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Pathoma Female Genital System/Gestation Pathology
Chapter 13 - Female Genital System and Gestation
Terms in this set (64)
Vulva - Basics
Skin and mucosa of the female gentalia external to the hymen (Labia majora, labia minora, mons pubis, & vestibule).
Lined by squamous epithelium.
Cystic dilation of the Bartholin gland.
D/t inflammation & obstruction of gland.
Presents in women of reproductive age as unilater, painful cystic lesion at the lower vestibule adjacent to the vaginal canal
Warty neoplasm of vulvar skin, often large.
MC d/t HPV 6 & 11 (condyloma acuminatum). secondary syphilis (condyloma latum) is a less common cause.
HPV causes koilocytic change producing koilocytes (hallmark)
Lichen schlerosis (vulva)
Thinning of the epidermis & fibrosis (sclerosis) of the dermis.
Presents in postmenopausal women as a white patch (leukoplakia) w/
parchment-like vulvar skin
Lichen simplex chronicus (vulva)
Hyperplasia of the vulvar squamous epithelium.
Presents as leukoplakia w/ thick, leathery vulvar skin.
Associated w/ chronic irritation and scratching.
Carcinoma arising from squamous epithelium lining the vulva.
Presents as leukoplakia, biopsy required for diagnosis.
HPV-related - D/t types 16 & 18. 40-50 y/o. VIN → CA.
Non-HPV realted - D/t long-standing lichen sclerosis. >70 y/o.
Extramammary paget disease
Characterized by malignant epithelial cells in the edidermis of the vulva.
Present as erythematous, pruritic ulcerated vular skin.
*Is only CIS, no underlying carcinoma.
Paget cells are - PAS+, Keratin+, S100-.
Melanoma is - PAS-, Keratin-, S100+.*
Normal vaginal canal development
Squamous epithelium from the lower 2/3 of the vagina (derived from urogenital sinus) grows upward to replace the columnar epithelium lining of the upper 1/3 of the vagina (derived from the Mullerian ducts).
Focal persistence of columnar epithelium in the upper 1/3 of the vagina.
In utero diethylstilbestrol (DES) increases risk.
Clear cell adenocarcinoma (vagina)
Malignant proliferation of glands with clear cytoplasm.
Complication of DES-associated vaginal adenosis.
Malignant mesenchymal proliferation of immature skeletal muscle.
Present in child < 5 y/o as bleeding and a grape-like mass protruding from the vagina or penis.
Rhabdomyoblast (hallmark cell) exhibits
cytoplasmic cross-striations, +desmin, & +myogenin
Carcinoma arising from squamous epithelium lining the vaginal mucosa.
Associated w/ high risk HPV (16, 18, 31, & 33).
Cancer from lower 2/3 of vagina → Inguinal nodes.
Cancer from upper 1/2 of vagina → Iliac nodes.
Cervix - Basics
Exocervix - Nonkeratinizing squamous epithelium.
Endocervix - A single layer of columnar cells.
Junction between these is called transformation zone.
High/low risk types.
High-risk HPV factors
DNA virus that infects lower genital tract, especially transformation zone.
High-risk - HPV types 16, 18, 31, & 33.
Low-risk - HPV types 6 & 11.
*High risk HPV produce E6 & E7.
E6 destroys p53 (cell regulator).
E7 detroys Rb (holds E2F).*
Cervical intraepithelial neoplasia
Characterized by koilocytic change, disordered cellular maturation, nuclear atypia, & increased mitotic activity within cervical epithelium. Progresses in a stepwise fashion.
CIN I - <1/3 of the thickness (66% reverse).
CIN II - <2/3 of the thickness (33% reverse).
CIN III - Slightly less than entire thickness (Low% reverse).
CIS - Entire thickness (no reversibility).
Cervical carcinoma - Basics
Passes through BM.
Presents in women 40-50 y/o with vaginal bleeding, especially postcoital, or cervical discharge.
Key risk factor - High-risk HPV.
2ndary risk factors - Smoking &
Squamous cell carcinoma (80%) & adenocarcinoma (15%),
related to HPV.
