Systemicist

Pathology.. Lecture # 9& 10 Title : Female Genital Tract

Done by: Dema Mhmd Khdier

A man may die, nations may rise and fall…….But an idea lives on

Vulva afeect all the linning of gt Some diseases can affect the vulva: 1) 2)Bartholin cyst :Obstruction of the excretory ducts of the gland 3)Dermatologic disorders 4) Non-specific epithelial disorders 5)Tumors Tumors & tumor like lesions Condyloma accuminatum : Hyperpigmented papules on genital skin OR Genital warts appear. caused by human papillomavirus (HPV) infection. 1) Condyloma accuminatum :

1)Usually multiple lesions 2)Associated with HPV 6 and HPV 11 Koilocytosis hollow. low grade 3) Not precancerous 4) May coexist with foci of (VIN grade I ) 2) Vulvar intraepithelial neoplasia (VIN) 1)Classic VIN Differentiated VIN _Young patients (40-60 y) _HPV associated _Usually multiple **low grade VIN (VINI) _HPV 6, 11 _NOT precancerous lesion _May coexist with conduloma accuminatum **High grade VIN: VIN II and VIN III (CIS) _HPV 16, 18 _May coexist with vaginal or cervical carcinoma. 2)Differentiated VIN _Older women > 60 y _NOT HPV associated _P53 mutation 3)Carcinoma of the vulva _3% of all genital tract cancers in women _Squamous cell carcinoma 95% _ Adenocarcinoma : 1-Bartholin gland CA 2 -Eccrine gland CA _ Extramammary paget disease _Melanoma _ Basal cell carcinoma (extremely rare Gross Appearance :white patch on a mucous membrane & associated with risk of cancer. Exophytic: describe solid organ lesions arising from the outer surface of the organ Most common on labia majora endophytic: grow inward into tissues in fingerlike projections from a superficial site of origin.

_ VIN and early CA appear as leukoplakia. Then exophytic or ulcerative endophytic

_HPV-positive tumors More often multifocal and appear warty.

_ HPV-negative tumors Usually unifocal. Histologic Subtype HPV associated vulvar SCC. _ Begin as classic VIN. _ Young patients _Poorly differentiated (basaloid) SCC HPV negative vulvar SCC. _Old patients _Associated with lichen sclerosis,lichen simplex chronicus, or differentiated VIN _ Well-differentiated (keratinizing) SCC. Tumor Spread All patterns tend to remain confined to the vulva for a few years. _Direct invasion _ Involvement of regional nodes _ Hematogenous spread. Prognosis depends on the stage: 1)The size of the tumor (< 2 cm good) 2)The depth of invasion. 3)LN involvement

Extramammary Paget Disease (Breast) A form of intraepithelial carcinoma **The majority of vulvar Paget have NO underlying carcinoma. _ Arise from epithelial proginator cells. **Occasionally an underlying carcinoma of sweat gland may be present. _May invade locally and metastasize Vagina Primary diseases are rare: 1) Congenital anomalies 2) 3) Primary tumors **Vagina is more often secondarily involved in the spread of cancer or infections arising in , vulva, bladder, or rectum. 1) Vaginal intraepithelial neoplasia (VAIN) &Squamous cell carcinoma Uncommon, old women, HPV associated, Low grade VAIN : VAIN I (flat condyloma) High grade VAIN :VAIN II, VAIN III

2)Vaginal adenosis : The presence of Mullerian type epithelium in the vagina

_Endocervical type, most common Mullerian : All epithelia of the female genital tract derived from Vaginal adenosis: presence of glandular epithelium within the vagina. _Tuboendometrioid

Exposure to diethylstilbestrol (DES) in utero Precursor to vaginal clear cell carcinoma 3)clear cell carcinoma **Young women in their late teens to early 20s **Exposure to DES in utero in 2/3 of cases **The overall risk is < 1:1000 **In 2/3 the tumor arises in the vagina. **In 1/3 the tumor arises in the cervix. **Tumor cells contain glycogen. ** Relatively good prognosis. 4)Sarcoma botryoid _A rare vaginal tumor _infants &children < 5 years _Soft polypoid masses “punch of grapes” A subtype of embryonal rhabdomyosarcoma Treatment is CTX and surgery &/or RTH. Columnar cells are constantly changing into squamous Cervix cells& area of changing cells& abnormal cells to develop. Transformation Zone _Zone of squamo-columnar junction _ In young it is located on the ectocervix. 2)Dynamic, changes location in response to woman’s hormonal status 3) Unstable region in which replacement of one epithelia for another repeat (fight of epithelia) Ectropion (erosion) The portion of endocervical mucosa that extend beyond the external os to cover the ectocervix. **Physiological change **Appear red and moist.

1) “Inflammations of the cervix” --Extremely common and associated with a mucopurulent to purulent Noninfectious (non-specific) cervicitis -- Vaginal aerobes and anaerobes, streptococci, staphylococci, enterococci, and E.coli. Infectious (specific) cervicitis - STD -- Chlamydia trachomatis is the most common, 40% of STD clinics 2)Nabothian Cyst Cyst in the cervix lined by columnar mucus --secreting cells and associated with inflammatory cells Pathogenesis: --Inflammation lead to squamous metaplasia -- Overgrowth of the regenerating squamous epithelium blocks the orifices of endocervical glands in the transformation zone.

