Epithelial Ovarian Cancer June 14 2013

Front 1

a) True or False: Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer death in North America

b) What is the lifetime baseline risk of contracting EOC?

Back 1

a) True

b) 1.5%

Front 2

a) What percentage of ovarian cancer is EOC?

b) How many have Stage >= II disease?

c) What is the average decade of diagnosis?

Back 2

a) 85-90%

b) 75%

c) 60's

Front 3

a) List histologic types of EOC?

b) What is the most common?

Back 3

Serous (most common)
Mucinous
Clear cell
Endometrioid
Brenner
Neuroendocrine
Sarcomatous

Front 4

List risk factors for EOC.

Back 4

Estrogen
Nulliparity
Early menarche
Late menopause
Infertility
Age
Hereditary syndrome
BRCAI (40%)
BRCAII (15-20%)
Lynch II (10%)
Geographic location (North America)
Ethnicity (northern european, jew, icelandic, hungarian)
Drugs
Menopause HT (estrogen)
Family history of ovarian cancer (RR 3.0)
PCOS
Endometriosis

Front 5

List protective factors against EOC

Back 5

OCP use (RR 0.5)
Breast feeding
BSO
Tubal ligation

Front 6

a) Should CA125 be used to screen average-risk populations?

b) What percentage of women in the background population with no/benign disease have an elevated CA125?

Back 6

a) No.

b) 1%

Front 7

a) What other processes can cause an increase in CA125 level?

b) What is CA125?

Back 7

a)
Endometriosis
Menstruation
PID
Fibroids
Liver disease

b)
MUC16 gene product, binds mesothelin

Front 8

a) What percentage of women with early stage EOC have an elevated CA125?

b) Late stage EOC?

Back 8

a) 50%

b) 80%

Front 9

In asymptomatic post-menopausal women, does an elevated CA125 (>30U/ml) increase the risk of EOC?

Back 9

Yes.
If CA125 > 30U/ml, RR 35 for EOC w/i one year
If CA125 > 100U/ml, RR 200 for EOC w/i one year

Front 10

What percentage of women with invasive ovarian cancer will be BRCA I or II positive?

Back 10

13%

Front 11

a) What is the recommended screening strategy for ovarian cancer in women at average risk?

b) What is recommended for women on a yearly basis?

Back 11

a) None. Nothing has been shown to be effective. No North American expert groups recommend screening.

b) Pelvic exam

Front 12

a) What women are at highest risk of developing ovarian cancer?

b) Discuss screening of these women.

Back 12

a)
BRCA I
BRCA II
Lynch II

b)
Controversial. Consider risk reduction surgery. Consider OCP. Consider q6-12m CA125 and TVUS. No screening program has been shown to be effective.

Front 13

List the most common symptoms associated with EOC

Back 13

Pelvic/Abdominal pain
Urinary frequency/urgency
Early satiety
Bloating/increased pant size

Front 14

What is Meigs' syndrome?

Back 14

Pelvic Mass (benign ovarian fibroma)
Ascites
Pleural effusion

Front 15

a) What % of ovarian cancers are borderline (LMP)

b) Histologically, what distinguishes borderline ovarian tumours (LMP) from ovarian cancer?

c) Histologically, what distinguishes borderline tumours from benign ovarian cysts?

Back 15

a) 10-15%

b) no stromal invasion
(10% may have areas of microinvasion <3mm, covering <5% of tumour)

c)
atypia
cellular pleomorphism
mitotic activity
microscopic papilla
stratified epithelium

Front 16

List 5 features of physical exam or imaging that might help distinguish a borderline ovarian tumour from EOC?

Back 16

Fixed ovarian mass (exam)
Ascites (CT/US)
Omental caking (CT)
Mets (CT)
Nodal status (PET)

Front 17

After fertility-sparing surgery, what is the risk of recurrence of ovarian LMP in the contralateral ovary?

Back 17

15%

Front 18

What is the 5 yr survival for ovarian LMP at stage:

I
II
III
IV

Back 18

a) 99%
b) 98%
c) 96%
d) 80%

Front 19

How are patients with ovarian LMP staged?

