Pathology of uterus, cervix, and vagina

Question 1

Cervix pathology: HPV infection, pre-malignant lesions and CA

Answer 1

• 2 types of HPV: low risk (HPV 6, 11) and high risk (HPV 16, 18)
• High risk HPV much more likely to lead to dysplasia-> SCC
• Systems for classifying dysplasia: histologically (intraepithelial system) and cytologically (bethesda system), almost all dysplasia is due to HPV
• Dysplasia can be in the cervix (CIN: cervical intraepithelial neoplasia), vagina (VAIN: vaginal intraepithelial neoplasia), or vulva (VIN: vulvar intraepithelial neoplasia)
• CIN1/VAIN1/VIN1 = mild dysplasia = LSIL (low grade squamous intraepithelial lesion, bethesda system)
• CIN2/VAIN2/VIN2 = moderate dysplasia = HSIL (high grade)
• CIN3/VAIN3/VIN3 = severe dysplasia/CA in situ = HSIL

Question 2

Cervix pathology: dysplasia grades 1

Answer 2

• Grossly, a nl cervix has pink squamous epithelia surrounding the os and a transition from squamous to glandular (columnar) as you approach the os (os surrounded by columnar, columnar surrounded by squamous)
• A nl squamous layer has a basal layer that does not exceed 1/3rd of the total epithelial height
• Grossly, a CIN1 lesion demonstrates multiple white areas/plaques that are generally more peripheral from the os
• Histo: a CIN1 lesion demonstrates abundant koilocytes (squamous cells w/ hyper chromatic nuclei and perinuclear halo), and a basal layer that is still relatively short

Question 3

Cervix pathology: dysplasia grades 2

Answer 3

• CIN1 (LSIL) indicates HPV infection, but will regress in most women back to nl cervix
• CIN2 is very hard to distinguish from CIN1, and will either regress or progress to CIN3 (will mostly focus on CIN1, CIN3/CIS)
• CIN3 gross: white lesions extend into os and are more confluent/larger area
• Histo: CIN3 demonstrates little maturation of squamous cells w/ basal layer taking up most of the height of the epithelium (basal layer extends close to top)
• There are no koilocytes in CIN3, there is no invasion yet
• Most women w/ CIN3 started at CIN3 or CIN2, CIN1 almost always resolves

Question 4

Cervix pathology: SCC

Answer 4

• Looks like typical SCC: nests of squamous cells/keratin pearls beyond the basement membrane of the basal squamous cells
• SCC may be micro invasive (<7mm horizontal spread from original lesion), or frankly invasive (more than these limits, usually grossly visible lesion)

Question 5

Cervix pathology: adenoCA

Answer 5

• AdenoCA also indicates HPV infection
• CA in situ (CIS): Architecturally nl glands but w/ cellular changes that indicate CA (hyper chromatic and large nuclei, decreased mucus production)
• No stromal invasion, but are pre-malignant and will progress to CA
• Clear cell adenoCA: associated w/ intrauterine DES exposure (daughters or mothers who had DES exposure have high risk for clear cell adenoCA)
• Prognosis for adenoCA and SCC the same

Question 6

Vagina pathology

Answer 6

• Primary lesions are uncommon, usually invasive lesions from cervix
• Primary lesions also associated w/ HPV

Question 7

Vulva pathology: condyloma acuminatum

Answer 7

• Condyloma acuminatum (anogenital warts): epidermal manifestation of HPV infection
• Most common viral sexually transmitted disease in US
• Can be flat or pedunculated
• A different condyloma (lata) associated w/ syphilis
• Micro: hyperkeratotic squamous epithelium w/ abundant koilocytes (koilocytes indicate HPV infection) and very thick squamous epithelium
• Not a neoplasm, is a reactive hyperplastic process

Question 8

Vulva pathology: extramammary paget’s disease

Answer 8

• Mucinous adenoCA in situ w/in the epidermis: adenoCA cells scattered btwn the squamous cells rather than forming a discrete collection of cells
• Etiology unknown, but prognosis is excellent if isolated (if w/ another malignancy prognosis is poor)
• Must rule out mets from elsewhere
• Histo: pale central nuclei surrounded by mucus (pink) scattered throughout squamous epithelium, stains positive for musicamine (buzz word for extramammary paget’s)

Question 9

CA of vulva

Answer 9

• Mostly SCC, 50% associated w/ HPV and 50% not
• SCC that is associated w/ HPV: are first VIN2/3-> SCC, mostly in younger pts
• Slow growing SCC of vulva from HPV: bowen disease
• SCC of vulva that is not associated w/ HPV: usually arises from long standing lichen sclerosus (thickening of dermis)
• Typically in older pt (around 80)
• Sarcoma botryoides: embryonal rhabdomyosarcoma (think this if vulva lesion on a young child)