term used to describe the presence of mucoid material in the abdomen and pelvis surrounded by fibrous tissue. It can result secondary to a ruptured mucinous tumour of the ovary, a well differentiated appendiceal carinoma, any other gastrointestinal primary tumour or a mucocele of the appendix. Care should be taken to avoid rupture during surgery

BORDERLINE TUMOURS Low malignant potential 10% of all epithelial tumours Commoner in young women

BORDERLINE TUMOURS Low malignant potential 10% of all epithelial tumours Commoner in young women between 30 and 50 yrs. Histological criteria Epithelial hyperplasia Nuclear atypia and increased mitotic activity Detached cell clusters Absence of stromal invasion Metastases are uncommon They have very good prognosis

Direct or transcoelomic spread : • Omentum (most common) • Posterior cul de sac

Direct or transcoelomic spread : • Omentum (most common) • Posterior cul de sac • Paracolic gutters • Right hemidiaphragm • Capsule of the liver • Peritoneal surface of small and large intestines • Mesenteries • Parietal peritoneum

Lymphatic spread : Para-aortic nodes Pelvic nodes Supraclavicular nodes Retroperitoneal nodes

Lymphatic spread : Para-aortic nodes Pelvic nodes Supraclavicular nodes Retroperitoneal nodes

 Para-aortic node metastases are 20% in stages I and II and 65% in

Para-aortic node metastases are 20% in stages I and II and 65% in stage IV. Pelvic lymph nodes are seen in 30% of stage I and II and 67% of stage III and IV.

Haematogenous : late stages Lungs Liver (Parenchymal) Bone and brain (rarely)

Haematogenous : late stages Lungs Liver (Parenchymal) Bone and brain (rarely)

Clinical features : Malignancies are more common in extremes of age group – younger

Clinical features : Malignancies are more common in extremes of age group – younger and older age Malignancy 50 -60 yrs Borderline between 30 & 50 yrs. Younger age group germ cell tumours are more common Older age group epithelial tumours

Symptoms : Majority of epithelial ovarian tumours are asymptomatic They are diagnosed in late

Symptoms : Majority of epithelial ovarian tumours are asymptomatic They are diagnosed in late stages Abdominal distension and pain Feeling of a lump in the abdomen

 Dyspepsia, Bloating Abdominal discomfort Loss of appetite and loss of weight Pressure symptoms

Dyspepsia, Bloating Abdominal discomfort Loss of appetite and loss of weight Pressure symptoms like urinary frequency, retention or constipation Abnormal uterine bleeding or postmenopausal bleeding in feminising tumour

Advanced stage symptoms may be due to ascites Omental deposits Bowel – altered bowel

Advanced stage symptoms may be due to ascites Omental deposits Bowel – altered bowel habits Pulmonary metastases – cough and haemoptysis

Signs General examination Cachexia Supraclavicular lymph nodes Breast lumps Thyroid nodules Pleural effusion

Signs General examination Cachexia Supraclavicular lymph nodes Breast lumps Thyroid nodules Pleural effusion

Abdominal examination : Mass in the pelvis or abdomen Bilateral tumours Boders vague and

Abdominal examination : Mass in the pelvis or abdomen Bilateral tumours Boders vague and ill-defined Hard or varying consistency Fixity or restricted mobility Ascites Hepatomegaly Other abdominal masses suggestive of lymph node metastases

Bimanual examination : Hard fixed mass Uterus may be felt separate Nodules in the

Bimanual examination : Hard fixed mass Uterus may be felt separate Nodules in the cul de sac due to secondary deposits

Differential diagnosis : Benign ovarian tumour Gastrointestinal problems like colonic cancer and stomach cancer

Differential diagnosis : Benign ovarian tumour Gastrointestinal problems like colonic cancer and stomach cancer (history of altered bowel habits, bleeding per rectum and other gastrointestinal symptoms should warrant a search for the same) and diverticulitis Lymphoma (presence of other lymph node enlargement is suggestive)

