Pathology of the uterus, vulva, and vagina Flashcards
endophytic
enDophytic = DOWN into the tissue
exophytic
OUT from the surface
Pagetoid
Single cells/clusters PERCOLATING through the epithelium
Molluscum Contagiosum
In adults, usually genital Common in children on extremities via sharing of towels Flesh colored, pearly skin lesions 1-5 mm, PAINLESS Endophytic growth with eosinophilic inclusion bodie
Condyloma Acuminatum
HPV 6 and 11 Hyperkeratosis and parakeratosis Especially papillae tips Hypergranulosis and elongated rete ridges Koilocytes
Koilocytes
Raisonoid nuclei Perinuclear clearing HPV!!
Trichomonas
flagellated protozoan; frothy yellow d/c, dysuria, dyspareunia; “strawberry cervix” on colposcopy
Candida
normal vaginal flora, but can overgrow (DM, Abx, pregnancy); curdlike d/c and pruritis
Actinomyces
“sulfur granule” with clublike projection non-copper IUD non-pathogenic
Vulvar Intraepithelial Neoplasia
Nuclear atypia (koilocytic) and lack of maturation= DYSPLASIA HPV 16, 18, other high-risk
VIN III / SCCIS
Increased mitoses, full thickness dysmaturity (cells at the surface look the same as those near the base)
HPV-associated SCC
♀
Inflammatory-associated SCC
♀ > 70 years HPV NEGATIVE Lichen sclerosus/d-VIN Prominent keratin “pearls” in well-differentiated carcinoma Increased mitoses, pink cytoplasm
Lichen Sclerosus
Smooth white plaques/papules, resembles parchment Dermal fibrosis with perivascular mononuclear infiltrate Thinned epidermis w loss of rete pegs, hydropic degeneration of basal cells & superficial hyperkeratosis
Extramammary Paget Disease
Adenocarcinoma variant Make sure it’s not melanoma Red, crusted sharply demarcated map-like area Marked hyperkeratosis and “pale” basal epidermis Tumor cells with “halo” lie singly or in clusters (with occasional gland formation *) in epidermis NOT usually associated with underlying invasive carcinoma
Malignant Melanoma
Embryonal Rhabdomyosarcoma
Cambium layer: Dense zone of rhabdomyoblast present beneath the surface epithelium Grossly: Polypoid, rounded, bulky masses which fills and protrude from vagina, resembling GRAPE-LIKE clusters (sarcoma botryoides)
Adenosis
Glandular tissue in vagina +/- DES exposure Present in 35-90% of exposed women Mucinous epithelium Can progress to clear cell carcinoma
DES-associated: Clear Cell Carcinoma
Tubulocystic pattern of growth with dense hyaline stroma; clear cytoplasm with bland nuclei “kissing lesion”: Anterior upper 1/3 of vagina, often w discontinuous areas
Endocervical Polyps
2-5% adult women Can cause “spotting” Curettage curative Dilated glands, dense eosinophilic stroma
Squamous Cell Carcinoma
Increased mitoses, full thickness dysmaturity Infiltrating irregular nests of malignant squamous cells, eliciting a desmoplastic stromal response
How is the staging of cervical cancer done?
