Female Genital Tract & Breast

Infections of the Female genital tract

Herpes Simplex
Vulva, vagina and cervix Teenager, young women 1/3 will have clinical symptoms Painful red papule that progress to vesicles and coalesce to form ulcers Fever, malaise, tender inguinal nodes

Yeast (Candida)
10 % of women, enhanced by DM, OCP Leukorrhea, priritus
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Infections of the Female genital tract

Trichomonas
15 % of women in STD clinics Purulent vaginal discharge Strawberry cervix

Mycoplasma
Implicated in spontaneous abortion and chorioamnionitis

Gardnerella
Gram negative small bacilli
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Pelvic Inflammatory Disease

Pelvic pain, adnexal tenderness, fever & vaginal discharge Gonococcus, chlamydia & enteric bacteria Puerperal infections: Staphylococci, Streptococci, Clostridia, coliform bacteria
Acute suppurative salpingitis Salpingooophoritis Tuboovarian abscess Pyosalpinx/Hydrosalpinx Peritonitis Intestinal obstruction from adhesions Bacteremia Infertility

Complications

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VULVA
Bartholin Cyst
obstruction of the Bartholin duct, usually by a preceding infection 3 to 5 cm in diameter lined by either the transitional epithelium of the normal duct or squamous metaplasia.

Vestibular Adenitis
Vulvodynia inflammation of the surface mucosa and vestibular glands chronic, recurrent, and exquisitely painful
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VULVA
Non-Neoplastic Epithelial Disorders
Lichen sclerosus
also called chronic atrophic vulvitis, atrophy, fibrosis, and scarring
1) atrophy (thinning) of the epidermis, with disappearance of the rete pegs, 2) hydropic degeneration of the basal cells, 3) replacement of the underlying dermis by dense collagenous fibrous tissue, and 4) a monoclonal bandlike lymphocytic infiltrate

lichen simplex chronicus

hyperplastic dystrophy acanthosis & hyperkeratosis
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Lichen sclerosus

lichen simplex chronicus

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VULVA
Neoplasms
Benign
Papillary Hidradenoma
labia majora or interlabial folds identical in appearance to intraductal papillomas of the breast

Condyloma Acuminatum
verrucous gross appearance HPV, types 6 and 11 koilocytotic atypia (nuclear atypia and perinuclear vacuolization)-that is considered a viral "cytopathic" effect

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VULVA
Neoplasm
Pre-malignant and Malignant
Vulvar intraepithelial neoplasia
Pre-cancerous change nuclear atypia in the epithelial cells, increased mitoses, and lack of surface differentiation

Carcinoma
3 % of genital CA 85 % are SCCA, 15 % BCCA, adenoCA, melanoma

Malignant melanoma
less than 5% of all vulvar cancers and 2% of all melanomas in women

Pagets
pruritic, red, crusted, sharply demarcated, maplike area, occurring usually on the labia majora
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VAGINA
Congenital anomalies Gartner duct cyst

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VAGINA
Malignant & Pre Malignant Neoplasm
Vaginal Intraepithelial Neoplasia Squamous cell carcinoma -95 %
HPV asscociated Upper posterior vagina irregular spotting or the development of a frank vaginal discharge (leukorrhea).

Adenocarcinoma
0.14% DES-exposed young women from their mothers

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Embryonal Rhabdomyosarcoma
Also called sarcoma botryoides polypoid, rounded, bulky masses consistency of grapelike clusters the tumor cells are crowded in a so-called cambium layer; but in the deep regions, they lie within a loose fibromyxomatous stroma that is edematous
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CERVIX
Acute & chronic cervicitis
Acute cervicitis
characterized by acute inflammatory cells, erosion, and reactive or reparative epithelial change

Chronic cervicitis
inflammation, usually mononuclear, with lymphocytes, macrophages, and plasma cells

HSV-epithelial ulcers C. trachomatis lymphoid germinal centers T. vaginalis epithelial spongiosis

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CERVIX

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CERVIX
Endocervical polyp
2-5 % of adult women irregular vaginal "spotting" or bleeding small and sessile to large, 5-cm masses that may protrude through the cervical os a loose fibromyxomatous stroma harboring dilated, mucus-secreting endocervical glands, often accompanied by inflammation and squamous metaplasia
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CERVIX Intraepithelial
Neoplasia
Pathogenesis
Early age at first intercourse Multiple sexual partners Increased parity A male partner with multiple previous sexual partners The presence of a cancer-associated HPV The persistent detection of a high-risk HPV, particularly in high concentration (viral load) Certain HLA and viral subtypes Exposure to oral contraceptives and nicotine Genital infections (chlamydia)

