212/215/216 - Histology, Pathology of Female Reproductive System Flashcards
Vulvar Lichen simplex chornicus
- Cause
- Pathologic changes:
- Prognosis:
- Cause: Chronic irritation (ex: itching)
- Pathologic changes: Squamous cell hyperplasia; hyperkeratosis in reaction to itching
- Prognosis: benign; resolves when the irritating agent is taken away
- Note: Lichen sclerosus IS itchy, SCC may arise*
- Lichen simplex chronicus is CAUSED BY itching; no cancer risk*
What is histologic difference between endometrial hyperlasia with atypia vs. atypical hyperplasia?
How do their prognoses differ?
- Hyperplasia without atypia
- No nuclear changes
- Stroma present between glands
- May rarely progress to carcinoma
- Atypical hyperplasia
- Nuclear changes: round, clear chromatin, prominent nucleolus
- May progress to carcinoma up to 48% of the time
Is the following characteristic of usual or differentiated vulvar squamous cell carcinoma?
p53 Mutation
Differentiated
What kind of lesion does this describe:
“Crusted, red vulvar or perianal lesion”
What are to possible processes that it may represent?
Vulvar paget’s disease
- Usually a neoplasm of sweat glands or skin adenexae
- Somtimes represents an internal malignancy
- Colon cancer, urothelial carcinoma
What makes the “high-risk” HPV serotypes so high risk?
They integrate into the host chormosome
High risk = 16, 18, 31, 33
Low-risk serotypes (6, 11) do NOT integrate into the host chromosome, will cause warts
Is the following characteristic of usual or differentiated vulvar squamous cell carcinoma?
HPV-driven
Usual
What is the histological marker of chronic endometritis?
Plasma cells
Not normally in the endometrium; if they are there, implies chronic endometritis
Acute endometritis is less common, will see neutrophils
List the 4 theories for the origin of endometriosis
-
Regurgitation
- Retrograde menstruation
-
Benign metastases
- Lymph/vascular spread
- Metaplasia
- Extrauterine stem-progenitor cells
Most likely a combination of some or all of these
Is the following characteristic of usual or differentiated vulvar squamous cell carcinoma?
Arises from lichen sclerosus
Differentiated
Characteristic of Endometroid (type 1) or Serous (type 2) enometrial carcinoma?
PTEN mutation
Endometroid
What is the defining cell type present in a Syphilis chancer?
Plasma cells
Inactivation of which tumor suppressor is associated with endometrial hyperplasia?
PTEN
- And this is associated with endometroid (type 1) endometrial carcioma
What kind of epithelium is found in the fallopian tube?
Simple collumnar epithelium
What are the characteristic histological findings of endometriosis?
How many are needed for diangosis?
2/3 of the following in an ectopic location
- Endometrial glands
- Endometrial stroma
- Hemosiderin-laden macrophages (evidence of hemorrhage)
What is the most common type of cancer in the cervix?
Squamous cell carcinoma
Develops in the transformation zone in the background of dysplasia
What is the major function of the simple cuboidal epithelium (germinal epithelium) of the ovary?
- Projects inward to form glands
- Forms the capsule of the ovary
- Is a serous, peritoneal membrane
- Is the source of primordial oocytes
c. Is a serous, peritoneal membrane
* Stupid name - turns out eggs come from the hindgut, not the germinal epithelium lmao*
What is the histologic feature of vaginal epithelium?
Pyknotic nuclei
- Small, focal, condensed
- Spaces in between = cells swelling with glycogen in response to rising estrogen (before menstruation)
What in which stage of meiosis are oocytes arrested during fetal development?
Prophase I
As the follicle matures, continues until Mataphase II; only progresses from here if fertilized
Characteristic of Endometroid (type 1) or Serous (type 2) enometrial carcinoma?
Papillary or glandular growth pattern
Serous
Histologic differences between leiomyosarcoma and leiomyoma? (3)
Leiomyosarcomas may have:
- Nuclear atypia
- Mitoses
- Necrosis
Need 2/3 to diagnose
If none are present = leiomyoma (fibroid)
If 1 is present it falls into some weird category - if we are ever tested on it may the power of Dr. Wolniak be with us all <3
What is the difference between the corpus albicans vs. atretic follicles?
-
Corpus albicans comes from a mature follicle
- After ovulation, follicul becums corpus luteum
- No pregnancy -> corpus luteum dies, becomes corpus albicans
- Atretic follicle = all follicles that were never selected to become mature follicles
Which cells does HPV infect?
Basal cells of the transformation zone
- Transformation zone: squamous mucosa of the ectocervix -> glandular mucosa of the endocervix
- These cells ar vulnerable because they are naturally metaplastic
List 4 risk factors for cervical cancer
- Multiple sexual partners
- Early initiation of sexual activity
- There is more transformation zone epithelium during adolescent hormonal states
- High parity
- Smoking
At what stage of follicular develpent is the follicle 10mm or greater in size?
