Gynecology Oncology Flashcards
(147 cards)
1
Q
What is the definition of sensitivity
A
Proportion of patients with disease who have a positive screening test result
2
Q
What is the definition of specificity
A
Proportion of patients without disease who have a negative screening test result
3
Q
Recommended gynecologic cancer screenings
A
Only recommended is pap test
Any clinical presentation or physical exam suspicious for ovarian, endometrial or vulva cancer should be referred appropriately
4
Q
Adnexal mass workup to rule out ovarian cancer
A
Transvaginal ultrasound
CA 125
Surgical excision for biopsy confirmation
5
Q
Post-menopausal bleeding workup to rule out endometrial cancer
A
Endometrial biopsy
or dilatation and curettage for biopsy confirmation
6
Q
Vulvar lesion workup to rule out vulva cancer
A
Excision biopsy
7
Q
Post- cancer care and follow up for gynecological cancers
A
Cancer follow up for 5-10 years post treatment to monitor recovery from treatment and recurrence
If no relapse after 510 years then discharge from cancer follow up
Endometrial cancer usually fu by family doctor according to guidelines based on stage (focused symptom inquiry, pelvic - rectal examination, frequency)
Ovarian, primary peritoneal and fallopian tube cancer suually have no guidelines due to high mortality
Vagina patients fu by rad onc
Vulva cancer fu in colposcopy unit
8
Q
What is elevated AFP usually indicative of
A
Sggests embryonal cell cancer, mixed germ cell cancer
9
Q
What is elevated CA 125 usually indicative of
A
Suggests ovarian cancer
10
Q
Pelvic mass indication for surgery
A
- Emergency
Ovarian torsion, ectopic pregnancy, appendix abscess, ruptured tubal ovarian abscess, cyst complicated by hemorrhage - Non-emergency indications
Large, persistent, enlarging and symptomatic cyst, complex persistent mass, any mass suspicious for malignancy
11
Q
Differential diagnosis for ovarian masses
A
- Functional - follicular cyst, luteal cyst, theca lutein cyst
- Benign epithelialtumor - cystadenoma
- Benign germ cell tumour - teratoma (dermoid cyst)
- Sex cord tumour - Granulosa cell tumours (can be benign or malignant), Leydig cell tumour (can be benign or malignant)
- Benign connective tissue tumour - fibroma, thecoma
- benign endometrial tumor: endometrioma (chocolate cyst) from endometriosis
- ovarian cancer: epithelial ovarian cancer, germ cell tumors, sex cord stroma tumor (Granulosa cell tumor, Leydig cell tumor)
- metastasis to ovary: breast cancer, gastric cancer, colon cancer, endometrial cancer
12
Q
Extra-ovarian adnexal mass differential diagnosis
A
Tubal - ectopic pregnancy, hydrosalpinx, tubo-ovarian cst, pyosalpinx, pelvic abscess, fallopian tube cancer
Benign OBGYN pathology - para-ovarian cyst, para-tubal cyst, pedunculated fibroid
13
Q
What is adnexa
A
Ovaries, fallopian tube or connective tissue surrounding uterus
14
Q
Differential diagnosis uterins mass
A
- physiology: pregnancy
- benign: leiomyoma, adenomyosis, adenomatoid tumor, hematometra (uterine hematoma)
- malignant: uterine sarcoma, uterine carcinosarcoma, endometrial carcinoma, metastasis (from another reproductive tract primary malignancy)
15
Q
GI tract mass differential diagnosis
A
ascitis
constipation
benign tumor: mesenteric cyst
malignancy: colorectal cancer, appendix tumor, peritoneal carcinomatosis
infectious: abscess, inflammatory bowel disease (Crohn’s disease)
16
Q
urinary tract mass ddx
A
distended bladder
17
Q
abdominal wall mass ddx
A
infection: abscess
vascular: hematoma
neoplasm: sarcoma
18
Q
lymph node mass ddx
A
benign: lymphocele, lymphadenopathy
malignant: lymphoma, metastatic lymphadenopathy
19
Q
Most common differnetial diagnosis of abdomianl mass for pre-menopausal women
A
adnexal mass: follicular cyst, corpus luteum cyst, polycystic ovarian syndrome (PCOS), dermoid cyst, endometriosis, Sertoli-Leydig cell tumors, salpingitis
intra-uterine mass: pregnancy (intra-uterine or ectopic), fibroids
20
Q
Most common differnetial diagnosis of abdomianl mass for post-menopausal women
A
adnexal mass: ovarian cancer, metastasis to ovary
GI tract mass: colon cancer
21
Q
Work up of pelvic mass
A
- Imaging
a) u/s (diagnosis, cystic, differentiate benign vs malignant)
b) CT (with contrast is good for evaluation of abscess, GI tract lesions, lymphadenopathy)
c) MRI (with contrast, superior for characterization and differentiating benign vs malignant, fu to indeterminate ultrasound, identifying fatty or hemorrhagic components to masses) - Lab investigations
- CBC, b-hCG, AFP, Ca-125
- vaginal swab for STIs - Surgery
