1. بسم الله الرحمن الرحيم

2. Dr. T Allameh Associated professor of Ob & Gyn of IUMS
Ovarian cancer
Dr. T Allameh
Associated professor of Ob & Gyn of IUMS

4. Ovarian cancer Epithelial 90% Germ cell tumors
(20-25% of all benign and malignant ovarian neoplasms, only 3% of these are malignant )
Sex cord stromal tumor %

7. Epithelial cancers are the most common ovarian malignancies
Usually asymptomatic until they have metastatized patients have advanced disease at diagnosis in more than 2/3 of cases
It has the highest fatality –to case ration of all the gynecologic malignancies

8. Epithelial ovarian cancer
APPROXIMATELY 90% OF OVARIAN CANCERS ARE DERIVED FROM TISSUES THAT COME FROM THE COELOMIC EPITHELIUM OR MESOTHELIUM

9. pathology of invasive cancer
75% of epithelial cancers are of the serous histologic type
Mucinous %
Endometriosis %
Clear cell 1%,
Brenner 1%
Undifferentiated 1%
Occur more often in ages of 50-70

10. Border line tumors
Are lesions that tend to remain confined to the ovary for long periods
Occur predominantly in premenopausal women ( y )
Good prognosis

11. Borderline tumors
Epithelial proliferation with papillary formation and pseudostratification
Nuclear atypia and increased mytotic activity
Absence of true stromal invasion ( without tissue distraction )
20-25% of borderline malignant tumors spread beyond the ovary

12. Serous tumors
Develop by invagination of the surface ovarian epithelium
Psammoma bodies (focal of foreign material )

13. Borderline serous tumors
10% of all ovarian serous tumors
50% occur before the age of 40 y
10% have extra ovarian implans (invasive and non invasive)
The invasive implants resemble well differentiated serous carcinoma

14. Malignant serous carcinoma
Stromal invasion is present
Well differentiated ( papillary and grandular structures predominant )
Moderately differentiated
Poorly differentiated (solid sheets of cells , nuclear pleomorfism and highly mitotic activity )
Calcified psammoma bodies in 80%

15. Mucinous tumors Have loculi lined with mucin secreting epithelial
8-10% of epithelial of ovarian tumors
May reach enormous size

16. Bordeline mucinous tumors
Often a diagnosis difficult to make
Well differentiated mucinous epithelium may be seen adjacent to a poorly differentiated focus

17. Malignant mucinous carcinoma
8-10% are bilateral
95-98% are intraovarian
Most ovarian mucinous carcinomas contain intestinal type cells
Can not be distinguished from metastasis carcinoma of the GI (basis of histology alone )
Primary ovarian neoplasm rarely metastasized to the mucosa of the bowel ( commonly involved the serous )

18. Pseudomyxoma peritoneal
The neoplastic epithelium secrets large amount of gelatinous mucinous material , most commonly secondary to :
a well differentiated appendiceal
carcinoma
an ovarian mucinous carcinoma
A mucocell of the appendix

19. Endometriod tumors 6-8% of epithelia tumors
Similar to those seen in uterine cavity
A malignant potential of endometriosis is very low

20. Borderline endometriod tumors
Wide morphologic spectrum
Resemble an endometrial polyp or complex endometrial hyperplasia
Some have a prominent fibromatus component (adenophibroma)

21. Malignant endometrial carcinoma
Are characterized by adenomatos pattern with all the potential variations of epithelial found in the uterus
Greatest opportunity to multifocal disease
Entometriod tumors of the ovary are often associated with similar lesions in the endometrium

22. Mutifocal disease
Metastatic from the uterus to the ovaries have a 30-40% five year survival
Synchronous multifocal disease have a 75-80% five year survival

23. Clear cell carcinoma
The tumors are made up of clear cells and hobnail cells
The tall clear cells have abundant clear or vacuolated cytoplasm ,hyperchromatic irregular nuclear and nucleoli of various size
Is the histlogically identical to that seen in the uterus or vagina of the young patient who has been exposed to DES in uterus

24. Brennr tumors Borderline the epithelium dose not invade the stroma
Resemble low grade papillary transitional cell carcinoma of the urinary
bladder

25. Malignant brenner tumors
The tumor infiltrates the tissue with associated destruction

26. Transitional cell tumors
Resemble transitional cell carcinoma of the urinary bladder
An appointment finding is that those ovarian carcinomas that contain more than 50% of transitional cell carcinoma are more sensitive to chemotherapy and have a more favorable prognosis
Differ from malignant Brenner tumor in that they are more frequently diagnosed in advanced stage ( poorer survival rate )

