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Outline:
This lecture will, in general, follow and cover the subject material in the 7th Edition of Robbins. Required Reading: Kumar, Abbas, and Fausto, Ed. Robbins
and Cotran: Pathologic Basic of Disease, 7th. Ed., El Sevier Saunders, 2005,
pp.1060-1078.
Pathology of Vulva, Vagina and Cervix
General Objectives
To understand some of the more common nonneoplastic vulvar, vaginal and cervical lesions To understand the concept of vulvar dystrophy, vulval intraepithelial neoplasia (VIN) and cervical squamous intraepithelial lesion (SIL)
Specific Objectives
From your reading assignments in Robbins and following the lectures, you should be able to complete the following objectives. Many of the examination questions will come from them.
List several conditions which may present as a white plaque-like lesion on the vulva. List the cardinal histologic features of lichen sclerosis and squamous hyperplasia. Compose a list of the important clinical histologic features of VIN (vulvar intraepithelial neoplasia).
List the similarities and dissimilarities of vulvar Pagets disease vs. Pagets disease of the breast. Select the histologic features that differentiate acute from chronic cervicitis. Know the salient features and importance of the squamo-columnar junction and transformation zone.
Match the lesions associated with and the oncogenic effects of the following serotypes of HPV 6, 11, 16, 16, & 31. Concept and classification of cervical precancerous changes (the Bethesda system and CIN system). List risk factors which may predispose to cervical carcinoma.
Embryology
Anatomy
Pathology
Cervical Herpes
Trichomonas Vaginalis
BY ATHROPOD Phtirus Pubis
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Trichomonas
11
VIRAL
Cytomegalovirus, Hepatitis B Virus, Epstein-Barr Virus, Molluscum Contagiosum Virus
BACTERIAL
Group B Streptococci; Gram Negative Bacilli
PROTOZOAL
Enteromoeba Histolytica
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Candida albicans
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Bartholins Cyst
Cystic dilation of the Bartholin gland due to obstruction of Bartholins duct. Usually preceded by acute infection and may result in a Bartholins abscess. Swelling in the posterior aspect of the labium majus (up to 5 cm), associated with pain and discomfort. Occurs at all ages. Cysts are either excised or opened permanently.
Pathology of Vulva, Vagina and Cervix 14
Bartholin Cyst
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Vulvar Dystrophy
Lichen Sclerosis
Occurs anywhere on the body. All age groups, but most common after menopause Clinically: pale skin with atrophy Histologically: atrophy of epidermis and dense sclerosis of dermis with a mononuclear cell infiltrate about blood vessels.
Pathology of Vulva, Vagina and Cervix 16
Lichen Sclerosis
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Lichen Sclerosis
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Develops slowly, discomfort, predisposes to acute infections Pathogenesis: unknown (genetic, hormones) It is not a pre-malignant lesion, but increases risk of carcinoma slightly.
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Squamous Hyperplasia
Similar to Lichen Sclerosis Histologically: Hyperplasia of the vulvar squamous epithelium with hyperkeratosis. No significant increased risk of carcinoma. Biopsy is indicated in all vulvar lesions.
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Benign tumors
Papillary hidradenoma
Condyloma acuminatum
Carcinoma and vulvar intraepithelial neoplasia (VIN) Malignant melanoma
Malignant tumors
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Papillary Hidradenoma
Well circumscribed nodule, most commonly on labia majora. Benign proliferation of sweat glands, tubular ducts lined by columnar cells and surrounded by myoepithelial cells.
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Condyloma Acuminatum
Benign papillary (wart-like) lesion on the mucosa of the vulva, perianal region, urethra, cervix and vagina. Caused by human papilloma virus (HPV types 6 and 11). Flat condyloma (HPV associated lesion) is usual pattern for cervix.
Pathology of Vulva, Vagina and Cervix 23
Histologically: papillary proliferation of squamous epithelium with nuclear atypia and perinuclear vacuolization (koilocytosis) in the surface cells. Frequently regress spontaneously and are not precancerous lesions.
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Condyloma Acuminatum
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HPV Changes
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Uncommon malignancy (3% of all female genital cancers). Most occur in women over age 60 years. The majority (85%) are squamous cell carcinoma. Others include melanoma, adenocarcinoma, and basal cell carcinoma.
Pathology of Vulva, Vagina and Cervix 28
Two groups of squamous cell carcinoma differ in etiology: pathogenesis and clinical presentation First group is associated with HPV, preceded by vulvar intraepithelial lesion and multicentric. Vulvar intraepithelial lesion (in situ carcinoma, Bowens Disease) is frequently multicentric, 90% of cases associated with HPV, high risk of progression to invasive cancer.
Pathology of Vulva, Vagina and Cervix 29
Second group of vulvar squamous cell carcinoma is associated with vulvar dystrophy, unclear etiology. Metastatic spread is linked to size and depth of tumor. Most commonly involves regional lymph nodes, lung, and liver. Less than 2 cm in diameter have 60-80% 5-year survival rate.
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Red sharply demarcated lesion on the labia majora. Microscopic features are similar to Pagets Disease of the breast, clusters of anaplastic tumor cells within the epidermis and its appendages. These cells are surrounded by clear halo (micropoly-saccharide). Very good prognosis (without invasion or associated carcinoma).