3)Endocervical Common, 2-5% of all adult woman -- Inflammatory in origin, NOT premalignant ,,, Lead to vaginal spotting

Morphology: * Most arise in endocervical canal. * Loose fibro myxoid stroma * Dilated endocervical glands * Inflammation + squamous metaplasia

mucopurulent : mucus and pus purule nt :liquid Chlamydia trachomatis : bacterium ,,,,most commonly spread through vaginal, oral, and anal .

Tumors of The Cervix Nearly all invasive cervical SCC arise from precursor epithelial changes (CIN) Not all cases of CIN progress to invasive cancer, many persist without change or even regress CIN & Cervical Carcinoma Cervical CA is major cause of cancer-related deaths in females, particularly in the developing world The Pap smear is the most successful cancer screening test ever developed. Increased detection of preinvasive and potentially curable early cancers Pathogenesis 1)The peak age incidence of CIN is 30 years 2)The peak age incidence of CA is 45 years 3) Sexual transmitted disease caused by HPV…. _ HPV can be detected in nearly all precancerous lesions and invasive CA. _High-risk HPV: 16, 18, 45, and 31 _low-risk HPV: 6, 11, 42, and 44 ** Condyloma accuminatum, not precancerous Risk factors of CIN and invasive carcinoma 1)Early age at first intercourse 2)Multiple sexual partners 3)A male partner with multiple sexual partners 4)Persistent infection by "high-risk" HPV 5)Low socioeconomic class 6)Increased parity 7) Exposure to OCPs and nicotine 8)Genital infections (as chlamydia trachomatis) 9)Immunodeficiency as HIV ***May begin as low-grade CIN and progress to higher grade or may begin as high-grade CIN. On the basis of histology: CIN I: Mild dysplasia (flat condyloma) CIN II: Moderate dysplasia CIN III: Severe dysplasia and carcinoma in situ Terminology & Progression

Low grade squamous intraepithelial lesion CIN, cervical intraepithelial neoplasia

Cytology : (cells) & used SIL Biopsy : used CIN Invasive Carcinoma of the Cervix The most common cervical carcinomas are squamous cell carcinomas (75%) -Adenocarcinomas - Adenosquamous carcinomas Small-cell neuroendocrine carcinomas (<5%) Morphology Carcinomas of the cervix develop in TZ . Range from microscopic foci of early stromal invasion to grossly conspicuous tumors Grossly visible tumors May be exophytic, or Encircling the cervix and penetrating into the underlying stroma "barrel cervix" Tumor Spread 1)Extension into the parametrial soft tissues 2) Extension to bladder and rectum 3)Spread to pelvic lymph nodes depends on: -Tumor depth and the presence of LVI 4) Distant metastases occur late including: Para-aortic LNs and other organs

***Tumor stage is the most important prognostic factor. Clinical Course The vast majority of cervical neoplasms are diagnosed in the preinvasive phase. --More advanced cases are symptomatic: , , painful coitus (), and dysuria Most common cause of death is renal failure Body of : 1)Proliferative phase (mitoses) 2)Early secretory 3)Late secretory & predecidual )الخطوات بالترتيب ( changes . 4) Menstrual & stromal breakdown

Endometritis “Inflammation of the endometrium” Etiology: 1)Pelvic inflammatory disease (PID) : Gonoccoci , chlamydia, enteric bacteria 2) Retained products of conception : Streptococci and staphylococci 3)Foreign body as IUCD 4) Tuberculosis usually due to spread from tuberculous

Morphology: Acute 1)Rarely seen by pathologists 2)Neutrophilic infiltration of superficial epithelium and endometrial glands Chronic endometritis 1)Lymphoplasmacytic infiltrate 2)Plasma cells are essential for diagnosis 3)TB granulomatous endometritis Clinically : 1)Fever 2) Abdominal pain 3) Menstrual abnormalities (AUB) 4) and ectopic pregnancy due to damage to the fallopian tubes The growth of the basal (non-functional) layer of the endometrium down into the The uterine wall is thickened due to Reactive hypertrophy of the myometrium.

The uterus is enlarged and globular. Menorrhagia : menstrual bleeding lasting for longer than 7 days

C/P: Menorrhagia, ,& dysmenorrhea : painful periods or menstrual cramps, is pain during menstruation.

Endometriosis The presence of endometrial glands and stroma outside the endomyometrium. _10% of women in their reproductive years _ 50% of women with infertility Clinical picture: 1)Dysmenorrhea and pelvic pain 2)Pelvic mass filled with blood as chocolate cyst .3)Infertility

Site: Frequently multifocal 1)(Ovaries, the most common site) 2)Pouch of Douglas 3)Uterine ligaments 4) Fallopian tubes 5) Rectovaginal septum 6)Pelvic peritoneum 7)Vulva and vagina 8) Laparotomy scars 9) Umbilicus, lymph nodes, lungs Pathogenesis : 1- Regurgitation through ( MOST ) 2- Differentiation of coelomic epithelium . 3- Extra pelvic dissemination ( this the only way explains the in lymph node and lungs ) Morphology: Functioning endometrium, which undergoes cyclic bleeding. Gross appearance: 1)Red-blue to brown nodules or implants 2)lie on or just under the serosal surface 3)In ovaries, the lesions may form large blood-filled cysts (chocolate cysts) Microscopic examination: Finding two out of three features: Endometrial glands, endometrial stroma, or hemosiderin pigment Complications: 1) Organization of the blood leads to fibrosis 2)Adherence of pelvic structures, sealing of the tubal ends and distortion of the ovaries (frozen pelvis)

The End