a) exploratory laparoscopy and surgical excision of mass
22
Q
Hydrosalpinx definition
A
blocked fallopian tube from previous pelvic inflammatory disease or surgery
23
Q
Common adnexal pass pathology in children and adolescents
A
higher risk of ovarian malignancy
24
Q
most common type of ovarian cancer
A
germ cell tumours
25
common adnexal mass pathology in pregnant women
ectopic pregnancy
luteal cyst
theca lutein cyst
26
Clinical presentation of adnexal mass
many are asymptomatic
mass effect -- abdo distension, urinary urgency, frequency , GI anorexia, early satiety, bloating, dyspnea
Chronic pelvic pain - deep dyspareunia, congestive dysmenorrhea (associated with endometriosis and chronic PID)
27
Adnexal mass complications
torsion
rupture
hemorrhage (intra cystic or intra peritoneal)
infection (pelvic abscess)
28
Benign vs malignant adnexal mass characteristics
```
Benign -
commonly unilateral
simple cyst
gravity dependent layering of cyst content
calcification
well circumscribed shape
thin septation
no blood flow
no ascites, no other masses
no adhesions
slow growing
```
```
Malignant -
commonly bilateral
mixed/complex solid and cystic
solid component that is nodular or papillary, not hyperechoic
usually no calcification
irregular shape
irregular multilocular (many chambers)
may have thick septation (>3 mm)
vascularity in solid component
may have ascites, peritoneal masses/nodularity, enlarged nodes, adhesions, matted bowels
fast growing
```
29
Role for minimally invasive biopsy (ex. image guided needle biopsy) for ovarian cancer
not recommended due to risk of worse prognosis from rupturing mass
30
Management of benign adnexal mass
1. Conservative - asymptomatic benign mass, observation
2. Medical management
For ovarian cyst, ovarian suppression to suppress cyst formation by decreasing LH and FSH
- high estrogen including OCP
- GnRH agonist including Leuprolide
3. Surgical management if symptomatic, complications, infeertility
drainage of cyst, surgical removal of mass, hysterectomy and/or salphingectomy and/or oophorectomy
31
Management of malignancy adnexal mass
based on staging of disease
management is combination of chemotherapy and/or radiotherapy and/or surgical excision of mass
32
Risk factors for epithelial ovarian cancer
demographics: older age, there >50% of ovarian tumor in women age >50 are malignant; Caucasian; Ashkenazi-Jewish ancestry
increased estrogen: nulliparity, delayed child bearing, early menarche, late menopause
family history: breast cancer, colon cancer, endometrial cancer, ovarian cancer
genetic: BRCA 1 and 2 mutations, which account for 10-15% of ovarian cancer cases; HNPCC (hereditary non-polyposis colorectal cancer aka Lynch syndrome)
setting: industrialized countries with high dietary fat intake
other: infertility
gynecologic diseases: polycystic ovarian syndrome, endometriosis
social history: smoking
33
Protective factors for epithelial ovarian cancer
Decreased estrogen - pregnancy, breastfeeding
OCP
Surgery - tubal ligation, hysterectomy, bilateral salphingo-oophorectomy
34
Types of ovarian cancer
Many of the types below can be benign or malignant
1. Epithelial in 70% of cases
a) serrious (MC), usually benign
b) Mucinous usually benign
c) endometrioid
d) clear cell
e) Brenner
f) undifferentiated
2. Non epithelial in 30% of cases
a) germ cell tumour (dysgerminoma, immature teratoma, yolk sac tumour, embyonal, carcinoma, choriocarincoma)
b) sex cord stream (granuloa-theca cell tumour, Sertoli-Leydig cell tumour)
c) metastatic (GI, breast, endometrial, lymphoma)
35
Serious epithelial ovarian cancer pathology
lining similar to fallopian tube epithelium
malignant - microscopic appearance papillary, may have complex glands, cysts, irregular nests of cells, atypica, contain Psamomma bodies (calcified concentric concretions)
36
Muncious ovarian cancer pathology
mucinous epithelial cells
benign - formation of mucinous glands with normal architecture, no stream invasion, no atypia
Multi-septated cystic mass with thin walls, may beocme very large
Malignant - atypica, stratification, papillae, loss of glandular architecture, necrosis, complex gland
smooth capsule cystic and solid tumours stromal invasions, solid growth
37
Pathophysiology of ovarian cancer
Loss of p53 tumour suppressor gene in most ovarian cancer leading to proliferative growth
38
Metastatic pathways of ovarian growth
Local invasion --> intravasation --> survival in circulation --> extravasation --> colonization
39
Why are lymphatics more optimally sited to entry, metastasis and transport of cancer cells?
