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PATHOLOGY OF FEMALE REPRODUCTIVE SYSTEM DISEASES OF VULVA • VULVITIS • The five most important infectious agents producing vulvitis are: • HUMAN PAPILLOMA VIRUS (HPV), • HERPES GENITALIS • GONOCOCCAL • SYPHILIS • CANDIDAL VULVITIS. TUMORS Condylomas and Vulvar Intraepithelial Neoplasia (VIN) • condylomata acuminata (anogenital warts) is strongly associated with HPV 6 and HPV 11 • may be papillary and elevated or flat • few millimeters to many centimeters • red-pink to pink-brown • Histologically: perinuclear cytoplasmic vacuolization with nuclear angular pleomorphism and koilocytosis • they are not precancerous. HIGH-GRADE (VIN) & CARCINOMA OF THE VULVA • TWO BIOLOGIC FORMS OF VULVAR CARCINOMA • 1-seen in relatively younger patients, in cigarette smokers • type 16 is present in 75% to 90% of cases • coexisting vaginal or cervical carcinoma, carcinoma in situ. • the tumor tend to be poorly differentiated squamous cell carcinoma VULVAR CARCINOMA • 2-occurs in older women. it is not associated with HPV, • unifocal lesion • the overlying epithelium lacks the typical cytologic changes of VIN, • it may display dyskeratotic cells. • tumors tend to be well differentiated and highly keratinizing. VAGINITIS • A relatively common clinical problem • usually transient • not serious. • produces a vaginal discharge (leukorrhea). • cause by bacteria, fungi& parasites. • ppt factors include DM, systemic antibiotic therapy ,after abortion or pregnancy, or in elderly persons with compromised immune function, and in patients with the acquired immunodeficiency syndrome. VAGINAL INTRAEPITHELIAL NEOPLASIA AND SQUAMOUS CELL CARCINOMA • Occur in women older than age 60 years • A preexisting or concurrent CIN or cervical ca is frequently present. • PREDISPOSING FACTORS: • HPV infection detected in nearly all cases of vaginal intraepithelial neoplasia & more than half of cases of invasive squamous cell carcinoma of the vagina. • Diethylstilbestrol: vaginal clear cell adenocarcinoma, usually encountered in young women whose mothers took diethylstilbestrol during pregnancy. • vaginal adenosis: small glandular or microcystic inclusions appear in the vaginal mucosa appear as red granular foci and are lined by mucus-secreting or ciliated columnar cells. from such inclusions that the rare clear cell adenocarcinoma arises. CERVICITIS • Extremely common • Associated with a mucopurulent to purulent vaginal discharge • These inflammations have been variously subdivided into noninfectious and infectious cervicitis. • Many of infectious agents are transmitted sexually like GC, chlamydia trachomatis, Tricho. vaginalis, Herpis simplex type II……. TUMORS OF THE CERVIX CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN) AND SQUAMOUS CELL CARCINOMA • nearly all invasive cervical squamous cell carcinomas arise from precursor epithelial changes referred to as CIN. • N.B: NOT all cases of CIN progress to invasive cancer, and indeed many persist without change or even regress. • since the introduction of the papanicolaou (PAP) smear 50 years ago, the incidence of cervical cancer has decreased. • In populations that are screened regularly, cervical cancer mortality is reduced by as much as 99%. PAP SMEAR CERVICAL INTRAEPITHELIAL NEOPLASIA CIN • CIN I: mild dysplasia • CIN II: moderate dysplasia • CIN III: severe dysplasia & carcinoma in situ • low-grade squamous intraepithelial lesions (LSIL)= CIN I • high-grade squamous intraepithelial lesions(HSIL)= CIN II OR III • The higher the grade of CIN, the greater the likelihood of progression to cancer. EPIDEMIOLOGY AND PATHOGENESIS • the peak age incidence of CIN is about 30 years • the peak age incidence of invasive carcinoma is about 45 years. • precancerous changes usually take many years, perhaps decades, to evolve into overt carcinomas. Risk factors for the development of CIN and invasive carcinoma • 1-Early age at first intercourse • 2-multiple sexual partners • 3-A male partner with multiple previous sexual partners. • 4-persistent infection by "high-risk" papillomaviruses. • higher incidence in lower socioeconomic groups, • Rare among virgins, and the association with multiple pregnancies. • HPV can be detected by molecular methods in nearly all precancerous lesions and invasive cervical carcinoma. • certain high-risk HPV types, including 16, 18, 45&31account for the majority of cervical Ca. • while in condylomas, which are benign lesions, are associated with infection by low-risk HPV types( 6, 11, 42, and 44) • although many women harbor these viruses, only a few develop cancer, suggesting other influences on cancer risk. among the other well-defined risk factors are cigarette smoking and exogenous or endogenous immunodeficiency MORPHOLOGY • CIN I OR FLAT CONDYLOMA. this lesion is characterized by koilocytotic changes mostly in the superficial layers of the epithelium. • koilocytosis, is composed of nuclear hyperchromasia and angulation with perinuclear vacuolization produced by cytopathic effect of HPV. • IN CIN II the dysplasia is more severe, with maturation of keratinocytes delayed into the middle third of the epithelium. • It is associated with some variation in cell and nuclear size, heterogeneity of nuclear chromatin and mitoses above the basal layer, extending in to the middle third of the epithelium. • IN CIN III ( CARCINOMA IN SITU) there is greater variation in cell and nuclear size, marked chromatin heterogeneity, disorderly orientation of the cells, and normal or abnormal mitoses; these changes affect virtually all layers of the epithelium and are characterized by loss of maturation. differentiation of surface cells and koilocytotic changes have usually disappeared CIN I, II AND III INVASIVE CARCINOMA OF THE CERVIX • the most common cervical carcinomas are squamous cell carcinomas (75%), followed by adenocarcinomas and adenosquamous carcinomas (20%), and smallcell neuroendocrine carcinomas (<5%). • the squamous cell lesions are increasingly appearing in younger women, now with a peak incidence at about 45 years, some 10 to 15 years after detection of their precursors. • the only reliable way to monitor the course of the disease is with careful follow-up and repeat biopsies. • The relative proportion of adenocarcinoma has been increasing in recent decades; glandular lesions are not detected well by pap smear and other screening techniques. MORPHOLOGY • invasive carcinomas of the cervix develop in the region of the transformation zone . • range from microscopic foci of early stromal invasion to grossly conspicuous tumors encircling the os. CLINICALLY • Seen in women who have never had a pap smear or who have not been screened for many years. • Vaginal bleeding, leukorrhea, painful coitus (dyspareunia), or dysuria • Mortality is strongly related to tumor stage and, to cell type. • Most patients with advanced disease die as a result of local invasion rather than distant metastasis.
