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3rd year - Obstetrics and Gynecology > Gynecology Oncology > Flashcards

Gynecology Oncology Flashcards

1
Q

What is the definition of sensitivity

A

Proportion of patients with disease who have a positive screening test result

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2
Q

What is the definition of specificity

A

Proportion of patients without disease who have a negative screening test result

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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

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4
Q

Adnexal mass workup to rule out ovarian cancer

A

Transvaginal ultrasound

CA 125

Surgical excision for biopsy confirmation

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5
Q

Post-menopausal bleeding workup to rule out endometrial cancer

A

Endometrial biopsy

or dilatation and curettage for biopsy confirmation

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6
Q

Vulvar lesion workup to rule out vulva cancer

A

Excision biopsy

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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

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8
Q

What is elevated AFP usually indicative of

A

Sggests embryonal cell cancer, mixed germ cell cancer

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9
Q

What is elevated CA 125 usually indicative of

A

Suggests ovarian cancer

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10
Q

Pelvic mass indication for surgery

A
  1. Emergency
    Ovarian torsion, ectopic pregnancy, appendix abscess, ruptured tubal ovarian abscess, cyst complicated by hemorrhage
  2. Non-emergency indications
    Large, persistent, enlarging and symptomatic cyst, complex persistent mass, any mass suspicious for malignancy
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11
Q

Differential diagnosis for ovarian masses

A
  1. Functional - follicular cyst, luteal cyst, theca lutein cyst
  2. Benign epithelialtumor - cystadenoma
  3. Benign germ cell tumour - teratoma (dermoid cyst)
  4. Sex cord tumour - Granulosa cell tumours (can be benign or malignant), Leydig cell tumour (can be benign or malignant)
  5. Benign connective tissue tumour - fibroma, thecoma
  6. benign endometrial tumor: endometrioma (chocolate cyst) from endometriosis
  7. ovarian cancer: epithelial ovarian cancer, germ cell tumors, sex cord stroma tumor (Granulosa cell tumor, Leydig cell tumor)
  8. metastasis to ovary: breast cancer, gastric cancer, colon cancer, endometrial cancer
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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

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13
Q

What is adnexa

A

Ovaries, fallopian tube or connective tissue surrounding uterus

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14
Q

Differential diagnosis uterins mass

A
  1. physiology: pregnancy
  2. benign: leiomyoma, adenomyosis, adenomatoid tumor, hematometra (uterine hematoma)
  3. malignant: uterine sarcoma, uterine carcinosarcoma, endometrial carcinoma, metastasis (from another reproductive tract primary malignancy)
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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)

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16
Q

urinary tract mass ddx

A

distended bladder

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17
Q

abdominal wall mass ddx

A

infection: abscess
vascular: hematoma
neoplasm: sarcoma

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18
Q

lymph node mass ddx

A

benign: lymphocele, lymphadenopathy
malignant: lymphoma, metastatic lymphadenopathy

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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

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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

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21
Q

Work up of pelvic mass

A
  1. 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)
  2. Lab investigations
    - CBC, b-hCG, AFP, Ca-125
    - vaginal swab for STIs
  3. Surgery
    a) exploratory laparoscopy and surgical excision of mass
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22
Q

Hydrosalpinx definition

A

blocked fallopian tube from previous pelvic inflammatory disease or surgery

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23
Q

Common adnexal pass pathology in children and adolescents

A

higher risk of ovarian malignancy

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24
Q

most common type of ovarian cancer

A

germ cell tumours

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25
Q

common adnexal mass pathology in pregnant women

A

ectopic pregnancy

luteal cyst

theca lutein cyst

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26
Q

Clinical presentation of adnexal mass

A

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)

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27
Q

Adnexal mass complications

A

torsion

rupture

hemorrhage (intra cystic or intra peritoneal)

infection (pelvic abscess)

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28
Q

Benign vs malignant adnexal mass characteristics

A 
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
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29
Q

Role for minimally invasive biopsy (ex. image guided needle biopsy) for ovarian cancer

A

not recommended due to risk of worse prognosis from rupturing mass

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30
Q

Management of benign adnexal mass

A
  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
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31
Q