1. Lack of brasement membrane
2. Few intercellular junctions
3. Large calibre
4. Slower flow velocity
5. Similiarity of lymph to interstitial fluid
40
Order of gynecological organs for propensity for metastasis
Ovarian > cervical > uterine
41
Mechanisms for the spread of ovarian metastasis
direct extension into nearby structures including reproductive structures (ovaries, fallopian tube, uterus), bladder, sigmoid colon
detaching from primary tumor to seed omentum and peritoneum causing peritoneal carcinomatosis
may involve pelvic or para-aortic lymph nodes
rarely disseminates via bloodstream to distant organs
42
Clinical presentation of ovarian cancer
Tends to be asymptomatic in early stage
Non specific symptoms (abdo, urinary, GI, OBGYN) - nausea, anorexia, dyspepsia, early satiety, bloating, increased abdominal girth, urinary frequency urgency, constipation, post menopausal bleeding AUB
43
Investigations for ovarian cancer
```
1. Blood work
Ca-125 in post menopausal women only
CBC, lytes
BUN, Cr
liver function test
```
2. Imaging - TVUS, abdo and pelvis CT with contrast
44
What's the deal with CA-125
tumor marker, which is not specific but useful for tracking response to treatment
there are multiple causes for elevated CA-125 including
1. gynecologic malignancy: ovarian cancer, uterus cancer
2. gynecologic diseases: benign ovarian tumor, endometriosis, pregnancy, fibroids, pelvic inflammatory disease, menstruation
3. non-gynecologic malignancy: pancreatic cancer, stomach cancer, colon cancer, rectal cancer
4. non-gynecologic diseases: liver cirrhosis, pancreatitis, renal failure
45
Ultrasound findings suggestive of ovarian cancer
bilateral lesions
large ovarian lesion (>20mL in pre-menopausal women; >10mL in post-menopausal women)
multilocular cyst
heterogeneous mass with solid areas, multiple septa, irregular
ascites, evidence of metastasis
46
Diagnosis of ovarian cancer
Pathology of surgical excised specimen, which usually occurs after surgical excision of tumour
47
Management of ovarian cancer
Based on TMN staging
Stage 1 - surgery (bilateral salpingectomy-oophorectomy +/- hysterectomy +/- omentectomy +/- perintoneal washing +/- peritoneal/lymph node biopsy) +/- adjuvant chemo
Stage 2+ - may have neoadjuvant chemo, then cytoreduction (aka tumour debulking), adjuvant chemo
48
What is cytoreduction
en-bloc resection of ovarian tumour, reproductive organs, sigmoid colon with primary bowel re-anastomosis
49
What is used for adjuvant chemo for ovarian cancer
Platinum (Carboplatin or Cisplatin) + Taxane (Taxol or Taxotere), which can be delivered intra-peritoneally or by IV
50
Ovarian cancer screening
Screening in high risk group (familial ovarian ca, other ca, BRCA-1 or 2 mutation) with TVUS and CA-125 is controversial
US not sensitive and not specific in asymptomatic
CA-125 not specific
51
Types of benign ovarian cysts
Follicular cyst
Lutein cyst
Theca-lutein cyst
others include dermoid, cyst adenoma, endometriomas, PCOS
52
Functional cyst definition ovarian
Cyst as result of normal function of menstural cycle, which include follicular cyst and corpus luteal cyst
53
Follicular cyst ovarian definition
follicle that failed to rupture during ovulation, lined with granulosa cells
54
Corpus luteal ovarian cyst definition
corpus luteum failes to regress after 14 days, becoming cystic or hemorrhagic
55
Risk of lutein cyst
very vascular and thin wall - higher risk of intra-cystic bleeding and rupture
56
theca- lutein cyst ovarian definition
atretic follicles stimulated by abnormal b-hCG level
57
Ovarian functional cyst symptoms
```
pelvic pain (may radiate to lower back and thighs) including dyspareunia, dyschezia corresponding to menstrual cycle (before period begins or
before it ends), nausea, vomiting, breast tenderness, abdominal fullness or heaviness, urinary frequency
```
58
Ovarian follicular cyst clinical presentation
usually asymptomatic, risk of rupture / bleeding / torsion / infarct
59
Ovarian corpus luteal cyst presentation
pelvic pain, higher risk of rupture and bleeding
60
ovarian Intra-cystic hemorrhage presentation
localized abdominal / pelvic pain, tachycardia, hypotension, local peritoneal signs
61
ovarian cyst rupture
acute generalized abdominal / pelvic pain (with radiation to shoulder), nausea & vomiting, tachycardia, hypotensive, generalized peritoneal signs
62
intra-peritoneal hemorrhage presentation
generalized abdominal / pelvic pain, tachycardia, hypotension, generalized peritoneal signs
63
ovarian cyst torsion presentation
acute localized abdominal / pelvic pain, nausea & vomiting, tachycardia, local peritoneal signs
64
ovarian cyst diagnosis
usually diagnosed based on visualization of cyst on pelvic us
65
follicular ovarian cyst us findings
4-8 cm diameter
unilocular
66
corpus luteal cyst us findings
10-15 cm diameter
firmer than follicular cyst
67
Ovarian cyst treatment
wait 6 weeks and re-examine with pelvic ultrasound as cyst usually regresses with cycle
ovarian suppression with oral contraceptive pill to prevent development of new cysts
if symptomatic or suspicious mass on imaging, then surgical exploration to rule out ovarian cancer
68
ovarian cyst indication for surgery
indication for surgery: mass suspicious of ovarian cancer, symptomatic cyst, large cyst