Pathology of Vulva, Vagina and Cervix 31
Malignant Melanoma
Rare tumors (5% of all vulvar cancers). Peak incidence is 6-7 decades. Histologic and biologic characteristics are similar to melanomas elsewhere.
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Malignant Melanoma
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Vagina
Vaginal intraepithelial neoplasia and squamous cell carcinoma Adenocarcinoma Embryonal rhabdomyosarcoma
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Vagina (cont.)
Congenital Anomalies
Garthners duct cysts: common, derived from Wolffian duct rests, located on lateral wall of vagina submucosal cyst (up to 2 cm). Mucous cyst: derived from Mullerian epithelium. Atrasia Total absence of vagina Double vagina: failure of total fusion of the Mullerian ducts.
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Vagina (cont.)
Skeletal muscle (rhabdomyoma) Stroma (stromal polyps) Leiomyoma Hemangioma Vaginal intraepithelial neoplasia and squamous cell carcinoma. Primary carcinoma of the vagina is extremely uncommon. Associated with vaginal intraepithelial neoplasia. Most are secondary to carcinoma of the cervix or vulva.
Pathology of Vulva, Vagina and Cervix 36
Vagina (cont.)
Vaginal Adenocarcinoma
Rare tumor. Increased frequency (0.14%) of clear cell adenocarcinomas in young women (15-20 years) whose mothers had been treated with diethylstilbestrol (DES) during pregnancy (for threatened abortion). Composed of vacuolated, glycogencontaining cells (clear cell).
Pathology of Vulva, Vagina and Cervix 37
Vagina (cont.)
Vaginal adenosis is a possible precursor. Careful follow-up of all DES-exposed women is mandatory. Surgery and radiation (80% eradication rate). Vaginal adenosis is a possible precursor.
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Vagina (cont.)
Very uncommon vaginal tumor. Mostly seen in infants and children (under age of 5 years). Histologically: small, crowded, spindle cells with cytoplasmic extensions from one end. Locally invasive and may cause death by penetration into peritoneum or obstruction of urinary tract. Surgery and chemotherapy.
Pathology of Vulva, Vagina and Cervix 39
Sarcoma Botryoides
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Cervix
Inflammations
Normal Ectocervix
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Squamo-columnar Junction
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Cervix (cont.)
Clinically: discharge, itching, discomfort. Acute cervicitis: edema, acute inflammatory cells, necrosis, and reactive epithelial change. Chronic cervicitis: chronic inflammatory cells, granulation tissue, and fibrosis. Clinical evaluation, culture, and Papanicolaou smear examination.
Pathology of Vulva, Vagina and Cervix 46
Acute Cervicitis
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Chronic Cervicitis
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Cervix (cont.)
Endocervical Polyps
Vaginal spotting or bleeding. Inflammatory (non-neoplastic) growth within the endocervical canal (up to 5 cm). Simple curettage or excision.
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Cervix (cont.)
Are pre-malignant change. Dysplasia alteration in morphology Carcinoma in situ (CIS) malignant lesion confined to epithelium Cervical intraepithelial neoplasia (CIN)
CIN I: mild dysplasia, involving basal third of epithelium CIN II: moderate dysplasia, involving lower and middle third of epithelium CIN III: severe dysplasia or CIS, involving all layers of epithelium
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Cervix (cont.)
70% of women without treatment progress to invasive carcinoma. CIN begins at the squamo-columnar junction in the transformation zone. Peak incidence for CIS is 30 years old. CIS diagnosis by Schiller test, PAP smear and colposcopy.
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High-grade SIL
Normal
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Cervix (cont.)
Epidemiology Risk factors for cervical cancer
Early age at first intercourse Multiple sexual partners High-risk male sexual partners Most frequently implicated viruses are HPV (most frequent) and HSV 2. HPV 6 and 11 condylomas HPB 16, 18, 31, 33 dysplasia/carcinoma
Pathology of Vulva, Vagina and Cervix 55
Cervix (cont.)
Is an invasive cervical carcinoma. Most common complaint is bleeding after intercourse. Spreads via lymphatics or direct extension. May block cervical os, obstructing menstrual flow and lead to infection. May cause ureteral compression, hydronephrosis and renal failure.
Pathology of Vulva, Vagina and Cervix 56
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Cervix (cont.)
Stage 0 CIS Stage I confined to cervix Stage IA microinvasive cancer, <5 mm in depth Stage IB invasive cancer, >5 mm in depth Stage II extends beyond cervix into upper 1/3 of vagina, but not onto pelvic wall Stage III extends to pelvic wall or lower 1/3 of vagina Stage IV extends beyond pelvis into bladder or rectum with distant metastases
Pathology of Vulva, Vagina and Cervix 58
Cervix (cont.)
Stage 0: 100% Stage I: 90% Stage II: 75% Stage III: 35% Stave IV: 10-15%
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Cervix (cont.)
Lesions which are high in the endocervical canal Inconclusive or failed colposcopy, such as positive cytology and negative biopsy Ca in situ on punch or colposcopic biopsy in which there are large or multifocal lesions on the cervix Questionable microinvasion
Pathology of Vulva, Vagina and Cervix 60
Cervix (cont.)
There are three main types of biopsy procedures used to provide tissue for histology evaluation:
Colposcopic directed biopsy (visible lesion delineated by colposcopy) Punch biopsy Cone biopsy
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