Back 19

Same as for EOC.

Front 20

risk factors for developing EOC

Back 20

- 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 21

factors that reduce risk of EOC

Back 21

- 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 22

% of inherited ovarian cancers BRCA1 and 2 account for

Back 22

- > 90%

Front 23

indications for BRCA testing

Back 23

- 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
- 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 24

locations of BRCA1 and 2

Back 24

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

Front 25

risks for developing ovarian cancer w/ BRCA1/2

Back 25

- 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 26

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

Back 26

- thorough pelvic examination
- TVU/S
- CA125

Front 27

time to perform BSO in BRCA1/2

Back 27

- upon completion of child-bearing or at age 35

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

Front 28

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

Back 28

- invasive peritoneal implants (as opposed to noninvasive implants)

Front 29

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

Back 29

- cortical inclusion cysts

Front 30

Common laboratory findings of women w/ EOC

Back 30

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

- CA19-9/CEA may be elevated in mucinous

Front 31

conditions that can result in falsely elevated CA125

Back 31

- PID
- endometriosis
- leiomyoma
- pregnancy
- menstruation

Front 32

% of EOC w/ serous histology

Back 32

- > half

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

Front 33

What are psammoma bodies?

Back 33

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

Front 34

2nd most common histologic type of EOC after serous

Back 34

- 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 35

% of EOC that are mucinous

Back 35

- 5-10%

Front 36

What is pseudomyxoma peritonei?

Back 36

- 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 37

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

Back 37

- endometriosis
- 5-10% of EOC

Front 38

What are Brenner tumours?

Back 38

- 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 39

definition of mixed carcinoma

Back 39

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

Front 40

main DDx for primary peritoneal carcinoma

Back 40

- malignant mesothelioma

Front 41

criteria for diagnosis of PPC when both ovaries present

Back 41

- 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 42

What is the most frequent location of spread for EOC?

Back 42

- omentum

Front 43

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

Back 43

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

Front 44

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

Back 44

- no
- no demonstrable survival benefit

Front 45

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

Back 45

45%

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

Front 46

favourable prognostic factors for EOC

Back 46

- 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 47

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

Back 47

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

Front 48

factors that make the best candidate for secondary cytoreductive surgery

Back 48

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

Front 49

What percentage of epithelial ovarian cancers are hereditary?

Back 49

10

Front 50

Which of the following is not a risk factor for ovarian cancer?

a. Nulliparity
b. Late menopause
c. Combination oral contraceptive pill use
d. Hereditary nonpolyposis colon cancer (HNPCC)

Back 50

c. Combination oral contraceptive pill use

Front 51

Which of the following genetic mutations is associated with the highest risk of developing ovarian cancer?

a. Phosphatase and tensin homolog (PTEN)
b. Hereditary Breast Ovarian Cancer Syndrome 1 (BRCA1)
c. Hereditary Breast Ovarian Cancer Syndrome 2 (BRCA2)
d. MutL homolog 1, colon cancer, nonpolyposis type 2 (MLH1)

Back 51

b. Hereditary Breast Ovarian Cancer Syndrome 1 (BRCA1)

Front 52

A 40-year-old woman with a BRCA1 mutation undergoes a MIS BSO for risk reduction. By what percentage is her breast cancer risk reduced by her BSO?

Back 52

50%

Front 53

A 55-year-old healthy woman undergoes exploration for a large pelvic mass. Frozen section analysis of her right ovary notes “mucinous low malignant potential, cannot exclude invasion.” There is no other obvious disease. What surgical procedures should be performed, in addition to total abdominal hysterectomy and bilateral salpingo-oophorectomy?

Back 53

Pelvic washings, omentectomy, multiple peritoneal biopsies, bilateral pelvic and para-aortic lymph node dissection, appendectomy (mucinous!)

Front 54

A 27-year-old nulligravida who desires future fertility underwent a MIS LSO for a 7-cm cyst. The cyst was removed intact, and washings were negative. Final pathology revealed a serous low malignant potential tumor. What is the most appropriate management?

