Female GU Disorders Flashcards

Question 1

Q

Cervix

Anatomy

Answer

A

Endocervix ⇒ columnar epithelium w/ glands
Ectocervix ⇒ ∆ in mucosa in response to hormonal influences
- At birth: squamocolumnar junction @ ectocervix
- In a young adult:
  - Ectocervix is everted
  - Exposes glandular columnar endocervical mucosa to the vagina
  - Undergoes squamous metaplasia
    - Metaplastic region = Transformational zone

Question 2

Q

Transformational Zone

Answer

A

Area of cervical metaplasia
Extends from the _farthest area glandular mucosa reach_ed to where it is now
Origin of most squamous cell carcinomas of the cervix

Question 3

Q

Acute Cervicitis

Answer

A

Acute inflammation of the cervix
Sx: abnl vaginal bleeding, abnormal vaginal discharge, dyspareunia
Etiologies:
- Post-partum
- Staph or Strep
- Gonococcal infection

Question 4

Q

Chronic Cervicitis

Answer

A

More common
Non-infectious etiologies:
- Chemical irritant, foreign bodies, IUD
Infectious etiologies:
- Non-specific ⇒ vaginal flora
  - Predisposing factors include childbirth, surgery, hormone flux
- Specific
  - Bacterial: Chlamydia trachomatis
    - Produces follicular cervicitis
  - Fungal: Candida albicans
    - ↑ incidence in DM, abx therapy, pregnancy, alkaline vaginal pH
    - See pruritis and discharge
  - Protozoal and parasitic: Trichomonas vaginalis
    - Foamy green-gray discharge, seen on wet mount or pap
  - Viral: HPV, Herpes

Question 5

Q

Endocervical Polyp

Answer

A

Benign lesions
Common in 4^th to 6^th decade
Can cause postmenopausal bleeding
Arise in endocervical canal
Soft lesions, contains endocervical glands
Rarely become neoplastic

Question 6

Q

Microglandular Endocervical Hyperplasia

Answer

A

Benign lesions

↑ Glandular proliferation

Usually seen in pregnant or post-partum pts or those w/ hx of OCP use

Question 7

Q

Cervical Neoplasms

Overview

Answer

A

Most common are squamous cell disorders
Preceded by an identifiable precursor lesion that may progress to invasive cancer
Very preventable
- Sign. ↓ incidence since Pap smear screening
- Most cases ⇒ never screened or inadequately screened
Average age is 40-45 y/o
HPV is the most important factor in cervical oncogenesis
- Detected in > 75% of cases
- Also seen in pre-malignant conditions (dysplasia)

Question 8

Q

Cervical Carcinoma

Risk Factors

Answer

A

High risk sexual behavior
- Early age at first intercourse (< 18 y/o)
- Multiple sexual partners
- High risk male sexual partners
Smoking
HIV infection
Organ transplant
STI infection
DES (diethylstilbestrol) exposure
Hx of cervical cancer or HGSIL
Infrequent or absent Pap screening tests

Question 9

Q

Human Papillomavirus (HPV)

Characteristics

Answer

A

dsDNA virus
Causes proliferative squamous lesions
Low risk types: 6 and 11
- Cause condyloma acuminatum
High risk types: 16,18, 31,33, 35
- Cause high grade lesions and cervical cancer

Question 10

Q

Human Papillomavirus (HPV)

Natural History

Answer

A

HPV is a necessary but not sufficient factor for development of squamous cervical neoplasia
Most infections transient w/ little risk of progression
Persistent infection @ 1-2 yrs strongly predicts risk of CIN 3 or cancer regardless of age
- Carcinogenic potential:
  - HPV-16 > HPV-18 > 31, 33, 35
- Persistent HPV infection risk factors
  - Cigarette smoking
  - Compromised immune system
  - HIV infection
Most common in teenagers to early 20s
Pts < 21 y/o have an effective immune response that clears the infection
- Most cervical neoplasia also will spontaneously resolve in this population
- Newly acquired HPV infection ⇒ same low chance of persistence regardless of age
HPV detection in pts > 30 y/o more likely to reflect persistent infection
HPV related cervical CA are very slow to progress
- 3-7 yrs for severe dysplasia → invasive cervical cancer
- Squamous epithelium origin ⇒ squamous cell carcinoma
- Columnar epithelium origin ⇒ adneocarcinoma

Question 11

Q

Condyloma Accuminatum

Answer

A

“Genital Warts”

Can see in many sites ⇒ vulva, vagina, cervix, perineum
On cervix, tends to see acanthosis and hyperkeratosis
Koilocytes ⇒ transformation of squamous cell, indicative of HPV
- Clearing of cytoplasm next to nucleus (where viral particles are)
- Multinucleation
Usually caused by HPV 6 and/or 11

Question 12

Q

Squamous Intraepithelial Lesion (SIL)

Overview

Answer

A

Spectrum of progressive intraepithelial changes:
- Minimal atypia → mild dysplasia → moderate dysplasia → severe dysplasia → carcinoma in situ → invasive squamous cell carcinoma
- Most lesions will not progress but cannot know which will ⇒ must screen and tx everyone
HPV 16 and 18: commonly causes precursor dysplastic lesions → cancer
Characteristic changes:
- Loss of basal polarity, crowded overlapping basal growth pattern, generalized disorientation
- Nuclear hyperchromaticity, pleomorphism, ↑ N:C ratio
- Mitotic activity at all epithelial levels
- Morphologically abnormal mitotic figures

Question 13

Q

Squamous Intraepithelial Lesion (SIL)

Histologic Classification

Answer

A

Abnormal (immature) cells have ↑ N/C ratio, hyperchromatic nuclei, mitoses

Based on cervical biopsy results:

Mild dysplasia = Low Grade SIL = Cervical Intraepithelial Neoplasia I (CIN I)
- Abnormal cells in bottom ⅓ of cervical squamous epithelium
Moderate dysplasia = High grade SIL = CIN II
- Abnormal cells in lower ⅔ of epithelium
Severe dysplasia = High grade SIL = CIN III
- Abnormal cells in top ⅓ of epithelium
CIS (carcinoma in situ) = high grade SIL
- Abnormal cells extend to the top of epithelium

Question 14

Q

Squamous Intraepithelial Lesion (SIL)

Bethesda System Classification

Answer

A

Low Grade Intraepithelial Lesion (LGSIL)

CIN I or HPV infection (koilocytes, etc.)

