2 Cervical and Uterine Abnormalities Flashcards
Cystic structure that forms when columnar epithelium is covered by squamous epithelium —> glandular material becomes retained
Nabothian cysts
What do nabothian cysts look like?
Translucent or yellow
Range in size form millimeters to 3 cm
Are nabothian cysts bad?
Nope - they’re benign and asymptomatic
You usually just see them incidentally on speculum exam
Excision is not required
Where do cervical polyps come from?
Etiology unknown but may be due to chronic inflammation of cervical canal
Usually <3 cm and benign
Sx of cervical polyps
May cause post-coital bleeding or abnormal uterine bleeding
Polypectomy is indicated for symptomatic patients
What are the different histological layers of the cervix?
Exocervix
Transformation zone
Endocervical canal
What types of cells make up the exocervix?
Stratified squamous epithelium
What type of cells make up the endocervical canal?
Single layer mucin-producing columnar cells
What types of cells make up the transformation zone?
Squamo-columnar junction
Metaplastic squamous epithelium
When performing a Pap smear, adequate sampling requires…
Presence of endocervical sampling
How does the HPV virus infect the cervix?
Enters the cervical epithelium through microlacerations that occur during intercourse
TZ/metaplastic tissue is very susceptible to virus vs squamous tissue
HPV infects the basal layer first and only locally infects neighboring cells
Once the HPV virus infects the cervix, what happens?
Can remain latent for months to years until the host immune system no longer can successfully suppress the virus or poorly understood co-factors are present
Mature basal epithelial cells containing viral HPV migrate away from teh basement membrane towards the surface
______ causes 50-60% of squamous cell carcinoma of the cervix
HPV 16
_____ causes 40-60% of adenocarcinoma of the cervix
HPV 18
HPV 16 —> what type of cervical cancer?
Squamous cell carcinoma (from the squamous layer)
HPV 18 —> what type of cervical cancer?
Adenocarcinoma (from the columnar cells)
What do E6 and E7 do for HPV?
Blocks the protective apoptotic process (why your body doesn’t clear them)
HPV 16 and 18 cause cervical cancer, and HPV ___ and ____ cause genital warts
6, 11
_____ of sexually active adults will acquire a genital tract HPV infection before the age of 50
75-80%
Risk factors for HPV
Multiple sex partners**** Early onset of sexual activity Hx of STIs Smoking Immunosuppression Long-term oral contraceptive use Multiparity (maintenance of transformation zone —> adenocarcinoma)
What are the two HPV vaccines
Gardasil 9 (covers Types 6, 11, 16, 18, 31, 33, 45, 52, 58)
Cervarix (just covers 16 and 18)
Do you still need Pap smears if you got the HPV vaccine?
YES
Requirements vary by age but you still need regular screening
What are the two components of a Pap smear?
Cytology - evaluating the cellular makeup of the cervix (any abnormal cells?)
HPV testing - performed in conjunction with the Pap smear to assess for HPV-DNA
Are Pap smears considered STD screening?
No - it’s only a screening for cervical cancer
What is combined (co-testing) cervical cancer screening?
Pap smear and HPV DNA testing together
Pap + HPV is 86.4% sensitive, vs 49% for Pap alone and 75% for HPV alone
When should you start cervical cancer screening?
Starting at the age of 21 despite age of sexual debut
Only 0.1% of cases of cervical cancer occur before age 20, and screening prior to age 21 does NOT reduce their rate of cervical cancer
Exception: high-risk pops (ie immunocompromised)
Why don’t we screen adolescents for HPV?
HPV infection is acquired shortly after initiation of intercourse
Nearly all cases are cleared within 1-2 years w/o producing neoplasticism change
Early onset screening increases anxiety, morbidity, accrual of higher expenses and causes overuse of follow-up procedures
What should adolescent patient encounters include?
Contraceptive counseling
STI screening (urine sample, speculum exam not required for asymptomatic women)
Gardasil education/administration
Safe sex practices
No pap unless high-risk (immunocompromised)
Cervical cancer screening guidelines for women aged 21-29
Cytology performance ALONE q3 years
Do NOT perform HPV DNA testing
Cervical cancer screening guidelines for women aged 30-64
Cytology + HPV DNA testing q5 years
OR
Cytology alone q3 years
OR
HPV alone q5 years
Patients at high-risk for developing cervical cancer who need yearly screening
HIV (+) (q6 months the year of dx, then q1 year)
Immunocompromised
Personal Hx of cervical cancer
Hx of CIN II/III
Exposure to diethylstilbestrol (DES) in utero (removed from market in 1970)
When do you stop screening for cervical cancer?