Advanced tumors invade through anterior wall into bladder → blocking of ureters → hydronephrosis w/ postrenal failure → death.
Screening of cervical carcinoma
Goal is to catch CIN before it become carcinoma.
Pap smear is screening gold standard.
Cells scraped from transformation zone.
Classified as low grade (CIN 1) or high grade (CIN 2-3).
Abnormal pap smear is followed by colposcopy & biopsy.
Pap smear limitations
Inadequate sampling of transformation zone (false negative).
Limited efficacy for adenocarcinoma (incidence has not gone down).
Prevention of cervical carcinoma
5 Immunization points
(1)Vaccine cover HPV types 6, 11, 16, & 18.
(2)Antibodies against 6 & 11 protect against condylomas.
(3)antibodies against 16 & 18 protect against CIN & carcinoma.
(4)Protection lasts 5 years.
(5)Pap smears are still necessary.
Endometrium & myometrium - Basics
Endometrium - Mucosal lining of uterus.
Myometrium - Smooth muscle wall underlying endometrium.
Endometrium is hormonally sensitive:
*Growth d/t estrogen (proliferative).
Preparation d/t progesterone (secretory).
Shedding d/t loss of progesterone (menstrual).*
Secondary amennorrhea d/t loss of the
basalis (stem cells of the endometrium)
Result of overaggresive D&C.
Lack of ovulation. Estrogen driven proliferative phase w/o a subsequent progesterone-driven secretory phase.
Proliferative glands break down and shed → dysfunctional uterine bleeding, especially during menarche & menopause.
Bacterial infection of the endometrium.
D/t retained products of conception (after delivery or miscarriage).
Presents as fever, abnormal uterine bleeding, & pelvic pain.
Chronic inflammation of the endometrium.
Classified histologically -
Must see plasma cells
, lymphocytes also present.
Causes - Retained products of conception, chronic PID (chlamydia), IUD, & TB (granulomas).
Presents as abnormal bleeding, pain, & infertility.
Hyperplastic protrusion of endometrium.
Presents as abnormal uterine bleeding.
Side effect of tamaxifen - Anti-estrogenic effects on the breast but weak pro-estrogenic effects on the endometrium.
Endometriosis - Basics
Endometrial glands & stroma outside of the uterine endometrial lining.
Presents as dysmenorrhea (pain during menstruation) & peliv pain; may cause infertility.
Impants classically appear as yellow-brown "gun-powder' nodules.
Ovary - MC site. Formations of chocolate cyst.
Uterine ligaments - Pelvic pain.
Pouch of Douglas - Pain with defecation.
Bladder wall - Pain with urination.
Bowel serosa - Abdominal pain & adhesions.
Fallopian tube mucosa - Scarring increase risk for ectopic tubal pregnancy.
Hyperplasia of endometrial glands relative to stroma.
D/t unopposed estrogen (obesity, polycystic ovary syndrome, & estrogen replacement).
Presents as postmenopausal uterine bleeding.
Classified histologically - Growth pattern (simple/complex) & cellular atypia (+/-). Presence of atypia is the most important predictor.
Endometrial carcinoma - Basics
Malignant proliferation of endometrial glands.
Presents as postmenopausal bleeding.
Hyperplasia pathway or Sporadic pathway.
Endometrial carcinoma - Hyperplasia pathway
Endometrial hyperplasia → carcinoma.
Risk factors (estrogen exposure) - Early menarche/late menopause, nulliparity, infertility w/ anovulatory cycles & obesity.
Average age is 60 y/o.
Histology is endometrioid (looks normal).
Endometrial carcinoma - Sporadic pathway
Carcinoma arises in an atrophic endometrium.
Average age is 70 y/o.
Histology is serous - Characterized by papillary structures with spammoma bodies.
p53 mutation is common.
Key points to distinguish from leiomyosarcoma
Benign neoplastic proliferation of smooth muscle arising from myometrium. MC tumor in females.
Enlarge during pregnancy, shrink after menopause.
