Reproductive - Female Pathology Flashcards
Bartholin cyst
P: unilateral, painful cystic lesion at lower vestibule adjacent to vaginal canal; in premenopausal women
M: inflammation and obstruction of gland -> cystic dilation
Condyloma
P: warty neoplasm of vulvar skin
M: HPV 6, 11 (condyloma acuminatum); secondary syphilis (condyloma latum)
Koilocytes (hallmark of HPV-infected cells)
Rarely progress to carcinoma
Lichen sclerosis
P: white patch (leukoplakia) with parchment-like (paper thin) valvular skin; post-menopausal women
M: thinning of epidermis and fibrosis (sclerosis) of dermis
Benign, slightly increased risk of squamous cell carcinoma
Lichen simplex chronicus
P: leukoplakia with thick, leathery vulvar skin
M: chronic irritation and scratching; hyperplasia of vulvar squamous epithelium
No increase risk of squamous cell carcinoma
Vulvular carcinoma
P: leukoplakia (biopsy to distinguish from other causes)
M: squamous epithelium lining vulva
1) HPV-related (type 16, 18) - vulvar intraepithelial neoplasia with koilocytic change, disordered cell maturation, nuclear atypia, mitotic activity
2) Non HPV-related - long-standing sclerosis (chronic inflammation/irritation); older women (> 70 yo)
Extramammary Paget Disease
P: erythematous, pruritic, ulcerated vulvar skin
M: malignant epithelial cells in epidermis of vulva
No underlying carcinoma (whereas in nipple there is underlying carcinoma)
Distinguishing Extramammary Paget Disease and Melanoma
Paget cells: PAS+, keratin+, S100-
Melanoma: PAS-, keratin-, S100+
PAS = mucous secreting Keratin = epithelial
Adenosis
P: Focal persistence of columnar epithelium in upper 1/3 of vagina
(During development, squamous epithelium from lower 2/3 from urogenital sinus grows upward and replace columnar lining of upper 1/3 from Mullerian ducts)
Assoc. with exposure to diethystilbestrol in utero
Clear cell adenocarcinoma
M: malignant proliferation of glands with clear cytoplasm
Rare, but feared, complication of DES-associated vaginal adenosis
Embryonal rhabdomyosarcoma (Sarcoma botryoides)
P: bleeding and grape-like mass protruding from vagina or penis of child (usually < 5yo)
M: Malignant mesenchymal proliferation of immature skeletal muscles
Spindle-shaped tumor cells
Cytoplasmic cross-striations
Positive for desmin and myogenin
Vaginal carcinoma
Usually secondary to cervical squamous cell carcinoma
Squamous epithelium carcinoma lining vagina mucosa
Assoc. with high risk HPV (16, 18) -> vaginal intraepithelial neoplasia
Lower 2/3 of vaginal spreads to inguinal nodes
Upper 1/3 of vaginal spreads to regional iliac nodes
What is the histology of cervix?
Exocervix: nonkeratinizing squamous epithelium
Endocervix: single layer of columnar cells
Transformation zone = junction
HPV Infection
Sexually transmitted DNA virus that infects lower genital tracts, particularly cervical transformation zone
Persistent infection -> cervical dysplasia
High Risks: 16, 18, 31, 33
Low Risks: 6, 11
High risk HPV produce E6 (p53) and E7 (Rb) -> increase risk of CIN
Cervical intrapepithelial neoplasia
P: koilocytic change, disordered cellular maturation, nuclear atypia, increased mitotic activity
CIN I: < 1/3 thickness
CIN II: < 2/3 thickness
CIN: < 3/3 thickness
Carcinoma in situ: entire thickness
Progression not inevitable (CIN I often regress)
Higher grade more likely to progress to carcinoma and less likely to regress
Cervical carcinoma
P: middle-aged women with vaginal bleeding, postcoital bleeding, cervical discharge
M: invasive carcinoma from cervical epithelium; high-risk HPV infection
secondary factors: smoking, immunodeficiency (AIDS)
80% Squamous and 15% adenocarcinoma (both HPV related)
Can invade through anterior uterine wall into bladder -> blocks ureters -> hydronephrosis with postrenal failure common cause of death
What is the gold standard for screening cervical carcinoma?
