Early detection of ovarian, endometrial and vulval cancers

1. Early detection of ovarian,
endometrial and vulval cancers
Aboubakr Elnashar
Benha university, Egypt
Aboubakr Elnashar

2. Ovarian Cancer Early
detection
Aboubakr Elnashar
Benha university Hospital, Egypt
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3. Incidence
• 4.4% of cancers in women
• Highest incidence in N. America and N. Europe
– lifetime 1 in 70 women
• Less common in developing countries
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4. Mortality
• US: 4th
leading cause of cancer death in women. (after
lung, breast and colon)
• 5-year survival rate: 35%
• The “silent killer”: asymptomatic in early
stages
• 75% diagnosed with advanced stage disease
• Woman’s lifetime risk of dying from ovarian cancer is
1.1%
• When detected early:
Surgical debulking and chemo more effective
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5. Challenges for early detection
1. Natural history: not well understood
 No well-defined precursor lesion
 Length of time from localized tumor to
dissemination: unknown
2. Vague non specific symptoms
3. The ovary is deep seated in the pelvis
4. Tests used for screening: unreliable
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6. Risk factors
• Majority: no known risk factors
• Most significant: genetic predisposition
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7. Risk factors: Heredity
 10% of epithelial ovarian cancer: familial
 3 familial syndromes
• familial breast-ovarian cancer syndrome
• site-specific ovarian cancer
• cancer family syndrome (Lynch type II)
 Familial breast-ovarian cancer and site-specific
ovarian cancer syndromes both associated with
mutations of the BRCA1 suppressor gene;
account for 90% of familial ovarian cancers
(Rollins,G. 2000)
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8.  5-10% of all cases of breast and ovarian cancer
have genetic predisposition:
• BRCA 1
• BRCA 2
• Mismatch repair genes (Lynch type 1 and 2)
endometrial, colorectal and ovarian cancer.
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9. Additional Risk Factors
• Age
– ≥50 y account for ~80% of
all cases (ave. age at dx :
61y)
• Reproductive history
– early menarche
– nulliparity
– age >30y at 1st
child-
bearing
– late menopause
• Fertility drugs
– prolonged use of CC
especially without
achieving pregnancy
• Personal history of breast
cancer
• HRT> 5 years
– 30% increased risk
• Talcum powder
– use talc powder on
genital area
(American Cancer Society, 2001)
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10. Protective factors
• Multiparity:
First pregnancy before age 30y
• Lactation
• Oral contraceptives:
5 y of use cuts risk nearly in half
• Tubal ligation, removal of fimbrial end
• Hysterectomy
• Bilateral oopherectomy
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11. Delays in Diagnosis
• Lack of severity and specificity of early symptoms
– Early signs/symptoms:
bloating, gas, indigestion, abdominal fullness or
discomfort, constipation, pelvic pressure,
urinary frequency, abnormal vaginal bleeding,
fatigue, back pain, leg pain
• Early stage tumors difficult to detect on pelvic
exam
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13. Screening Strategies
• US: TV and TA
• Color-flow Doppler
• CA-125
• Other tumor markers
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14. Ultrasound
• TVS has better resolution than TAS
• Sensivity: 81%
• Specificity: 98.9%
• Allows earlier stage detection
• Limitations
PPV in asymptomatic women: poor
inability to detect malignances when ovaries are
normal size
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15. Color-flow Doppler
• Used in conjunction with TVS
• Measures resistance in blood vessels supplying
the ovaries
• May provide additional information to help
distinguish malignant from benign masses
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16. CA-125
• Poor sensitivity:
elevated in only 50% of women with Stage I disease
• Poor specificity:
elevated in many gynecologic and non-gynecologic
malignancies as well as benign conditions
 Elevation in:
82% of advanced ovarian cancer
 1% of healthy women
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17. CA-125
Malignant conditions
• Cervical CA
• Fallopian tube CA
• Endometrial CA
• Pancreatic CA
• Colon CA
• Breast CA
• Lymphoma
• Mesothelioma
Benign conditions
• Endometriosis/Menses
• Uterine fibroids
• PID
• Pregnancy
• Diverticulitis
• Pancreatitis
• Liver disease
• Renal failure
• Appendicitis
• IBD
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18. • Approved marker to test for recurrence
• Single most sensitive and specific marker for
ovarian cancer to date
• Addition of other markers might improve
sensitivity and specificity
• Longitudinal assessment may also improve
sensitivity and specificity
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19. CA-125 Epithelial tumors (especially
serous
α Fetoprotein (AFP) Endodermal sinus tumors
Embryonal carcinomas
Mixed germ cell tumors
Human chorionic
gonadotropin (hCG)
Choriocarcinoma
Embryonal carcinomas
Mixed germ cell tumors
Polyembryoma
Lactate Dehydrogenase
(LDH)
Dysgerminoma
Mixed germ cell tumors
Serum Tumor Markers
DiSaia& Creasman, 2007Aboubakr Elnashar