Gross exam show
multiple, well-defined, white, whorled masses.
Key points to distinguish from leiomyoma
Malignant proliferation of smooth muscle arising from the myometrium.
Arises de novo, NOT from leiomyomas.
Areas of necrosis & hemorrhage.
Necrosis, mitotic activity, & cellular atypia.
Ovary - Basics
Corpus luteum problem
The functional unit of the ovary is the follicle, which consists of an oocyte surrounded by granulosa & theca cells.
Hemorrhage into a corpus luteum can result in a hemorrhagic corpus luteal cyst.
Degeneration of follicles results in follicular cysts (no clinical significance in small numbers).
Normal function of a follicle
-LH (from pituitary) acts on theca cells to induce androgen production.
-FSH (from pituitary) acts on granulosa cells to convert androgen (from theca cells) to estradiol.
-Estradiol drives proliferative phase of the endometrial cycle.
-Estradiol surge induces LH surge, which leads to ovulation.
-Ovulation marks beginning of secretory phase of the endometrial cycle.
-After ovulation, the follicle becomes a corpus luteum which secretes progesterone.
Progesterone (from corpus luteum) drives the secratory phase.
Polycystic ovarian disease (PCOD) - Basics
Multiple ovarian follicular cysts d/t hormone imbalance.
Characterized by increase LH and low FSH (LH:FSH >2).
Classic presentation - Obese young woman with infertility, oligomenorrhea, & hirsutism.
Associated w/ insulin resistance & the development of type 2 diabetes.
Polycystic ovarian disease (PCOD)
(1)Increased LH induces excess androgen production (theca cells) resulting in hirsutism.
(2)Androgen is converted to estrone in adipose tissue.
(3)Estrone feedback further decreases FSH resulting in degeneration of follicles.
Surface epithelial tumors - Basics
MC type of ovarian tumor (70%). Derived from coelomic epithelium which can produce 4 types of tumor.
Prognosis is generally poor.
CA-125 is a useful serum marker.
Surface epithelial tumors
Serous - Full of watery fluid.
BRCA1 carriers are at increased risk in both ovary and fallopian tube serous carcinomas.
Mucinous - Full of mucus-like fluid.
Surface epithelial tumors - Mucinous & serous
Benign (Cystadenomas) - Single cyst w/ a simple, flat lining. MC age 30-40.
Malignant (Cystadenocarcinomas) - Complex cysts w/ a thick shaggy lining. MC age is 60-70.
Borderline - Good prognosis, but have metastatic potential.
Surface epithelial tumors
Endometrioid - Endometrial-like glands. May arise from endometriois. Associated w/ independent endometrial carcinoma.
Brenner - composed of bladder-like epithelium, usually benign.
Germ cell tumors - Basics
2nd MC type of ovarian tumor (15%).
MC age is 15-30.
Fetal tissue - Cystic teratoma & embryonal carcinoma
Oocytes - Dysgerminoma.
Yolk sac - Endodermal sinus tumor.
Placental tissue - Choriocarcinoma.
Germ cell tumors - Cystic teratoma
Cystic tumor composed of fetal tissue derived from 2-3 embryologic layers.
MC germ cell in females (10% bilateral).
Struma ovarii - Composed primarily of thyroid tissue.
(squamous cell carcinoma of skin)
Germ cell tumors - Dysgerminoma
Composed of large cells w/ clear cytoplasm & central nuclei (resemble oocytes).
MC malignant germ cell tumor.
Testicular counterpart is seminoma.
Serum LDH may be elevated.
Germ cell tumors - Endodermal sinus tumor
Mimics the yolk sac. Malignant.
MC germ cell tumor in children.
Serum AFP is elevated.
Histology - Schiller-Duval bodies (glomerulus-like structures).
Germ cell tumors - Choriocarcinoma
Composed of trophoblasts & syncytiotrophoblasts, mimics placental tissue but
villi are absent
Early hematogenous spread.
High β-hCG is characteristic (syncytiotrophoblasts).
Poor response to chemotherapy.
Germ cell tumors - Embryonal carcinoma
Composed of large primitive cells. Malignant.