Pap smear
Abnormal pap smear followed by confirmatory colposcopy (magnifying glass) and biopsy
Limitations: inadequate sampling, not for adenocarcinoma
Immunization for HPV infection
Quadrivalent: HPV 6, 11, 16, 18
Protection lasts 5 years
Pap smears still necessary due to limited number of HPV covered by vaccine
What are the layers of lining of uterine cavity? What hormones regulate the layers?
Myometrium: smooth muscle wall underlying endometrium
Endometrium: mucosal lining of uterine cavity
Hormone sensitive
- growth by estrogen, secretory phase by progesterone, shedding by loss of progesterone
Asherman syndrome
P: secondary amenorrhea after dilation and currettage (D&C)
M: overaggressive D&C -> loss of basalis (stem cell layer for regeneration of endometrium) and scarring
Anovulatory cycle
P: lack of ovulation, dysfunctional uterine bleeding during menarche and menopause
M: estrogen-driven proliferative phase without subsequent progesterone-driven secretory phase -> proliferative glands break down and shed
Acute endometritis
P: fever, abnormal uterine bleeding, pelvic pain
M: bacterial infection of endometrium; from retained products of conception (after delivery/miscarriage) -> acts as nidus for infection
Tx: gentamycin + clindamycin with or without ampicillin
Chronic endometritis
P: abnormal uterine bleeding, pain, infertility
M: chronic inflammation of endometrium (from products of contraception, chronic pelvic inflammatory - chlamydia, IUD, TB)
Lymphocytes and plasma cells (Plasma cells for diagnosis as lymphocytes are normally found in endometrium)
Endometrial polyp
P: abnormal uterine bleeding
M: hyperplastic protrusion of endometrium
Can arise from tamoxifen (pro-estrogenic on endometrium)
Endometriosis
P: dysmenorrhea (pain during menstruation), pelvic pain; may cause painful intercourse and infertility; cyclic bleeding from ectopic tissue
M: retrograde menstruation with implantation at ectopic site -> endometrial glands AND stroma outside of uterine endometrial lining -> cycle just like normal endometrium
Uterus is normal sized
Increased risk of carcinoma at site of endometriosis, especially the ovary
Tx: oral contraceptives, NSAIDs, leuprolide, danazol
Sites of Endometriosis
Ovary (chocolate cysts) Uterine ligaments (pelvic pain) Pouch of douglas (pain with defecation) Bladder wall (pain with urination) Bowel serosa (abdominal pain and adhesions) Fallopian tube mucosa (scarring increases risk for ectopic pregnancy) - "gun-powder" nodules
Adenomyosis
Endometriosis involving uterine myometrium
Uterus is enlarged
Tx: hysterectomy
Endometrial hyperplasia
P: postmenopausal uterine bleeding
M: Unopposed/excessive estrogen stimulation (obesity, polycystic ovary syndrome, estrogen replacement) -> hyperplasia of endometrial glands relative to stroma
Risks: anovulatory cycles, HRT, polycystic ovarian syndrome, granulosa cell tumor
Cellular atypia is the most important predictor for progression to carcinoma
Simple hyperplasia progresses 30%; Complex hyperplasia rarely
Endometrial carcinoma
P: postmenopausal bleeding at 55-65 yo
M: malignant proliferation of endometrial glands (most common invasive carcinoma of female genital tract)
2 pathways: hyperplasia and sporadic
Increased myometrial invasion -> lower prognosis
Hyperplasic endometrial carcinoma
Estrogen exposure risks -> hyperplasia
Histology: endometrioid (normal endometrium-like)
60 yo
Sporadic endometrial carcinoma
Arise in atrophic endometrium with no evident precursor lesion
Histology: papillary structures, psammoma bodies, p53 mutation
70 yo, aggressive tumor