High Grade Intraepithelial Lesion (HGSIL)

CIN II or CIN III or CIS

Question 15

Q

Squamous Intraepithelial Lesion (SIL)

Cytologic Classification

Answer

A

Based on squamous cell characteristics via pap-smear:

ASCUS: atypical squamous cells of undetermined significance
ASC-H: atypical squamous cells, cannot exclude high grade
LGSIL: low grade squamous intraepithelial lesion
- Includes HPV (koilocytes), mild dysplasia, and CIN I
HGSIL: high grade squamous intraepithelial lesion
- Includes moderate and severe dysplasia, CIN II, CIN III, and CIS
Squamous cell carcinoma
- Look for features suspicious of invasion

Question 16

Q

Management of SIL

Answer

A

3 components:
1. Rule out invasive cancer
2. Determine extent and distribution of non-invasive lesions
3. Eradicate lesions by the easiest, cost effective method available while preserving reproductive capacity when and where possible
Testing sequence:
- Pap test for cytologic diagnosis
- If abnormal, proceed to:
- Colposcopy w/ acetic acid application (abnormalities include mosaicism, and punctation) and punch biopsy of abnormal areas found on colposcopy
- If biopsies show SIL ⇒ diagnostic excisional procedure (ex. electro-loop excision) of transformation zone
- Endocervical curettage to evaluate lesion distribution

Question 17

Q

Papanicolaou test

“Pap smear”

Answer

A

Liquid-based and conventional methods
- Exfoliated cells are collected from transformation zone of cervix
- Contaminating blood, discharge, and lubricant may interfere w/ specimen interpretation
Liquid based has advantages
- Cytology, HPV testing, evaluate ASCUS, test for gonorrhea and chlamydia
- No difference in sensitivity or specificity for detection of CIN
Ancillary Testing ⇒ other infections such as Candida can be seen
- Can also add on testing for HPV, Gonorrhea, Chlamydia, and Trichomonas
Results:
- ~50 mil Pap tests performed yearly
- 3.5 mil (7%) reported as abnormal
- 800k reported as LSIL (1.6%)
- 250k reported as HSIL

Question 18

Q

High-Risk HPV

Testing

Answer

A

Only test for high-risk HPV (HPV-16/18)
- Adjunct to cytology for cervical CA screening in pts 30-65 y/o
- Used in some pts w/ hx of prior ⊕ HPV result
- 2 FDA approved HPV DNA genotyping tests (one for HPV-16 and one for HPV-16 and 18)
- No role for testing for low-risk HPV genotypes
Reflex Testing
- High-risk HPV testing performed in response to abnl biopsy result
- Used to determine need for colposcopy in pts 21-29 y/o w/ an ASCUS cytology result
Co-testing
- HPV testing is performed at the same time as cervical cytology

Question 19

Q

Human Papillomavirus (HPV)

Vaccination

Answer

A

Recommended vaccine schedule
- Ideally given prior to sexual activity
- Females and males
- Routinely should be offered at 11-12 y/o
- Catch up offered at 13-26 y/o in girls, 13-21y/o in boys (unless MSM or immune compromise)
- Can administer as early as 9 y/o
Dosing: different dosing regimens based on age @ time of vaccination
- Use the CDC Vaccine app for specifics
Cervical screening recommendations unchanged based on vaccination
Long term efficacy of the vaccine has not been established ⇒ booster?

Question 20

Q

Cervical Cancer

Screening Guidelines

Answer

A

Age to start screening
- Start at age 21 for everyone
  - Regardless of age of sexual initiation or other high-risk behaviors
  - Earlier screening ⇒ ↑ anxiety, morbidity, and expense
Initiation of reproductive health care should not be predicated on cervical cancer screening
Younger patients who are sexually active need STI screening and discussion of birth control
Screening Recommendations will be different for special populations including:
- HIV ⊕
- Immunocompromised
- DES exposed individuals
- Previously treated for CIN 2, CIN 3, or cervical cancer
Discontinuation of Screening
- Specific recommendations to stop screening in pts > 65 y/o or those s/p hysterectomy
Annual well visits are recommended even if cervical cancer screening is not performed at each visit

Question 21

Q

Abnormal Cytology

Management

Answer

A

Follow-up depends on cytology results:

ASCUS
- Perform HPV DNA testing for ‘high risk’ HPV types
  - If ⊖ HPV ⇒ repeating cytology testing in 3 yrs
  - If ⊕ HPV ⇒ repeat cytology at 6 and 12 months
Higher grade lesions ⇒ colposcopy
LSIL ⇒ colposcopy
Exception is pts 21-24 y/o ⇒ repeat cytology in 12 months b/c many will have resolution in a year
HSIL or ASC-H ⇒ colposcopy always (no age difference)

Question 22

Q

Colposcopy

Answer

A

Magnification of the cervix to allow for visualization of the transformation zone
- Also look in lateral fornices and upper vagina
Identify areas of abnormality
- Can use green filter, acetic acid, or Lugol’s iodine to better differentiate
Colposcopy directed biopsy: will give you a histological dx of CIN
Follow-up will depend on the results
- Normal histology or CIN: repeat co-test in 1 year (cytology w/ high-risk HPV testing)
- CIN 2 or 3: recommend excision

Question 23

Q

Cervical

Excisional Procedures

Answer

A

Loop electrosurgical excision procedure (LEEP)
- Uses cautery to excise transformation zone and lesion
- Can be done in the office under local anesthesia
- Allows for new growth of cells
Cold Knife Cone (CKC)
- Uses a scalpel to excise the transformation zone and lesion
- Done in the OR
- Higher risk of bleeding
- Allows for a larger specimen w/o cautery artifact for pathology
- Better look at the margins
- Esp. for glandular lesions

Question 24

Q

Squamous Intraepithelial Lesion (SIL)

Progression

Answer

A

Once full thickness dysplasia is present (CIS) ⇒ break through BM ⇒ invasive squamous cell carcinoma

Question 25

Q

Microinvasive Squamous Cell Carcinoma

Answer

A

Only a small area of invasive disease is seen (< 5x7 mm)

Term ‘microinvasive’ is used

Question 26

Q

Invasive Squamous Cell Carcinoma

Clinical Characteristics

Answer

A

Presents as abnormal vaginal bleeding usually following intercourse or douching
10-20% of pts report:
- Bloody malodorous discharge
- Pain often radiating to the sacral region
Sx of locally advanced or metastatic disease: weight loss, pallor, BLE edema, rectal pain, hematuria
Gross examination: Ulcerative, exophytic (fungating) or infiltrative patterns of growth

Question 27

Q

Invasive Squamous Cell Carcinoma

Modes of Spread

Answer

A

Spreads by direct local invasion to the adjacent tissues
- Lateral spread may reach bony pelvis
  - Can encompass and obstruct one or both ureters
  - Most common cause of death in these pts
Lymphatic spread late
Hematogenous spread even later

Question 28

Q

Verrucous Carcinoma

Answer

A

Variant of squamous cell carcinoma
Well-differentiated
Can get very large
Does not invade ⇒ won’t metastasize

Question 29

Q

Cervical Glandular Cell

Abnormalities

Answer

A

Atypical
- Glandular cells
- Endocervical cells
- Endometrial cells
Endocervical adenocarcinoma in situ (AIS)
Adenocarcinoma
- Endocervical
- Endometrial
- Extrauterine
- Not otherwise specified (NOS)

Question 30

Q

Cervical Adenocarcinoma

Answer

A

Originate from glandular columnar epithelium.