Agressive w/ early metastasis.
Sex cord-stromal tumors - Granulosa-theca cell tumor
Age based presentation
Produces estrogen, therefore presents with signs of estrogen excess.
Prior to puberty - Precocious puberty.
Reproductive age - Menorrhagia/metrorrhagia.
Postmenopause (MC) - Endometrial hyperplasia with postmenopausal uterine bleeding.
Sex cord-stromal tumors - Sertoli-Leydig cell tumor
Composed of sertoli cells that form tubules & leydig cells (between tubules) w/ Reinke crystals (hallmark).
May produce androgen causing hirsutism & virilization.
Sex cord-stromal tumors - Fibroma
Benign tumor of fibroblasts.
Associated with pleural effusions & ascites (Meigs syndrome).
Krukenberg tumor - Metastatic mucinous tumor that involves both ovaries. MC d/t gastric carcinoma (diffuse type (signet ring cells)). Bilaterality helps distinguish from primary.
Pseudomyxoma peritonei - Massive amounts of mucus in the peritoneum. D/t mucinous tumor of appendix w/ metastasis to ovary.
Implantation of fertilized ovum as a site other than the uterine wall.
MC site is the lumen of the fallopian tube.
Key risk factor - Scarring (PID or endometriosis).
Classic presentation - LRQ pain after a missed period.
Miscarriage of fetus before 20 weeks gestation.
Presents as vaginal bleeding, cramp-like pain, & passage of fetal tissues.
MC d/t chromosomal anomalies (especially trisomy 16)
Other causes - Hypercoagulable states, congenital infection, exposure to teratogens (especially in the first 2 weeks).
Alcohol - MCC of mental retardation, facial abnormalities & microcephaly.
Cocaine - Intrauterine growth retardation & placental abruption.
Thalidomide - Limb defects.
Cigarette smoke - Intrauterine growth retardation.
Isoretinoin - Spontaneous abortion, hearing & visual impairment.
Tetracycline - Discolored teeth.
Warfarin - Fetal bleeding.
Phenytoin - Digit hypoplasia & cleft lip/palate.
Implantation of the placenta in the lower uterine segment, overlying the cervical os.
Presents as 3rd trimester bleeding.
Separation of placenta from decidua.
Common cause of still birth.
Presents with 3rd trimester bleeding & fetal insufficiency.
Improper implantation of placenta into the myometrium.
Presents with difficult delivery of the placenta & postpartum bleeding.
Often requires hysterectomy.
Pregnancy-induced hypertension, proteinuria, & edema.
Preeclampsia + seizures = Eclampsia.
levated *L*iver enzymes, &
LP = *H*emolysis, *E*levated *L*iver enzymes, & *L*ow
Sudden infant death syndrome
Death of a health infant (1 month - 1 year) without obvious cause.
Risk factors - Sleeping on stomach, exposure to cigarette smoke, & prematurity.
Hydatidiform mole - Basics
Abnormal conception characterized by swollen & edematous villi w/ proliferation of trophoblasts. Uterus is larger and β-hCG is higher than expected.
W/o prenatal care classically presents in 2nd trimester as passage of grape-like masses through vagina.
W/ prenatal care presents as absent fetal heart sounds, and "snowstorm" appearance is seen on US.
Treatment is D&C.
Hydatidiform mole - Partial mole
Risk for choriocarcinoma
Genetics - Normal ovum, 2 sperm, 69 chroms.
Fetal tissue - Present.
Villous edema - Some are edematous.
Trophoblastic proliferation - Focal proliferation.
Risk for choriocarcinoma - Minimal.
Hydatidiform mole - Complete mole
Risk for choriocarcinoma
Genetics - Empty ovum, 2 sperm, 46 chroms.
Fetal tissue - Absent.
Villous edema - Most are edematous.
Trophoblastic proliferation - Diffuse.
Risk for choriocarcinoma - 2-3%
*May arise as a complication of gestation. These respond well to chemotherapy.
May arise from the germ cell pathway. These do not respond well.*
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