Leiomyoma (Fibroids)
P: Asymptomatic; can include abnormal uterine bleeding (iron deficiency), infertility, pelvic mass. Premenopausal (20-40yo); African american
M: benign neoplastic proliferation of smooth muscle from myometrium; most common tumor in females
Estrogen associated (premenopausal, multiple, enlarges during pregnancy, shrinks after menopause)
Multiple well-defined, white, whorled masses
Leiomyosarcoma
P: postmenopausal (middle age) women, African American
M: malignant proliferation of smooth muscle from myometrium
De novo (NOT from leiomyoma), single lesion with necrosis, hemorrhage, mitotic activity and cellular atypia. May protrude from cervix and bleed
Highly aggressive; tend to recur
Basic histology and function of ovary
Functional unit = follicle
Oocyte surrounded by granulosa and theca cells
1) LH induces androgen production from theca
2) FSH stimulates granulosa to convert androgen to estradiol
3) Estradiol surge induces LH surge leading to ovulation
4) After ovulation, residual follicle becomes corpus luteum and secretes progesterone (drives secretory phase)
Hemorrhagic corpus luteal cyst
Hemorrhage into corpus luteum; early pregnancy
Degeneration of follicles results in follicular cysts - small number are common
Polycystic ovarian disease
P: obese woman, amennorhea, infertility, hirsutism; 5% of women
M: hormone inmbalance
1) high LH induces androgen production in theta cells (hirsutism)
2) Androgens converted to estrone in adipose
3) Estrone inhibits FSH
4) Decreased FSH results in cystic degeneration of follicles
High LH, low FSH, high T, high E (from aromatization)
Assoc. with insulin resistance (type 2 diabetes 10-15 years later) and endometrial carcinoma (high circulating estrone)
Tx: weight reduction, low dose OCP or medroxyprogesterone (decreases LH/androgenesis), spironolactone (acne/hirsutism), clomiphene (for those who want pregnancy), metformin (diabetes/metabolic syndrome)
What are the 3 cell types of ovary?
Surface epithelium
Germ cells
Sex cord stroma
Surface epithelial tumors
Most common types of ovarian tumors (70%)
Coelomic epithelium (embryologically produces epithelial lining of fallopian tube (serous), endometrium, and endocervix (mucinous cells)
2 most common subtypes: serous and mucus (both cystic)
Present late with vague abdominal symptoms or compression (urinary frequency) Poor prognosis (worst of genital tract cancers)
Spread locally (peritoneum); CA-125 for monitoring treatment and recurrence; not for diagnosis
Serous cystadenoma
Surface epithelial tumor of ovary (45% of ovarian tumors); Benign
Premenopausal (30-40 yo)
Histology: fallopian tube-like epithelium; single cyst (often bilateral) with simple, flat lining
Mucinous cystadenoma
Surface epithelial tumor of ovary; Benign
Histology: intestine-like tissue
Multilocular cyst lined by mucus-secreting epithelium
Serous cystadenocarcinoma
Surface epithelial tumor of ovary (45% of ovarian tumors; Malignant and bilateral Postmenopausal women (60-70 yo)
Histology: complex cysts with thick, shaggy lining; psammoma bodies
Assoc. with BRCA1 (serous carcinoma of ovary and fallopian tube - prophylactic salpingo-oophorectomy)
Mucinous cystadenocarcinoma
Surface epithelial tumor of ovary; malignant
Pseudomyxoma peritonei - intraperitoneal accumulation of mucinous material from ovarian or apendiceal tumor
Endometrioid tumor
Surface epithelial tumor of ovary; malignant
Endometrial-like glands
May arise from endometriosis
15% associated with independent endometrial carcinoma (endometrioid type)
Brenner tumor
