Female Reproductive Pathology M. Kent Froberg, MD

Female Reproductive PathologyFemale Reproductive Pathology

M. Kent Froberg, MDM. Kent Froberg, MD

ObjectivesObjectives

In this series of lectures we will ascend the In this series of lectures we will ascend the female reproductive tract from the vulva to female reproductive tract from the vulva to ovaries. At each anatomic site we will discuss ovaries. At each anatomic site we will discuss the major clinical conditions including the major clinical conditions including physiological, inflammatory, infectious and physiological, inflammatory, infectious and neoplastic disorders. Two hours will be neoplastic disorders. Two hours will be devoted to sexually transmitted infections. devoted to sexually transmitted infections. There will be an emphasis on major There will be an emphasis on major characteristics of tumors at each site and characteristics of tumors at each site and pathogenic mechanisms of non-neoplastic pathogenic mechanisms of non-neoplastic disease.disease.

VULVAR DYSTROPHY (leukoplakia)VULVAR DYSTROPHY (leukoplakia)

Age: any but most menopausalAge: any but most menopausal Gross: smooth-surfaced, dry, stiff, white, atrophic vulvaGross: smooth-surfaced, dry, stiff, white, atrophic vulva Micro: Micro:

lichen sclerosus: epidermal atrophy, dermal fibrosislichen sclerosus: epidermal atrophy, dermal fibrosis squamous hyperplasia: epithelium thick, squamous hyperplasia: epithelium thick,

hyperkeratotic (now called lichen simplex chronicus)hyperkeratotic (now called lichen simplex chronicus) Effects: fissures, uclers, infections, pruritis; few Effects: fissures, uclers, infections, pruritis; few ca ca Dx: biopsyDx: biopsy DDx: lichen sclerosus, lichen simplex chronicus, chronic DDx: lichen sclerosus, lichen simplex chronicus, chronic

dermatitis, Paget Disease, VIN, vulvar cancerdermatitis, Paget Disease, VIN, vulvar cancer

Vulvar Dystrophy (leukoplakia)Vulvar Dystrophy (leukoplakia)

Dry-appearing, white patches on vulvar skin

Vulvar dystrophy is a common clinical entity with several etiologies making Bx of the affected area necessary.

Vulvar Dystrophy affecting perineal skin

One of the most common causes of leukoplakia is lichen sclerosus et atrophicus

Lichen sclerosus: atrophic epidermis and homogenized collagen within dermis

Mild inflammation in lichen sclerosis

Atrophic adenexal structures in lichen sclerosis

Lichen Simplex Chronicus with hyperkeratosis & epidermal hyperplasia

Vitiligo of vulva

VULVAR NEOPLASMS: BENIGNVULVAR NEOPLASMS: BENIGN

Papillary hidradenomaPapillary hidradenoma localized, benign, sweat gland tumorlocalized, benign, sweat gland tumor structure: papillae of ductal lining structure: papillae of ductal lining

cellscells Condylomas (STD-related warts)Condylomas (STD-related warts)

accuminatum: caused by human accuminatum: caused by human papilloma virus infection (HPV) papilloma virus infection (HPV) koilocytosiskoilocytosis

lata: syphilitic wartlata: syphilitic wart

Papillary hidradenoma

Vulvar Papillary Hidradenoma with a lobular configuration of papillae covered by benign epithelium

Papillary Hidradenoma

Vulva: CarcinomaVulva: Carcinoma

Precursor: vulvar intraepithelial neoplasia (VIN) Precursor: vulvar intraepithelial neoplasia (VIN) some pts present with vulvar dystrophy some pts present with vulvar dystrophy

(leukoplakia) (leukoplakia) Progressive grades of dysplasia I, II, III (III Progressive grades of dysplasia I, II, III (III

also called Bowen’s disease or carcinoma in also called Bowen’s disease or carcinoma in situ) situ)