In situ adenocarcinoma (AIS)
- Only affects glands
- No stromal response to indicate invasion
Invasive adenocarcinoma
- Incidence ↑
  - May be up to 25% of cervical CA
- Also associated w/ HPV
- Some secrete mucin
- Some are associated w/ DES (clear cell carcinoma)

Question 31

Q

Granuloma Inguinale

(Donovanosis)

Answer

A

Organism: Calymmatobacterium granulomatis
Clinical and histology:
- Large ulcerated lesions contain inflamed granulation tissue and numerous MΦ
- Bacteria are found in the cytoplasm of neutrophils, histiocytes and plasma cells (Donovan bodies)
  - Assumes the shape of a safety pin
Infection is more common in the tropics

Question 32

Q

Lymphogranuloma Venereum (LGV)

Answer

A

Caused by Chlamydia trachomatis
Clinical::
- Transient vesicles on penis or vagina that are often unnoticed
- Followed by inguinal lymphadenopathy w/ formation of “bubos”
  - Inflamed lymph nodes esp. in the groin area
  - Bubos contain infected, purulent material
    - Must be aspirated or they may rupture

Question 33

Q

Vulvar Dystrophy

Answer

A

Many different types referred to by many different names
Lesions are usually white, scaly and fissured (leukoplakia)
Two main types:
- Lichen sclerosis (most common type)
- Squamous hyperplasia

Question 34

Q

Benign Vulvar Lesions

Question 35

Q

Vulvar Intra-epithelial Neoplasia (VIN)

Answer

A

Spectrum of dysplastic changes ranging from mild to severe
- Characterized by nuclear and epithelial atypia
- Similar to SIL of the cervix
Clinical presentation: pts may be asymptomatic or have pruritis
Gross appearance:
- ⅓ of pts ⇒ lesions are hyperpigmented
- Remainder are pink, white, grey or red
- Can be macular or papular, single or multiple
Microscopic appearance: dyskeratotic cells scattered throughout lesion
- VIN I (mild dysplasia): changes confined to lower ⅓
- VIN II (moderate dysplasia): changes in lower ⅔
- VIN III (severe dysplasia and CIS): full thickness
- CIS: also referred to as Bowen’s disease
Caused by HPV, usually seen in young women 20-35 y/o
Progression to invasive carcinoma is rare (6%)
- If it occurs, usu. in postmenopausal women or immunosuppressed pts

Question 36

Q

Vulvar Paget’s Disease

Characteristics

Answer

A

Slowly growing intra-epithelial multi focal neoplasm
Arises de novo in the epidermis from totipotent intra-epithelial precursor cells
Can involve the dermis
Occurs in genital, perianal and axillary regions
Lesion may be pruritic
Usu. seen in post-menopausal Caucasian women
Rarely associated w/ underlying sweat gland adenocarcinoma
Unlike Paget’s disease of the nipple (100% of cases show underlying ductal breast carcinoma)
Treatment is wide local excision
Recurrences are common b/c Paget cells extend beyond confines of visible gross lesion

Question 37

Q

Vulvar Paget’s Disease

Morphology

Answer

A

Gross:
- Has a red, eczematoid appearance
- Tends to occur on the labia majora
Microscopic appearance:
- Paget’s cells often occur in nests surrounded by small hyperchromatic basaloid cells
- Isolated Paget cells may file upward in the epithelium
- Cytoplasm is pale and occasionally vacuolated
- Nuclei are vesicular w/ finely distributed chromatin
- Nucleoli are prominent
- Mitotic figures are infrequent

Question 38

Q

Vulvar Invasive Squamous Cell Carcinoma

Characteristics

Answer

A

Incidence in U.S. is 1.5/100k, represents 3% of all genital carcinoma
Seen in older women, usually > 60 y/o
Gross Appearance & Clinical Presentation
- Pain, discomfort, itching and exudation
- Tumor is usually an exophytic or endophytic ulcer located on labia majora or labia minora
Microscopic appearance
- Usually well-differentiated
Pattern of Spread:
- Inguinal nodes
- LN w/in the pelvis, rectum
- Parailiac nodes

Question 39

Q

Squamous Carcinoma of the Vulva

Staging

Answer

A

Stage I: Tumor confined to vulva, 2 cm. or less in diameter. No suspicious groin nodes.
Stage II: Tumor confined to vulva > 2 cm. w/o suspicious groin nodes.
Stage III: Extension beyond vulva. No suspicious groin nodes.
Stage IV: Grossly positive groin nodes, regardless of size of 1° tumor
- Likelihood of regional node metastases most related to size of 1° tumor

Question 40

Q

Squamous Carcinoma of the Vulva

Management

Answer

A

Microinvasive Vulvar Squamous Carcinoma
- Depth of invasion < 1 mm. and not associated w/ inguinal LN metastasis
- Stage IA
- Treatment is local excision
Invasive carcinoma
- If lesion has a depth > 1 mm. ⇒ groin node dissection is done
Other prognostic factors include diameter of lesion, tumor ulceration, grade and confluent growth

Question 41

Q

Verrucous Carcinoma of Vulva

Answer

A

Distinct variant of squamous carcinoma w/ a unique biologic course
Resembles a large condyloma acuminatum
Usually seen in post-menopausal women
Very well-differentiated squamous lesion
Usually no nodal metastasis
Tx w/ wide local excision

Question 42

Q

Adenocarcinoma of the Vulva

Answer

A

Similar to adenocarcinoma seen in the cervix

Question 43

Q

Infectious Vaginitis

Answer

A

Bacteria
- Garderella vaginalis (Hemophilus vaginalis)
  - Accounts for 90% of nonspecific infections
  - See clue cells on pap smear
Fungal
- Candida
Parasite
- Trichomonas vaginalis
Virus
- HPV

Question 44

Q

Benign Vaginal Lesions

Question 45

Q

Vaginal Intra-epithelial Neoplasia (VAIN)

Answer

A

Less common than VIN and CIN
Annual incidence is 3/100k
Epidemiology is same as for cervical intra-epithelial neoplasia (CIN) i.e. exposure to HPV
VAIN most often affects the upper vagina
Multi-focal in > 50% of pts
Asymptomatic, can be detected on colposcopy
Microscopic changes are same as for CIN
Many pts have other lower genital tract neoplasms (cervix, vulva)

Question 46

Q

Vaginal Squamous Cell Carcinoma

Answer

A

Most common carcinoma of vagina
Infrequent, accounts for 1% of all gynecologic malignancies
Seen mostly in older women (60-70)
Must be differentiated from vaginal extension of cervical or vulvar cancer and from metastatic tumors
- Valid dx of 1° vaginal CA requires no cervical or vulvar CA @ time of dx and for ≥ 10 years before dx
Commonly occurs in upper portions of posterior wall
Can spread dorsally to the parametrium, bladder and rectum
Most often metastasizes to pelvic lymph and inguinal nodes
May be silent lesions, or present as vaginal bleeding or discharge (leukorrhea)

Question 47

Q

Embryonal Rhabdomyosarcoma

“Sarcoma Botryoides”

Answer

A

Most common neoplasm of lower genital tract in girls
- Seen in those < 5 y/o
Originates from undifferentiated mesenchyme w/ striated muscle differentiation (embryonal rhabdomyoblasts)
Grossly distinctive: polypoid grape-like mass, may be seen at introitus
Prognosis is poor

Question 48

Q

Diethylstilbestrol (DES)

Answer

A

Synthetic, estrogen administered to women w/ high-risk pregnancies in 1940’s-1960’s
Prenatal Diethylstilbestrol (DES) exposure results in:
- Vaginal adenosis
- Atypical adenosis
- Dysplasia
- Clear cell adenocarcinoma of vagina and cervix

Question 49

Q

Vaginal Adenosis

Answer

A

Related to prenatal Diethylstilbestrol (DES) exposure
Involves upper ⅓ of the vaginal anterior wall
Mucosa is replaced by glandular epithelium
- Can then undergo squamous metaplasia
Similar changes can occur in the cervix
Pathogenesis:
- Adenosis develops from persistent residual embryonic glandular epithelium
- May be a precursor lesion for clear cell adenocarcinoma of the vagina
  - Adenosis → atypical adenosis → dysplasia → clear cell adenocarcinoma