At age 65 if in the past 10 years:
• Evidence of 3 prior consecutive negative results w/ cytology alone
• Two consecutive negative co-testing results
• The most recent test to have occurred within 5 years
• Can not have a hx of CIN 2+ within last 20 years
Does not apply to women considered high risk
Do not resume screening even if a woman reports a new sexual partner(s)
When does screening stop in women after hysterectomy?
Assuming cervix is removed, stop at time of the surgery
Hysterectomy must have been performed for benign disease, and no Hx of CIN 2+ within last 20 years
When performing speculum exam and an abnormal cervical lesion is noted, what should you do?
Perform biopsy, not Pap smear
A pap is a SCREENING tool, whereas a biopsy is DIAGNOSTIC
What are the steps in the grading system for abnormal Pap smears?
ASCUS
LSIL
HSIL
What does ASCUS mean?
Atypical cells of undetermined significance
Causes in the absence of HPV:
Chlamydia trachomatis, herpes simplex
Vulvovaginal atrophy
What is LSIL?
Low grade lesion, usually consistent with CIN I
Features: enlarged, hyperchromatic nuclei, abundant cytoplasm
What is HSIL?
High grade lesions (sometimes called ASC-H)
Assume HPV DNA present
Lesions usually consistent with CIN II-III, AIS
Features: enlarged, hyperchromatic nuclei, little/no cytoplasm
What does it mean when the Pap smear results are returned as Unsatisfactory?
Negative cytology means no endocervical cells - you didn’t sample the transformation zone
Unsatisfactory cytology is due to insufficient squamous component
What is important to know about combined screening?
Important to differentiate between transient and persistent HPV infection
If cytology negative and HPV DNA positive (for 16/18) —> COLPOSCOPY
If cytology negative and HPV DNA positive (other subtypes) —> repeat pap and HPV in 1 year, if positive agin —> colposcopy
Persistently positive HPV DNA test (x2) is associated with…
21% chance CIN II/III will be present within 36 months
CIN I lesions involve _________ of the epithelial lining
Lower 1/3
Typically regress in 12 months
CIN II lesions involve ______ of the epithelial lining
Lower 2/3
43% regress, 35% persist and 22% progress
CIN III lesions involve _______ of the epithelial lining
More than 2/3
32% of lesions regress, 56% persist, and 14% progress
What is considered a satisfactory colposcopy?
Complete visualization of the transformation zone
When is a colposcopy considered unsatisfactory?
Incomplete visualization of transformation zone
Have to perform endocervical curettage
What is a LEEP?
Loop Electrosurgical Excision Procedure
High electrical current density results in rapid heating of the nearby tissue
Steam envelope surrounding the wire is created which vaporizes adjacent tissue, which is then sent for pathology
When is LEEP contraindicated?
In patients if invasion is suspected, they have glandular abnormality on pap, or patient is pregnant
Can you do a LEEP on a pregnant woman?
Not unless you want her to go into labor RIGHT NOW
LEEP has _____ cure rate for CIN
90-95%
Has replaced laser surgery for treatment of CIN
What follow up instructions do you give for LEEP?
Avoid heavy lifting for 4 weeks to avoid bleeding
Malodorous vaginal discharge for 2-3 weeks is normal
Avoid intercourse for 4 weeks
Avoid douches, creams, and tampons within the vagina for 4 weeks
First menses after LEEP is heavier due to partial removal of endocervical canal
Complications of LEEP
Bleeding
Infection
Cervical obliteration, incompetence, stenosis (can cause sampling issues in the future)
Associated with preterm delivery (measure cervical length at 2nd trimester U/S)
Associated with preterm delivery after PPROM
3rd most common GYN cancer
Cervical cancer
What are the two types of cervical cancer?