Management of malignancy adnexal mass

A

based on staging of disease

management is combination of chemotherapy and/or radiotherapy and/or surgical excision of mass

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32
Q

Risk factors for epithelial ovarian cancer

A

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

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33
Q

Protective factors for epithelial ovarian cancer

A

Decreased estrogen - pregnancy, breastfeeding

OCP

Surgery - tubal ligation, hysterectomy, bilateral salphingo-oophorectomy

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34
Q

Types of ovarian cancer

A

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)
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35
Q

Serious epithelial ovarian cancer pathology

A

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)

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36
Q

Muncious ovarian cancer pathology

A

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

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37
Q

Pathophysiology of ovarian cancer

A

Loss of p53 tumour suppressor gene in most ovarian cancer leading to proliferative growth

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38
Q

Metastatic pathways of ovarian growth

A

Local invasion –> intravasation –> survival in circulation –> extravasation –> colonization

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39
Q

Why are lymphatics more optimally sited to entry, metastasis and transport of cancer cells?

A
  1. Lack of brasement membrane
  2. Few intercellular junctions
  3. Large calibre
  4. Slower flow velocity
  5. Similiarity of lymph to interstitial fluid
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40
Q

Order of gynecological organs for propensity for metastasis

A

Ovarian > cervical > uterine

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41
Q

Mechanisms for the spread of ovarian metastasis

A

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

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42
Q

Clinical presentation of ovarian cancer

A

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

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43
Q

Investigations for ovarian cancer

A 
1. Blood work 
Ca-125 in post menopausal women only 
CBC, lytes 
BUN, Cr 
liver function test
  1. Imaging - TVUS, abdo and pelvis CT with contrast
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44
Q

What’s the deal with CA-125

A

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

  1. gynecologic diseases: benign ovarian tumor, endometriosis, pregnancy, fibroids, pelvic inflammatory disease, menstruation
  2. non-gynecologic malignancy: pancreatic cancer, stomach cancer, colon cancer, rectal cancer
  3. non-gynecologic diseases: liver cirrhosis, pancreatitis, renal failure
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45
Q

Ultrasound findings suggestive of ovarian cancer

A

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

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46
Q

Diagnosis of ovarian cancer

A

Pathology of surgical excised specimen, which usually occurs after surgical excision of tumour

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47
Q

Management of ovarian cancer

A

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

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48
Q

What is cytoreduction

A

en-bloc resection of ovarian tumour, reproductive organs, sigmoid colon with primary bowel re-anastomosis

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49
Q

What is used for adjuvant chemo for ovarian cancer

A

Platinum (Carboplatin or Cisplatin) + Taxane (Taxol or Taxotere), which can be delivered intra-peritoneally or by IV

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50
Q

Ovarian cancer screening

A

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

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51
Q

Types of benign ovarian cysts

A

Follicular cyst

Lutein cyst

Theca-lutein cyst

others include dermoid, cyst adenoma, endometriomas, PCOS

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52
Q

Functional cyst definition ovarian

A

Cyst as result of normal function of menstural cycle, which include follicular cyst and corpus luteal cyst

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53
Q

Follicular cyst ovarian definition

A

follicle that failed to rupture during ovulation, lined with granulosa cells

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54
Q

Corpus luteal ovarian cyst definition

A

corpus luteum failes to regress after 14 days, becoming cystic or hemorrhagic

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55
Q

Risk of lutein cyst

A

very vascular and thin wall - higher risk of intra-cystic bleeding and rupture

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56
Q

theca- lutein cyst ovarian definition

A

atretic follicles stimulated by abnormal b-hCG level

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57
Q

Ovarian functional cyst symptoms

A 
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
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58
Q

Ovarian follicular cyst clinical presentation

A

usually asymptomatic, risk of rupture / bleeding / torsion / infarct

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59
Q

Ovarian corpus luteal cyst presentation

A

pelvic pain, higher risk of rupture and bleeding

60
Q

ovarian Intra-cystic hemorrhage presentation

A

localized abdominal / pelvic pain, tachycardia, hypotension, local peritoneal signs