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CERVIX HPV & CA

HPV DNA is detected by hybridization techniques in over 95% of cervical CA Specific HPV types are associated with cervical cancer (high risk) versus condylomata (low risk);
low (include types 6, 11, 42, 44, 53, 54, 62, and 66) and high-risk types (include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68)

Experimental data indicate that viral (E6 and E7) genes of high risk HPVs can disrupt the cell cycle via binding to RB with up-regulation of Cyclin E (E7) and p16INK4;
the two viral oncogenes cooperate to promote DNA synthesis while interrupting p53mediated growth arrest and apoptosis of genetically altered cells.

The physical state of the virus differs in different lesions,

integrated into the host DNA in cancers, free (episomal) viral DNA in condylomata and most precancerous lesions.44

Certain chromosome abnormalities, including deletions at 3p and amplifications of 3q, have been associated with cancers containing specific (HPV-16) papillomaviruses Recent data indicate that vaccines directed against papillomaviruses can prevent infection and the development of precancerous disorders

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CERVIX Intraepithelial
Neoplasia
Cervical Intraepithelial Neoplasia (CIN) I Cervical Intraepithelial Neoplasia (CIN) II Cervical Intraepithelial Neoplasia (CIN) III
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Low Grade Squamous Intraepithelial Lesion (LSIL) High Grade Squamous Intraepithelial Lesion (HSIL)

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CERVIX

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CERVIX

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CERVIX

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Invasive Cervical Carcinoma

40 to 45 years for invasive cancer and about 30 years for high-grade precancers. fungating (or exophytic), ulcerating, and infiltrative cancers extends by
direct spread (peritoneum, urinary bladder, ureters, rectum, and vagina) Lymphatics Distant metastasis (Liver, lungs, bone marrow )
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Invasive Cervical Carcinoma

Patterns
Keratinizing SCCA - (Well differentiated) Non-keratinizing (moderately diff) Small cell squamous CA (poorly diff) Small cell undifferentiated (neuroendocrine/ oat cell CA) associated with high risk HPV (type 18)

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Staging Cervical Carcinoma

Stage 0. Carcinoma in situ (CIN III) Stage I. Carcinoma confined to the cervix
Ia. Preclinical carcinoma, that is, diagnosed only by microscopy Ia1. Stromal invasion no greater than 3 mm and no wider than 7 mm (so-called microinvasive carcinoma) Ia2. Maximum depth of invasion of stroma greater than 3 mm and no greater than 5 mm taken from base of epithelium, either surface or glandular, from which it originates; horizontal invasion not more than 7 mm Ib. Histologically invasive carcinoma confined to the cervix and greater than stage Ia2

Stage II. Carcinoma extends beyond the cervix but not onto the pelvic wall. Carcinoma involves the vagina but not the lower third. Stage III. Carcinoma has extended onto pelvic wall. On rectal examination, there is no cancer-free space between the tumor and the pelvic wall. The tumor involves the lower third of the vagina. Stage IV. Carcinoma has extended beyond the true pelvis or has involved the mucosa of the bladder or rectum. This stage obviously includes those with metastatic dissemination.
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UTERUS
Dating the endometrium

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Histology of menstrual cycle

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UTERUS
Dysfunctional uterine bleeding
Excessive prolonged estrogenic stimulation Persistent proliferative phase Lack of ovulation
Endocrine d/o Ovarian lesion Metabolic disturbance

Anovulatory endometrium with stromal breakdown (DUB)

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UTERUS
Endometritis
1) in patients suffering from chronic PID (gonococcal) (2) in patients with postpartal or postabortal endometrial cavities, usually due to retained gestational tissue (3) in patients with intrauterine contraceptive devices (4) in patients with tuberculosis,

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UTERUS
Endometriosis
presence of endometrial glands or stroma in abnormal locations outside the uterus. Impt cause of dysmenorrhea, pelvic pain, infertility & other problem
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Endometriotic cyst lining

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UTERUS
Adenomyosis
presence of endometrial tissue in the uterine wall (myometrium) small adenomyotic nests results in menorrhagia, colicky dysmenorrhea, dyspareunia, and pelvic pain
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Adenomyosis