Cervical Squamous cell (most common - 65-85%)
• Microinvasion (≤3mm)
•Invasive (>3mm or visible lesion)
Cervical adenocarcinoma
• Subtypes: Endocervical, endometrioid, clear cell, adenoid cystic
Cytology features in cervical cancer
Columnar cells with elongated nuclei
Nuclear Enlargement
Hyperchromatic nuclei
Mitosis and apoptotic bodies
Clinical presentation of cervical cancer
Frequently asymptomatic
ABNORMAL VAGINAL BLEEDING most common sx
Post-coital bleeding
Pelvic pain, unilateral with radiation into the hip/thigh (sign of advanced disease)
Vaginal discharge (watery, mucous, purulent, malodorous)
Most widely used system for staging cervical cancer
International Federation of Gynecology and Obstetrics (FIGO)
Staged by clinical examination of the bladder, uterus and rectum via colposcopy, cystoscopy, and proctoscopy
What imaging modality is best for evaluating local extension of cervical cancer?
MRI superior to CT
What imaging modality is used for evaluating for hydronephrosis/retroperitoneal spread of cervical cancer?
MRI or CT
What imaging modality is used for evaluating thoracic involvement in cervical cancer?
CXR or CT
PET scan if CT/CXR show no metastasis
Uterine fibroids arise from…
Smooth muscle cells within the uterine wall
Fibroids are made up of…
Collagen, smooth muscle, and elastin surrounded by a pseudocapsule
Present in 20-25% of women of childbearing age
Fibroids are 2-3x more common in ______ women
African American
Etiology of uterine fibroids is unknown but _______ is implicated in their growth
Estrogen
Myomas contain higher concentration of estrogen receptors than what is observed in the surrounding myometrium
+/- growth in presence of hormonal therapy and pregnancy
_______ increases mitotic activity and possibly suppresses apoptosis within the fibroids
Progesterone
How are uterine fibroids classified?
By anatomic location within the myometrium
Name that uterine fibroid:
Lie just beneath the endometrium
Submucosal (Type 0, I, II)
Name that uterine fibroid:
Lie just at the serosal surface of the uterus
Subserosal
Name that uterine fibroid:
Lie within the uterine wall
Intramural
Name that uterine fibroid:
Fibroids that are attached by a stalk to endometrium
Pedunculated submucosal fibroid
Name that uterine fibroid:
Fibroids that are attached by a stalk to the outer layer of the uterus
Pedunculated subserosal fibroid
Symptoms of uterine fibroids vary based on…
Location and size
Abnormal uterine bleeding occurs with fibroids when…
Submucosal fibroids increase the surface area of the endometrium, leading to menorrhagia (+/- Fe anemia)
Why do you get pain with uterine fibroids?
Degeneration, myometrial contractions, dyspareunia
Why do you get pelvic pressure with fibroids?
Mass effect —> compression of surrounding organs
Why do you get infertility with uterine fibroids?
Submucosal fibroids —> impingement of intrauterine cavity
Can also lead to spontaneous abortion
PE findings for uterine fibroids
Uterine Enlargement
Irregular shape
Masses
You think your patient has uterine fibroids. What Labs/imaging you wanna get?
Transvaginal U/S
Saline-infused sonohystogram (done in office)
Hysteroscopy (done in OR)
MRI
H/H
What is saline-infused sonohystogram?
Performed in office under US guidance
Pediatric catheter is advanced within intrauterine cavity and H2) is instilled to define fibroid size/location
What is a hysteroscopy?
Performed in OR
Utilizes a camera that is advanced into the intrauterine cavity to define fibroid size and location
Downside: only sees the ones INSIDE the uterus
What is the standard of care for fibroid treatment in the US?
There is none.
Symptoms should drive the treatment, SO DO A GOOD HISTORY AND PHYSICAL 🙄
Medical options for the treatment of uterine fibroids
GnRH analogs
Steroid therapies
Transexamic acid
Surgical options for the treatment of uterine fibroids
Hysteroscopy can resection
Endometrial ablation
Labroscopic myomectomy
Abdominal myomectomy
Laparoscopic radiofrequency ablation
Uterine artery embolization
MRI-guided focused ultrasonography
What is Depot Lupron?
GnRH agonist that will decrease fibroid size
Basically shuts off estrogen/progesterone
Benefits of Depot Lupron
Improves anemia prior to surgery
Decreases blood loss during surgery
Allows minimally invasive approach
May play primary role in treatment near menopause
Downside of Depot Lupron
Not approved for use over 6 months
When we say “steroidal therapies” for the treatment of uterine fibroids, what do we mean?
