Gyne Onc: Epithelial Ovarian Cancer - Williams Gyne

Front 1

lifetime risk of developing ovarian cancer for women in U.S.

Back 1

- 1 in 78 (1.3%)

- 9th leading cause of cancer in women
- 5th leading cause of cancer-related deaths

Front 2

risk factors for developing EOC

Back 2

- nulliparity
- early menarche
- late menopause
- white race
- increasing age
- residence in North America and Northern Europe
- family history *
- personal Hx of breast cancer
- ethnic background (European Jewish, Icelandic, Hungarian)

Front 3

factors that reduce risk of EOC

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- child-bearing (plateaus after 5 births)
- breastfeeding
- OCP use (50% decrease)
- TL
- hysterectomy
- BSO (best evidence)
- diet low in fat but high in fibre, carotene, and vitamins

- HT, perineal talc increase risk

Front 4

% of inherited ovarian cancers BRCA1 and 2 account for

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- > 90%

Front 5

indications for BRCA testing

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- recommended:
- personal Hx of both breast and ovarian cancer
- personal Hx of ovarian cancer and a 1st, 2nd, or 3rd degree relative w/ breast cancer at =< age 50 or ovarian cancer at any age
- personal Hx of ovarian cancer at any age; of Ashkenazi Jewish ancestry
- personal Hx of breast cancer at =< age 50 and a 1st, 2nd, or 3rd degree relative w/ ovarian or male breast cancer at any age
- Ashkenazi Jew and personal Hx of breast cancer at =< age 40
- 1st or 2nd degree relative w/ known BRCA1 or 2 mutation

- considered:
- personal Hx of breast cancer at =< age 40
- bilateral breast cancer (esp. if first cancer at =< age 50)
- breast cancer at =< age 50 and a 1st, 2nd, or 3rd degree relative w/ breast cancer at =< age 50
- Ashkenazi Jew w/ breast cancer at =< age 50
- breast or ovarian cancer at any age and >= 2 1st, 2nd, or 3rd degree relatives w/ breast cancer at any age

Front 6

locations of BRCA1 and 2

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- BRCA1 on chromosome 17q21
- BRCA2 on chromosome 13q12

Front 7

risks for developing ovarian cancer w/ BRCA1/2

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- BRCA1: 39-46%
- BRCA2: 12-20%

- cumulative lifetime risk of developing breast cancer w/ BRCA1/2: 65-74%

- both genes are autosomal dominant w/ variable penetrance

Front 8

components of screening in women w/ BRCA1/2 mutation that do not wish prophylactic surgery

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- thorough pelvic examination
- TVU/S
- CA125

Front 9

time to perform BSO in BRCA1/2

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- upon completion of child-bearing or at age 35

- 90% effective in BRCA1/2
- ~100% effective in HNPCC

Front 10

histologic criteria for borderline tumours

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- at least 2 of:
- nuclear atypia
- stratification of the epithelium
- formation of microscopic papillary projections
- cellular pleomorphism
- mitotic activity
- absence of stromal invasion

- up to 10% of LMP tumours will exhibit areas of microinvasion
- foci measuring <3mm in diameter and comprising <5% of tumour

Front 11

What is the most reliable indicator of poor prognosis in borderline tumours?

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- invasive peritoneal implants (as opposed to noninvasive implants)

Front 12

From what structures in the ovarian stroma are most EOCs found to originate?

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- cortical inclusion cysts

Front 13

Common laboratory findings of women w/ EOC

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- increased CA125
- thrombocytosis (> 400 x 10^9/L)
- hyponatremia ~125-130 mEq/L (SIADH)

- CA19-9/CEA may be elevated in mucinous

Front 14

conditions that can result in falsely elevated CA125

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- PID
- endometriosis
- leiomyoma
- pregnancy
- menstruation

Front 15

% of EOC w/ serous histology

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- > half

- often will contain other cell types as a minor component (< 10%)

Front 16

What are psammoma bodies?

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- extracellular round laminar dark eosinophilic collections of calcium
- pathognomonic for serous type

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2nd most common histologic type of EOC after serous

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- endometrioid adenocarcinomas (15-20%)

- usually better differentiated and slightly better prognosis

- 15-20% has coexisting endometrial adenocarcinoma (usually synchronous tumour)
- often will have pelvic endometriosis

Front 18

% of EOC that are mucinous

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- 5-10%

Front 19

What is pseudomyxoma peritonei?

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- clinical term used to describe the finding of abundant mucoid or gelatinous material in the pelvis and abdominal cavity, surrounded by thin fibrous capsules

- rarely primary ovarian mucinous carcinoma, usually metastases to ovary
- should exclude appendiceal or other GI sites of origin

Front 20

With what benign condition is clear cell adenocarcinoma most frequently associated?

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- endometriosis
- 5-10% of EOC

Front 21

What are Brenner tumours?

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- transitional cell tumours
- may be benign or malignant
- resemble carcinomas arising from the urinary tract

- characterized by having a dense, unusually abundant fibrous stroma w/ embedded nests of transitional epithelium

Front 22

definition of mixed carcinoma

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- if >10% of an ovarian cancer exhibits a second cell type
- common combinations: mixed clear cell/endometrioid, serous/endometrioid

Front 23

main DDx for primary peritoneal carcinoma

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- malignant mesothelioma

Front 24

criteria for diagnosis of PPC when both ovaries present

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- both ovaries must be normal in size or enlarged by a benign process
- involvement in the extraovarian sites must be greater than the involvement on the surface of either ovary
- ovarian tumour involvement must be either non-existent, confined to the ovarian surface epithelium without stromal invasion, or involving the cortical stroma w/ tumor size less than 5x5mm

Front 25

What is the most frequent location of spread for EOC?

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- omentum

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When is it appropriate to follow w/ observation w/ no further Tx after surgery in EOC?

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- stage IA or IB, grade 1 or 2 EOC (after complete staging procedure)

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Are second-look surgeries routinely performed to assess residual disease?

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- no
- no demonstrable survival benefit

Front 28

overall 5-year survival rate of EOC (all stages)

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45%

- cf. uterine (84%) and cervical (73%)

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favourable prognostic factors for EOC

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- younger age
- good performance status
- cell type other than mucinous and clear cell
- well-differentiated tumour
- smaller disease volume prior to surgical debulking
- absence of ascites
- smaller residual tumour following primary cytoreductive surgery

Front 30

definition of "platinum-refractory" and "platinum-resistant" EOC

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- platinum-refractory: progress during primary chemotherapy
- platinum-resistant: relapse w/in 6 months

Front 31

factors that make the best candidate for secondary cytoreductive surgery

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1. platinum-sensitive disease
2. a prolonged disease-free interval
3. a solitary-site recurrence
4. no ascites