Question 50

Q

Clear Cell Adenocarcinoma

Vagina and Cervix

Answer

A

Related to prenatal Diethylstilbestrol (DES) exposure
- < 14% w/ DES exposer develop adenocarcinoma
Seen in young women (average age 19 years)
Tumor may be large or small
Usually asymptomatic
Located in the upper ⅓ of anterior vaginal wall
Microscopically, resembles clear cell carcinoma of uterus and ovary
It spreads locally and later metastasizes to pelvic LNs and blood stream

Question 51

Q

Uterine & Adnexal

Embryology & Anatomy

Question 52

Q

Uterine

Size Variation

Answer

A

Continuously grows in size from birth → puberty
Signficant growth during pregnancy
Does not revert to nulliparous size until menopause

Question 53

Q

Menstrual Cycle

Phases

Question 54

Q

Menstrual Endometrial Changes

Answer

A

D__ay 1-14 ⇒ proliferative endometrium
- Preovulatory
- Simple glands
- Mitotic figures within endometrial glands
Day 14 ⇒ ovulation
- Post-ovulatory
Day 17 ⇒ subnuclear vacuoles
- Presence means that ovulation has occurred
Day 21 ⇒ secretory endometrium
- Gland complexity
- Stromal edema
- Secretions in glands
Day 23 ⇒ pre-decidua around vessels
Day 26 ⇒ entire stroma now decidualized
Day 28 ⇒ menstrual endometrium
- Structure breaks down
- Endometrial balls
- “Crumbling”

Question 55

Q

Menstrual Cycle

Summary Chart

Question 56

Q

Endometrium of Pregnancy

Question 57

Q

Dysfunctional Uterine Bleeding (DUB)

Answer

A

Abnormal bleeding w/o lesion of the endometrium
Very common
Seen most often around menarche and menopause
Etiologies:
- Anovulatory Bleeding
- Inadequate luteal phase
- Irregular shedding

Question 58

Q

Anovulatory Bleeding

Answer

A

Most common cause of DUB
No corpus luteum ⇒ excess estrogen, no progesterone
Then estrogen declines and get bleeding
Bleeding variable in amount and erratic
Most are d/t subtle hormonal imbalances
Some cases 2/2 obesity, malnutrition, chronic systemic disease, endocrine disorders, polycystic ovaries, etc.

Question 59

Q

Inadequate Luteal Phase

Answer

A

Inadequate progesterone secretion from corpus luteum

See menstruation 6-9 days after LH surge

Question 60

Q

Irregular Shedding

Answer

A

Heavy bleeding d/t extended secretion of progesterone from corpus luteum
See secretory and proliferative phases together on biopsy
- Proliferative endometrium with stromal breakdown

Question 61

Q

Uterus

Congenital Abnormalities

Answer

A

Fusion defects & Atresias

Question 62

Q

Endometritis

Answer

A

Inflammation of the endometrium

Acute Endometritis
- Usually near time of delivery or miscarriage
- Caused by retained products of conception (POC)
- Infection by Strep or Staph
Chronic Endometritis
- See plasma cells in endometrium
- Risk factors include IUD, PID, retained POC
Special forms of endometritis
- TB, Mycoplasma, Chlamydia, fungi, Herpes simples, CMV, Parasites, sarcoid

Question 63

Q

Uterine

Drug Effects

Answer

A

Estrogens
- Stimulates the endometrium
- Duration of exposure more important than dose
- Can get hyperplasia or carcinoma from prolonged administration
Oral Contraceptives
- Shortens proliferative phase, secretory changes develop slowly
- After a few cycles, atrophied endometrium w/ decidualized stroma
Known adverse reactions d/t oral contraceptives:
- Thromboembolism w/ sudden death
- Hepatic adenoma that can present as sudden intraperitoneal bleeding, jaundice
- Intimal fibrosis and luminal narrowing of small arteries

Question 64

Q

Intrauterine Device (IUD)

Answer

A

Induce acute and chronic inflammation and decidual reaction

↑ incidence of infections, particularly actinomycosis

Answer 59

A

Endometrial glands and stroma outside the uterus
- ‘Ectopic endometrial tissue’
Most common sites of occurrence:
1. Ovary
2. Uterine ligaments
3. Rectovaginal septum
4. Cul de sac and pelvic peritoneum
5. Intestine and appendix
6. Mucosa of cervix, vagina, fallopian tubes
7. Laparotomy scars
Seen in women of reproductive age (6-10%)
Clinical manifestations:
- Pelvic pain, dysmenorrhea, infertility, dysuria, rectal pain

Answer 60

A

Regurgitation theory
- Retrograde flow of products of menstruation
- 90% of women have this and most don’t have endometriosis
Benign metastasis theory
- Spread by vessels or lymphatics
Extrauterine stem/progenitor cell theory
- Cells @ ectopic locations that differentiate into endometrium

Answer 61

A

Endometriotic implants show:

Release of proinflammatory and other factors
Endometriotic stromal cells contain aromatase ⇒ ↑ estrogen production
- Not in normal endometrial stromal cells
- Conveys a survival advantage
- Ass. w/ endometrioid and clear cell ovarian CA

Answer 62

A

Gross:
- Dark, ‘powder burns’ on laparoscopy, undergoes cyclic bleeding
- Ovaries can have large cysts containing degenerated bloody material (chocolate cysts)
- Uterus does not enlarge (in contrast to adenomyosis)
Microscopic:
- Endometrial glands and stroma
- May be difficult to identify d/t surrounding hemorrhage and fibrosis
- Sometimes just see hemosiderin-laden MΦ
  - MΦ + correct clinical sx ⇒ dx of ‘presumptive endometriosis’
- Atypical endometriosis shows cytologic atypia and/or glandular crowding
  - Looks like atypical endometrial hyperplasia
  - May be precursor to endometriosis-related ovarian CA

Answer 63

A

Presence of endometrial glands and stroma within the myometrium
Common, benign
Most often seen in peri-menopausal women
Present w/ bleeding and dysmenorrhea
Uterus can become enlarged w/ thickened myometrium
Can respond to hormones and cycle
Treatment: hysterectomy
Does not have malignant potential

Answer 64

A

Common cause of abnormal bleeding
Seen in women in 40s and 50s
Can be sessile or pedunculated
Polypoid fragments of tissue w/ epithelium on three sides
Stromal cells contain chromosomal rearrangements similar to other benign mesenchymal tumors
Glands are ‘along for the ride’
- Can become hyperplastic but very rarely become malignant

Answer 65

A

Another cause of abnormal bleeding
Precursor to endometrial adenocarcinoma (most common type)
1% becomes malignant
- Simple (non-atypical) → atypical (EIN) → carcinoma
Morphologically:
↑ Gland to stroma ratio
Abnl epithelial growth relative to normal endometrium
Vary in size and shape