Mature follicle (ready to pop out)
Which one of the following changes the least in morphology during the menstrual cycle?
A. Uterine glands
B. Ovarian follicles
C. Uterine tube epithelium
D. Vaginal epithelium
E. Cervical histology
E. Cervical histology
Characteristic of Endometroid (type 1) or Serous (type 2) enometrial carcinoma?
p53 mutation
Serous
Characteristic of Endometroid (type 1) or Serous (type 2) enometrial carcinoma?
Fused glands with stroma in between (cribiforming)
Endometroid
Which normal cell function is disrupted by HPV’s E6 protein?
p53-mediated Apoptosis
Viral protein E5 marks p53 for degradation
-> p53 cannot use p21 ot arrest the cell cycle
=> cells with DNA damage that would normally die or be repaired get to progress through the cell cycle and proliferate
What is a major role of the theca interna of a secondary follicle?
A. Forms a connective tissue capsule
B. Protective layer of the ovulated ovum
C. Site of entry of estrogen into the bloodstream
D. Produces progesterone
E. Metabolic support of the egg
C. Site of entry of estrogen into the bloodstream
At what stage of follicular development does the follicle develop a cavity?
Secondary (aka antral) follicle
What are the roles of glycogen and low pH in the vaginal epithelium?
-
Glycogen = favorable environment for sperm
- Spaces between cells fill with glycogen in response to estrogen, which rises pre-ovulation
- Low pH = protection against infection
List the two types of endometrial stromal tumors
- Endometrial stromal nodule
- Benign, well-circumscribed
- Endometrial stromal sarcoma
- Infiltrative
- May recur, late distant mets are uncommon but can happen
List 2 histopalologic hallmarks of cervical squamous cell carcinoma
Keratinization
Intracellular bridges
- Note: hallmark of HPV infection = koliocyte; koliocytes do NOT mean SCC; they just mean HPV infection*
- Another note: Adenocarcinoma of the cervix is rare, will see glands*
When you are looking at a PAP smear, can you determine if dysplasia is mild, moderate, or severe?
No!
- PAP smear looks at cells only
- Can only tell if they’re low grade or high grade (LSIL or HSIL)
- Need biopsy to determine the thickness of the displasia
- Mild = bottom 1/3
- Moderate = involves middle 1/3
- Severe = involves full thicknes
List 3 key histologic characteristics of HSV-2
- Multinucleation
- Molding - Nuclei fit and shape to one another
- Margination - Chromatin pushed to the edge of the nucelus
Also pink nuclear inclusions - Cowdry A
Descrive the pattern of proliferation of atypical cells in the epithelium in Paget’s disease
Atypical cells spread in the epithelium without invasion
Proliferate and grow between layers of skin cells
Pagetoid pattern
What are the respective drivers of usual-type and differentiated vulvar squamous cell carcinoma?
- Usual
- HPV-driven (like cervical cancer)
- Usually seen in pre-menopausal women
- Differentiated
- HPV-independent
- Associated with lichen sclerosus
- Typically seen in older women
Characteristic of Endometroid (type 1) or Serous (type 2) enometrial carcinoma?
Indolent, lymphatic spread
Endometroid
Characteristic of Endometroid (type 1) or Serous (type 2) enometrial carcinoma?
Arises in the setting of unopposed estrogen
Endometroid
What gene is most frequently mutated in uterine serous carcinomas?
Describe the “typical patient”
p53
Older (65-75), in a background of atrophic endometrium
Serous carcinoma = Type 2 endometrial carcioma
The other type (Type 1, endometroid) occurs in younger pts, backgorund of endometrial hyperplasia
Which layer fo the uterine corpus is most responsive to hormones?
Functionalis
(Basalis doesn’t really change much in response to hormones)
What type of epithelium is present in the vagina?
Stratified squamous (non-keratinized)
Note: no glands! lubrication is from the cervix and greater vestibular glands
How does the epithelium of the fallopian tube change during the menstrual cycle?
- Estrogen (folliclular phase) -> more ciliated cells
- Less estrogen (in luteal phase) -> more peg cells
Very few ciliated cells in menopause
At what stage of follicular development do cells become stratified?
Primary follicle
Which cell types are found in tthe theca interna of a follicle?
Theca cells: produce androgens
Granulosa cells: aromatize androgens to estrogen
Characteristic of Endometroid (type 1) or Serous (type 2) enometrial carcinoma?
Arises in the setting of an atropic endometrium
Serous
Describe the key histoligic features of the endometrium during each phase:
- Menstrual phase:
- Proliferative phase:
- Secretory phase:
-
Menstrual phase:
- Stratum functionale has shed
- Prominent basal glands
- Low estrogen, low progesterone
-
Proliferative phase:
- Stratum functionale is rebuilding
- Glands are straight
- High estrogen, low progesterone
-
Secretory phase:
- Sratum functionale has wavy glands
- Dilated with glycogen-rich fluid (due to progesterone)
- High estrogen, high progesterone
What are koliocytes?
