primary ovarian cancer

1. OVARIAN CANCER
Prepared by Mohamedi

2. lists
• Introduction
• Epidemiology
• Risk factors
• Types of ovarian cancer
• Diagnosis
• Staging methods
• Treatment
• Prognosis

3. Introduction
• Ovarian cancer is abnormal proliferation of ovarian cells
• These malignant ovarian lesions include primary lesions arising from
normal structures within the ovary and secondary lesions from
cancers arising elsewhere in the body

4. Epidemiology
• Ovarian malignancy comprises 15-20% of genital
malignance
• It is seventh most commonly diagnosed cancer among
women in world and tenth in china(chinise-anti cancer-
association)
• More prevalent in U.S.A and Scandinavian but less in
latin America and Asian country in Japan and India
• It fourth common cause of cancer deaths in women
exceed only by breast, colon and lung malignancies

5. Epidemiology
• It is leading cause of gynecological cancer death.(WHO cancer
statistic 2015)
• It is common in whites than African America
• Median age is 63 year
• Avarage risk life time is 1/70

6. Risk factors
• .Patient characterics
Increasing age
personal history of breast cancer
.Genetic factors
family histry of ovarian cancer
BRCA1/2 mutation
hereditary nonpolyposis colorectal cancer

7. Risk factors
• .Reproductive factors
• null parity
• late menopause
• early menarch
• infertility
• polycystic ovarian disease
• endometriosis
• ovulation inducing drug
• hormonal replacing therapy

8. Risk factors
• .Environmental factors
• obesity and high fat diet
• cigarette smoking

9. Risk factors
• A high risk for developing epithelial ovarian cancer is for null parous
women
• A lower risk for those who have children, breast fed, undergone tubal
ligation and taken oral contraceptives
• Strong risk factor is a family history of ovarian cancer
• Only5-10% of tumours result from a known genetic disposition
• Life time risk:
• General population 1.8%
• One first degree relative 5%
• Two first degree relatives 25-50%

10. Protective factors
Decreasing the risk of ovarian cancer
• Oral contraceptive use
• Maximum benefit seen after 5 years of use
• Breastfeeding
• Full-term pregnancy
• Tubal ligation
• NSAIDs, aspirin, and acetaminophen?

11. Classification of ovarian cancer
Epithelial
Serous 42%
Endometrioid 15%
Mucinous 12%
Clear cell 6%
Undifferentiated 17%
Germ Cell and Stromal 8%
Sex cord tumour

12. Type of ovarian cancer
Epithelial ovarian cancers
• It is thought to arise from epithelium covering the fimbria of the fallopian
tubes, or the ovaries, both of which are derived from the coelomic
epithelium in fetal development. This coelomic epithelium is also involved
in formation of the müllerian ducts, from which the fallopian tubes, uterus,
cervix, and upper vagina develop
Types of epithelial ovarian cancer
• Serous (from fallopian tube)
• Endometrioid (endometrium)
• Mucinous (cervix)
• Clear cell (mesonephros)

13. Common histological type of Epithelial ovarian
cancers
Pappillary serous
• Most common type of epithelial ovarian cancer.
• May contain psammoma bodies
• Is often associated with CA 125 elevation.
Endometrioid
Associated with endometriosis or an independent uterine cancer of similar histology.
May occur with early stage disease in younger patients, although advanced disease is also possible.
Mucinous
Rarely be associated with pseudomyxoma peritoneii.
CA 125 level may not be markedly elevated.
Relatively chemoresistast.
Differential diagnosis of a mucinous ovarian tumor includes metastatic disease from an appendiceal
primary.

14. Common histological type of Epithelial
ovarian cancers
Clear cell
• The most chemoresistant type of ovarian cancer.
• Often contain “hobnail” cells with cleared out cytoplasm due to
glycogen.
• Associated with endometriosis or humorally mediated hypercalcemia.