surgery = laparoscopic cystectomy or oophorectomy
usually surgery not done for corpus luteal cyst due to very high risk of rupture and subsequent bleeding from cyst into abdominal cavity
69
ovarian cyst indication for surgery
indication for surgery: mass suspicious of ovarian cancer, symptomatic cyst, large cyst
surgery = laparoscopic cystectomy or oophorectomy
usually surgery not done for corpus luteal cyst due to very high risk of rupture and subsequent bleeding from cyst into abdominal cavity
70
Benign ovarian cyst presentation and complications
many asymptomatic
mild symptoms from mass effect including abdo distension, urinary frequency
acute complications: torsion, rupture, hemorrhage, infection
71
Malignant ovarian cyst presentation
nausea, anorexia, dyspepsia, bloating, early satiety
mass effect - abdo distension, urinary frequency, constipation
post menopausal bleeding
constitutional symptoms - weight loss
ascites
72
Benign ovarian cyst mass characteristics
```
Unilateral
Small
(<20cc
in
pre-‐menopausal;
<10cc
in
post
menopausal)
Slow
growing,
may
regress
Soft
No
adhesions,
no
vascularity
```
73
malignant ovarian cyst mass characteristics
```
Bilateral
Large
(>20cc
in
pre-‐menopausal;
>10cc
in
post
menopausal)
Fast
growing
Firm
Adhesion,
vascularity
```
74
Benign adnexal mass features
commonly unilateral
```
Can
be
simple
cyst
Gravity
dependent
layering
of
cyst
content
CalciPication
Well
circumscribed
shape
May
have
thin
septation
```
no blood flow
usually no ascites, no other masses, no adhesions
slow gorwing
75
malignant adnexal mass features
commonly bilateral
```
Mixed
/
complex
solid
and
cystic
Solid
component
that
is
nodular
or
papillary,
not
hyperechoic
Usually
no
calciPication
Irregular
shape
Irregular
multilocular
(many
chambers)
May
have
thick
septation
(>3mm)
```
vascularity in solid component
```
May
have
ascites
May
have
peritoneal
masses
/
nodularity,
enlarged
nodes
Adhesions, matted bowels
```
fast growing
76
benign cystic teratoma (dermoid cyst) epidemiology
most common ovarian germ cell neoplasm
10-20% of all ovarian tumour, 90% of all ovarian tumour in young females
77
Dermoid cyst pathophysiology
germ cell tumor containing usually containing all 3 cell lines (endoderm, mesoderm, ectoderm) with ectoderm predominance
dermoid cyst usually are thick wall encapsulating skin, hair and teeth tissue filled with thick sebaceous
thick sebaceous can cause aseptic peritonitis and severe chronic adhesions if dermoid cyst is ruptured into peritoneal cavity
30% of dermoid cyst contain teeth, which is visible on X-ray
may contain cartilage, bone, muscle, thyroid tissue (aka struma ovarii that secretes of thyroid hormone), gastrointestinal tract (may cause carcinoid syndrome)
dermoid cyst have long pedicles with high risk of torsion
78
dermoid cyst clinical presentation
abdominal / pelvic pain
abominal vaginal bleeding
urinary symptoms: frequency, difficulty voiding
risk of ovarian torsion: acute localized abdominal / pelvic pain, nausea & vomiting, tachycardia, local peritoneal signs
79
Dermoid cyst diagnosis
usually diagnosed based on visualization of cyst on pelvic ultrasound
80
Dermoid cyst findings on us
dermoid cyst ultrasound findings: unilocular, smooth walled, mobile cyst with calcification
calcification on ultrasound or X-ray is pathognomonic for dermoid cyst
10-20% of dermoid cysts are bilateral
81
Dermoid cyst treatment
indication for surgery: large cyst >8cm, symptomatic cyst
| surgery = laparoscopic cystectomy
82
most common benign neoplasm from uterus
adenomyosis and leiomyoma
83
Leiomyoma (aka fibroid) epidemiology
mc pelvic tumour in women
common in reproductive age
symptomatic in 10-20% of women
in 90% of excised uteri
84
fibroids risk factors
black women
early menarche (<10 years old)
Diet - red meats, alcohol
85
fibroids protective factors
higher parity
diet - green vegetables, fruits, vitamin A
Smoking
86
Pathophysiology of leiomyoma
benign tumour originating from myometrial smooth muscle with minimal malignant potential (1/1000)
estrogen stimulates uterine smooth muscle proliferation and progesterone results in inhibition of apoptosis of uterine muscle
as tumour outgrows blood supply if can have degenerative changes including hyaline degen, cystic degen, red/carneous degen (hemorrhage into tumour), fatty degen, calcification, sarcomatous degen
typically regress after menopause, where enlarging post menopause is suspicious of malignancy
87
fibroid classification
according to location
Submucosal - directly underneath endometrium
Can be type 0,1,2
Type 0 completely in uterine cavity
Type 1 <50% in uterine wall
Type 2 >50% in uterine wall
can be intramural - inside myometrium
can be subserous - underneath serosa
88
Management of submucosal uterine fibroids
type 0,1 are hysteroscopically resectable
Type 2 needs to be resected by abdo surgery
89
submucosal fibroid presentation
typically cause inferitlity and bleeding
90
subserous fibroid presentation
typically cause pain
91
intramural fibroids presentation
can cause infertility
92
how do fibroids cause infertility
distort uterine cavity
93
how do submucosal fibroids cause heavy menstrual bleeding
abnormal uterine vasculature
impaired endometrial hemostasis
dysregulation of angiogenesis