Back 54

Close observation

Front 55

Which of the following is the worst prognostic feature associated with low malignant potential (LMP) tumors?

a. Advanced stage
b. Invasive implants
c. Mucinous histology
d. Stromal microinvasion

Back 55

b. Invasive implants

Front 56

Which of the following is FALSE regarding ovarian cancer symptoms?
a. Most women with ovarian cancer experience symptoms 20 to 30 days per month.
b. Women with ovarian cancer do not have symptoms until the disease is very advanced.
c. The most frequent symptoms associated with ovarian cancer include urinary urgency, pelvic pain, and bloating. d. None of the above

Back 56

b. Women with ovarian cancer do not have symptoms until the disease is very advanced.

Front 57

What percentage of patients with stage I ovarian cancer have a normal cancer antigen 125 (CA125) level?

Back 57

50%

Front 58

Which of the following conditions can create an elevated CA125 level?

a. Leiomyomas
b. Endometriosis
c. Congestive heart failure
d. All of the above

Back 58

d. All of the above

Front 59

Which of the following radiologic tests is most helpful in a patient with suspected advanced ovarian cancer?

a. Transvaginal ultrasound
b. Positron emission tomography (PET) scan
c. Magnetic resonance (MR) imaging of the pelvis
d. Computed tomography (CT) scan of the abdomen and pelvis

Back 59

d. Computed tomography (CT) scan of the abdomen and pelvis

Front 60

Which one of the following women does not need referral to a gynecologic oncologist?

a. A 35-year-old with a complex 7-cm adnexal mass and a CA125 level of 75
b. A 60-year-old with a complex 7-cm adnexal mass and a CA125 level of 75
c. A 35-year-old with a complex 7-cm adnexal mass, ascites, and a CA125 level of 75
d. A 50-year-old with a complex 7-cm fixed adnexal mass and a CA125 level of 25

Back 60

a. A 35-year-old with a complex 7-cm adnexal mass and a CA125 level of 75

Front 61

In the photomicrograph below, to what structures are the white arrows pointing? (Hint—this finding is pathognomonic for the most common histologic cell type of epithelial ovarian cancer.)

a. Signet rings
b. Hobnail cells
c. Keratin pearls
d. Psammoma bodies

Back 61

d. Psammoma bodies

Front 62

Shown here, what is the most common cell type of epithelial ovarian cancer associated with endometriosis?

a. Mucinous
b. Clear cell
c. Endometrioid
d. Papillary serous

Back 62

b. Clear cell

Front 63

A 27-year-old presents to the emergency department with a complaint of increasing abdominal distension, constipation, and weight loss. A CT scan reveals a 10-cm right adnexal mass and retroperitoneal lymphadenopathy. Her serum CA125 level is 45, β-hCG is less than 5, and AFP and LDH levels are normal. Her serum calcium level is 15. What is the most likely diagnosis?

a. Lymphoma
b. Small cell ovarian cancer
c. Primary hyperparathyroidism
d. Malignant germ cell tumor of the ovary with bone metastasis

Back 63

b. Small cell ovarian cancer

Front 64

Which of the following is NOT a characteristic of Krukenberg tumors?
a. They are bilateral.
b. They usually arise from primary gastric tumors.
c. They are usually the only site of metastatic disease.
d. They are comprised of mucinous and signet ring cells.

Back 64

c. They are usually the only site of metastatic disease.

Front 65

What is the most common method of ovarian cancer spread?
a. Lymphatic
b. Hematogenous
c. Direct extension
d. Tumor exfoliation

Back 65

d. Tumor exfoliation

Front 66

Which of the following correctly indicates the cephalad border of the para-aortic lymph node dissection for ovarian cancer clinically confined to the ovary?

Back 66

A

Front 67

A 40-year-old woman with a right-sided pleural effusion undergoes exploratory laparotomy for a pelvic mass and elevated CA125 level.
Cytologic analysis of the pleural fluid reveals no malignant cells. Upon exploration, the finding below is seen. Which FIGO stage is she?