Unlike endometrial cancers, the STAGING of cervical cancers is based on clinical factors
Adenocarcinoma in situ (AIS)
Hyperchromasia Mucin Depletion Luminal Mitoses High N:C ratio Almost always HPV-related
Proliferative phase of menstrual cycle
Estrogen as mitogen Histology Straight tubular glands Mitoses (*) Nuclear stratification
Secretory Phase of menstrual cycle
↑ Progesterone, E2 falling Histology “S-shaped” tortuous, coiling glands, secretory activity Subnuclear vacuoles “piano keys”
Menstrual Phase
↓↓ E2 and Progesterone Histology Stromal/glandular breakdown Inflammation Intravascular fibrin
Exogenous Hormone Effect
Hypersecretory glands (short-term) Decidualized stromal cells Inactive glands (chronic)
Pregnancy
Hormones: Progesterone, hCG Histology: Stromal decidualization Arias-Stella Reaction Hypersecretory glands w architectural complexity, nuclear enlargement, no mitoses
Menopause
>6 months without menstruation Thin endometrium w/o mitoses ↓ Cervical mucous and glycogenation Cystic atrophy
Abnormal Uterine Bleeding
Irregularity in menstrual cycle Amenorrhea- lack of menstruation Menorrhagia- heavy or prolonged Metrorrhagia- irregular Dysfunctional: no pathologic cause identified
Endometrial Polyps
Dense pink stroma, haphazardly arranged glands Cystic dilatation, hormonally unresponsive
Endometritis
Clinically PID Acute ↑ polys in stroma & glands (top) Curettage curative Chronic Plasma cells (bottom) Infertility
Adenomyosis/Endometriosis
Endometrial glands and stroma in abnormal location Infertility, dysmenorrhea In uterine wall = adenomyosis Extrauterine = endometriosis Activated inflammatory cascade
Leiomyoma
Gross: Single or multiple Spherical, Firm “White, Whorled” Well circumscribed Most common uterine tumor Menometrorrhagia, infertility, mass Whorled bundles of bland smooth muscle cells Hormonally responsive Treatment: Surgery Embolization GnRH agonist Nothing
Leiomyosarcoma
Malignant smooth muscle tumor Infiltrating, polypoid mass HIGH GRADE BY DEFINITION Hemorrhage, necrosis Most common uterine sarcoma 40-60 years Behavior: Rapid increase in size Metastasizes to lungs 5-year survival: 15-40%
Type I Endometrial Cancer
Pre-menopausal Risk factors: Unopposed estrogen, Genetics Background hyperplasia Minimal invasion/spread ER/PR positive
HNPCC
Mutated mismatch repair genes: Microsatellite instability 4 genes: MLH1, PMS2, MSH2, MSH6 Heterodimers with dominant & “recessive” element ♂ present w colon cancer; ♀ w endometrial cancer Women: 25-50% lifetime risk colorectal CA, 25-70% LR endometrial, 10% LR ovarian or stomach
Endometrial Hyperplasia
Physiologic response to unopposed estrogen: polyclonal process or EIN: clonal proliferation (PTEN mutation) AUB or asymptomatic Treatment: Hormonal Curettage Surgery
Simple Hyperplasia
Increased gland to stroma ratio Rarely progresses to cancer Treated with progestins Crowded, hyperchromatic glands Thickened, “fluffy” endometrium
Complex Hyperplasia
+/- Atypia Glandular crowding and architectural complexity 5-30% progress to cancer Diffuse involvement of endometrial cavity
Endometrial Carcinoma
Usually PMB, but many asymptomatic Peak in 5th and 6th decades 85% endometrioid Resembles endometrial glands Exophytic (protruding) mass of tightly packed glands without intervening stroma
Prognosis of endometrial carcinoma
Depends on stage and spread
Treatment of endometrial carcinoma
Surgery Radiation Vaginal brachy Whole pelvis Chemotherapy
Type II Endometrial Cancer
Post-menopausal Aggressive 10-20% endometrial cancers p53 mutation
Serous Carcinoma
Type II cancer Papillary growth, atypia Disseminated at presentation
Malignant Mixed Müllerian Tumor (Carcinosarcoma)
Biphasic tumor Homologous (left) vs Heterologous (right)
What are the most important lesions to remember in a patient with abnormal uterine bleeding?
polyps, adenomyosis, leiomyomas, hyperplasia and carcinoma But most cases aren’t due to lesions
Grade vs stage
GRADE is the degree of differentiation STAGE is the extent of spread
Difference between type I and type II endometrial cancers
Type I endometrial cancers occur in younger women and are estrogen-dependent with a generally good prognosis Type II endometrial cancers occur in older women, have higher grade histology and poorer prognosis
What gene(s) is (are) mutated in type II endometial cancers usually?
p53
What gene(s) is (are) mutated in type I endometial cancers usually?
BRAF, mismatch repair proteins (MLH-1), β-catenin
What is this?
Lichen sclerosis