Any form of BC - OCPs, Mirena, Ortho Evra, NuvaRing
Indicated for patients with prolonged, heavy menses with no SUBmucosal fibroids
When is Lysteda (transexamic acid) indicated for treating fibroids?
For patients with prolonged, heavy menses with no SUBMUCOSAL fibroids
It’s an oral antifibrinolytic used for menorrhagia - can demonstrate 50% decrease
Used only during menstrual cycle (two 650mg tab TID)
Does a myomectomy preserve fertility?
Yep
What types of fibroids can be treated with a myomectomy?
Intramural, subserosal, and pedunculated fibroids
Indicated for patients with pressure symptoms
Can be done laparoscopically too
What is the patient ed regarding pregnancy for patients who have a myomectomy?
Delay pregnancy for 3-6 months
Must have a c-section 2˚ to risk of uterine rupture
Which surgical treatment for uterine fibroids is only performed on submucosal fibroids?
Hysteroscopy
Non-ionic solution used as distention media and a heated loop is used to respect fibroid
Risks of hysteroscopy
Fluid overload and hyponatremia
Must monitor their I&Os
Upsides of hysteroscopy
Outpatient procedure
Return to normal activities 1-2 days later
Return to sexual activity one month post-op
Possible complication of hysteroscopic resection
Asherman’s Syndrome
Can —> infertility
What surgical treatment for fibroids precludes any future childbearing?
Endometrial ablation
Preserves uterus and treats menorrhagia without distortions to uterine cavity BUT a pregnancy afterwards is DISASTEROUS - embryo would implant in myometrium 😬)
Pro’s of endometrial ablation
Can be in or out patient
Distention medium is small amount of CO2 so no risk of fluid overload
Takes less than 2 min and patient goes home in 1-2 hours
Can be performed at anytime during menstrual cycle
Con’s to endometrial ablation
Since no distortion of the uterine cavity is allowed, polyps and submucosal fibroids have to be removed first
Does not address fibroid symptomatology in general
Childbearing is rare afterwards and outcomes poor if they do conceive b/c of risk of placenta accreta
What is placenta accreta?
Embryo implants into the myometrium
What happens when you get preggers after an endometrial ablation
Tell me more about uterine artery embolization
Preserves uterus but NOT fertility
Arteriogram identifies blood supply to fibroid. Catheter is placed into uterine artery and embolizing agent infused until blood flow ceases
Done by interventional radiology
Candidates for uterine artery embolization
Patient does not desire future childbearing
What are contraindications for uterine artery embolization?
Numerous and large fibroids
Side effects and complications of uterine artery embolization
Post embolization Syndrome requires overnight hospitalization to manage pain
Non-purulent vaginal discharge
Endometritis and uterine infection
Recurrence rate is 10-15%
Embolization agent found in non-target tissues
• Ovaries —> premature ovarian failure
Uterine necrosis, sepsis, bacteremia, and death
Growth of endometrial glands and stroma into uterine myometrium
Adenomyosis
What is the etiology of adenomyosis?
Unknown
Ovarian hormones implicated in process
Invagination of endometrium (myometrium weakens with degeneration)
Associated with parity, esp c-sections
Clinical presentation of adenomyosis
Menorrhagia
Dysmenorrhea
Pelvic pain
History of previous uterine surgery (c-section or myomectomy)
PE findings for adenomyosis
Bimanuel exam reveals diffuse uterine enlargement (globular, size not exceeding 12w gestation)
Definitive diagnosis of adenomyosis requires…
Histologic examination after hysterectomy
Imaging can AID in Dx but there is no standard criteria
• U/S 72% sensitive, 81% specific
• MRI 77% sensitive, 89% specific
Treatment for adenomyosis
Meds to improve dysmenorrhea and menorrhagia
• OCPs
• Mirena
• NuvaRing
Surgery
• HYSTERECTOMY = definitive treatment
• Uterine artery embolization
• Endometrial ablation (high failure rate - just don’t do it)
The presence of endometrial glands and stroma outside the endometrial cavity and uterine musculature
Endometriosis
Usually located in the pelvis (OVARIES, posterior curl-de-sac, uterine surface) but can be elsewhere
Most common diagnosis responsible for hospitalization in women aged 15-44
Endometriosis
What is the etiology of endometriosis
Really unknown
Retrograde menstruation - retrograde flow of endometrial tissue through Fallopian tubes and peritoneum
Deficient cellular immunity (increased risk of AI disorders)
Hereditary
Clinical presentation of endometriosis
Premenstrual pelvic pain that subsides after menses
Associated with infertility in 30-40% of women
Dysmenorrhea
Dyspareunia
Most are asymptomatic
Elevated CA-125
PE findings for endometriosis
Tenderness at posterior cul-de-sac
Fixed or retroverted uterus 2˚ to adhesions
Endometriomas that cause adnexal masses or tenderness
How is endometriosis diagnosed?