15. Types of ovarian cancer
• .feature of epithelial ovarian cancers
• . Partially cystic lesions with solid components
• .They have smooth surface or covered with papillary projections
• NB. cyst may contain fluid ranges from straw - color to opaque brown
or hemorrhagic
• These cancer mostly spread initially in peritonial cavity as most of
time found particullary under the diaphragms, paracolic
gutters,bladder other sites are Surface of the liver, Mesentery and
serosa of the large and small bowel, Omentum, Uterus,Para-aortic and
pelvic lymph nodes

16. SYMPTOMS
• Abdominal pain
• Nausea and vomiting
• Abdominal distention (from ascites)
• Dyspnea
• Constipation or diarrhea
• Abnormal vaginal bleeding

17. SIGNS
• Abdominal mass
• Pelvic mass
• Pleural effusion
• Ascites
• Ventral hernia
• Inguinal nodes

18. Malignant germ cell tumors
.They are thought to derive from primitive germ cells in the embryonic
gonad. GCT of the ovary is much rarer than GCT of the testis in males, and
much of the development of the management approach has been based on
experience with male GCT. GCT is much more common in young women but
occasionally occurs in infants and older women
• Types of germ cell tumor
• Dysgerminoma
• Endodermal sinus tumor
• Malignant teratoma
• EmbryonalCarcinoma
• Choriocarcinoma

19. Germ cell tumour
• Germ cell tumors represent about 20% of all ovarian tumors
• Malignant germ cell tumors represent <5% of all ovarian tumors in the
United States
• Median age of diagnosis of malignant germ cell tumor is 16-20 years
but the range is 6 months old to 70 years old
• 50-75% of malignancies present as stage I
• Disease-free 10-year survival for early stage disease is >95%
• Advanced stage survival rates are 60-80%

20. dysgerminoma
• 50% of malignant germ cell tumors
• Histologically equivalent to seminoma in men
• 10-15% bilaterality
• May arise in females with dysgenetic gonads
• One of two most common malignant ovarian neoplasms observed in
pregnancy
• (other one is serous cystadenocarcinoma of low malignant potential)

21. dysgerminoma
• May secrete hCG
• May produce LDH
• Predilection for lymph node spread
• Acutely radiosensitive tumor but standard is now post operative
platinum-based chemo for fertility preservation
• Even cure rates for stage III disease with chemo currently exceeds
90%

22. Endodermal Sinus Tumor
• Second most common germ cell tumor comprising 20% of malignant
germ cell tumors
• Secretes alpha-fetoprotein (AFP) – useful diagnostic tool
• Schiller-Duval bodies
• Spread is lymphatic but has propensity for hematogenous
dissemination to lungs
• Extremely rapid growth
• Must have post-operative chemotherapy

23. Embryonal carcinoma
• One of most malignant cancers arising from ovary
• Resembles embryonal carcinoma of adult testes
• Represents 3-4% of malignant ovarian germ cell tumors
• Mean age of diagnosis is 15 years
• More than half of patients with hormonal abnormalities such as
precocious puberty, irregular uterine bleeding, amenorrhea and
hirsutism
• Secretes hCG and AFP
• Treatment is surgery and combination chemotherapy

24. Malignant teratoma
• Represent 15% of all germ cell tumors
• Most common in first two decades of life, rare after menopause
• Composed of three germ layers but with immature or embryonal
structures

25. Choriocarcinoma (non-gestational)
• Most rare germ cell tumor (<1%)
• Often associated with sexual precocity
• Secretes hCG

26. Malignant germ cell tumors
• Common characteristics of GCT
• Rapid growth
• Predilection for lymphatic spread
• Frequent mixtures of tumor types
• Predominantly unilateral pattern of ovarian involvement (except for
dysgerminoma)

27. Malignant germ cell tumors
NB: Many GCTs produce tumor markers that can be measured in the blood and
then used to monitor response to treatment and for follow-up care.
• Endodermal sinus tumors secrete alpha-fetoprotein
• choriocarcinoma, and dysgerminomas occasionally secrete beta human
chorionic gonadotropin (bHCG).
• Dysgerminoma may secrete lactate dehydrogenase and placental
alkaline phosphatase