Cells infected with HPV
- Large w/expanded halo around cells
- Large, crinkled nuclei
- Represent dysplasia, NOT cancer
Koliocytes will be present in any HPV infection: includes high and low risk
Vulvar Lichen sclerosus
- Typical presentation:
- Typical patient:
- Pathologic changes:
- Prognosis:
- Typical presentation: Itchy, whitis scaly plaques
- Typical patient: Older patients
- Pathologic changes: Thinning (atrophy) of epithelium with stromal hyalinization
- Prognosis: SCC (differentiated type) may arise
Which endometrial phase is characterized by vacuoles?
Early secretory
- Early secretory = vacuoles
- Mid-secretory = coiled vessels
- Late secretory = spiral arteries
Which of the following is a characteristic of primary follicles?
A. Has a stratified epithelium
B. Has a cavity
C. Is 10 mm in diameter
D. Has a simple squamous epithelium
E. Has a cumulus oophorus
A. Has a stratified epithelium
- B = secondary follicle
- Secondary follicle = more mature than primary
- D = primordial follicle
- C, E = mature follicle
Which of the following is an important effect of progesterone?
A. Secretory phase of the endometrium
B. Triggers ovulation
C. Follicle development
D. Maintenance of the corpus luteum
E. Initiation of menstruation
A. Secretory phase of the endometrium
List the parts fo the fallopian tube, from the part closest to the ovary to the uterus
- Infundibulum
- Ampulla
- Isthmus
- Intramural segment (inserts into the wall of the uterus)
Which of the following is characteristic of the vagina?
A. Elaborate, branched mucous glands
B. Washed out epithelial cells with pyknotic nuclei
C. Vascular submucosa
D. Serosa with a high fat content
E. Muscularis externa with an inner longitudinal layer and outer circular layer
B. Washed out epithelial cells with pyknotic nuclei
Which part of the uterus is retroperitoneal?
Cervix
The rest is peritonealized
- Broad ligament = transverse mesentery of the uterus
- All peritonealized organs have mesenteries?
Characteristic of Endometroid (type 1) or Serous (type 2) enometrial carcinoma?
Extremely atypical cells
Serous
- High nucleus:cytoplasm ratio
- Large, darkly stained nuclei w/ prominent nucleoli
- Many atypical mitoses
Characteristic of Endometroid (type 1) or Serous (type 2) enometrial carcinoma?
Aggressive, lymphatic and intraperitoneal spread
Serous
What endometrial changes occur in adenomyosis?
Endometrial glands in the stroma within the myometrium
Essentially, endometriosis confined to the myometrium
Which normal cell protein is disrupted by HPV’s E7 protein?
What is the result?
Rb-E2F complex
- Normally, Rb is bound to the trasncription factor E2F
- Prevents E2F from aberrently upregulating transcription
- Also, Rb provides positive feedback to p16
- p16 also inhibits phosphorylation (and activation) of E2F
Degradation of Rb by viral protein E7 results in uncontrolled cell division, accumulation of DNA damage
Also, p16 builds up: surrogate marker for high-risk HPV
What histologic features characterize proliferative endometrium? (3)
How do these features change in secretory edometrium? (3)
-
Proliferative (estrogen, no progesterone)
- Tubular/straight glands
- Pseudostratified columnar epithelium
- Mitoses
-
Secretory (estrogen + progesterone)
- Cytoplasmic vacuoles (early)
- Coiled glands (mid-secretory)
- Decidualized stroma, spiral arterioles (late)
Which HPV serotypes are most likely to lead to dysplasia? (4)
What is the natural course of infection with these serotypes?
16, 18, 31, 33
These are high-risk serotypes BUT:
- Most infections will resolve (without progressing to dysplasia)
- Most cases of dysplasia will resolve (without progressing to invasive carcinoma)
- Cases that do progress take years to go from low-grade to high grade, and then years to go from high-grade to invasive
KEY: we can prevent invasive carcinoma with screening!
Which layer of the uterine mucosa is shed during menstruation?
Describe the changes to the mucosa that result in shedding
Stratum functionale
- During proliferation and differentiation, a spiral artery ascends into the striatum functionale from the stratum basale
- When progesterone drops, this artery constricts, cutting off the blood supply to the functionale
- This causes cell death and shedding of the stratum functionale
The rest of the spiral artery stays behind in the stratum basale
What kind of vulvar lesion does this describe:
“Finger-like projections with a fibrovascular core”
What usually causes this lesion?
Condyloma acuminatum
Usually caused by low-risk HPV serotypes (6, 11)
NOT pre-malignant
(Will still see koliocytes)
Which cell protein is a surrogate marker of high-risk HPV infection?
P16
- Increases in high-risk HPV infection because viral protein E7 binds Rb, resulting in overexpression of p16
