Lecture 2 Female Genital tract

1. Lecture 2 Female Genital tract Dr. Basim Shehab Ahmed

2. Cervical intra epithelial neoplasia CIN: It is precancerous epithelial changes that can be detected by cytological examination before any gross abnormality is occurred (by many years, as long as 20years). * Only fraction of CIN progress to invasive CA, * On the basis of histological examination, precancerous changes are graded into: CIN I---mild dysplasia, CIN II---moderate dysplasia, CIN III---severe Dysplasia & carcinoma in situ. Notes: 1. Sometimes depending on cytological examination, Precancerous changes divided into Low grade & high grade lesion (squamous intraepithelial lesions (SIL)): Low grade (SIL) = CIN I High grade (SIL) = CIN II & III

3. 2. Progression from low grade to high grade lesions can occur & regression of low grade lesions is a fact. e.g. CIN I show regression in 50% --60%, persist in 30% of cases & progress to CIN III 20%, while CIN III show regression only in 33% & progress to invasive carcinoma in 6%--74%. Age incidence:: CIN is around 30 years while invasive cervical carcinoma is about 45 years (proved the fact that CIN is preceding the invasive carcinoma for many years). Racial factor: Low incidence of cervical carcinoma among Jewish women, & more common among white female.

4. Risk factors & pathpogenesis (for both CIN & INVASIVE CARCINOMA): (1)Early age of first intercourse (most important factor). (2)Multiple sexual partners. (3)A male partner with multiple previous sexual partners. (4) Persistent infection (high risk) HPV type 16,18,31,33,35,39,45,….. in 90% 0f CIN & Invasive carcinoma. These above factors are called prominent risk factors. (5)Lower socioeconomic group. (6) rare among the virgins. (7)Multiple pregnancies. (8) smoking & immunodeficiency. All these factors pointed strongly to the likelihood of sexual transmission of a causative agent (mainly HPV). 85%_ 90% of CIN are positive to HPV (high malignant potential types 16, 18, 31, 33, 35, 39, 45, 52, 56, 58….). These subtypes of viruses integrated into host cellular genome & they start to produce proteins that inhibit or inactivate tumor suppressor genes (P53), & activate certain genes called Cyclin E, which result into uncontrolled cellular proliferation (tumor formation).

5. Morphology of CIN: Important notes on CIN: 1. Large majority of cases of CIN are occurred at areas of squamous metaplasia at transformation zone & it's endocervical glands. 2. All these CIN lesions are shared many cytological features of invasive carcinoma, include: i. enlargement, irregular nuclei. ii. increased mitotic activity. iii. Alteration of maturation patterns. iv. Diminution or absence of cytoplasmic glycogen (decrease or lack of iodine staining by Schiller's test. CIN I:mild dysplasia or flat condylomas: characterized by Koilocytotic changes limited to superficial 1/3 of cervical epithelium (positive HPV). CIN II:moderate dysplasia: characterized by Dysplasia (variation in cell & nucleus size) affects superficial 1/2 of epithelium (most of layers). Normal looking mitosis above the basal layer. Superficial layer of epithelium is still well differentiated (flat & keratinized) or sometimes show koilocytosis

6. CIN III:severe dysplasia: characterized by Dysplasia affects all layers of epith. Normal or abnormal mitosis above the basal layer. Superficial differentiated squamous cells of Koilocytotic changes are absent. CIN III may progress from CIN I or may start as CIN III de novo. Dysplatic changes of CIN III may extend into endocervical glands, but the changes are confined to the surface epithelium & its glands. (carcinoma in situ). Invasive CA of cervix: Age incidence: young female with peak incidence 45 year (10_15 years history of precancerous lesions).