Surface epithelial tumor of ovary; benign
Solid tumor that is pale yellow-tan in color and appears encapsulated. “Coffee bean” nuclei on H&E staining
Histology: bladder-like epithelium
Germ cell tumors
2nd most common ovarian tumor (15%)
Reproductive age; mimics tissues normally produced by germ cells
- Fetal tissue - cystic terotoma, embryonal carcinoma
- Oocytes - dysgerminoma
- Yolk sac - endodermal sinus tumor
- Placental tissue - choriocarcinoma
Cystic teratoma
Germ cell tumor of ovary, most common germ cell tumor in females; 10% bilateral
Fetal tissue from two or three embryologic layers (skin, hair, bone, cartilage, gut, and thyroid)
Mature teratoma (“Dermoid cyst”): benign
Immature teratoma - aggressively malignant (usually neural ectoderm) or somatic malignancy (squamous cell carcinoma of skin) indicates malignant potential
Strauma ovarii
Cystic teratoma of ovary with thyroid tissue
Can present as hyperthyroidism
Dysgerminoma
Germ cell tumor of ovary
Large cells with clear cytoplasm and central nuclei (oocytes); uniform cells. Most common malignant germ cell tumor (testicular seminoma)
Elevated LDH, hCG
Assoc. with Turner syndrome
Good prognosis; responds to radiotherapy
Endodermal sinus tumor
Cystic termatoma of ovary (testes in boys)
Yolk sac; most common in children (sacrococcygeal area)
Yellow, friable, solid mass
Elevated AFP
Schiller-Duval bodies (glomerulus-like structures)
Choriocarcinoma
Germ cell tumor of ovary; malignant
Trophoblasts and syncytiotrophoblasts; mimics placental tissue, but absent chorionic villi
Can develop during or after pregnancy in mother or baby
Small, hemorrhagic tumor with early hematogenous spread (genetically programed to invade blood vessels) - to lungs
High beta-HCG (produced by synctiotrophoblasts)
May lead to theca-lutein cysts in ovary
Poor response to chemotherapy
Embryonal carcinoma
Germ cell tumor of ovary
Malignant tumor of large primitive cells (able to move and spread)
Aggressive with early metastasis
Granulosa-theca cell tumor
Sex cord-stromal tumor of ovary; malignant but minimal risk for metastasis
Neoplastic proliferation of granulosa and theca cells
Produces estrogens
Signs of estrogen excess (precocious puberty; menorrhagia/metrorrhagia; endometrial hyperplasia with postmenopausal uterine bleed)
Call-Exner bodies - small follicles filled with eosinophilic secretions
Sertoli-Leydig cell tumor
Sex cord-stromal tumor of ovary
Sertoli cells that form tubules and Leydig cells (between tubules) with characteristic Reinke crystals (pink cells with crystals)
Signs of androgen excess: hirsutism, virilization
Fibroma
Sex cord-stromal tumor of ovary
Benign tumor of fibroblasts; bundles of spindle-shaped fibroblasts
Meigs syndrome
Fibroma with pleural effusions (hydrothorax) and ascites
Pulling sensation in groin
Syndrome resolves with removal of tumor
Krukenberg tumor
Metastatic tumor of both ovaries
Most commonly from metastatic gastric carcinoma (diffuse type - secretes mucous)
Bilaterality distinguish metastases from primary mucinous carcinoma
Mucin=secreting signet cell adenocarinoma
Pseudomyxoma peritonei
Massive amoung of mucus in peritoneum
“jelly belly”
Mucinous tumor of appendix; usually with metastasis to the ovary
Ectopic pregnancy
P: lower quadrant abdominal pain a few weeks after missed period; lower than expected increased hCG
Implantation of fertilized ovum at site other than uterine wall; most common is lumen of fallopian tube
Key risk: scarring - salpingitis from PID, endometriosis, ruptured appendix, prior tubal surgery, history of infertility)