Answer 66

A

Linked to prolonged estrogen stimulation of the endometrium
- Anovulation
- ↑ Estrogen production
- Exogenous estrogen
Conditions promoting hyperplasia include:
- Obesity
  - Peripheral conversion of androgen to estrogen
- Menopause
- Polycystic ovarian disease (including Stein-Leventhal syndrome)
- Functioning granulosa cell tumors of the ovary
- Excessive cortical function (cortical stroma hyperplasia)
- Prolonged admin of estrogenic substances (estrogen replacement therapy)
Same influences pathogenetic in some endometrial CA

Answer 67

A

Inactivation of the PTEN tumor suppressor gene
- Via deletion and/or inactivation
Plays a role in development of hyperplasia and endometrial carcinoma
- Seen in 20% of hyperplasia, 30-80% of endometrial carcinomas

Answer 68

A

Historically used 4 categories:
- Based on simple vs. complex architecture & no atypia vs. atypia
- Low-grade hyperplasia ⇒ no or minimal atypia
- High-grade hyperplasia (aka atypical hyperplasia) ⇒ has characteristics of intraepithelial neoplasia
  - Morphologic features ⇒ gland crowding and cytologic atypia
  - Genetic characteristics ⇒ PTEN mutations
Now WHO uses only two categories:
- Non-atypical hyperplasia
- Atypical hyperplasia aka “Endometrial Intraepithelial Neoplasia (EIN)”

Answer 69

A

↑ Gland-to-stroma ratio but retain intervening stroma
Rarely progress to adenocarcinoma
May evolve into cystic atrophy when estrogen stimulation is withdrawn
Management:
If no further fertility desired ⇒ hysterectomy
If fertility desired ⇒ trial of progestin therapy and follow up

Answer 70

A

Complex patterns of proliferating glands w/ nuclear atypia
Glands are complex w/ branching and may be ‘back-to-back’
- Approaches appearance of adenocarcinoma
Cells are rounded instead of elongated and poorly oriented to BM
Hysterectomy in these pts shows adenocarcinoma in 23-48%

Answer 71

A

Some endometrial hyperplasia can show altered cellular differentiation (metaplasia)
- Including presence of squamous, ciliated cell, and mucinous metaplasia
May result from ∆ in epithelial-stromal relationships
- Induces basal endometrial cells to follow different differentiation pathways
Less easily classified

Answer 72

A

Atypical hyperplasia precursor lesion
- Both show PTEN mutations
  - ↑ signaling via PI3K/AKT pathway
  - ∆ Expression of estrogen receptor-dependent target genes
- Can see also activating mutations in KRAS
PIK3CA mutations in CA, but not hyperplasia
- May relate to ability to invade
20% of sporadic tumors show DNA mismatch repair gene defects
- Also seen in women from HNPCC families
50% of poorly diff CA shows TP53 mutations
Links demonstrating estrogen-dependence:
- Ovarian estrogen-secreting tumor & HRT ⇒ ↑ risk of endometrial CA
- Extremely rare in women w/ ovarian agenesis and those castrated early in life

Answer 73

A

Obesity
DM
- Abnl glucose tolerance in > 60%
HTN
Infertility
- Pts are often nulliparous w/ hx of functional menstrual irregularities consistent w/ anovulatory cycles
Unopposed estrogen stimulation

Answer 74

A

Localized polypoid tumor vs diffuse tumor involving entire endometrial surface
Usu. spreads by myometrial invasion → periuterine structures
Can spread into broad ligaments ⇒ palpable mass on pelvic exam
Eventually, tumor disseminates to regional LNs
Later, may metastasize to lungs, liver, bones, and other organs
Histology:
- Tends to be well-differentiated and mimic normal endometrial glands (85%)
  - Called endometrioid endometrial adenocarcinoma
- Others may show mucinous, tubal, or squamous differentiation

Answer 75

A

3-step grading system for endometrioid tumors:

Grade 1: Well-differentiated, easily recognizable glandular patterns
Grade 2: Moderately-differentiated, well-formed glands mixed w/ solid sheets of malignant cells
Grade 3: Poorly-differentiated, solid sheets of cells w/ few glands, more nuclear atypia and mitotic activity

Answer 76

A

Endometrial adenocarcinomas may show mucinous, tubal, or squamous differentiation
Up to 20% contain foci of squamous differentiation
- Squamous elements may be benign-appearing
- Some moderately or poorly differentiated endometrioid CA contain squamous elements that are malignant
Previously called adenoacanthoma and adenosquamous carcinoma
Now just grade carcinomas based on glandular differentiation alone and use the term squamous differentiation

Answer 77

A

Less estrogen-dependent and less often preceded by hyperplasia than Type I
Often arise in setting of endometrial atrophy
Pts are usu. older @ time of dx
Accounts for 15% of endometrial carcinoma
All non-endometrioid carcinomas classified as grade 3 (poorly differentiated) regardless of histologic pattern
Subtypes:
- Serous adenocarcinomas
  - Resemble subtypes of ovarian CA
- Clear cell carcinoma
- Malignant Mixed Muellerian Tumor (MMMT)

Answer 78

A

90% of Type II w/ mutations in tumor suppressor, TP53
- 1° missense mutations ⇒ accumulation of altered protein
- Same mutation seen in EIN
Most common subtype is serous carcinoma
- Suggests that serous CA starts as surface epithelial neoplasm → adjacent gland structures → endometrial stroma
Poor prognosis
- Tends to exfoliate
- Undergo transtubal spread
- Implant on peritoneal surfaces like ovarian CA
Often beyond uterus at dx

Answer 79

A

Arise in small atrophic uteri (post-menopausal women)
Tumors usu. large bulky tumors or deeply invasive into myometrium
Invasive lesions can show papillary growth pattern ⇒ papillary serous carcinoma
Marked cytologic atypia including high N/C ratio, atypical mitotic figures, and prominent nucleoli
Relatively superficial endometrial involvement may be ass. w/ extensive peritoneal disease
- Suggests spread by routes other than direct invasion ⇒ tubal or lymphatic transmission
- More common Type II
Can also have a predominantly glandular growth pattern w/ marked cytologic atypia
Poor prognosis

Answer 80

A

Commonly Type II Endometrial CA
Vacuolated spaces within cells
Very poor prognosis

Answer 81

A

Applies to Type I and Type II

Staging based on extension:
- Stage I: confined to the corpus uteri itself
- Stage II: involves corpus and cervix
- Stage III: extended outside the uterus but not outside the true pelvis
- Stage IV: extended outside the true pelvis or obviously involves mucosa of bladder or rectum
Cases in various stages can also be sub-grouped into 3 grades:
- G1: well-differentiated adenocarcinoma
- G2: differentiated adenocarcinoma w/ partly solid (< 50%) areas
- G3: predominantly solid or entirely undifferentiated carcinoma or serous or clear cell carcinoma
  - Includes all Type II CA

Answer 82

A

Carcinosarcomas ⇒ Malignant Mixed Mullerian Tumor (MMMT)
Adenosarcomas ⇒ composed of stromal neoplasias in association w/ benign glands
Pure stromal (mesenchymal) neoplasms ⇒ ranges from benign (stromal nodule) to malignant (stromal sarcoma)

