Female Repro Tract Pathology (Hillard) Flashcards
Mayer-Rokitansky -Kuster-Hauser Syndrome
mullerian ageneis; missing fallopian tubes, uterus, and upper third of the vagina, presents with amenorrhea; but normal breast, pubic hair and vulvar development
Bartholin Cyst
benign vulvar lesion; results from obstruction of the Bartholin glands; cysts are non tender, unilateral, soft mass (3-5 cm) in the posterior aspect of the vaginal introitus; fluid is white or clear
Infected Bartholin Cyst
benign vulvar lesion; abscess; fluid is green or yellow; lesion is painful, warm, +/- surrounding edema and cellulitis; most common bug is E. coli
Lichen Sclerosus
benign vulvar and anogenital skin lesion; inflammatory disorder with activated T cells; most common in postmenopausal women; pruritis, dyspareunia, dysuria; white plaques; risk for TP53 positive keratinizing squamous cell carcinoma; histo thinning (atrophy), edematous band with lymphocytic infiltrate
Dyspareunia
painful sexual intercourse
Lichen Sclerosus has increased risk for what?
TP53 positive keratinizing squamous cell carcinoma
Histology of Lichen Sclerosus
thinning (atrophy), edematous band with lymphocytic infiltrate
Squamous Cell Hyperplasia (Lichen Simplex Chronicus)
thickening of skin (vulva) due to chronic, uncontrolled rubbing or scratching, appears as thickened reddened surface which can whiten over time. Associated with contact dermatitis, lichen sclerosis, and squamous cell carcinoma
Squamous Cell Hyperplasia (Lichen Simplex Chronicus) can be associated with other disorders?
contact dermatitis, psoriasis, lichen sclerosis, and squamous cell carcinoma
Condyloma Acuminatum
anogenital wart caused by HPV (6,11); sexual intercourse; laten phase can last weeks to months; skin-colored exophytic plaques; cauliflower-like appearance
Fleshy, skin-colored papules and plaques with a cauliflower appearance around the anogenital region should make you consider what?
Condyloma Acuminatum caused by HPV (6,11); low risk for progression to SCC
Histological findings of Condyloma Acuminatum?
hyperplastic papillary projections compromised of squamous cells with parakeratosis (surface keratinocytes with nuclei); some cells are kolicytic atypia (enlarged hyperchromic nuclei with a surrounding cleared-out halo space)
Vulvar carcinoma
SCC is the most common. 2 types:
1. Basaloid/Warty SCC
2. Keratinizing SCC
both arise from Vulvar intraepithelial neoplasia (VIN)
HPV related SCC of the vulva arises from what?
Vulvar intraepithelial neoplasia (VIN)
Basaloid / Warty Squamous Cell Carcinoma
Avg age 60 yrs; “Classic VIN”, associated with HPV (16 and 18)
Keratinizing Squamous Cell Carcinoma
Avg age 76 yrs; “Differentiated VIN”; caused by chronic irritation (lichen sclerosus or squamous cell hyperplasia); freq with TP53 mutations
Keratinizing Squamous Cell Carcinoma has a high frequency with what mutation?
TP53 mutations; causes an abnormal p53 tumor suppressor protein
Classic VIN
high risk HPV driven Basaloid / Warty SCC; full thickness atypia; lots of mitotic figures on histo; can progress to invasive SCC
Differentiated VIN
Non-HPV related vulvar SCC; basal/parabasal atypia; can lead to keratinizing SCC; with KSCC will show invasive nest of squamous cells showing keratinization
Papillary Hidradenoma
benign neoplasm; solitary, well-circumscribed vulvar dermal or subcutaneous nodule; columnar and myoepithelial cells with apocrine (sweat gland) differentiation; arises from the mammary-type glands along the primitive milk-line
What embryonic structure does papillary hidradenoma of the vulvar arise?
arises from the mammary-type glands along the primitive milk-line
What identical lesion of the papillary hidradenoma is seen in the breast?
intraductal papilloma
Extramammary Paget’s Disease (EMPD)
intraepithelial adenocarcinoma; sweat gland and keratinocyte differentiation; pruritic, ill-defined, erythematous +/- white crusted lesion with a “map-like” quality; immunostain CK7 positive
A pruritic, ill-defined, erythematous +/- white crusted lesion with a “map-like” quality in the anogenital region should make you think of what?
Extramammary Paget’s Disease (EMPD)
Lesion that is immunostain CK7 positive
Extramammary Paget’s Disease (EMPD)
What are Gartner duct cyst derived from?
Wolffian (mesonephric) remnants
What are Mullerian cyst derived from?
Mullerian (paramesonephric) duct
Gartner duct cyst and Mullerian cyst
submucosal cyst in reproductive age women; found on the anterior lateral walls of the vagina, can protrude into the orifice; asymptomatic, when symptomatic can cause vaginal pressure and painful intercourse
Diethylstilbestrol (DES) exposure
in utero exposure to DES predisposes women to vaginal clear cell adenocarcinoma; females exposed have increased patches of vaginal adenosis that turns into clear cell adenocarcinoma
Why was DES used?
nonsteroidal estrogen that addressed issues in pregnancy including miscarriage, preterm delivery, and post-partum lactation suppression
Why was DES discontinued?
discontinued in 1971 because linked to vaginal clear cell carcinoma in daughters of women who used the drug during pregnancy
Vaginal Embryonal Rhabdomyosarcoma (Sarcoma Botryoides)
uncommon tumor found in infants and young girls, protruding bulky; polypoid, grape-like mass; invasion can result in death; embryonal rhabdomyoblasts
Histogenesis of Vaginal Embryonal Rhabdomyosarcoma (Sarcoma Botryoides)?