94
Most commonly used imaging modality to diagnose fibroids
TVUS
95
pathology of leiomyoma
round well circumscribed encapsulated smooth muscle cells (elongated, spindle-shaped, with a cigar-shaped nucleus in whirled distribution forming
bundles) with large amount of extracellular matrix surrounded by thin pseudo capsule of areolar tissue and compressible smooth muscle
96
Fibroid treatment
A) Observation
indication: asymptomatic; minimally asympatomatic; fibroids <6-8cm or stable in size; not submucosal fibroids; or currently pregnant
observation = follow up with ultrasound
B) Treatment
indication for treatment: symptomatic, rapidly enlarging, intra-cavitary fibroids
treatment modality is individualized based on the fibroid (type, size, location), severity of symptom, patient age and reproductive plans
1) medical treatment
anemia: iron deficiency
analgesia: NSAID
control menorrhagia: tranexamic acid, oral contraceptive pill (OCP), progestin
hormonal therapy to reduce fibroid size: GnRH agonist (Leuprolide), Danazol, GnRH antagonist, selective progresterone receptor modulator
mechanism of action: hormonal therapy decreases estrogen and progesterone, which reduces fibroid size
GnRH agonist usually used for 6 months to reduce fibroid size and reduce bleeding before myomectomy or hysterectomy
2) interventional radiology
uterine artery embolization to shrink fibroids and improve menorrhagia
contraindication: women considering child bearing
3) surgery
surgery options: myomectomy (hysteroscopic, trans-abdominal, laparoscopic), hysteroscopic resection of fibroid and endometrial ablation, hysterectomy
myomectomy preserves fertility
contraindication: pregnancy due to risk of bleed and pregnancy loss
97
Endometriosis risk factors
older age >25 years
family history of endometriosis increases risk by 7-10 times if 1st degree relative
obstructive anomalies of genital tract
nulliparity
98
Endometriosis pathophysiology
endometriosis = growth of endometrial tissue outside uterine cavity, which can include
ovaries (endometrioma)
broad ligament, vesicoperitoneal fold
peritoneal surface of cul-de-sac, uterosacral ligament
rectosigmoid colon, appendix
rarely may occur outside abdomen and pelvis including lungs
99
Theories regarding pathophysiology of endometriosis
a) retrograde menstruation (Sampson’s theory): trans-tubal regurgitation during menstruation results in seeding of endometrial cells in pelvis, which account for endometriosis
most commonly found in dependent sites of pelvis
b) immunologic theory: altered immunity (decreased NK cell activity) limit clearance of transplanted endometrial from pelvic cavity
c) metaplasia of ccoelomic epithelium: endogenous biochemical factor may induce undifferentiated peritoneal cells to differentiate and develop into endometrial tissue
d) vascular / lymphatic dissemination: aberrant dissemination of endometrial cells via vasculature or lymphatic system to elsewhere
100
Endometriosis clinical presentation
endometriosis may be asymptomatic
classic symptoms = chronic pelvic pain + combination of 4 D’s (dysmenorrhea, dyspareunia, dychezia, dysuria)
menstrual symptoms: cyclic symptoms of dysmenorrhea (painful menstruation) which may progress to chronic persistent pain worse at menstruation, sacral backache, pre-menstrual
and post-menstrual spotting, dyspareunia (pain during sexual intercourse)
infertility in 30-40% cases
urinary symptoms: frequency, dysuria, hematuria
bowel symptoms: constipation or diarrhea, hematochezia, dyschezia
recto-vaginal exam: tender modularity of uterine ligament, fixed retroversion of uterus
pelvic exam: firm, fixed adnexal mass
101
Endometriosis investigations
blood work: CA-125, which may be elevated in endometriosis
| laparoscopy to visualize lesion and biopsy
102
Endometriosis lesion - what possibilities could you visualize
mulberry spots = dark blue or brownish-black implants on uterosacral ligaments, cul-de-sac or anywhere in pelvis
endometrioma = chocolate cysts on ovaries
power-burn lesions = endometriosis on peritoneal surface
early white lesions and clear blebs
peritoneal pockets
103
Pathology of endometriosis biopsy
endometrial epithelium, gland, stroma or hemmosiderein-laden macrophages
104
Endometriosis diagnosis
definitive diagnosis of endometriosis based on all of the following:
1. direct visualization of endometriosis lesion on laparoscopy
2. biopsy and pathology showing >2 of the endometrial epithelium, gland, stroma or hemosiderin-laden macrophages
however, most cases of endometriosis are diagnosed clinically based on constellation of symptoms to spare patient from invasive laparoscopy
105
Endometriosis treatment
treatment of endometriosis depend on certainty of diagnosis, severity of symptoms, extent of disease, desire for future fertility
1) Medical management
analgesia: acetaminophen, NSAID, opioids
hormonal therapy to inhibit proliferation of endometrial tissue
1st line = pseudo-pregnancy with cyclic or continuous OCP, medroxyprogesterone, progesterone IUD
2nd line = pseudo-menopause with GnRH agonist (Leuprolide, Triptorelin, Goserelin, Nafarelin, Burserlin)
```
mechanism of action: decrease estrogen to inhibit endometrial proliferation that responds to estrogen