Together, these tumors comprise < 5% of endometrial malignancies

Answer 83

A

Endometrial adenocarcinoma w/ stromal differentiation
Consists of adenocarcinoma mixed w/ stromal (sarcoma) elements
- Arising from the same cell type
- Sarcomatous components may include striated muscle cells, cartilage, adipose tissue, and bone
Bulky, polypoid tumors, can protrude through cervical os
Outcome is determined by depth of invasion and stage
Grade and type of adenocarcinoma matters too
- Poorest outcome w/ serous differentiation
Tumors are highly malignant
- 5-yr-survival rate 25-30%
MMMTs occur in postmenopausal women and present w/ postmenopausal bleeding
Many have hx of previous radiation therapy

Answer 84

A

Benign epithelial component w/ malignant mesenchyme

Large broad-based endometrial polypoid growths
- May prolapse through cervical os
Dx based on malignant appearing stroma + benign but abnormally shaped endometrial glands
Presents w/ abnormal bleeding
Women in 4^th to 5^th decade
Low grade malignancy
- 25% recur
- Rarely spread beyond pelvis
Estrogen-sensitive

Answer 85

A

Neoplasms that resemble normal stromal cells:

Stromal Nodule (Benign Mesenchymal Endometrial Tumor)
- Well-circumscribed aggregates of endometrial stromal cells in the myometrium
- Mean age 47 yrs
- Presents w/ abnormal bleeding
Stromal Sarcoma (Malignant Mesenchymal Endometrial Tumor)
- Neoplastic endometrial stroma lying between muscle bundles of the myometrium
  - Can infiltrate myometrial tissue OR penetrate lymphatic channels (old term: endolymphatic stromal myosis)
- ~50% of these tumors recur
- Distant metastases can occur decades later
  - ~15% of pts die from metastatic tumors
- 5-yr-survival rate 50%
- Often ass. w/ chromosomal translocations that create fusion genes (like other sarcomas)

Answer 86

A

Benign tumor of myometrium

Most common uterine neoplasm
- Maybe the most common tumor in women
Commonly known as ‘fibroids’
Present in 20-30% of women over age 30
- Usu. found in middle aged women
Most leiomyomas regress after menopause
Very common in black women
Estrogen can make leiomyomas larger
Progesterone and pregnancy ⇒ ± rapid ↑ in size and hemorrhagic degeneration

Answer 87

A

40% have abnormal karyotype

Simple chromosomal abnormality

Rearrangement of chromosomes 12q14 and 6p
- Involves HMGIC and HMGIY genes
  - Encode DNA-binding factors that regulate chromatin structure
Up to 70% of leiomyomas have mutations in MED12 gene
- Ultimately stimulates gene expression

Answer 88

A

Many asymptomatic
Sx include: pain, pressure sensation, bladder compression → urinary frequency, sudden pain if disruption of blood supply occurs
Submucosal leiomyomas are most responsible for abnormal bleeding and infertility
Cause uterine enlargement
Complications: spontaneous abortion, DIC, dystocia, postpartum hemorrhage
Malignant transformation (leiomyosarcoma) is extremely rare

Answer 89

A

Gross pathology:
- Sharply circumscribed, discrete, round, firm, gray-white tumors w/ ‘whorled’ appearance
- Usu. seen in myometrium of uterine corpus
- Can occur within the:
  - Myometrium (intramural)
  - Just beneath the endometrium (submucosal)
  - Beneath the serosa (subserosal)
  - Rarely can involve uterine ligaments, lower uterine segment, or cervix
- Large tumors may develop areas of yellow-brown to red softening (red degeneration)
Histology:
- Whorled bundles of smooth muscle cells that resemble uninvolved myometrium
- Usu. individual muscle cells are uniform in size and shape and have characteristics of nl SM (oval nucleus and long, slender ‘cigar-shaped’ cytoplasm)
- Should not see many mitotic figures

Answer 90

A

Common:
- Atypical or bizarre (symplastic) tumors
  - See nuclear atypia and giant cells
- Cellular leiomyomas
Rare:
- Benign metastasizing leiomyoma
  - Uterine tumor that extends into vessels and migrates to other sites, most commonly the lung
- Disseminated peritoneal leiomyomatosis
  - Presents as multiple small nodules on the peritoneum

Answer 91

A

Uterine leiomyomas, even when extensive, may be asymptomatic
- If asymptomatic, don’t need to treat
If symptomatic, treatment options include:
- Hysterectomy
- Myomectomy
- Embolization of vessels to the leiomyoma
- Endometrial ablation (if bleeding is the major sx)

Answer 92

A

Rare
- 1.3% of uterine malignancies, 25% of uterine sarcomas
- 1/800 tumors of uterine smooth muscle
Peak incidence 40-60 y/o
Pts usu. present w/ vaginal bleeding, pelvic pain
Leiomyosarcomas are not thought to originate from an existing leiomyoma
Diagnosis:
- Main criterion is ↑ mitotic figures
  - Need 10 mitoses per 10 HPF
- Moderate-marked nuclear or large (epithelioid) cells & 5 mitoses/10 HPF ⇒ ± leiomyosarcomas dx
- Cellular tumors w/ 5-9 mitoses /10 HPF and minimal atypia ⇒ ‘tumors of uncertain malignant potential’
Treat w/ TAH-BSO
- May recur after surgery
> 50% metastasize → lungs, bone, brain
5-yr-survival 40%

Answer 93

A

Gross:
- Most leiomyosarcomas are intramural and fairly large (average size 9 cm)
- Soft, gray, fleshy mass w/ necrosis, hemorrhage
Microscopic:
- Cells are spindled, can show pleiomorphism/atypia
- ± Moderate-marked nuclear or large (epithelioid) cells
- ± Hypercellularity

Answer 94

A

Most common lesions of the ovary

Surface inclusion cysts
- Secondary to invagination of surface epithelium
Follicle cysts (aka Cystic follicles)
- Arise from unruptured follicles or follicles that rupture
- Seal and undergo atresia
- Lined by surface epithelium that may be luteinized
- Often multiple
- ± ↑ estrogen ⇒ endometrial hyperplasia
- May rupture and cause abd pain
Corpus luteum cysts
- Seen in ovaries of repro age women
- May rupture

Answer 95

A

Affects 6-10 % of reproductive age women
Clinical manifestations:
- Hyperandrogenism, menstrual abnl, polycystic ovaries, chronic anovulation, ↓ fertility
- Insulin resistance and ∆ adipose tissue metabolism
  - Ass. w/ obesity and Type 2 DM
  - Ass. w/ premature atherosclerosis
↑ Risk for endometrial hyperplasia and carcinoma
Pathogenesis:
- Dysregulation of androgen biosynthesis
- Insulin resistance
  - Admin of insulin mediators ass. w/ resumption of ovulation
Morphology of ovary:
- Numerous cystic follicles or follicle cysts that enlarge the ovaries
  - Isolated cysts seen in 20-30% of all women

Answer 96

A

Usually in postmenopausal women
Present w/ sx similar to PCOS
Gross: uniform enlargement of both ovaries w/ white/tan appearance on sectioning
Microscopic: hypercellular stroma w/ luteinization of stromal cells

Answer 97

A

80% of ovarian tumors are benign
- Benign tumors more common in young women (20-45)
- Malignant tumors more common at later age (45-65)
Ovarian CA is 3% of all cancer in females
5^th most common cause of CA death in US women
Higher mortality rate than other genital CA
Often dx after spread beyond the ovary
Most are non-functional
Some tend to be bilateral
Large tumors ⇒ abd distension and discomfort, GI and urinary sx