20. Human epididymis protein 4 (HE4)
• Alone and the combined analysis of CA125
and HE4 improve the diagnostic accuracy of
adnexal masses.
(Lenhard. 2011)
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21. Current Screening Guidelines
• “Routine screening for ovarian cancer by US,
tumor markers, or pelvic examination is not
recommended.
(American Cancer Society, AAFP and ACOG)
• There is insufficient evidence to recommend for
or against the screening of asymptomatic
women at increased risk of developing ovarian
cancer.”
(Canadian Task Force on Periodic Health Examination)
 Counsel high risk women about potential harms
and benefits of screening
(ACP)
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22. • NIH Consensus Conference
– women with presumed hereditary cancer
syndrome should undergo
Annual pelvic exams
CA-125 measurements
TVS
When childbearing is complete or at age 35y:
prophylactic bilateral oopherectomy
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23. Recommendations
 Screening of the general population is not cost effective
and not indicated
• High risk group: TVS and CA125
• ASK about family history of cancers: Familial ovarian
cancer (5-10%): genetic test.
• When women present with non-specific GI complaints;
include Ov Ca in DD
• Stop ovulation induction after one year
• Bimanual exam and rectal exam as part of pelvic exam
• Biopsy any surgically removed ovarian tissue.
• Assessment of risk of malignancy in an adnexal mass.
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24. RMI=U x M xCA125
 Score 200 in the detection of ovarian malignancies
• Sensitivity: 78%
• Specificity: 87% Aboubakr Elnashar

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26. Papillary serous cystadenocarcinoma. thick septations with
soft tissue nodularity (curved white arrows) and wall nodularity
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27. Papillary serous tumor of low malignant potential
Sagittal TAS: a predominantly cystic mass with irregular
papillary projections without vascularity by color Doppler
ultrasound (B) (white arrows) and solid components (white
arrowhead).
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28. Endometrial cancer Early
detection
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29. Incidence
 3.8% of all cancers in women
 higher in developed countries
 Early presenting cancer (PMB).
 Diagnosed in early stages in >90%.
 Population screening is not cost/effective.
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30. Risk actors
• >50yrs
• Hypertension
• Obese
• Type II diabetes
• Ethnic: caucasian (but aggressive in negro)
• Heredity:
small No. but high risk
HNPCC: Hereditary Non Polyposis Colorectal Ca:
Ca at earlier age
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31.  Hormonal: <menarche:>menopause
nulliparity
unopposed oestrogens x6
Tamoxifen x3
PCO – anovulation
Estrogen-secreting tumorsEstrogen-secreting tumors
• History of primary breast cancer
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33. PRE-INVASIVE LESIONS
Pathology Malig. Potential
Metaplasia Replacement of usual
gland cell by cells
having cilia, sq. cells
Little or none
Simle hyperplasia Irregular glands, minor
budding or out
pouching
1-3% over 15y
Complex
hyperplasia
Back to back glands,
budding, papillary
process, minor
stratification
3-4% over 13y
Atypical hyperplasia Atypisim + back to back
+ budding
23% over 10y
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34. Modalities of early detection
1. Endometrial sampling
 Aspiration curettage
Aspiration cannula
Brush cytology
 Indication:
any persistent bleeding (regardless of the age).
 Less invasive
 Risks:
discomfort, bleeding, infection, uterine perforation
(rare)
35-75% samples insufficient for diagnosis
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37. Procedure
Bimanual examination to asses the uterus.
The cervix is then visualised and cleaned.
A tenaculum is applied to the anterior lip of the cervix, and is used to provide gentle traction whilst a
sound is inserted though the cervical os. This minimises the risk of perforation.
Dilators may be required if there is difficulty in passing the sound.
When the position and size of the uterine cavity have
been assessed, the pipelle is inserted through the cervical
os and advanced until gentle resistance is felt.
The inner piston of the device is then withdrawn to create
suction and the endometrial sample is obtained by moving
the pipelle up and down within the uterine cavity by
approximately 2-3 cm but not beyond the cervical os.
This procedure should be repeated at least four times and
the device rotated 360° to ensure adequate coverage of
the area.
The pipelle is then withdrawn from the cervical os and the
endometrial sample expelled into a solution of formalin
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38. 2. D & C
– More invasive
– “gold standard”
– At best only 65% of endometrium sampled
 Routine Pap smear:
inadequate
Assessment: too insensitive and non specific.
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39. 3.TVS
 Helpful in
• evaluating vaginal bleeding
• Follow up of PCOS by TVS/biopsy.
• Follow up of high risk women.
• Tamoxifen: less reliable {thickness up to 10mm
can be normal}
Markedly thickened
endometrium and evidence
of myometrial invasion at the
fundus (arrow) suggest
endometrial cancer.
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40. Endometrial carcinoma
TVS: heterogeneous, cystic, and vascular
hyperechoic tissue filling the endometrial cavity
(arrows).
B: sagittal US image showing the same.
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41. Axial TVS: thickened cystic echogenic soft tissue
filling the endometrial cavity (arrows
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42. 4. TVS color Doppler
superior to other methods in early detection
5.Hysteroscopy:
The lesion show frank dimply appearance with
irregular polylobed growing edge.
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43. Early detection strategy
• Combination of risk assessment and directed
testing if:
– Symptoms: PMB
– High risk groups (Tamoxifen, HNPCC)
– TVS: endometrium ≥ 5mm in
postmenopausal: Endometrial biopsy
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44. Screening
• Benefits ?
– Inadequate evidence that screening with TVS
or endometrial sampling would reduce the
mortality from endometrial cancer.
• Harm?
– Screening of asymptomatic women with TVS:
unnecessary additional examinations because
of its low specificity
– Endometrial biopsy: discomfort, bleeding,
infection, perforation (rare)
– Cancers may be missed on both
– Screening of unproven benefit
(National Cancer institute 2005)Aboubakr Elnashar