short term (<6 months) due to risk of osteoporosis unless estrogen and progesterone are added
```
side effects: menopausal symptoms including hot flashes, vaginal dryness, reduced libido
2) Surgery
indication for surgery: uncertainty of diagnosis, pain not responsive to medical therapy, complication (torsion, rupture), severe invasive disease involving other organs (bowel, bladder, ureter, pelvic nerve), infertility, endometrioma
conservative = laparoscopy with laser, electro-cautery +/- laparotomy for ablation, resection, lysis of adhesion, ovarian cystectomy of endometriomas
conservative surgery may preserve fertility, and best time to become pregnant is immediately after conservative surgery
definitive = bilateral salpingo-oophorectomy +/- hysterectomy
106
Adenomyosis aka endometriosis interna epidemiology
mean age of presentation 40-50
107
Adenomysosi pathophysiology
ectopic endometrial glands and stroma within uterine musculature that cause hypertrophy and hyperplasia of myometrium, resulting in a diffusely globular enlarged uterus
in contrast, endometriosis exists outside uterus
localized hypertrophy and hyperplasia of myometrium (nodules) are classified as adenomyoma
108
Adenomyosis clinical presentation
often asymptomatic
menstrual symptoms: menorrhagia, dysmenorrhea
pelvic symptoms: chronic pelvic pain / discomfort, dyspareunia, dyschezia
bimanual pelvic exam: enlarged, globular uterus usually symmetrically bulky <14cm, which is mobile and have no adnexal pathology
Halberd’s sign = tender, softened uterus on premenstrual bimanual pelvic exam
109
Adenomyosis investigation
MRI is best imaging for adenomyosis in that it can distinguish it from fibroids and exclude malignancy: increased signal intensity iand / or characteristic thickening
ultrasound: uterine wall thickening
endometrial sampling to rule out other pathology
110
Adenomyosis diagnosis
1) suspected adenomyosis if enlarged uterus on ultrasound or MRI
2) diagnosis by pathology of biopsy
presence of endometrial tissue in myometrium is pathognomonic for adenomyosis
111
Adenomyosis treatment
1) Medical management
menorrhagia: iron supplement to prevent iron deficiency anemia, OCP, Medroxyprogesterone,
analgesia: NSAID
indication for hormonal therapy: symptomatic patients who still might want to bear child
hormonal therapy can be Danazol, GnRH agonist (Leuprolide)
mechanism of action: hormonal therapy decreases estrogen and progesterone, which reduces proliferation of adenomyosis
2) Surgery
indication: symptomatic patients who completed child bearing
procedure: hysterectomy, which is definitive treatment
conservative surgery is difficult, which may include endometrial ablation / resection, laparoscopic myometrial electrocoagulation, uterine artery embolization
112
Features of uterine fibroids on ultrasound
fibroids are usually hypo echoic, but can be iso-echoic or hyper-echoic compared to normal myometrium
usually well encapsulated well circumscribed mass
calcification (echogenic foci with shadowing)
cystic areas of necrosis or degeneration may be seen
113
Features of endometrial cancer on ultrasound
endometrial heterogeneity and irregular endometrial thickening
thickened endometrium (>5mm thickness in post-menopausal women) - thickened endometrium can be due to endometrial cancer, benign endometrial proliferation, endometrial hyperplasia or endometrial polyps
disruption of sub-endometrial halo suggest myometrium invasion
114
Endometrial hyperplasia pathophysiology
endometrial hyperplasia is excessive proliferation of endometrium, usually under influence of high level of estrogen unopposed by progesterone
endometrial hyperplasia is considered a precursor and may progress to endometrial cancer
115
Endometrial hyperplasia pathology
endometrial hyperplasia described in terms of architecture of glands (simple vs. complex) and cellularity (atypia vs. no atypia) into 4 types of endometrial hyperplasia from lowest to
higher risk of progression to endometrial cancer
1) simple hyperplasia = normal glandular architecture, no cellular atypia, ~1% risk of progression to cancer
2) complex hyperplasia = complex abnormal glandular architecture, no cellular atypia, <5% risk of progression to cancer
3) simple atypical hyperplasia = normal glandular architecture, cellular atypia, ~10% risk of progression to cancer
4) complex atypical hyperplasia = complex abnormal glandular architecture, cellular atypia, ~30% risk of progression to cancer
116
what is atypia
dysplastic characteristics of cells, which include combination of the following
structure: cell stratification, tufting, loss of nuclear polarity
nucleus: large irregular sized hyperchromatic nucleus, dented / folded contour, coarse clumping chromatin, >1 prominent nucleoli
chromosomes: abnormal chromosomes, aneuploid chromosome numbers
cytoplasm: big nucleus to cytoplasm ratio
mitosis: increased number of mitosis
117
Endometrial hyperplasia management
medical management: hormone therapy (cyclic or continuous progesterone) therapy to shed endometrium
surgical arrangement: hysterectomy especially for atypical hyperplasia (simple or complex)
118
Types of endometrial cancer
endometrial cancer classified into 2 types based on pathology
Type 1 (80% of endometrial cancer)
pathology: endometrioid adenocarcinoma grade 1 or 2
