PathoBasic - Vulva, Vagina, Cervix E.Obermann
Vulva Inflammatory Changes Non-neoplastic lesions «Skin type lesions» Lichen sclerosus Infection: HSV, Candida Fibroepithelial stroma polyp Cutaneous Neoplasia Soft Tissue Neoplasia HPV related lesions Non HPV related lesions Angio..lesions
Vulva Inflammatory Changes Desquamat. inflamm. Vaginitis Non-neoplastic lesions Fallopian tube prolaps Adenosis Neoplasms Clear cell carcinoma
Vulva Non-neoplastic lesions Neoplasms Microgland. Hyperplasia Mesonephric Duct Remnant CIN Squamous cell carcinoma Ais Adenocarcinoma
Vulva Lichen sclerosus Clinical Issues Typically 5th decade "porcelain white" plaques Premalignant disease Early: Lichenoid lymphocytic infiltrate and vacuolization of basal epidermal layer Well developed: Hyalinization and edema in superficial dermis DD VIN, differentiated type Lichen planus Morphea Late-stage radiation dermatitis
Vulva Infection: HSV + Candida Herpes simplex infection Microscopic Pathology Ulcerated epidermis or intraepidermal blister Intracellular ballooning multinucleation, nuclear molding, and ground glass Differential Diagnoses Squamous cell carcinoma Reparative changes adjacent to ulcer Candida infection Microscopic Pathology Ortho- and parakeratosis with acanthosis and variable spongiosis Epidermal neutrophil migration ± subcorneal vesicles Hyphae, pseudohyphae, and budding yeast
Clinical Issues More common during pregnancy Vulva, vagina, and rarely cervix Local excision Macroscopic Features Usually < 5 cm Typically polypoid or pedunculated Vulva/Vagina/(Cervix) Fibroepithelial Polyp Microscopic Pathology Central fibrovascular core Variably cellular stroma Stellate and multinucleate stromal cells Cytologic features range from small, bland nuclei with dispersed chromatin to enlarged and hyperchromatic with irregular contours (pseudosarcomatous)
Vulva Usual VIN Clinical Issues Pruritus 4th-5th decade Full- or near full-thickness epithelial involvement Atypical parakeratosis ± koilocytotic atypia Nuclear enlargement with hyperchromasia Brisk mitotic activity often with abnormal forms and apoptosis Etc Grading 1-3 resp. LSIL/HSIL G2p16 HPV-related
Vulva Differentiated VIN Clinical Issues Typically 7th-8th decade Pruritus Epithelial thickening with prominent parakeratosis, elongation, and anastomosis of rete ridges Premature keratinization with squamous eddies and keratin pearls Enlarged, hypereosinophilic keratinocytes with prominent intracellular bridges Prominent cytologic atypia of basal layers Etc No grading No HPV association
Clinical issues Vulvovaginal region, also extragenital sites Subcutaneous mass, usually < 3 cm Local excision adequate treatment Benign, nonrecurring Vulva Cellular Angiofibrom Typically well-demarcated border Short intersecting fascicles of spindle-shaped cells Numerous small to medium-sized vessels Interspersed delicate collagen bundles Occasionally exhibits cytologic atypia
Clinical Issues Most common in 4th decade 30-40% risk of local, nondestructive recurrence Usually < 5 cm Multinodular growth with well-defined lobules Abundant myxoid stroma Thin-walled, curvilinear vessels Stromal inflammatory cells, particularly polymorphonuclear leukocytes Vulva Superficial Angiomyxoma
Vulva Deep aggressiv Angiomyxom Clinical Issues Reproductive-aged women 30-40% risk of local, destructive recurrence if incompletely excised Macroscopic Features Poorly demarcated with soft, gelatinous consistency Microscopic Pathology Infiltrative, uniformly hypocellular tumor Copious myxoid matrix containing bland spindleshaped stromal cells Medium to large-sized vessels, often with hyalinized walls Collections of smooth muscle ("myoid bundles")
Vagina Desquamative Inflammatory Vaginitis Etiology/Pathogenesis autoimmune or erosive lichen planus? Clinical Issues > 50 years bleeding, and purulent vaginal discharge erythema Majority require treatment > 1 year Dense acute and chronic inflammatory infiltrate Thinning &/or desquamation of squamous epithelium
