Female Genital System and Reproductive Pathology Flashcards
Bartholin Cyst
Bartholin gland normally secretes lubrication into vestibule.
Usually unilateral enlarged painful cystic lesion secondary to inflammation and plugging of the gland.
Located at lower vestibule adjacent to the vaginal canal.
Generally women of reproductive age (infections/STD’s)
Not uncommon
Can be accompanied by abscess.
Condyloma
Warty neoplasm of vulvar skin, often large
MC due to HPV 6 and 11. (low risk based on DNA sequencing)
Characterized by koilocytic change
Rarely progresses to carcinoma
Lichen sclerosis
Thinning of epidermis and fibrosis of dermis
Leukoplakia w/ parchment-like vulvar skin
MC in postmenopausal women
Benign, associated w/ slightly increased risk of SCC
Lichen simplex chronicus
Hyperplasia of vulvar squamous epithelium
Leukoplakia w/ thick, leathery skin
Associated w/ chronic irritation and scratching
Benign; no increased SCC risk
Vulvar carcinoma
Arises from squamous epithelium of vulva
Rare
Presents as leukoplakia (biopsy may be required to distinguish from lichen sclerosis)
Etiology: May be HPV –> VIN (High risk - 16, 18, 31, 33) = 40-50 years old; or non-HPV related (long standing lichen sclerosis) = 70+ years old.
Extramammary Paget Disease
Malignant epithelial cell in the epidermis of the vulva
Presents as erythemetous, pruritic, ulcerated skin
*Key ddx is carcinoma (PAS +; Keratin +; and S100-) vs. melanoma (PAS-, Keratin -, and S100+)
Represents as carcinoma in situ (no underlying malignancy which is not the case w/ Paget’s disease of the breast)
Adenosis
Focal persistence of columnar epithelium in upper 2/3rds of vagina
Increased incidence in females exposed to DES (drug used to be given to mothers to prevent miscarriage) in utero
Can lead to clear cell adenocarcinoma
Clear cell adenocarcinoma
Malignant proliferation of glands with clear cytoplasm
Rare complication of DES-associated vaginal adenosis
Discovery of this and other complications lead to cessation of DES usage
DES complications in DES mom
Slightly increased risk of breast CA (estrogen like compound)
DES complications in DES daughter
- ) Adenosis –> clear cell adenocarcinoma
2. ) Smooth muscle problems in tubes/uterus. Increased ectopic risk.
Embryonal rhabdomyosarcoma
Malignant mesenchymal proliferation of immature skeletal muscle
Rare
Presentation: Bleeding and grape-like mass protruding from vagina or penis of child usually
Vaginal carcinoma
Carcinoma arising from squamous epithelium lining the vaginal mucosa
Usually related to high-risk HPV (16,18,31,33)
Precursor lesion is vaginal intraepithelial neoplasia (VAIN)
Regional lymph node spread: Lower 1/3 goes to inguinal nodes; Upper 2/3 goes to regional iliac nodes (due to embryological differences)
HPV infection
Sexually transmitted DNA virus
Infects lower genital tract, esp. cervix in transformation zone (strat squamous to simple columnar of exo/endo cervical border)
Persistent infection leads to risk for CIN
High risk: 16,18,31,33
Low risk: 6 and 11
High risk proteins:
E6: increases destruction of p53
E7: increases destruction of Rb
CIN: characterized by koilocytic change, nuclear atypia, and increased mitotic activity. Divided into grades based on cells involved.
CIN 1 - bottom 1/3 portion has dysplasia (reverses 66%)
CIN 2 - middle 2/3 has dysplasia (33% reverse)
CIN 3 - Almost all have dysplasia (rare reversal)
Carcinoma in situ (cannot reverse)
CIN progresses stepwise, but is not inevitable
Cervical carcinoma
Invasive carcinoma that arises from cervical epithelium
MC in middle-aged women (40-50)
Presents as vaginal bleeding or post-coital bleeding
Key risk factor is high risk HPV infection. Secondary factors include smoking (cervical and pancreas are two non-logical smoking related cancers) and immunodeficiency. (usually clears HPV infection)
Most common subtypes:
Squamous cell carcinoma (most common) and adenocarcinoma (rarer, but also due to HPV)
Often invade through anterior uterine wall into bladder –> hydronephrosis.