28. Sex-cord stromal tumors
• These include tumors arising from the sex cords granulosa cells; and
the specialized stroma of the genital ridge, theca. They comprise fewer
than 5% of all ovarian tumors. granulosa cell tumors are malignant
they behave in a much less malignant fashion than epithelial ovarian
cancers Granulosa cell tumors and pure Sertoli cell tumors commonly
secrete estrogen

29. Granulosa cell tumor
• Equal occurrence in reproductive age and postmenopausal women
• Inhibin can be used as a serum tumor marker
• Often produce estrogen
• Approximately 10% of patients will harbor an endometrial carcinoma
• Call-Exner bodies
• Fertility sparing surgery may be performed but any patient stage 2 or
above should have adjuvant chemotherapy

30. Sertoli-Leydig (Androblastoma)
• Account for 0.2% of all ovarian cancers
• Can secrete testosterone
• Overall 5-yr survival is 70-90%
• Fertility sparing surgery may be performed but stage 2 and above need
chemotherapy

31. Gynandroblastoma
• Combined elements of granulosa cell and Leydig cells
• May produce estrogens or androgens

32. Early Symptoms of ovarian cancer
• Feeling of abdominal distension and vague
discomfort.
• Features of dyspepsia such as flatulence and
eructations.
• Loss of appetite with a sense of bloating after
meals.
• In pre-existing tumor.
− Appearance of dull aching pain and tenderness over one area.
− Rapid enlargement of the tumor.

33. Late symptom of ovarian cancer
• Abdominal swelling which may be rapid.
• Dull abdominal pain.
• Sudden loss of weight.
• Respiratory distress — may be mechanical due to
ascites or due to pleural effusion.
• Menstrual abnormality is conspicuously absent
except in functioning ovarian tumors

34. Signs of ovarian cancer
• general Examination reveals
• Cachexia and pallor of varying degree.
• Jaundice may be evident in late cases.
• Left supraclavicular lymph gland (Virchow’s) may
be enlarged (Fig. 23.21).
• Edema leg or vulva is characteristic of malignant
and not of benign neoplasm.

35. Signs of ovarian cancer
Per abdomen
• Liver may be enlarged, firm and nodular.
• A mass is felt in the hypogastrium; too often it
• may be bilateral. It has got the following features:
− Feel — solid or heterogenous.
− Mobility — mobile or restricted.
− Tenderness — usually present.
− Surfaces — irregular.
− Margins — well-defined but the lower pole is
usually not reached.
− Percussion — usually dull over the tumor;
• may be resonant due to overlying intestinal
• adhesions.

36. Signs of ovarian cancer
Per vaginum
• The uterus may be separated from the mass felt
• per abdomen
• Nodules may be felt through the posterior
fornix. If it is more than 1 cm, the diagnosis of
malignancy is almost certain

37. Figo staging system of ovarian cancer
• “Simplified” FIGO Staging of Ovarian Carcinoma
• Stage Criteria
• I Tumor confined to the ovaries
• II Extension to other pelvic structures
• III Abdominal or lymph node involvement
• IV Distant metastasis

38. 2014 FIGO ovarian cancer staging system
Stage IGrowth limited to ovaries
Stage Ia: One ovary; no malignant cells in ascites; no tumor on external surface;
capsule intact
Stage Ib: Like Ia but 2 ovaries
Stage Ic: Ia or Ib but with tumor on surface of one or both ovaries; or ruptured
capsule; or with malignant ascites or positive peritoneal washings
Stage II:Growth involving one or both ovaries with pelvic extension
Stage Iia: Extension and/or metastases to uterus and/or tubes
Stage Iib: Extension to other pelvic tissues
Stage Iic: IIa or IIb but with tumor on surface of one or both ovaries; or with
capsule(s) ruptured; or with malignant ascites or positive pelvic washings