45. Prevention
1.Women at average risk or increased risk.
No role for routine screening
At the onset of menopause, women should be
informed about
risks and symptoms of endometrial cancer
encouraged to report any unexpected bleeding or
spotting
(ACOG, 2006; Smith, 2011).
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46. 2. Lynch syndrome cancers
include colon, endometrium, small bowel, renal pelvis
and ureter, and ovary, among others
(Vasen, 1999).
Referral for genetic counseling can further clarify the
risk to predict which patients may benefit from specific
germline testing
(Balmana, 2006; Chen, 2006).
Endometrial cancer is the most common “sentinel
cancer: gynecologists play an essential role in the
identification of women with HNPCC
(Lu, 2005).
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47. In women at high risk for endometrial cancer due to
HNPCC
Annual screening by endometrial sampling should
begin at age 35 years
(Burke, 1997; Smith, 2011).
Criteria for screening potential mutation carriers of
this syndrome include
colorectal or other Lynch syndrome-associated
cancers in three first-degree relatives
occurring in at least two successive generations
 in one individual under the age of 50 years.
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48. Prophylactic hysterectomy:
100% risk reduction.
(Schmeler, 2006).
{women with HNPCC have a high lifetime risk of
developing endometrial cancer (40 to 60%)},
BSO
{10- to 12% lifetime risk of ovarian cancer}.
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49. Vulval cancer early detection
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50. Incidence
• Rare.
• Elderly women 70 – 80yrs
• 2/3 of cases are diagnosed in late stages.
• 90% have visible lesion
• 90% squamous Ca
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51. High risk groups
• Post menopausal
• DM- hypertension
• Smoking
• Dystrophy
• Chronic granulomatous lesion
• HPV virus
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52. Symptoms
persistent pruritus (56%)
vulval pain (29%)
visible/palpable vulval swelling (16%)
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53. PRE-INVASIVE LESIONS
I. Vulva dystrophy: nonneoplastic epithelial disorders
1. Leukoplekia
2. kraurosis vulvae
3. Lichen sclerosis? : white, glistening sheets with clearly defined
margins and involves the labia, the perineum and the
perianal region.
II. VIN:
I, II & III (progression VIN I to VIN III rare)
(Annual rate of progression VIN III to CA ~10%)
III. Paget`s disease
a non-squamous intraepithelial neoplasia associated with proliferation of
atypical glandular cells of the apocrine type. A bright scarlet,slightly
raised, velvety plaque with clearly defined serpiginous edges.
±associated with paget`s of breast
IV. Melanoma-in-situ
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54. Epithelial Vulvar Diseases (ISSVD 1989)
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55. Paget's disease of the labium majus. A bright
scarlet,slightly raised, velvety plaque with clearly
defined serpiginous edges.
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56. VIN 3 with extensive
perineal and perianal
involvement.
Early-stage squamous cell
cancer of the vulva.
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57. Pigmented, multifocal,
high-grade VIN.
Multifocal leukoplakia
typical of high-grade VIN.
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58. Modalities
• Colposcopy
• Acetic Acid test
• Toulidine blue test
• Biopsy
Vaginoscopy showing multifocal acetowhite HPV
lesions after application of 5-percent acetic acid
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59. Strategy
• Assessment if
symptomatic, postmenopausal
other evidence HPV genital disease
symptomatic Lichen Sclerosus
• Refer to gynae oncologist
Pagets Disease
Melanoma-in-situ
VIN III
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60. Recommendations
• Follow up of vulval dermatoses (LS).
• Chronic pruritis vulvae should be investigated.
• Look at the vulva whenever doing colposcopy
• Follow up cases of CIN, more liable to develop VIN
(field effect).
• Follow up HPV related changes, warts.
• Biopsy any
suspicious lesion
pigmented/hyperkeratotic area.
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62. Thank you
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