Clinical Issues Chronic pain, dyspareunia, vaginal bleeding, discharge 1 months -30 years after hysterectomy Vagina Fallopian tube prolaps Tubal epithelium with secretory, ciliated, and intercalated cells Organized smooth muscle bundles Differential Diagnoses Polypoid granulation tissue Endometriosis Endometrioid adenocarcinoma Mesenchymal lesions of vagina
Vagina Adenosis Clinical Issues DES-related (90%) Müllerian-type epithelium replacing squamous mucosa or forming glands in lamina propria Simple or cystic glands ± papillary infoldings Squamous, microglandular, and intestinal metaplasia can occur Differential Diagnoses Endometriosis Clear cell carcinoma
Clinical Issues Exposure to DES Anterior wall, upper 1/3 of vagina Vaginal bleeding or discharge Tubulocystic (most common), papillary, solid Marked nuclear atypia Mitotic activity usually < 10/10 HPF Ancillary Tests CK7 and EMA positive Vagina Clear Cell Carcinoma Differential Diagnoses Atypical adenosis Arias-Stella reaction in adenosis or endometriosis Metastatic renal/ endometrial clear cell carcinoma
Cervix Microglandular Hyperplasie Clinical Issues Reproductive age Tightly packed tubular or cystically dilated glands Intraluminal mucin with sprinkling of acute inflammatory cells Scant intervening stroma with variable amounts of acute and chronic inflammation Differential Diagnoses Endometrial adenocarcinoma Endocervical adenocarcinoma Clear cell adenocarcinoma
Clinical issues Typically incidental finding Vagina Mesonephric Duct Remnants Located deep to normal endocervical glands Individual small clusters or linear arrays of small to medium-sized round tubules Intraluminal, densely eosinophilic material Ancillary Tests EMA, calretinin, pax-2, Bcl-2, androgen receptor, and CD10 (luminal) positive Differential Diagnoses Mesonephric carcinoma Cervical involvement by endometrial adenocarcinoma Adenocarcinoma in situ
Cervix Intraepithelial Neoplasia Acanthosis, hyperkeratosis, parakeratosis, papillomatosis Koilocytotic atypia Mitoses typically in lower 1/3 (LSIL) or all layers (HSIL) Koilocytotic atypia Increased nuclear size and hyperchromasia Crowded, often uniformly enlarged nuclei with irregular nuclear contours Differential Diagnoses Squamous metaplasia Atrophy CIN2 p16
Squamous Cell Carcinoma Clinical Issues Abnormal Papanicolaou smear High-risk HPV (types 16, 18) most common Often squamous differentiation Variants: spindle, lymphoepithelial-like, "warty," verrucous, papillary, squamous/squamotransitional, basaloid Differential Diagnoses HSIL with endocervical gland involvement Adenoid basal carcinoma Glassy cell carcinoma Small cell neuroendocrine carcinoma Large cell neuroendocrine carcinoma (vs. basaloid SCC) Retraction artifact (vs. lymphovascular invasion) Displacement artifact (vs. lymphovascular invasion)
Clinical Issues Age: 38 years (mean) High-risk HPV infection (esp. HPV-18) Often coexistent squamous intraepithelial lesion Preservation of normal glandular architecture Abrupt transition from normal to neoplastic Enlarged, hyperchromatic, pseudostratified nuclei with apical eosinophilic to mucinous cytoplasm Apical mitoses and apoptotic bodies Cervix Adenocarcinoma in situ Differential Diagnoses Invasive endocervical adenocarcinoma Reactive endocervix
Clinical Issues Abnormal vaginal bleeding "Barrel-shaped" cervix No gross abnormality (~ 20%) Cervix Adenocarcinoma, usual type Closely packed or irregularly spaced glands Cribriform, microglandular, papillary, cystic, or solid growth Apical mitoses and apoptotic bodies frequent Ancillary Tests p16 + (strong diffuse), CEA +, Vimentin/ER/PR - Differential Diagnoses Microglandular hyperplasia Endocervical adenocarcinoma in situ Endometrial adenocarcinoma