Malignant cells are embryonal rhabdomyoblasts
Vaginal Squamous Cell Carcinoma and VAIN
starts with premalignant lesions VAIN; high-risk HPV (16 and 18); metastasizes in lymphatic pattern
Premalignant lesion of vaginal squamous cell carcinoma
Vaginal intraepithelial neoplasia (VAIN); caused by high risk HPV (16 and 18)
VAIN
Vaginal intraepithelial neoplasia (VAIN); caused by high risk HPV (16 and 18); Premalignant lesion of vaginal squamous cell carcinoma
Lymphatic spread of vaginal SCC of lower 2/3rd of vagina?
inguinal and femoral lymph nodes
Lymphatic spread of vaginal SCC of upper vagina?
regional iliac lymph nodes to periaortic lymph nodes
Which type of HPV is the most common cause of carcinoma?
HPV 16
HPV
Human papillomavirus; DNA virus; causes almost all cervical and vaginal carcinomas; most common cause is HPV 16; second runner up is HPV 18
Pathogenesis of HPV?
High-risk HPV integrates into the squamous cell genome of E6 and E7 oncogenes and promotes oncogenesis.
E6: increases telomerase (no division limit)
E6: degrades p53 (removes the brakes)
E7: drives cell proliferation by inactivating p21 and binding to RB
How does HPV affect E6?
E6: increases telomerase (no division limit)
E6: degrades p53 (removes the brakes)
How does HPV affect E7?
E7: drives cell proliferation by inactivating p21 and binding to RB
HPV has a predilection for which zone in the cervix?
transformation zone (T zone)
Progression of cervical dysplasia
normal squamous epithelium to low grade dysplasia (LSIL/CIN I) to moderate dysplasia (CIN II) and then severe dysplasia / carcinoma in situ (HSIL/CIN III)
CIN I
low-grade squamous cervical intraepithelial neoplasia (CIN) lesion, lack of maturation in the lower third of epithelium with koilocytes seen in upper layers; LSIL
LSIL
Low-grade squamous intraepithelial lesion; 60% regress, 30% persist and 10% progress to high-grade SIL; CIN I
HSIL
High-grade squamous intraepithelial lesion; 30% regress, 60% persist, and 10% progress to carcinoma! (CIN II and III)
What is the screening tool for cervical dysplasia?
a pap test; sample is taken from the cervix at the transformation zone, sample is stained with a Papanicolaou stain - specifically used to stain for squamous cells
Molecular screening techniques for cervical neoplasms
Real-time PCR-based assays or Hybrid capture are used to check for high risk HPV (16 and 18); is it a true dysplastic atypia?
What are the screening guidelines for Pap Testing
Start at age 21yrs; cytology every 3 yrs until 30 yrs; 30-60 yrs every 5 yrs w/ molecular test; stop screening at >65 yrs
Colposcopy
if pap test picks up abnormality cervix can be visualized through a coloscope; acetic acid is applied, causing coagulation and dysplasia turn acetowhite.
Low grade lesions vs high grade lesions on colposcopy
low-grade lesions show faint or fine punctation;
high-grade lesions show more coarse punctation
Punctation
refers to a dotted or stippling vascular pattern seen on colposcopy of the cervix
Treatment for high-grade dysplasia of the cervix
Cervical conization -cone-shaped piece of tissue is cut out from the cervix;
or LEEP (loop electrosurgical excision) - electric current runs through wire loop and cuts away abnormal tissue
Cervical adenocarcinoma in situ (AIS)
most cervical cancers are squamous but sometimes ENDOcervix is infected and causes glandular lesions; causing AIS; characterized by hyperchromatic nuclear enlargement with pseudostratification; can progress to invasive adenocarcinoma
Average age for cervical cancer?
45-50 yrs
Most common type of cervical cancer?
SCC (80%) and adenocarcinoma (15%)
Vaccination for cervical cancer?
three vaccines; recommended for both males and females age 11 or 12
Endocervical polyps
common benign growth in the ENDOcervix that protrudes beyond the epithelial surface of the cervix; occurs during reproductive years; can present with spotting; simple excision (polypectomy) is curative
Histology of proliferative phase endometrium in the menstrual cycle?
cellular blue stroma; tubular glands with pseudostratification; mitotic figures
Histology of secretory phase endometrium in the menstrual cycle?
tortuous, serrated glands with secretory material; decidualized stroma; “piano key” vacuoles
“piano key” vacuoles on histology
The early secretory phase of the menstrual cycle; subnuclear vacuoles that mimic the appearance of piano keys
Anovulatory
lack of ovulation
What are the 3 most common causes of AUB caused by hormonal imbalances during menarche and during the perimenopausal period?
- Ovarian lesion (PCOS - polycystic ovarian syndrome
- Metabolic disorder - obesity
- Endocrine disorders - thyroid, adrenal, pituitary