 Retroperitoneal sarcoma Pedunculated fibroids Pelvic inflammatory disease Endometriosis Pelvic kidney Functional cysts

Retroperitoneal sarcoma Pedunculated fibroids Pelvic inflammatory disease Endometriosis Pelvic kidney Functional cysts

Investigations : Routine investigation like blood count, urine routine RFT, LFT Tumour markers Chest

Investigations : Routine investigation like blood count, urine routine RFT, LFT Tumour markers Chest X-ray Ultrasound scan

 Colonoscopy Gastroscopy Barium enema / barium swallow Pap smear Endometrial biopsy Intravenous pyelogram

Colonoscopy Gastroscopy Barium enema / barium swallow Pap smear Endometrial biopsy Intravenous pyelogram CT and MRI

TAS followed by TVS done Ultrasound features of malignancy Solid or echogenic areas Multilocularity

TAS followed by TVS done Ultrasound features of malignancy Solid or echogenic areas Multilocularity Thick and fronded septations Bilaterality

 Papillary projections Doppler may show increased vascularity Ascites It also detects liver parenchymal

Papillary projections Doppler may show increased vascularity Ascites It also detects liver parenchymal metastases Enclarged pelvic and para-aortic nodes Detects hydroureter and hydronephrosis

CT and MRI They detect the extend of invasion, lymph node involvement, retroperitonial or

CT and MRI They detect the extend of invasion, lymph node involvement, retroperitonial or omental involvement So that surgery can be planned

Tumour markers : CA 125 levels are useful in differentiating malignant from benign neolplasms.

Tumour markers : CA 125 levels are useful in differentiating malignant from benign neolplasms. Useful tumour marker in epithelial ovarian cancer More useful in postmenopausal woman The cut off value is 30 U/m. L The test has a sensitivity of 81% and a specificity of 75% Above 95 U/m. L is taken as significant RMI is calculated from CA 125 level Age and ultrasound

 Premenopausal women in endometriosis and pelvic tuberculosis CA 125 level may be raised.

Premenopausal women in endometriosis and pelvic tuberculosis CA 125 level may be raised. More than 200 U/m. L indicate malignancy

TUMOUR MARKERS IN OVARIAN CANCER Tumour type Serum marker Epithelial ovarian cancer CA 125

TUMOUR MARKERS IN OVARIAN CANCER Tumour type Serum marker Epithelial ovarian cancer CA 125 Mucinous cystadenocarcinoma CEA and CA 19 -9 Serious and mucinous OCCA and OCA Endodermal sinus tumour AFP Choriocarcinoma h. CG Enbryonal cell carcinoma h. CG and AFP Dysgerminoma PLAP, LDH Granulosa cell tumour Inhibin

Screening : At the present moment screening with ultrasound is only indicated in high

Screening : At the present moment screening with ultrasound is only indicated in high risk women. High risk women need to undergo genetic screening, use of oral contraceptives for chemoprophylaxis and can be offered prophylactic oophorectomy STAGING Ovarian epithelial tumours are staged according to the FIGO system Essentially a surgical staging Histological and cytological finding also taken in account

FIGO STAGING FOR CARCINOMA OVARY Stage Growth limited to ovaries I Ia Growth limited

FIGO STAGING FOR CARCINOMA OVARY Stage Growth limited to ovaries I Ia Growth limited to one ovary, no ascites, no tumour on external surface; capsule intact Ib Growth limited to both ovaries No ascites; no tumour on external surface; capsule intact Ic Tumour either stage Ia or Ib but with tumour on the surface of one or both ovaries; or with capsule ruptured; or with ascites present containing malignant cells or with positive peritoneal washings.