derived from atypical endometrial hyperplasia
estrogen responsive
good prognosis
```
Type 2 (20% of endometrial cancer)
pathology: endometrioid adenocarcionma grade 3 or non-endometrioid pathology (serous, clear cell, mucinous, squamous, transitional, mesonephric or undifferentiated)
usually no precursor lesion identified
less estrogen responsive
poor prognosis
```
119
Most common gynecological malignancy in North America
Endometrial cancer
120
Endometrial risk factors
older age where 75% cases present in post-menopausal women (peak incidence age of 70)
Type 1 (Endometrioid Adenocarcinoma) Risk Factors
excess estrogen unopposed by progesterone which stimulate proliferation and growth of endometrium including:
1. increased fat: obesity, diabetes mellitus
2. OB&GYN history: nulliparity / infertility, early menarche, late menopause, anovulation (no progesterone to shed endometrium)
3. medical condition: polycystic ovarian syndrome (PCOS), estrogen-producing ovarian tumour
medication: Tamoxifen, estrogen only hormone replacement therapy
4. genetic: HNPCC (hereditary non-polyposis colorectal cancer aka Lynch syndrome), Cowden Syndrome
5. family history: endometrial cancer, ovarian cancer, breast cancer, colon cancer
Type 2 (Serous Clear Cell Carcinoma) Risk Factors
1. type 2 endometrial cancer is not related to estrogen
2. medication Tamoxifen
121
Pathology of endometrial cancer
atypical complex endometrial hyperplasia, except invasion beyond basement membrane into connective tissue
122
Mechanisms through which endometrial cancer can spread
direct extension into local structures including vagina, ovary, omentum, bladder, bowels
lymphatic spread to pelvic and para-aortic lymph nodes
trans-tubal dissemination into peritoneal cavity
hematogenous spread, usually to lungs and liver
123
Endometrial cancer presentation
abnormal uterine bleeding: menorrhagia, inter-menstrual bleeding in pre-menopausal women; post-menopausal bleeding in post-menopausal women
***abnormal uterine bleeding is the most common and often the only symptom of endometrial cancer (present in 75-90% of endometrial cancer cases)***
***post-menopausal bleeding is endometrial cancer until proven otherwise***
mass effect in advanced stage: abdominal bloating, pelvic pressure / pain, bowel dysfunction
OB&GYN symptoms: abnormal vaginal discharge, abnormal pap smear findings
constitutional symptoms: weight loss
association with obesity, acanthuses nigricans, metabolic syndrome
124
Endometrial cancer investigations
1) Biopsy
indication: post-menopausal vaginal bleeding, patient age >40 with abnormal uterine bleeding, patient age <40 with risk factors of endometrial cancer and abnormal uterine bleeding
biopsy can be done by endometrial biopsy done in office, dilatation & curettage (D&C) under general anesthesia or hysteroscopic biopsy
1st line = endometrial biopsy in office; 2nd line = D&C or hysteroscopic biopsy if endometrial biopsy is inconclusive or technically challenging
biopsy results and pathology is the most important investigation to confirm diagnosis or rule out endometrial cancer
2) Trans-Vaginal Ultrasound
trans-vaginal ultrasound can be an additional investigation to guide further investigations, but cannot replace biopsy for definitive diagnosis
indication for trans-vaginal ultrasound: unsatisfactory endometrial biopsy and low risk for cancer; negative biopsy but persistent symptoms
trans-vaginal ultrasound findings that indicate need for biopsy include any of the following:
a) endometrisum thickness >5mm
b) inadequate visualization of endometrium
c) heterogeneous endometrial appearance
3) Staging
pre-operative blood work: CBC, electrolytes, BUN, creatinine, liver function test, INR, aPTT
pre-operative work-up: urine analysis, ECG
chest X-ray
125
Endometrial cancer diagnosis
pathology of biopsy
126
Differential diagnosis of post menopausal vaginal bleeding
```
vaginal atrophy in 50% cases
endometrial cancer in 10% cases
endometrial hyperplasia, polyps
pathology to cervix, vulva, caruncle
trauma
```
127
Endometrial cancer treatment
surgery: total abdominal hysterectomy and bilateral salphingo-oophorectomy (TAHBSO) +/- dissection of pelvic and / or peri-aortic lymph nodes +/- removal of extra tissue if local spread or metastasis including omentectomy
a) surgery is curative treatment and provides staging
b) surgery alone is curative in low stage endometrial cancer <2
adjuvant therapy: radiation, chemotherapy, progesterone
a) adjuvant therapy depend on staging, risk of recurrence, patient age, patient preference
b) usually progesterone in low recurrence risk cases; radiotherapy in intermediate recurrence risk cases; chemotherapy for high recurrence risk cases
128
Endometrial cancer screening
screening with routine transvaginal ultrasound or routine endometrial biopsy in asymptomatic post-menopausal women is NOT recommended
PAP smear is NOT a acceptable screening test due to high rate of false negatives
routine endometrial biopsy or trans-vaginal ultrasound may be considered as screening in patients with HNPCC syndrome
129
Cervical cancer risk factors
medical condition: immune suppression, HIV
OB&GYN history: high parity, sexually transmitted infections (STI) especially HPV, not undergoing Pap smear
social history: smoking
