Ovarian Cancer

Ovarian Cancer

Dr. Ezdehar Nassif Ali

Carcinoma of the ovary is most common in the wealthy nations of the world and the major cause of death from a gynecological cancer.
Mean age at presentation is (64)years . It is recognized that women with hereditary cancer present early with age at diagnosis of (54 )years.
More than 60% of women diagnosed with stage III/IV
The lifetime risk of ovarian cancer in the general population is (1.4%). While if women have one family member affected the risk is(5%) and further increases to (40-50%) if two first degree relatives are affected.

• Aetiology and risk factors

The molecular events leading to malignancy remain poorly understood , a number of gene mutations resulting in suppression of a tumour suppressor genes , such as p16 and p53,along with overexpression of oncogenes, such as HER2,have been associated with sporadic epithelial ovarian cancer.
• There is a recognized association with germline mutations in BRCA1 and BRCA2 genes in hereditary epithelial ovarian cancer.
The process of malignant change is associated with reproduction and ovulation, there are two main theories:
1 -Incessant ovulation theory : This relates to continuous ovulation causing repeated trauma to the ovarian epithelium leading to genetic mutation and development of a cancer.
2- Excess gonadotrophins secretion : This promotes higher levels of estrogens which in turn leads to epithelial proliferation and malignant transformation of the ovarian epithelium.

• Increased risk of ovarian cancer :

50 years of age or older
Familial factors
o Family history of breast, ovarian, or colon cancer
o Personal history of breast or colon cancer
o Familial cancer syndrome (10%)
 BRCA (breast cancer) gene mutation
 Hereditary nonpolyposis colon cancer (HNPCC)
Other potential risk factors
 Early menarche (younger than 12 years of age)
 Late menopause (older than 52 years of age)
 Hormone replacement therapy
 First pregnancy at older than 30 years of age
 Infertility, endometriosis


Decreased risk of ovarian cancer :
Taking birth control pills for more than 5 years
Breastfeeding
Pregnancy
A hysterectomy or a tubal ligation
Prophylactic oophorectomy in case of BRCA mutation.

Classification

 Epithelial
Serous , Mucinous , Endometroid , Clear cell , and Undifferentiated .

 Germ cell tumours
Dysgerminoma ,Endodermal sinus tumour(yolk sac),Teratoma , Choriocarcinoma and Mixed.

 Sex cord tumours
Granulosa cell tumour, Sertoli -leydig cell tumour, and Gynandroblastoma.

 Metastatic ( including krukenberg tumours originate from the stomach)

Staging of ovarian cancer
Ovarian cancer staging is based on clinical-pathological assessment ,and like other gynecological cancers uses the FIGO staging system.
Overall, 25 % of patients present with stage I disease, 10 % stage II, 50 %stage III and 15 % stage IV disease.
Metastatic spread is by direct spread to peritoneum and other organs and by lymphatic spread to pelvic and para-aortic nodes.
A high percentage of women with advanced disease have evidence of peritoneal disease on the diaphragmatic peritoneum.


Tumour markers used in ovarian carcinoma
Ca 125
Epithelial ovarian cancer (serous), borderline ovarian tumours
Ca 19-9
Epithelial ovarian cancer (mucinous), borderline ovarian tumours
Inhibin
Granulosa cell tumours
B-hCG
Dysgerminoma, choriocarcinoma
AFP
Endodermal sinus ( yolk sac tumour) , teratoma

Epithelial ovarian cancer

 Epithelial ovarian cancer is the leading cause of death from gynecological cancer. It derived from ceolomic epithelium of the ovary, fallopian tube, and peritoneum. It is heterogeneous group of neoplasm differ in histological and molecular feature and clinical behavior (low malignant potential, frankly invasive malignant neoplasm).
Most women diagnosed with epithelial ovarian cancer have symptoms, however these symptoms are nonspecific and often vague. The difficulty with clinical diagnosis is the main reason that patients with ovarian carcinoma present with late stage disease this has a dramatic effect on survival.

• Serous tumour: Half of epithelial ovarian cancer , most serous carcinoma have both solid and cystic elements but some may be mainly cystic . They often affect both ovaries. Psammoma bodies are pathognomonic of ovarian type serous carcinoma. Mostly present in advance disease.
Endometroid tumour: These are ovarian tumours that resemble endometrial carcinomas , is associated with endometriosis, endometrial cancer. Most are cystic ,often unilocular , and contain turbid brown fluid.
Mucinous :15% of epithelial ovarian cancer ,majority benign. They are usually multilocular ,thin walled cysts with smooth external surface containing mucinous fluid .It grow quite large reaching 30 cm and weight 40 kg. Malignant mucinous bilateral in 10-20%, benign is unilateral.

• Germ cell tumour

• Malignant germ cell tumours occur mainly in young women and account for approximately 10 per cent of ovarian tumours.
• They are derived from primordial germ cells within the ovary .
• The most common presenting symptoms are a pelvic mass, 10 per cent acutely with torsion or hemorrhage and due to the age incidence some present during pregnancy.
• Seventy per cent of germ cell tumours are stage I; spread is by lymphatics or blood-borne.
• Dysgerminomas account for 50 per cent of all germ cell tumours , they are bilateral in 20 per cent of cases and will occasionally secrete B-HCG.


Sex cord stromal tumours
These tumours account for approximately 10 percent of ovarian tumours.
• Generally, they are tumours of low malignant potential with a good long-term prognosis. A significant percentage of these tumours present with manifestation of their hormone production commonly as irregular bleeding ,postmenopausal bleeding or precocious puberty in young girls.
• Some morbidity may arise from the increased oestrogen production (granulose, theca or Sertoli cell)
or androgen (Seroli- Leydig or steroid cell) causing precocious puberty, abnormal menstrual bleeding and an increased risk of uterine cancer.
• The peak incidence is around the menopause, the exception is juvenile granulosa cell tumour , commonly presenting in girls under ten years of age and causing precocious puberty.