39. 2014 FIGO ovarian cancer staging system
Stage III:Tumor involving one or both ovaries with peritoneal implants outside the pelvic
and/or positive retroperitoneal or inguinal nodes; superficial liver metastasis;
tumor limited to true pelvis but with histologically verified malignant extension to
small bowel or omentum
Stage IIIa: Grossly limited to true pelvis with negative nodes with histologically confirmed
microscopic seeding of abdominal peritoneal surfaces
Stage IIIb: One or both ovaries; histologically confirmed implants of abdominal peritoneal
surfaces, none exceeding 2cm in diameter; nodes negative
Stage IIIc: Abdominal implants 2cm in diameter and/or positive retroperitoneal or inguinal nodes
Stage IV: Growth involving one or both ovaries with distant mets; if pleural effusion is present,
there must be positive cytologic test results to allot a case to stage IV; parenchumal liver
metastasis equals stage IV

40. Five-year survival by stage and grade
Stage Grade 1 Grade 2 Grade 3
I 91% 74% 75%
II 69% 60% 51%
III-IV 38% 25% 19%

41. Special investigations
To confirm Malignancy
• Cytologic examination for detection of malignant
cells
• Tumor marker
To identify the extent of lesion
• Straight X-ray
• Barium enema
• Cytologic examination
• Sonography
• Computed Tomography (CT)
• Magnetic Resonance Imaging (MRI
• Positron Emission Tomography (PET)

42. Special investigations
• To detect the Primary Site
Barium meal X-ray.
Gastroscopy/colonoscopy.
Mammography

43. Diagnosis of ovarian cancer
Clinical
• Clinical diagnosis in early stage is very
much deceptive because of
no age specificity
no specific symptom
Unrelated to duration of symptoms
Unrelated to the size of the tumor

44. Diagnosis of ovarian cancer
Operative
• Nature of peritoneal fluid
• Nature of the tumor
• Metastatic nodules on the peritoneal surfaces and
omentum.
Histological diagnosis: All ovarian tumors irrespective
of their nature must be subjected to histologic
examination. This not only confirms the diagnosis but
also identifies the type and grade of malignancy.

45. Management of ovarian cancer
Stage I treatment
• Best therapy is TAH/BSO, washings, with careful surgical staging
with or without omentectomy
• Ia grade 1 lesion generally no chemotherapy
• Young woman with Ia disease desirous of future childbearing:
• unilateral salpingo-oophorectomy may be option
• careful staging must be performed
• must consider tumor grade and self-containment of disease

46. Stage I treatment
• Stage Ib and Ic some institutions prefer chemotherapy, controversial
• Usually platinum analogue with paclitaxel (Taxol)
• Risk of therapy must be weighed against benefits of therapy
• Some randomized studies showing cisplatin arm with lower relapse rate but
overall 5-year survival was not statistically different from non-treatment arm
• Some prefer radiation over chemotherapy and some like both – again,
controversial

47. Stage II treatment
• TAH/BSO, omentectomy, washings, omentectomy, pelvic and
paraaortic node sampling
• Post-operative management is also controversial
• Usual chemotherapy is platinum-based agent and Taxol
• Some prefer radiation or combination radiation/chemo

48. Stage III treatment
• Survival rate related to residual tumor after surgery
• Post-operatively usually multi-agent platinum-based therapy lasting 6-
12 months or until maximal doses of certain drugs reached
• Second-look common in the past but not usually done now
• In general, most significant survival benefit of surgery is achieved
with cytoreduction of largest residual tumor mass to less then or equal
to 2cm in diameter.
• Cytoreductive surgery may not affect survival if largest diameter residual
disease is >2cm

49. Stage IV treatment
• Remove as much tumor as possible and administer post-operative
chemotherapy
• Obviously, poor survival

50. Prognostic factors in ovarian
malignancy
• Surgical stage of the disease — worse beyond
stage II
• Histological type — endometrioid tumor has got
a higher survival rate than serous type because the
former tumor is highly well-differentiated.
• Histological grade of the tumor — higher the
grade, poorer the prognosis.
• Peritoneal cytology — positive malignant cells,
higher the risk.
• Presence of ascites — higher the risk.
• Presence of metastatic disease before cytoreductive surgery — poor the prognosis and
shorter the survival.
• Volume of residual tumor after primary surgery
— when < 5 mm better the prognosis.
• Ploidy status – diploid tumors are prognostically
better compared to aneuploid tumors.
• Degree of oncogene expression

51. THANKS