sexual history: high risk behaviours including multiple partners, other STI (Herpes, trichomonad, Chlamydia), early age at first intercourse, high risk male partner
medication: oral contraceptive use
130
Cervical cancer pathophysiology
1) oncogenic HPV infection
HPV infection is necessary, but not sufficient in causing cervical cancer
HPV type 16 and 18 account for 75% of all cervical cancers
2) HPV infection induce dysplasia of transformation zone
HPV infect metaplastic epithelium at cervical transformation zone, which persist causing dysplasia
3) dysplasia progress to carcinoma in situ and then invasion
4) spread of cancer
cervical cancer spread via the following mechanism
direct extension into uterus, vagina, parametric, peritoneal cavity, bladder, rectum
lymphatic spread to pelvic and para-aortic lymph nodes
hematogenous spread to lungs, liver, bone
131
what is the transformation zone of the cervix
transformation zone is transition from endocervix to exocervix (endocervix canal is lined by simple columnar epithelium and ectocervix opening
into vagina is lined with stratified squamous epithelium)
132
Cervical cancer pathology
60% cervical cancer are squamous cell carcinoma, 30% cervical cancer are adenocarcinoma, 10% cervical cancer is unspecified
133
Cervical cancer clinical presentation
Symptoms
abnormal vaginal bleeding including post-coital bleeding, irregular bleeding, inter-menstrual bleeding, post-menopausal bleeding
vaginal discharge (sanguinous or purulent)
pelvic pain, usually unilateral radiating to hip or thigh
constitutional symptoms: weakness, weight loss, anemia
complication: fistula formation (vesico-vaginal fistula resulting in loss of urine through vagina; rectal-vaginal fistula resulting in loss of feces through vagina)
Signs
speculum exam: enlarged, irregular cervix with firm consistency, which may be friable, raised, reddened or ulcerated area
squamous cell carcinoma usually present with exophytic friable / fungating tumour
adenocarcinoma usually present with endophytic barrel shaped cervix
other signs in late disease: deep necrotic vaginal fornices
pelvic exam: nodular thickening of uterosacral ligament, nodular thickening of cardinal ligament
134
Indication for colposcopy
abnormal pap smear, abnormal cervix on speculum exam
pap smear is a screening test only and is inadequate for diagnostic purposes, thus an abnormal cervix on speculum exam should undergo colposcoy, not pap smear
135
what is colposcopy
magnifying scope to examine vulva, vagina and cervix, which can evaluate for areas of dysplasia for biopsy
136
colposcopy procedure
application of dyes to stain dysplastic areas for biopsy (acetic acid stains dysplastic areas white; Schiller’s test does not stain dysplastic cells and stains normal cells brown)
137
indication for endocervical cerrutage (ECC) biopsy on colposcopy
no lesion visible, entire lesion not visible
138
indication for diagnostic excision by loop electrosurgical excision procedure (LEEP) as biopsy during colposcopy
lesion extending into endocervical canal
positive ECC
discrepancy between pap test results
& colposcopy
micro invasive carcinoma
139
indication for cold knife connotation as biopsy during colposcopy
glandular abnormality on cytology
colposcopic finding with concern or margin interpretation
140
what provides definitive diagnosis of cerrvical cancer
pathology of biopsy
141
cervical cancer treatment
stage 1: surgery (total hysterectomy and pelvic lymphadenectomy) +/- chemoradiation therapy (see below) based on surgical specimen
stage >2: concurrent chemoradiation therapy
```
chemotherapy = Cisplatin +/- 5-fluorouracil (5-FU)
radiotherapy = external beam radiotherapy or brachytherapy (local application to vagina)
```
142
peak incidence age vulvar cancer
65-70
143
Vulvar cancer risk factors
HPV infection, strongly associated with vulvar cancer in younger women
OB&GYN history: vulvar intra-epithelial neoplasia (pre-cancerous change of multi centric white or pigmented plaques on vulva)
medical condition: immune suppression including HIV
social history: smoking
144
Vulvar cancer pathology
90% squamous cell carcinoma
other 10% include melanoma, basal cell carcinoma, Paget’s disease, Bratholin’s gland carcinoma
patterns of spread include
a) local spread to urethra, vagina, bladder, rectum, pelvic bone
b) lymphatic spread to inguinal and pelvic lymph nodes
c) hematogenous spread
145
Vulvar cancer clinical presentation
20% cases are asymptomatic at diagnosis
lesion / mass on labia majora or labia minora with pruritus or pain
- lesion may be raised red, white or pigmented plaque
vaginal bleeding, discharge
dysuria
pelvic exam: lesion on labia majora or minora, inguinal / femoral lymphadenopathy
146
Suspected vulvar cancer investigation
colposcopy with biopsy of suspicious lesion for definitive diagnosis based on pathology results
147
Vulvar cancer treatment
stage 0: local excision or superficial vulvectomy or laser ablation or local immune therapy (Imiquimod)
stage 1: radical local excision of tumor plus groin lymph node dissection
stage >2 = radical surgical excision +/- chemoradiation
side effects of treatment: surgical site infection, lymphedema, radiation fibrosis / cystitis / proctitis
overall 5 year prognosis ~80%