• Granulosa cell tumours are the most common sex cord stromal cell tumours accounting for over 70 percent of sex cord stromal tumours, may present as a large pelvic mass or pain due to torsion / hemorrhage.

Sertoli–Leydig cell tumours produce androgens in over 50 percent of cases . Patients present with a
pelvic mass and signs of virilization . Common symptoms are amenorrhea, deep voice and hirsutism.

Most sex cord tumours present as unilateral ovarian masses , measuring up to 15 cm in diameter.

Sign and symptoms

 Ovarian cancer previously called a silent killer without appreciable signs or symptom until advanced disease is obvious clinically.
 Commonly increase abdominal size, bloating ,abdominal or pelvic pain. urinary urgency, frequency, fatigue , upset stomach, indigestion, inability to eat normally, constipation and back pain. Pain during sex.
Abnormal vaginal bleeding rarely occur menstrual changes, nausea, vomiting or intestinal obstruction, weight loss.
 Urological symptom such as urgency, frequency.

Physical examination

 A pelvic-abdominal mass is palpable in most patients with ovarian cancer, malignant tumor is tend to be solid, nodular, fixed, but no pathognomonic sign distinguish these growth from benign tumor. Rectovaginal exam should be performed.
 The presence of fluid wave or flank bulging suggests the presence of ascites diagnose of ovarian cancer until prove otherwise. In advance disease upper central abdominal mass signifying omental caking.
 Auscultation of the chest (malignant pleural effusion).
 Palpation of lymph node, supraclavicular and inguinal .
 Breast and rectum exam to assess tumor originated from these organs.


Investigations
1-CBP, thrombocytosis
2- Electrolyte hyponatremia
3- Serum CA125 is glycoprotein not produce by normal epithelium but produced by benign and malignant tumor (normal value less than 35 ml unit /ml).
Half of stage 1 ovarian cancer normal value (false negative), false positive in PID, endometriosis, fibroid, pregnan, menstruation.
4-Serum CA 19-9, AFP,LDH, HCG, inhibin , estrogen and testosterone .
5-Imaging

Imaging

A. Sonography TVS, malignant multiloculated, solid, or echogenic, large than 5cm. thick septa, area of nodularity, papillary projection, neovascularity by Doppler flow. Ascites is easily detected.
B. Radiography CXR (pleural effusion, lung metastases).
C. CT scan do not detect small ovarian tumors see larger tumor and may able to see if tumor is growing into near by structures, and enlarge lymph node. In advance disease (detect tr. In liver, retroperitoneal, omentum , abdomen--) and guide surgical cytoreduction.
D. MRI, PET, bone scan of little benefit.
E. Barium enema X-ray to see if the cancer invaded colon or rectum, rarely used now colonoscopy instead can be used.

FIGO staging systemIGO definition

I Growth limited to ovaries
IA: Limited to one ovary: no external tumour , capsule intact ,no ascites
IB: Limited to both ovaries: no external tumour , capsule intact , no ascites
IC Either IA or IB, but tumour on surface of ovary or with capsule ruptured or with ascites positive for tumour cells.
II Growth limited to pelvis
IIA: Extension and or metastases to uterus or tubes
• IIB: Extension to other pelvic organs
• IIC :Either IA or IB, but tumour on surface of ovary or with capsule ruptured or with ascites positive for tumour cells.


III Growth limited to abdominal peritoneum or positive retroperitoneal or
Inguinal lymph nodes
IIIA: Tumour grossly limited to pelvis with negative nodes , but histologically confirmed microscopic
Peritoneal implants.
IIIB :Abdominal implants <2 cm in diameter
IIIC :Abdominal implants >2 cm diameter or positive retroperitoneal or inguinal lymph nodes.

IV Growth involving one or both ovaries with distant metastases

Must have positive cytology on pleural effusion , liver parenchyma.

Treatment

After the diagnostic tests are done, your cancer care team will recommend one or both treatment options.
Surgery
Chemotherapy
Early stage disease (stage 1a, stage 1b ) grade 1 managed by de bulking surgery include bilateral salpingoophorectomy plus total abdominal hysterectomy plus infracolic omentectomy plus systemic pelvic lymphadenectomy , ascitic fluid for cytology and removal of any visible deposits , no need for chemotherapy.
Advanced stage disease (stage1a and 1b) high grade and (stage 1c- stage 4) managed by de bulking surgery plus chemotherapy in form of 6 cycles carboplatin and paclitaxel .
No role for second look surgery.
In case of recurrent disease treatment by additive chemotherapy.

Surveillance

After treatment early stage ovarian cancer followed every 2-4 month for 1st, 2 year, then twice/year. 3 times / year and then annually, by complete physical and pelvic exam, serum CA. 125, imaging.

Prognosis depends on
1. stage of disease
2. Histology ; mucinous, clear cell type ( poor prognosis)
3. Smaller disease volume prior to surgical de bulking
4. Smaller residual disease following cyto reductive surgery.
5. Age at presentation.


Fallopian tube carcinoma
Fallopian tube cancer is a rare cancer, accounting for less than 1% of gynecology malignancies.
Primary carcinoma is usually unilateral , the mean age at diagnosis is 56 years .Many of the patients are nulliparous ,and infertility .
Tumour spread is identical to that of ovarian cancer ,and metastases to pelvic and para-aortic nodes are common . Most tumours involving the fallopian tube are metastatic from ovarian cancer ,but secondary spread from the breast and gastrointestinal tract also occurs.
The clinical diagnosis, investigation and treatment of Fallopian tube cancer is the same as epithelial ovarian cancer.

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