Answer 98

A

↑ Risk of ovarian CA:
- Nulliparous or low parity
- BRCA1 or BRCA2 mutation
  - 20-60% risk of ovarian CA by age 70
  - Most are serous cystadenocarcinomas
↓ Risk of ovarian CA:
- Oral contraceptive use

Answer 99

A

WHO Classify according to cell type of origin:

Surface/fallopian tube epithelium & endometriosis (most common)
Germ cells
- Pluripotent
- Migrate to ovary from yolk sac
Ovarian stroma
Can also see metastatic tumors to the ovary

Answer 100

A

Most common cell of origin for ovarian tumors

3 major histologic types of epithelium:
- Serous
- Mucinous
- Endometrioid
Each can be benign, borderline or malignant
- Depends on whether epithelial tumor cells invade ovarian stroma
Next can subclassify by other components:
- Cystic areas ⇒ cystadenomas
- Cystic and fibrous areas ⇒ cystadenofibromas
- Mostly fibrous areas ⇒ adenofibromas

Answer 101

A

Benign lesions
- Usually show flat epithelium and cystic areas
Malignant lesions
- Usually show papillary projections and solid areas
- Carcinomas can extend through tumor capsule & seed peritoneal cavity
  - Resulting in ascites
- Tumors grow slowly
  - Tumors usu. large & has spread beyond the ovary @ dx
- CA-125 is a marker for some ovarian CA
Borderline lesions
- Neither clearly malignant nor clearly benign
- Are in a ‘borderline’ category

Answer 102

A

Serous tumors (30% of all ovarian tumors)
- Benign ⇒ serous cystadenoma
- Borderline (low malignant potential)
- Malignant ⇒ serous (+/- papillary) cystadenocarcinoma
  - Most common ovarian CA (40%)
  - 65% are bilateral
Mucinous tumors
- Benign ⇒ mucinous cystadenoma
- Borderline (low malignant potential)
- Malignant ⇒ mucinous cystadenocarcinoma
Endometrioid tumors
- Clear cell adenocarcinoma
- Brenner Tumor

Answer 103

A

Type I
- Low grade tumors
- Often arise in ass. w/ borderline tumors or endometriosis
- Many histologic subtypes:
  - Low grade serous
  - Endometrioid
  - Mucinous
Type II
- High grade serous carcinoma
- Arises from serous intraepithelial carcinoma

Answer 104

A

Surface (Muellerian) Epithelium Tumors

30% of all ovarian tumors
- 40% of all ovarian malignancies
- # 1 ovarian malignancy (50% if we count borderline)
25% are malignant
- Benign and borderline most common ages 20-45
- Malignant later (unless familial)
Often large
Many are bilateral
- Especially if malignant
Lined by serous (tubal-like) epithelium
*

Answer 105

A

Low grade serous ovarian CA
- Less nuclear atypia and better survival
- May arise in ass. w/ serous borderline tumors
High grade serous ovarian CA
- Arises from in situ lesions in fallopian tube fimbriae or from serous inclusion cysts in ovary
  - BRCA1/2 women s/p prophylactic BSO had marked epithelial atypia in tubes
    - Named ‘Serous Tubal Intraepithelial Carcinoma’ (STIC)
  - Atypia also seen in sporadic high grade serous ovarian tumors
- Others arise from cortical inclusion cysts of ovary or implantation of detached fallopian tube epithelium where ovulation has disrupted ovarian surface

Answer 106

A

Unsure of risk factors for benign and borderline
Risk factors for malignant serous tumors:
- Nulliparity
- Family hx
- Heritable mutations
  - BRCA1 (5% of ovarian CA pts under 70)
  - BRCA2
  - Women w/ either of these have 20-60% ovarian CA risk by age 70

Answer 107

A

Serous cystadenoma
- Composed of one or several cysts w/ smooth inner & outer surfaces
- Cysts are lined by a layer of tall columnar, serous secreting, ciliated or non-ciliated cells w/ no atypia
- Occasional short papillary projections, lined by same kind of cells
- Outer surface of tumor is covered by mesothelial cells
When there is abundant fibrous stroma, benign serous tumor called a cystadenofibroma

Answer 108

A

Not clearly malignant or benign
See surface proliferation
No definite invasion into stroma
Concerning for invasive disease ⇒ must watch after removal

Answer 109

A

Depends of degree of differentiation

Composed of numerous cysts w/ many papillary projections and solid areas
Epithelium piles up ⇒ > 1 layer over the surface of the cysts
Solid masses of epithelial cells that invade into wall of the cysts
Cells are atypical w/ features of malignancy
Can see psammoma bodies
- Also seen in papillary thyroid CA and meningiomas

Answer 110

A

Depends on degree of differentiation: low grade vs high grade

Even if it has extended to the peritoneum

Borderline serous tumors
- May arise from or extend to peritoneal surfaces as non-invasive implants
- Possible behaviors:
  - Remain localized ⇒ asymptomatic
  - Slowly spread ⇒ intestinal obstruction or other complications after many yrs
  - Develop into low-grade carcinoma
    - Even then will usu. progress slowly
High-grade serous tumors
- Often widely metastatic throughout abd @ presentation
- Pts can experience rapid clinical deterioration

Answer 111

A

5-yr survival rate from diagnosis of:

Borderline serous tumor
- Confined to ovary: 100%
- Involving peritoneum: 90%
- May have protracted course and recur so 5-yr survival ≠ cure
Malignant serous tumor
- Confined to ovary: 70%
- Involving peritoneum: 25%

Answer 112

A

20-25% of all ovarian tumors
Mid adult life
Few are malignant
- 3% of all ovarian CA
Only 5% are bilateral, < serous tumors
Rarely involve surface of ovary
Many show mutations of KRAS proto-oncogene
Tall columnar, mucin-secreting cells
Often very large tumors
Can be malignant, benign or borderline
Pseudomyxoma peritoneii is a complication in 2-5% of pts
- Mucinous, jelly-like, material throughout abdomen
- Tends to reaccumulate after removal
- Also seen w/ mucinous tumors of appendix and colon

Answer 113

A

Benign

80% of ovarian mucinous tumors

Answer 114

A

Distinguished from cystadenomas by:
- Epithelial stratification, tufting, and/or papillary intraglandular growth
- May look similar to adenomas or villous adenomas of the intestine
Low malignant potential

Answer 115

A

Malignant growth
- Confluent glandular growth ⇒ “expansile” invasion
Tumors w/ marked epithelial atypia but no invasive features ⇒ “intraepithelial carcinomas”
- 95% 10-yr survival rate if Stage I
Stage I ⇒ 90% 10-yr survival rate
- Even if invasive
Mucinous carcinomas that have spread beyond the ovary ⇒ usually fatal, but rare

Answer 116

A

10-15% of all ovarian cancer
Most are malignant
See solid and cystic growth
40% are bilateral
Histologically similar to endometrial carcinoma
5-yr survival for Stage I is 75%
~15-20% of pts also have endometriosis
- Present ~10 yrs earlier than w/o endometriosis
Up to 30% of pts also have an independent endometrial carcinoma in the uterus
- Still a good prognosis, likely not a metastasis
Subtypes: Clear cell adenocarcinoma, Brenner tumors