HPV associated (especially types 16 & 18) HPV associated (especially types 16 & 18) Concurrent vaginal and/or cervical CA in Concurrent vaginal and/or cervical CA in

~20%~20%

Vulva: carcinomaVulva: carcinoma

Extramammary Paget diseaseExtramammary Paget disease Presents as pruritic, red, crusted, well-Presents as pruritic, red, crusted, well-

delineated lesion usually on labia majoradelineated lesion usually on labia majora Unlike Paget disease of breast - rarely Unlike Paget disease of breast - rarely

associated with underlying invasive cancer associated with underlying invasive cancer Confined to epidermis, hair follicles and Confined to epidermis, hair follicles and

sweat glands sweat glands Long survival, but may recur following Long survival, but may recur following

surgical excisionsurgical excision

Paget Disease of Vulva: tumor consists of intra-epidermal glandular cells

Paget Cells contain mucin

VULVA: CARCINOMAVULVA: CARCINOMA

Invasive carcinoma: may be preceeded by vulvar Invasive carcinoma: may be preceeded by vulvar intraepithelial neoplasia (VIN)intraepithelial neoplasia (VIN) squamous cell ca = 88%squamous cell ca = 88% spread spread pelvic and inguinal nodes pelvic and inguinal nodes Rx: radical resection vulva, pelvic + groin nodesRx: radical resection vulva, pelvic + groin nodes Prognosis: Prognosis:

no nodes + = 85% 5 yr survivalno nodes + = 85% 5 yr survival Groin nodes + = 66%Groin nodes + = 66% pelvic nodes + = 25%pelvic nodes + = 25%

Dx often delayedDx often delayed

Ulcerated Squamous Cancer

Exophytic Fissured Carcinoma

Vulvectomy

Nests of Squamous Cell Carcinoma with keratin whorls

Radical Vulvectomy for Squamous Cell Carcinoma

VULVAR CARCINOMAVULVAR CARCINOMA

Verrucous squamous cell carcinoma: Verrucous squamous cell carcinoma: rarely metastasizesrarely metastasizes histologically bland & grossly mimics condylomahistologically bland & grossly mimics condyloma

Adenocarcinoma: fewAdenocarcinoma: few from sweat glands? from sweat glands? Bartholin’s?Bartholin’s?

Melanoma:Melanoma: 5% of vulvar cancer5% of vulvar cancer delay in Dx delay in Dx 30% 5 yr survival 30% 5 yr survival

Verrucous Carcinoma: has gross appearance of condyloma

Verrucous Carcinoma of Vulva

VULVA: BARTHOLIN’S GLANDVULVA: BARTHOLIN’S GLAND

Normal: Normal: columnar-linedcolumnar-lined mucus-secreting cystmucus-secreting cyst narrow necknarrow neck

Chronic inflammation Chronic inflammation scarring scarring obstructs neck obstructs neck cyst cyst

Acute inflammation (often gonococcus, chlamydia) Acute inflammation (often gonococcus, chlamydia) abscess abscess

Swollen Bartholin’s Gland

Bartholin’s Cyst

Inflamed Bartholin’s Gland with squamous metaplasia

Wall of Bartholin’s cyst with acute & chronic inflammation

Bartholin’s Abscess

VULVO-VAGINAL INFLAMMATIONVULVO-VAGINAL INFLAMMATION

Gonorrhea in childrenGonorrhea in children Trichomonas (strawberry mucosa — red)Trichomonas (strawberry mucosa — red) Moniliasis (candidiasis): white patchesMoniliasis (candidiasis): white patches Herpes (vesicles)Herpes (vesicles) Senile vaginitis (drynessSenile vaginitis (drynessulcers, fissures)ulcers, fissures)