Back 67

IIIC

Front 68

What percentage of women with ovarian cancer clinically confined to the ovaries will be upstaged by surgery?

Back 68

33%

Front 69

Which of the following patients does not need adjuvant chemotherapy following surgery for epithelial ovarian cancer?
a. A 65-year-old following TAH BSO, omentectomy, multiple peritoneal biopsies, and pelvic and para-aortic lymph node dissection for a stage IC clear cell ovarian cancer.
b. A 45-year-old following TAH BSO, omentectomy, multiple peritoneal biopsies, and pelvic lymph node dissection for a stage IA grade 1 endometrioid adenocarcinoma of the ovary.
c. A 55-year-old followingTAH BSO, omentectomy, multiple peritoneal biopsies, and pelvic and para-aortic lymph node dissection for a stage IB grade 1 papillary serous carcinoma of the ovary.
d. A 70-year-old following TAH BSO, omentectomy, multiple peritoneal biopsies, and pelvic and para-aortic lymph node dissection for a stage IC grade 1 papillary serous carcinoma of the ovary.

Back 69

c. A 55-year-old followingTAH BSO, omentectomy, multiple peritoneal biopsies, and pelvic and para-aortic lymph node dissection for a stage IB grade 1 papillary serous carcinoma of the ovary.

Front 70

What is the goal of cytoreductive surgery for advanced ovarian cancer?

a. Remove all tumors larger than 1 cm
b. Remove all tumors larger than 2 cm
c. Remove all tumors larger than 0.5 cm
d. Remove all gross disease

Back 70

d. Remove all gross disease

Front 71

Which of the following chemotherapy regimens is associated with the longest overall survival for women with optimally debulked (less than 1 cm residual disease) stage III epithelial ovarian cancer?
a. Single agent carboplatin
b. Intravenous (IV) carboplatin and paclitaxel
c. Intraperitoneal (IP) cisplatin and paclitaxel
d. Intravenous (IV) carboplatin, paclitaxel, and bevacizumab

Back 71

c. Intraperitoneal (IP) cisplatin and paclitaxel

Front 72

A woman with a history of stage IIIC ovarian cancer who underwent optimal cytoreductive surgery followed by six cycles of intraperitoneal (IP) cisplatin and paclitaxel recurs 4 months after completion of chemotherapy. She complains of bloating and decreased appetite. Which of the following is the most appropriate treatment?
a. Tamoxifen
b. Intravenous (IV) carboplatin
c. IV carboplatin and paclitaxel
d. Pegylated liposomal doxorubicin

Back 72

d. Pegylated liposomal doxorubicin

Front 73

Which of the following chemotherapy regimens is appropriate treatment of a patient with recurrent platinum-sensitive ovarian cancer?

a. Carboplatin with paclitaxel
b. Carboplatin with gemcitabine
c. Carboplatin with pegylated liposomal doxorubicin
d. All of the above

Back 73

d. All of the above

Front 74

3 kinds of cystic ovarian tumors

Back 74

functional
neoplastic
endometrioma

Front 75

T/F: functional cysts can be malignant
T/F: neoplastic cysts can be malignant
T/F: endometriosis cysts can be malignant
T/F: solid tumors cysts can be malignant

Back 75

F
T
F
T

Front 76

3 kinds of functional ovarian cysts

Back 76

follicular
corpus luteum
theca lutein

Front 77

functional cysts are common/rare
they are related to ___

Back 77

common
ovulation

Front 78

follicular cysts are lined by ___ cells

Back 78

granulosa

Front 79

usual follicular cyst outcome

Back 79

spontaneous resolution within 2 weeks

Front 80

___ is one kind of corpus luteum cyst

Back 80

hemorrhagic corpus luteum

Front 81

menstrual abnormality associated with corpus luteum cyst
this can cause confusion with ___

Back 81

delay of menses
ectopic pregnancy

Front 82

usual outcome of corpus luteum cyst in the absence of pregnancy
usual outcome of corpus luteum cyst in the presence of pregnancy