61
Q

ovarian cyst rupture

A

acute generalized abdominal / pelvic pain (with radiation to shoulder), nausea & vomiting, tachycardia, hypotensive, generalized peritoneal signs

62
Q

intra-peritoneal hemorrhage presentation

A

generalized abdominal / pelvic pain, tachycardia, hypotension, generalized peritoneal signs

63
Q

ovarian cyst torsion presentation

A

acute localized abdominal / pelvic pain, nausea & vomiting, tachycardia, local peritoneal signs

64
Q

ovarian cyst diagnosis

A

usually diagnosed based on visualization of cyst on pelvic us

65
Q

follicular ovarian cyst us findings

A

4-8 cm diameter

unilocular

66
Q

corpus luteal cyst us findings

A

10-15 cm diameter

firmer than follicular cyst

67
Q

Ovarian cyst treatment

A

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
Q

ovarian cyst indication for surgery

A

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
Q

ovarian cyst indication for surgery

A

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
Q

Benign ovarian cyst presentation and complications

A

many asymptomatic

mild symptoms from mass effect including abdo distension, urinary frequency

acute complications: torsion, rupture, hemorrhage, infection

71
Q

Malignant ovarian cyst presentation

A

nausea, anorexia, dyspepsia, bloating, early satiety

mass effect - abdo distension, urinary frequency, constipation

post menopausal bleeding

constitutional symptoms - weight loss

ascites

72
Q

Benign ovarian cyst mass characteristics

A 
Unilateral
Small
(<20cc
in
pre-­‐menopausal;
<10cc
in
post
menopausal)
Slow
growing,
may
regress
Soft
No
adhesions,
no
vascularity
73
Q

malignant ovarian cyst mass characteristics

A 
Bilateral
Large
(>20cc
in
pre-­‐menopausal;
>10cc
in
post
menopausal)
Fast
growing
Firm
Adhesion,
vascularity
74
Q

Benign adnexal mass features

A

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
Q

malignant adnexal mass features

A

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
Q

benign cystic teratoma (dermoid cyst) epidemiology

A

most common ovarian germ cell neoplasm

10-20% of all ovarian tumour, 90% of all ovarian tumour in young females

77
Q

Dermoid cyst pathophysiology

A

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
Q

dermoid cyst clinical presentation

A

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
Q

Dermoid cyst diagnosis

A

usually diagnosed based on visualization of cyst on pelvic ultrasound

80
Q

Dermoid cyst findings on us

A

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
Q

Dermoid cyst treatment

A

indication for surgery: large cyst >8cm, symptomatic cyst

surgery = laparoscopic cystectomy

82
Q

most common benign neoplasm from uterus

A

adenomyosis and leiomyoma

83
Q

Leiomyoma (aka fibroid) epidemiology

A

mc pelvic tumour in women

common in reproductive age

symptomatic in 10-20% of women

in 90% of excised uteri

84
Q

fibroids risk factors

A

black women

early menarche (<10 years old)