7. Morphology of invasive cervical carcinoma Gross: (1) Polypoid, fungating mass (encircle external os), the commonest type. (2)Ulcerative: sloughing of central surface of tum. (3)Infiltrative: involve the underlying stroma, to the vagina, uterine corpus (endometrium & myometrium), parametrium (fix the uterus to the surrounding parametrial soft tissue of pelvis), & to the lower urinary tract (ureters). Hematogenous & lymphatic metastases are common. Mic: 75% are squamous cell carcinoma of varying differentiation. 20% adenosquamous carcinoma. 5% neuroendocrine carcinoma. Note:EBV & HTLV-1 viruses may play a role in etiology of invasive cervical carcinoma.

8. Clinical course: Preinvasive carcinoma & CIN III are appeared as white areas on colposcopic examination after application of diluted acetic acid. Advanced carcinomas:abnormal vaginal bleeding, leukorrhea, painful coitus (dyspareunia), dysuria. Staging of cervical carcinoma (FIGO) system: Stage 0: carcinoma in situ. Stage I: Cervical carcinoma confined to the uterus. Stage II: Cervical carcinoma extends beyond the uterus but not the pelvic wall or the lower third of vagina. Stage III: involve pelvic wall & / or lower third of vagina & /or hydronephrosis (non functioning kidney). Stage IV: Cancer invades mucosa of bladder or rectum, & /or beyond true pelvis. FIGO (Federation Internationale de Gynecologie et d' Obstetrique

9. Body of uterus (uterine corpus) Endometritis: Acute endometritis: mainly due to bacterial infections predisposing factors :parturition or miscarriage, retained products of conception. MIC: inflammation limited to the interstitium & is non specific. Removal of products of gestation will follow by resission of infection. Chr. Endometritis: Occur in: (1) Chronic gonorrheal pelvic disease. (2) TB either from military spread or drainage of TB salpingitis . (3) In Postpartal or postabortal endometrial cavities (due to retained gestational tissue). (4) Intrauterine contraceptive devices (IUD) . (5) Without evident cause (SPONTANEOUS) . Histologically:irregular proliferation of endometrial glands with chronic inflammatory cells (plasma cells, macrophages & lymphocytes)

10. Adenomyosis: It is a growth of basal layer of endometrium (endometrial stroma or glands or both) into myometrium. * uterine wall become thickened because of presence of endometrial tissue within myometrium & reactive hypertrophy of myometrium. * cyclic bleedinginto the nests is unusual because basal layer of endometrium is nonfunctional. * Marked involvement of uterine wall by adenomyosis will lead to menorrhagia, dysmenorrhea & pelvic pain before menstruation.

11. Endometriosis (EM): Appearance of foci of endometrium outside the uterus whether in pelvis (ovaries , pouch of Douglas , uterine ligament , tubes ….) or less frequently in more remote sites of peritoneal cavity , about umbilicus ,LN , lungs, heart ,bone etc. Pathogenesis: (1)Regurgitation theory: menstrual backflow through fallopian tubes &subsequent implantation (like in ovaries) but this not explain lesion in LN &lung. (2)Metaplastic theory: endometrial differentiation of coelomic epithelium, also this theory not explain lesion in LN &lung. (3)Vascular or lymphatic dissemination explain extrapelvic or nodal implants.

12. Morphology of endometriosis: Endometriosis almost always contains functional endometrium&undergo cyclic bleeding (unlike the adenomyosis) so these foci appear grossly as red blue to yellow brown nodules which are either microscopic to 1-2cm under serosal surface, when ovaries affected---endometriosis form large blood filled cyst transform into what is calledchocolate cyst,seepage &organization of blood---widespread fibrosis &adherence of pelvic structures, distortion of fimbriae, tubes & ovaries The histological diagnosis of endometriosis at all sites depends of finding within the lesions two of the followings three features (endometrial glands, stroma, & hemosiderin pigment).

13. Clinically: depend on distribution of lesion (symptoms & complications) 1. Scarring of oviduct &ovaries---discomfort in the lower abdomen & eventually causes infertility. 2. Rectal wall involvement----pain on defecation. 3. Bladder involvement----dyspareunia &dysuria . * In almost all cases, there is dysmenorrhea & pelvic pain because of intra pelvic bleeding & periuterine adhesion .