Stage Growth involving one or both ovaries with II pelvic extension IIa Extension and/or

Stage Growth involving one or both ovaries with II pelvic extension IIa Extension and/or metastases to the uterus or tubes IIb Extension to other pelvic tissues IIc Tumour either stage IIa or IIb but with tumour on surface of one or both ovaries; or with capsule ruptured; or with ascites present containing malignant cells; or with positive peritoneal washings

Stage Growth involving one or both ovaries with peritoneal implants III outside the pelvis

Stage Growth involving one or both ovaries with peritoneal implants III outside the pelvis or positive retroperitoneal or inguinal nodes. Superficial liver metastases equals stage III. Tumour is limited to the true pelvis, but with histologically proven malignant extension to small bowel or omentum IIIa Tumour grossly limited to the true pelvis with negative nodes but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces IIIb Tumour with histologically confirmed implants on abdominal peritoneal surfaces, none exceeding 2 cm in diameter. Nodes are negative. IIIc Abdominal implants greater than 2 cm in diameter or positive retroperitoneal or inguinal nodes

Stage IV Growth involving one or both ovaries with distant metastases. If pleural effusion

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

Management Staging laparotomy Ascites or peritoneal washings (50 -100 ml saline) taken cytology Washing

Management Staging laparotomy Ascites or peritoneal washings (50 -100 ml saline) taken cytology Washing from cul de sac, paracolic gutter and beneath hemidiaphragm Exploration of the abdomen and pelvis in a clockwise manner from the caecum cephalad

 Any suspicious areas should be biopsied Diaphragm can be sampled either by biopsy

Any suspicious areas should be biopsied Diaphragm can be sampled either by biopsy or by scraping Infracolic omentectomy Retroperitoneal space dissection to evaluate the pelvic and para-aortic nodes Enlarged nodes must be submitted for frozen section If there are no metastases a pelvic lymphadenectomy must be performed. Careful documentation of the operative findings

Surgery : Stage I & II total hysterectomy, bilateral salpingooophorectomy and infracolic omentectomy After

Surgery : Stage I & II total hysterectomy, bilateral salpingooophorectomy and infracolic omentectomy After a thorough surgical staging must be performed. In advanced cases maximal cytoreductive surgery must be attempted. Fertility sparing surgery – rarely there is also a place for conservative surgery in stage Ia grade-I in those younger women who mare anxious to conceive

 They should be under regular follow up After childbearing is completed Definitive surgery

They should be under regular follow up After childbearing is completed Definitive surgery is done High risk cases surgery followed by adjuvant chemotherapy with carboplatin and paclitaxel for 3 -6 cycles is desirable.

Advanced disease : Maximal cytoreductive or debulking surgery Residual disease should be less than

Advanced disease : Maximal cytoreductive or debulking surgery Residual disease should be less than 1 cm. The surgery typically consists of a total abdominal hysterectomy, Bilateral salpingo-oophorectomy and omentectomy In addition it may include resection of any metastatic lesions from the peritoneal surfaces or intestines Sometimes resection of part of the bladder or removal of the sigmoid and rectum may be necessary. If optimal cytoreduction has been achieved, chemotherapy for 6 -8 cycles is usually given.

 Interval cytoreductive surgery Second look surgery Postoperative management of advanced disease Intravenous carboplatin

Interval cytoreductive surgery Second look surgery Postoperative management of advanced disease Intravenous carboplatin and paclitaxel every 3 weeks for 6 -8 cycles Intraperitoneal cisplatin and paclitaxel is an acceptable alternative to intravenous route.

Neoadjuvant chemotherapy : Advanced disease preoperative chemotherapy for about 3 cycles followed by cytoreductive

Neoadjuvant chemotherapy : Advanced disease preoperative chemotherapy for about 3 cycles followed by cytoreductive surgery. After cytoreductive surgery chemotherapy followed This is useful in patients with massive ascites and pleural effusions

Immunotherapy : Cytokines have been used such as interferons and interleukin – 2 in

Immunotherapy : Cytokines have been used such as interferons and interleukin – 2 in combination with chemotherapy as second-line therapy. Survival rates : The survival rates in each stage depend on the grade of the tumour Stage I 76 -93% Stage II 60 -74% Stage III 23 -41% Stage IV 11%