Candidiasis with satellite lesions

White fungal patches on vulva and perineum

Candida

Candida yeast forms within keratin layer

Moist, inflamed vagina from Trichomoniasis

Wet mount of Trichomonas vaginalis (flagellated protozoan): is an STD

VAGINA: CONGENITAL LESIONSVAGINA: CONGENITAL LESIONS

Imperforate hymen:Imperforate hymen: Hematocolpos (blood Hematocolpos (blood

filling uterus)filling uterus) refluxreflux

Septate (“double”) vaginaSeptate (“double”) vagina

VAGINA: VAGINAL ADENOSISVAGINA: VAGINAL ADENOSIS

Islands of cervical glands beneath squamous ectocervixIslands of cervical glands beneath squamous ectocervix cervical eruptioncervical eruption

Cause: Cause: rarely congenitalrarely congenital most = maternal exposure to diethylstilbesterol (DES)most = maternal exposure to diethylstilbesterol (DES)

Asymptomatic but 0.1% Asymptomatic but 0.1% adenocarcinoma adenocarcinoma

Adenosis may occur after DES or estrogen exposure during early fetal development

Vaginal adenosis

Adenosis

Tuboendometrial glands in vaginal adenosis

Red, granular focus of vaginal adenosis within squamous mucosa

VAGINAL: CANCER (1)VAGINAL: CANCER (1)

Types: squamous cell carcinoma; adenocarcinoma; Types: squamous cell carcinoma; adenocarcinoma; sarcoma botryoides; yolk sac tumorsarcoma botryoides; yolk sac tumor

Squamous cell carcinoma:Squamous cell carcinoma: precursors: ca cervix or vulva; intraepithelial precursors: ca cervix or vulva; intraepithelial

neoplasia (VIN)neoplasia (VIN) spread: upper spread: upper pelvic nodes, lower pelvic nodes, lower inguinal inguinal staging: like cervixstaging: like cervix prognosis: stage 1 = 80% 5 yr; 3-4 = <20%prognosis: stage 1 = 80% 5 yr; 3-4 = <20%

Adenocarcinoma: clear cell type = DES-related; youngAdenocarcinoma: clear cell type = DES-related; young

Clear Cell Adenocarcinoma of vagina (arrow)

Uterus Cervix

Glycogen filled clear cells of Clear Cell Adenocarcinoma

VAGINA: CANCER (2)VAGINA: CANCER (2)

Embryonic rhabdomyosarcoma (sarcoma botryoides)Embryonic rhabdomyosarcoma (sarcoma botryoides) age: <5yrage: <5yr gross: rounded, grape-like (Greek: gross: rounded, grape-like (Greek: BotrysBotrys = grape) = grape)

bulky massbulky mass histology: small blue cell tumor may show histology: small blue cell tumor may show

myoblastic or strap cells; striations in somemyoblastic or strap cells; striations in some behavior: locally destructive; large ones behavior: locally destructive; large ones

metastasize metastasize Prognosis good if Rxed earlyPrognosis good if Rxed early

Protruding vaginal polypoid mass of Embryonal Rhabdomyosarcoma

Polypoid masses of Sarcoma Botryoides (embryonal rhabdomyosarcoma)

Cambian layer of sarcoma botryoides underlying vaginal epithelium

Muscle-like cells and rhabdomyoblasts in rhabdomyosarcoma

Cross striations may be present in cells of rhabdomyosarcoma (arrow)

VAGINA: CANCER (3)VAGINA: CANCER (3)

Endodermal sinus (yolk sac) tumorEndodermal sinus (yolk sac) tumor

like same tumor in ovarylike same tumor in ovary

histo: sheets & Schiller-Duval body (central blood histo: sheets & Schiller-Duval body (central blood

vessel surrounded by 2 layers of germ cells)vessel surrounded by 2 layers of germ cells)

synthesizes alpha fetoprotein (hyaline droplets that synthesizes alpha fetoprotein (hyaline droplets that

stain + by IHC; also stain + by IHC; also in blood) and alpha-1-trypsin in blood) and alpha-1-trypsin

prognosis: awfulprognosis: awful

Schiller-Duvall bodies of Endodermal Sinus (Yolk Sac) Tumor