female reproductive pathology m. kent froberg, md
TRANSCRIPT
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Female Reproductive PathologyFemale Reproductive Pathology
M. Kent Froberg, MDM. Kent Froberg, MD
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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.
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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
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Vulvar Dystrophy (leukoplakia)Vulvar Dystrophy (leukoplakia)
Dry-appearing, white patches on vulvar skin
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Vulvar dystrophy is a common clinical entity with several etiologies making Bx of the affected area necessary.
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Vulvar Dystrophy affecting perineal skin
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One of the most common causes of leukoplakia is lichen sclerosus et atrophicus
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Lichen sclerosus: atrophic epidermis and homogenized collagen within dermis
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Mild inflammation in lichen sclerosis
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Atrophic adenexal structures in lichen sclerosis
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Lichen Simplex Chronicus with hyperkeratosis & epidermal hyperplasia
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Vitiligo of vulva
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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
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Papillary hidradenoma
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Vulvar Papillary Hidradenoma with a lobular configuration of papillae covered by benign epithelium
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Papillary Hidradenoma
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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%
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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
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Paget Disease of Vulva: tumor consists of intra-epidermal glandular cells
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Paget Cells contain mucin
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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
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Ulcerated Squamous Cancer
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Exophytic Fissured Carcinoma
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Vulvectomy
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Nests of Squamous Cell Carcinoma with keratin whorls
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Radical Vulvectomy for Squamous Cell Carcinoma
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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
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Verrucous Carcinoma: has gross appearance of condyloma
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Verrucous Carcinoma of Vulva
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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
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Swollen Bartholin’s Gland
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Bartholin’s Cyst
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Inflamed Bartholin’s Gland with squamous metaplasia
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Wall of Bartholin’s cyst with acute & chronic inflammation
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Bartholin’s Abscess
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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)
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Candidiasis with satellite lesions
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White fungal patches on vulva and perineum
Candida
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Candida yeast forms within keratin layer
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Moist, inflamed vagina from Trichomoniasis
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Wet mount of Trichomonas vaginalis (flagellated protozoan): is an STD
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VAGINA: CONGENITAL LESIONSVAGINA: CONGENITAL LESIONS
Imperforate hymen:Imperforate hymen: Hematocolpos (blood Hematocolpos (blood
filling uterus)filling uterus) refluxreflux
Septate (“double”) vaginaSeptate (“double”) vagina
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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
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Adenosis may occur after DES or estrogen exposure during early fetal development
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Vaginal adenosis
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Adenosis
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Tuboendometrial glands in vaginal adenosis
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Red, granular focus of vaginal adenosis within squamous mucosa
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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
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Clear Cell Adenocarcinoma of vagina (arrow)
Uterus Cervix
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Glycogen filled clear cells of Clear Cell Adenocarcinoma
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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
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Protruding vaginal polypoid mass of Embryonal Rhabdomyosarcoma
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Polypoid masses of Sarcoma Botryoides (embryonal rhabdomyosarcoma)
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Cambian layer of sarcoma botryoides underlying vaginal epithelium
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Muscle-like cells and rhabdomyoblasts in rhabdomyosarcoma
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Cross striations may be present in cells of rhabdomyosarcoma (arrow)
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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
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Schiller-Duvall bodies of Endodermal Sinus (Yolk Sac) Tumor