LAPAROSCOPY
Shows erythematous, petechiae lesions on peritoneal surfaces, with thickened and scarred surrounding peritoneum
Ovaries can demonstrate lesions or endometriomas (“chocolate cysts”)
Adhesions
Most common site of endometriosis?
Ovaries
Will see “chocolate cysts” - endometriomas on the surface of the ovary
Treatment for endometriosis in patients with mild disease
Expectant management and NSAIDs
Treatment for moderate-severe endometriosis
Goal: interrupt stimulation of endometrial tissue
OCPs - those with continuous cycle preferred (cause atrophy of endometrial tissue and reduces risk of ovarian cancer)
Progestins (Depo-provera, Provera, Mirena****)
Depot Lupron for severe disease x 12 month
What do you need to know if you are giving Depot Lupron for endometriosis?
It’s a 12 month therapy (vs 6 month for fibroids)
Co administer with Norethindrone acetate to prevent bone loss
Risk factors for endometrial hyperplasia
Early menarche Late menopause Infertility, nulliparous OBESITY****** Treatment with Tamoxifen for BC Unopposed estrogen replacement therapy Diabetes PCOS Hx of BC or ovarian cancer Prior radiation for pelvic cancer Family Hx of lynch syndrome
Classification of endometrial hyperplasia
Simple hyperplasia without atypia
Complex hyperplasia without atypia
Simple atypical hyperplasia
Complex atypical hyperplasia
Pathophysiology of endometrial hyperplasia
Estrogen stimulates proliferation of endometrium
Progesterone has antiproliferative effects —> shedding of endometrial lining
Unopposed estrogen leads to endometrial hyperplasia and atypia
Adipose tissue releases estrogen which is why obesity is a risk factor
Clinical presentation of endometrial hyperplasia
Asymptomatic Post-menopausal bleeding Menorrhagia Intermenstrual bleeding Prolonged menses (>7 days) Decreased menstrual interval (<21 days) Oligomenorrhea/amenorrhea
Workup for suspected endometrial hyperplasia
Pelvic exam
Pelvic U/S (asses endometrial thickness - <4mm means malignancy unlikely)
Endometrial biopsy**
D&C hysteroscopy if complications preclude biopsy
Treatment for endometrial hyperplasia without atypia
Mirena
Provera 10mg qd x 3-6 months
Reassess with EMB to ensure resolution
Treatment for endometrial hyperplasia with atypia
Increased risk of endometrial cancer so be more aggressive
Hysterectomy is treatment of choice*****
Progesterone therapy
• Megace 40-80mg BID
• Mirena
• Reasses q3 months until resolution
Most common GYN cancer
Endometrial cancer
Mean age of incidence for endometrial cancer
50-69 years
______ is implicated as the causative factor for endometrial cancer
Estrogen
Exogenous estrogens vs alterations in estrogen metabolism
Type 1 endometrial cancer arises from…
Unopposed endogenous or exogenous estrogen
Favorable prognosis due to well-differentiated tumors
Typically adenocarcinoma (80% of all endometrial cancers)
Type 2 endometrial cancer arises…
Independently of estrogen and seen with endometrial atrophy
Poorly differentiated with poor prognosis
Typically Serous carcinoma or Clear cell carcinoma
Clinical presentation of endometrial cancer
Abnormal vaginal bleeding - ESP POST-MENOPAUSAL BLEEDING
Abdominal cramping
Back pain
Weight loss
Dyspareunia
Screening for endometrial cancer is recommended for women with…
Lynch Syndrome (aka HNPCC)
Perform Claris testing
How is endometrial cancer diagnosed?
CBC Endometrial biopsy (EMB) D&C Transvaginal U/S Pap smear CA-125 MRI/CT
Treatment for endometrial cancer
HYSTERECTOMY with bilateral salpingoophorectomy with pelvic and periaortic lymphadenectomy
+/- Radiation and chemo