Back 82

resolution within 8 weeks
resolution at development of yolk sac

Front 83

corpus luteum cysts present with ___
they are more common on L/R

Back 83

sudden pain
R

Front 84

compared with follicular cysts, CL cysts are ___

Back 84

more likely to cause pain
larger

Front 85

theca lutein cysts and ___ are caused by ___, e.g. from ___ (2)

Back 85

luteoma of preganancy
hCG
molar pregnancy
chorioca

Front 86

___ is a benign germ cell tumor

Back 86

dermoid cyst

Front 87

dermoid cysts are aka ___

Back 87

benign cystic teratoma

Front 88

3 benign epithelial tumors

Back 88

serous cystadenoma
mucinous cystadenoma
brenner tumor

Front 89

benign tumor of sex cord stroma

Back 89

fibroma

Front 90

serous/mucinous cystadenoma is more common
serous/mucinous cystadenoma is bigger
serous/mucinous cystadenoma is associated with psammoma bodies

Back 90

serous
mucinous
serous

Front 91

___ is a complication of mucinous cystadenoma

Back 91

pseudomyxoma peritonei

Front 92

u/s parameters distinguishing benign from malignant ovarian tumors

Back 92

size
laterality (bilateral worse)
structure (septated, complex)
ascites
vascualrity
solid/cystic components

Front 93

benign tumors are usually uni/bilateral

Back 93

uni

Front 94

structure of benign tumors (3)

Back 94

cystic
unilocular
thin septations

Front 95

structure of malignant tumors (3)

Back 95

solid elements present
multilocular
thick septations

Front 96

7 indications for surgery on ovarian cyst

Back 96

>5 cm and lasting>6 w
>10 cm
solid lesion
papillary vegetation present
ascites
palpable and present in premenarchal/postmenopausal
torsion/rupture suspected

Front 97

5 protective factors for ovarian ca

Back 97

OCP use
multiparity
breastfeeding
tubal ligation
hysterectomy

Front 98

tx for stage 1a or 1b epithelial ovarian ca (5)

Back 98

TAH
BSO
omentectomy
peritoneal washings
LN dissection

Front 99

tx for stage 2/3/4 epithelial ovarian ca

Back 99

debulking surgery
chemo

Front 100

chemo for advanced epithelial ovarian ca (2)

Back 100

carboplatin
taxol

Front 101

primordial germ cells become ___ (2 tumors)

Back 101

dysgerminoma
embryonal ca

Front 102

markers for dysgerminoma

Back 102

LDH

Front 103

markers for embryonal ca
embryonal cells become ___ (2) cells

Back 103

AFP
hCG
embryonic
extraembryonic

Front 104

embryonic cells give rise to ___ tumors

Back 104

immature teratoma

Front 105

marker for immature teratoma

Back 105

nothing!

Front 106

2 cell types with extraembryonic differentiation

Back 106

trophoblast
yolk sac

Front 107

trophoblast cells give rise to ___

Back 107

choriocarcinoma

Front 108

marker for choriocarcinoma

Back 108

hCG

Front 109

marker for yolk sac tumor

Back 109

AFP

Front 110

in contrast to epithelial tumors, germ cell tumors ___ (2)

Back 110

grow quickly
present early

Front 111

surgical tx for malignant germ cell tumors:
if bilateral disease, ___
if unilateral disease, ___

Back 111

TAH + BSO
unilateral SO

Front 112

in addition to surgery, give ___ for malignant germ cell tumor

Back 112

BEP chemo

Front 113

BEP means ___

Back 113

bleomycin
etoposide
cisplatin

Front 114

tx for sex cord stromal tumors

Back 114

USO

Front 115

Prognostic factors for EOC

Back 115

Younger age
Good performance status
Cell type other than mucinous and clear cell
Well-differentiated tumor
Smaller disease volume prior to surgical debulking
Absence of ascites
Smaller residual tumor following primary cytoreductive
surgery

Front 116

the best candidates for secondary cytoreductive surgery have?

Back 116

(1) platinum-sensitive disease,
(2) a prolonged disease-free interval,
(3) a solitary-site recurrence, and
(4) no ascites