Answer 117

A

See similar molecular similarities to endometrial endometrioid carcinoma

Mutations in PTEN, PIK3CA, ARIDIA and KRAS ⇒ ↑ PIEK/AKT pathway signaling
- PTEN mutations also seen in atypical endometriosis
Mutations in mismatch DNA repair genes and CTNNB1 (Beta-catenin)
TP53 mutations in poorly differentiated tumors
- Just like in endometrioid CA of endometrium

Answer 118

A

Uncommon variant of endometrioid carcinoma
Can see similar neoplasm in endometrium, cervix, uterus and vagina
May be solid or cystic
Microscopic:
- Large cells w/ clear cytoplasm or hobnail type cells
- Arranged in solid, tubular or papillary configuration
Aggressive tumor
- Poor prognosis if beyond ovary

Answer 119

A

Transitional cell tumors
Subtype of endometroid tumors
10% of ovarian epithelial tumors
Most are benign; usually unilateral
Usually solid and firm, 1-20 cm in diameter
Fibrous stroma containing scattered groups of transitional epithelial cells

Answer 120

A

Uncommon variant
Pronounced proliferation of fibrous stroma underlying columnar lining epithelium
Benign tumor
Usually small and multilocular
May have mucinous, serous, endometrioid or transitional epithelial components

Answer 121

A

Often presents w/ vague sx: GI complaints, urinary sx, pelvic pressure
- Often found when large
Benign tumors are removed ⇒ pt recovers
If malignant:
- May see ascites ⇒ can contain malignant cell
- Tumor can spread throughout peritoneum ⇒ tiny nodules seed the serosal surface
- May spread to liver, lungs, GI tract, opposite ovary
Serum CA-125
- Good marker for known disease to monitor recurrence/progression
- Not for screening

Answer 122

A

15-20% of ovarian tumors
Germ cells are totipotent ⇒ tumors can contain a variety of tissues
Most are mature teratomas (Dermoid Cysts) ⇒ benign
Others include:
- Immature teratoma
- Dysgerminoma
- Endodermal sinus (yolk sac) tumor
- Choriocarcinoma
- Embryonal carcinoma
- Mixed germ cell tumor

Answer 123

A

Benign teratomas
Most common type of ovarian germ cell tumor
Usually cystic ⇒ also called “Dermoid cysts”
10-15% are bilateral
Filled w/ sebaceous material, hair shafts, and other tissue types
Malignant transformation is rare

Answer 124

A

Malignant teratomas
Usually seen in children and young adults
Contain immature embryonic tissues
Mostly solid w/ focal necrosis and hemorrhage

Answer 125

A

Specialized type of monodermal ovarian teratoma

Entirely composed of mature thyroid tissue

Answer 126

A

Ovarian counterpart of seminoma

Always malignant, usually unilateral
50% of malignant ovarian germ cell tumors
2% of ovarian tumors
75% in 2^nd and 3^rd decades
Some produce gonadotropins
Microscopic:
- Large cells w/ clear cytoplasm and centrally located nuclei in cords or sheets
- Separated by thin, fibrous septa that contains lymphocytes

Answer 127

A

Malignant and very aggressive
Seen in children and young women
See yolk sac differentiation w/ Schiller-Duval bodies
- Looks like a glomerulus
Contain intracytoplasmic hyalin droplets
Droplets contain Alpha-fetoprotein (AFP) and alpha-1-antitrypsin (AAT)

Answer 128

A

Rare tumor
Histologically identical to choriocarcinoma of placental origin
Much more malignant w/ early widespread metastases
Produce chorionic gonadotropin (hCG)
Often seen as a component in combo w/ other germ cell tumor types

Answer 129

A

Solid tumor w/ necrosis and hemorrhage
Micro shows solid sheets and nests of large, primitive cells
Can see syncytiotrophoblast-like cells
- Secrete chorionic gonadotropin (hCG)
- Can also see ↑ alpha-fetoprotein (AFP) levels

Answer 130

A

5% of all ovarian tumors
Include:
- Granulosa cell tumor
- Thecoma and Fibroma
- Sertoli-Leydig cell tumor (Arrhenoblastoma)
- Leydig cell tumor (Hilus Cell Tumor)
- Lipid cell tumor

Answer 131

A

Epidemiology:
- 5% before puberty
- 40% after menopause
10% bilateral
Gross: smooth surface, lobulated, gray-yellow color
Micro: microfollicular w/ Call-Exner bodies
- See coffee-bean nuclei
75% associated w/ ↑ estrogen production
- Endometrial hyperplasia/carcinoma in adults
- Precocious puberty in children
↑ tissue and serum inhibin
Risk of recurrence or spread is 5-25%, usually indolent

Answer 132

A

65% in post-menopausal women
Nearly all are benign
Gross: round, firm, solid
Micro: fascicles of spindle cells, can sometimes see fat
May see ↑ estrogen production in thecomas
Can see ascites and right sided hydrothorax (Meigs’ Syndrome) w/ fibroma
Can be associated w/ Basal Cell Nevus syndrome

Answer 133

A

Sertoli-Leydig cell tumor
Leydig cell tumor (Hilus cell tumor)
Lipid cell tumor
- Rare, yellow or brown
- 25% malignant
Ovarian gynandroblastoma
Sex-cord Tumor w/ Annular Tubules
About 1/3 of cases are associated w/ Peutz-Jegher

Answer 134

A

Ovarian virilizing tumor
Rare tumor
Average age is 25 y/o
Resembles immature testis w/ Sertoli and Leydig cells
~15% are malignant

Answer 135

A

Ovarian virilizing tumor
Can see cells containing Reinke crystals
Benign

Answer 136

A

Ovarian virilizing tumor
Mix of Granulosa and Sertoli-Leydig cell tumor
Pts have abnl sexual development and gonads of indeterminant nature
50% have a coexistent dysgerminoma

Answer 137

A

7% of ovarian tumors are metastatic
50% of these are bilateral
Most often originate from stomach, large bowel, appendix, breast, uterus and lungs
Krukenberg tumors
- Usually bilateral and solid
- Diffuse infiltration by signet ring cells
- Most often from stomach

Answer 138

A

Acute infection of the fallopian tube
Usu. caused by bacteria from uterine cavity
# 1 organism is Gonococcus but can also involve E. coli, bacteroides, strept, chlamydia
Gonococci penetrate into subepithelial connective tissue
- Cause acute inflammation w/:
  - Pus accumulation in tube lumen w/ distension
  - Pus drains out of fimbriated end → pelvis
  - Fibrinous exudate on serosa
Nongonococcal bacteria can get to tubes via uterine lymphatics
Complications: PID, tubo-ovarian abscess (TOA)

Answer 139

A

Residual inflammation and alteration in tubes after an acute episode or repeated episodes of acute inflammation
Gross:
- Adherence of mucosal plicae and/or closure of fimbriated end
- fibrous adhesions between tubes, adjacent peritoneum and ovary
- Can result in pyosalpinx and/or hydrosalpinx
Micro: lymphocytic and plasmocytic infiltration

Answer 140

A

Subtype of chronic salpingitis
l% of pts w/ infertility problem have tuberculosis of oviducts
10% of women pts dying of tuberculosis have tuberculous salpingitis
- Source is from 1° tuberculosis somewhere else in the body
- Blood borne TB preferentially involves fallopian tubes vs other female genitalia
- Lesion starts from the mucosa → muscular layer