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UTERUS
Endometrial polyps
sessile masses of variable size that project into the endometrial cavity single or multiple 0.5 to 3 cm in diameter develop in association with generalized endometrial hyperplasia responsive to the growth effect of estrogen but exhibit no progesterone response
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Endometrial polyp
Asymptomatic or may cause bleeding

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UTERUS
Endometrial Hyperplasia
increased gland to stroma ratio inactivation of the PTEN tumor suppressor gene through deletion and/or inactivation

Simple hyperplasia without atypia

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UTERUS
CARCINOMA OF THE ENDOMETRIUM
most common invasive cancer of the female genital tract peak incidence is in the 55- to 65-year-old woman Associated with
1) obesity, (2) diabetes (3) hypertension (4) infertility

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UTERUS
CARCINOMA OF THE ENDOMETRIUM
85 % are adenocarcinomas polypoid tumor or as a diffuse tumor involving the entire endometrial surface grading system is applied to endometrioid tumors and
well differentiated (grade 1), with easily recognizable glandular patterns moderately differentiated (grade 2), showing well-formed glands mixed with solid sheets of malignant cell poorly differentiated (grade 3), characterized by solid sheets of cells with barely recognizable glands and a greater degree of nuclear atypia and mitotic activity

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UTERUS
CARCINOMA OF THE ENDOMETRIUM Staging of endometrial adenocarcinoma
Stage I. Carcinoma is confined to the corpus uteri itself. Stage II. Carcinoma has involved the corpus and the cervix. Stage III. Carcinoma has extended outside the uterus but not outside the true pelvis. Stage IV. Carcinoma has extended outside the true pelvis or has obviously involved the mucosa of the bladder or the rectum
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UTERUS
Other tumors
Carcinosarcomas
malignant stromal differentiation malignant mesodermal components, including muscle, cartilage, and even osteoid

Adenosarcomas
large broad-based endometrial polypoid growths malignant appearing stroma, which coexists with benign but abnormally shaped endometrial glands

Stromal tumors
(1) benign stromal nodules (2) endometrial stromal sarcomas.
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UTERUS
LEIOMYOMA
75% of females of reproductive age sharply circumscribed, discrete, round, firm, gray-white tumors whorled pattern of smooth muscle bundles on cut section usually makes these lesions readily identifiable on gross inspection

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UTERUS
LEIOMYOSARCOMA
uncommon malignant neoplasms bulky, fleshy masses that invade the uterine wall, or polypoid masses that project into the uterine lumen degree of nuclear atypia, mitotic index, and zonal necrosis
ten or more mitoses per ten high-power
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LEIOMYOSARCOMA peak incidence at 40 to 60 years of age metastasize through the bloodstream to distant organs, such as lungs, bone, and brain
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Fallopian Tube
Tumors and Cysts
Paratubal cysts Hydatids of Morgagni remanants of Mullerian duct

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Table 22-3. Ovarian Neoplasms (1993 WHO Classification)

Surface Epithelial-Stromal Tumors
Serous tumors
Benign (cystadenoma) Cystadenoma of borderline malignancy Malignant (serous cystadenocarcinoma)

Sex Cord-Stromal Tumors Granulosa-stromal cell tumors

Granulosa cell tumors Tumors of the thecoma-fibroma group Sertoli-stromal cell tumors; androblastomas Sex cord tumor with annular tubules GYnandroblastoma Steroid (lipid) cell tumors

Mucinous tumors, endocervical-like and intestinal type

Benign Of borderline malignancy] Malignant Benign Of borderline malignancy MalignantEpithelial-stromal

Endometrioid tumors

Germ Cell Tumors

TeratomaImmatureMature (adult)SolidCystic (dermoid cyst)Monodermal (e.g., struma ovarii, carcinoid) Dysgerminoma Yolk sac tumor (endodermal sinus tumor) Mixed germ cell tumors Malignant, Not Otherwise Specified

Adenosarcoma Mesodermal (mllerian) mixed tumor Clear cell tumors

Benign Of borderline malignancy Malignant

Transitional cell tumors Brenner tumor

Brenner tumor of borderline malignancy Malignant Brenner tumor Transitional cell carcinoma (non-Brenner

Metastatic Nonovarian Cancer (from Nonovarian Primary)

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