Surgical emergency; major complications: bleeding into fallopian tube (hematosalpinx) and rupture
Spontaneous abortion
P: vaginal bleeding, cramp-like pain, passage of fetal tissue
Miscarriage before 20 weeks (usually first trimester)
Chromosomal anomalies (trisomy 16), hypercoagulable states (antiphospholipid syndromes), congenital infections, exposure to teratogens (first 2 weeks)
Teratogen: Alcohol
Mental retardation, facial abnormalities, microencephaly
Teratogen: Cocaine
Intrauterine growth retardation, placental abruption
Teratogen: thalidomide
limb defects
Teratogen: Cigarette smoke
intrauterine growth retardation
Teratogen: isotretinoin
spontaneous abortion, hearing/visual impairment
Teratogen: tetracycline
discolored teeth
Teratogen: warfarin
fetal bleeding
Teratogen: phenytoin
digit hypoplasia, cleft lip/palate
Preeclampsia
P: pregnancy-induced hypertension, proteinuria, edema, particularly in 3rd trimester (5% of pregnancies)
Headaches, visual abnormalities
M: abnormality of maternal-fetal vascular interface in placenta; resolves with delivery
placental ischemia from impaired vasodilation of spiral arteries, resulting increased vascular tone
Eclampsia - seizures (IV magnesium sulfate to prevent/treat seizures)
Risks: preexisting hypertension, diabetes, chronic renal, autoimmune disorders
Mortality: cerebral hemorrhage, ARDS
HELLP (preeclampsia)
Thrombotic microangiopathy involving liver
Hemolysis
Elevated liver enzymes
Low platelets
Sudden infant death syndrome
P: infant expires during sleep
M: death of infant (1m-1y) without obvious cause
Risk factors: cigarette smoke exposure, sleeping on stomach, prematurity
Hydatidiform mole
P: grape-like masses (“clusters of grapes”, “honeycombed uterus”) through vaginal canal in 2nd trimester/
or absent fetal heart sound; snowstorm appearance on ultrasound
abnormally large uterus, increased beta-hCG
Abnormal conception characterized by swollen and edematous villi with proliferation of trophoblasts
Tx: dilatation and curettage
Subsequent beta-HCG monitoring for adequate mole removal and screen for choriocarcinoma
Partial hydatidiform mole
Normal ovum fertilized by two sperms (or one sperm duplicates)
69 chromosomes
Present fetal tissue
Some normal villi, focal proliferation
Minimal risk for choriocarcinoma
Complete hydatidiform mole
Empty ovum fertilized by 2 sperm (or 1 that duplicates)
46 chromosomes
Absent fetal tissue
Most villi are hydropic
Diffuse, circumferential proliferation around hydropic villi
2-3% risk for choriocarcinoma
2 Forms of Choriocarcinoma and Differences
Complication of gestation (spontaneous abortion, normal pregnancy, hydatidiform mole) or spontaneous germ cell tumor
Arising from gestation pathway responds well to chemotherapy.
Germ cell pathway does not respond well to chemotherapy.
Placenta previa
P: third-trimester bleeding (painless)
M: Implantation of placenta in lower uterine segment; placenta overlies cervical os (opening)
Often requires delivery by c-section (compress blood supply)
Risks: multiparity, prior C-section
Placental abruption (abruptio placentae)
P: third-trimester bleeding and fetal insufficiency; common cause of still birth
M: separation of placenta from decidua prior to delivery of fetus
May be associated with DIC
Risks: smoking, HTN, cocaine use
Life-threatening for both mother and fetus
Placenta accreta
P: difficult delivery of placenta and massive postpartum bleeding
M: Improper implantation of placenta into myometrium with little or no intervening decidua
Risks: prior C-sectio, inflammation, placenta previa
“accreta” = encased