Diet - red meats, alcohol

85
Q

fibroids protective factors

A

higher parity

diet - green vegetables, fruits, vitamin A

Smoking

86
Q

Pathophysiology of leiomyoma

A

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
Q

fibroid classification

A

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
Q

Management of submucosal uterine fibroids

A

type 0,1 are hysteroscopically resectable

Type 2 needs to be resected by abdo surgery

89
Q

submucosal fibroid presentation

A

typically cause inferitlity and bleeding

90
Q

subserous fibroid presentation

A

typically cause pain

91
Q

intramural fibroids presentation

A

can cause infertility

92
Q

how do fibroids cause infertility

A

distort uterine cavity

93
Q

how do submucosal fibroids cause heavy menstrual bleeding

A

abnormal uterine vasculature

impaired endometrial hemostasis

dysregulation of angiogenesis

94
Q

Most commonly used imaging modality to diagnose fibroids

A

TVUS

95
Q

pathology of leiomyoma

A

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
Q

Fibroid treatment

A

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
Q

Endometriosis risk factors

A

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
Q

Endometriosis pathophysiology

A

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
Q

Theories regarding pathophysiology of endometriosis

A

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
Q

Endometriosis clinical presentation

A

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
Q

Endometriosis investigations

A

blood work: CA-125, which may be elevated in endometriosis

laparoscopy to visualize lesion and biopsy

102
Q

Endometriosis lesion - what possibilities could you visualize

A

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
Q

Pathology of endometriosis biopsy

A

endometrial epithelium, gland, stroma or hemmosiderein-laden macrophages

104
Q

Endometriosis diagnosis

A

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
Q

Endometriosis treatment

A

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
Q

Adenomyosis aka endometriosis interna epidemiology

A

mean age of presentation 40-50

107
Q

Adenomysosi pathophysiology

A

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
Q

Adenomyosis clinical presentation

A

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
Q

Adenomyosis investigation

A

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
Q

Adenomyosis diagnosis

A

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
Q

Adenomyosis treatment

A

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
Q

Features of uterine fibroids on ultrasound

A

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
Q

Features of endometrial cancer on ultrasound

A

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
Q

Endometrial hyperplasia pathophysiology

A

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
Q

Endometrial hyperplasia pathology

A

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
Q

what is atypia

A

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
Q

Endometrial hyperplasia management

A

medical management: hormone therapy (cyclic or continuous progesterone) therapy to shed endometrium
surgical arrangement: hysterectomy especially for atypical hyperplasia (simple or complex)

118
Q

Types of endometrial cancer

A

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
Q

Most common gynecological malignancy in North America

A

Endometrial cancer

120
Q

Endometrial risk factors

A

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
Q

Pathology of endometrial cancer

A

atypical complex endometrial hyperplasia, except invasion beyond basement membrane into connective tissue

122
Q

Mechanisms through which endometrial cancer can spread

A

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
Q

Endometrial cancer presentation

A

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
Q

Endometrial cancer investigations

A

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
Q

Endometrial cancer diagnosis

A

pathology of biopsy

126
Q

Differential diagnosis of post menopausal vaginal bleeding

A 
vaginal atrophy in 50% cases
endometrial cancer in 10% cases
endometrial hyperplasia, polyps
pathology to cervix, vulva, caruncle
trauma
127
Q

Endometrial cancer treatment

A

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
Q

Endometrial cancer screening

A

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
Q

Cervical cancer risk factors

A

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
Q

Cervical cancer pathophysiology

A

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
Q

what is the transformation zone of the cervix

A

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
Q

Cervical cancer pathology

A

60% cervical cancer are squamous cell carcinoma, 30% cervical cancer are adenocarcinoma, 10% cervical cancer is unspecified

133
Q

Cervical cancer clinical presentation

A

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
Q

Indication for colposcopy

A

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
Q

what is colposcopy

A

magnifying scope to examine vulva, vagina and cervix, which can evaluate for areas of dysplasia for biopsy

136
Q

colposcopy procedure

A

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
Q

indication for endocervical cerrutage (ECC) biopsy on colposcopy

A

no lesion visible, entire lesion not visible

138
Q

indication for diagnostic excision by loop electrosurgical excision procedure (LEEP) as biopsy during colposcopy

A

lesion extending into endocervical canal

positive ECC

discrepancy between pap test results
& colposcopy

micro invasive carcinoma

139
Q

indication for cold knife connotation as biopsy during colposcopy

A

glandular abnormality on cytology

colposcopic finding with concern or margin interpretation

140
Q

what provides definitive diagnosis of cerrvical cancer

A

pathology of biopsy

141
Q

cervical cancer treatment

A

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
Q

peak incidence age vulvar cancer

A

65-70

143
Q

Vulvar cancer risk factors

A

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
Q

Vulvar cancer pathology

A

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
Q

Vulvar cancer clinical presentation

A

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
Q

Suspected vulvar cancer investigation

A

colposcopy with biopsy of suspicious lesion for definitive diagnosis based on pathology results

147
Q

Vulvar cancer treatment

A

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%

3rd year - Obstetrics and Gynecology (7 decks)

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