27. Small cell carcinoma
Mainly in young women who may have symptoms of hypercalcemia
Immunohystochemichal stains are helpful to differentiate this tumor from a lymphoma , leukemia

28. Clinical features
Peak incidence of invasive epithelial ovarian cancer is at y
Fewer than 1% occur before 21 y
30% of ovarian neoplasms in post menopausal women are malignant
7% of ovarian epithelial tumors in premenopausal patients are malignant

29. Borderline tumors Average age 46 y
The chance that a primary epithelial tumor will be of borderline or invasive malignancy before 40 y is 1/ 10 , after that age it rises 1/3

30. Etiology Low parity Infertility Talk use Galactose consumption
Early menarche
Late menopause
Repetitive disruption and repair of the surface epithelium may lead to mutation

31. Prevention 1 child RR 0.3- 0.4 OC for 5 or more years RR 0.5
(50% reduction in ovarian cancer )
2 children and OC for 5 or more years RR 0.3 ( 70% reduction in ovarian cancer )
Fenertidine ( 4hydroxyretinoic acid ) .
A vitamin A derivative

32. Screening BME Ultrasound :
TVS : > 95% sensitivity for the detection of early stage of ovarian cancer ( laparatomy for each ovarian cancer )
Trans abdominal + CA 125>30 u/ml (4 laparatomy for each ovarian cancer )
Transvaginal color flow
CA- 125 ( 50% in stage I , 60% in stage II )

33. Genetic risks of epithelial ovarian cancer
The life time risk of ovarian carcinoma for women in the USA is about 1.4%
Most epithelial ovarian cancer is sporadic
Familial or hereditary patterns in 5-10%

34. Hereditary ovarian cancer
BRCA 1 mutations (chromosome 17 )
% life time risk
BRCA2 mutations (chromosome 13 )
27 % life time risk
The mutations are inherited in an autosomal dominant fashion
Full pedigree analysis( maternal and paternal )
The risk of breast cancer in BRCA1 or BRCA2 mutation is 56-87% .

35. Hereditary ovarian cancers in general occur in women approximately 10 years younger than those with nonhereditary tumors

36. Pedigree analysis
In familis with 2first degree relatives (mother ,sister, or daughter ) with premenopausal epithelial ovarian cancer , the risk that a female first degree relative has an affected gene could be 35-40% .
In familis with a single degree relative and single second degree relative (grandmother ,aunt , first cousin , or grandaughter ,) with epithelial ovarian cancers the risk that a woman has an affected gene increase 2-10 fold higher than others.

37. 3- In families with a single post menopausal first degree relative with epithelial ovarian carcinoma a woman may not have an increased risk .
if the ovarian cancers occurs in a premenopausal relative , could be significant and a full pedigree analysis should be undertaken .

38. 4-women with a primary history of breast cancer have twice the expected incidence of ovarian cancer

39. Linch 2 syndrome Multiple adenocarcinoma :
familial colon cancer (lynch 1)
high rate of ovarian endometrial and breast cancers
other malignancies of GI and GU
The mutations are MSH2 , MLH 1, PMS 1 and PMS 2
RR for ovarian cancers

40. Management of women at high risk for ovarian cancers
Genetic counseling
TVS every 6 months
OC in young women who have completed their families may undergo prophylactic BSO
(peritoneal carcinomas occasionally can occur )
in women also have a strong family history of breast cancer , annual mammographic screening should be performed beginning at age 30
Women with a HNPCC syndrome should undergo periodic screening mammography , colonoscopy , and endometrial biopsy

41. Symptoms Most have no symptoms for long periods of time
Symptoms are vague and non specific
(Irregular menses urinary frequency or constipation, lower abdominal distention, pressure or pain )
In advance stage : ascites,abdominal distention , bloating ,constipation , nausea , anorexia or early satiety

42. Signs
Pelvic mass
Upper abdominal mass
Ascites

43. Diagnosis
CA 125 levels have been shown to be useful in distinguishing malignant from benign pelvic masses
For a postmenopausal patients with an adnexal mass and CA125 > 95u/ml there is a 96% PPV for malignancy
For premenopausal patients the specificity of the test is low

44. If a cystic mass is > 8cm
Solid
Fixed
Irregular

45. Pattern of spread
Transcoelomic
Lymphatic
Hematogenous

47. Treatment Complete surgical staging Peritoneal washing TAH- BSO
Pelvic lymphnod Dysection
Paraaortic sampling
Omentectomy
Chemotherapy
Taxol
carbopelatin