Local invasion over metastasis
Screen to catch dysplasia before it devleops into carcinoma.
Pap smear is gold standard for screening. Most successful screening tests ever developed. Look at nucleus/cytoplasm ratio etc.
Abnormal papsmear –> followed by confirmatory coposcopy and biopsy
Limitations of Pap smear: 1.) Inadequate sampling of transition zone (false negative).
2.) Limited efficacy in screeing for adenocarcinoma
Immunization: Effective in preventing HPV infections (HPV 6,11,16, and 18). Protection lasts for 5 years and must still undergo pap smears (31,33 and other high risks not covered)
Asherman Syndrome
Secondary amenorrhea due to loss of *basalis (regenerative layer of stem cells) and scarring
Result of overaggressive dilation and curretage (D&C)
Anovulatory cycle
Lack of ovulation
Results in estrogen-driven proliferative phase w/o progesterone-driven secretory phase
Common cause of dysfunction uterine bleeding, especially during menarche and menopause
Acute endometritis
Bacterial infection of endometrium
Usually due to retained products of conception
Presents as fever, abnormal uterine bleeding, and pelvic pain
Chronic endometritis
Chronic inflammation of endometrium
Characterized by
*plasma cells (lymphocytes are always present)
Common causes: retained products of conception, chronic PID, IUD, and TB
Presents with abnormal uterine bleeding, pelvic pain, and infertility.
Endometrial polyp
Hyperplastic protrusion of endometrium
Presents as abnormal uterine bleeding
Can arise as a side effect of tamoxifen
Enodmetriosis
Abnormal placement of endometrial glands and stroma outside uterine endometrial lining
Presents with dysmenorrhea (tissue cycles as well) and pelvic pain; may cause infertility.
3 theories:
- Retrograde theory
- Metaplastic theory
- Lymphatic dissemination theory
Common sites of involvement:
- 1.) Ovary - chocolate cyst
2. ) Uterine ligaments - pelvic pain
3. ) Pouch of Douglas - pain with defecation
4. ) Bladder wall- pain with urination
5. ) Bowel serosa - abdominal pain and adhesions - 6.) Fallopian tube mucosa - scarring ( increased risk of infertility and ectopic)
“gunpowder” lesions in soft tissue.
Adenomyosis is endometriosis of myometrium
Increased risk of CA at site of endometriosis. Esp. at the ovary.
Adenomyosis
Endometriosis of the myometrium.
Endometrial hyperplasia
Increase in the amount of endometrium glands in comparison to the surrounding stroma.
*Consequence of unopposed estrogen.
Classically seen in postmenopausal obese women with uterine bleeding.
Classified histologically: Based on architectural growth and cellular atypia.
**Most important predictor for progression to CA is cellular atypia
Endometrial Carcinoma
Malignant proliferation of endometrial gland
Presents as postmenopausal bleeding
Arises via two distinct pathways:
1.) Hyperplasia pathway –> due to unopposed estrogen. Endometroid histology –> aged 50-60
2.) Sporadic pathway – cancer from an atrophic endometrium w/o precursor lesion. Serous/Papillary histology –> elderly. Driven by p53 mutations. Can get psammoma bodies. Very aggressive.
Leiomyoma
Benign proliferation of smooth muscle arising from myometrium
Related to estrogen exposure (premenopausal)
Multiple (vs. leiomyosarcoma) , well-defined white whorled masses (leiomyosarcoma will have necrosis/hemorrhage.
Rise during pregnancy and shrinks after menopause.
Usually asymptomatic
When present sx include abnormal uterine bleeding, infertility, and pelvic mass.
Leiomyosarcoma
Malignant proliferation of smooth muscle arising from myometrium.
Arises denovo (not from leiomyoma)
Usually seen in postmenopausal women
Single lesion w/ necrosis and hemorrhage.
Necrosis, mitotic activity, and cellular atypia on histology.
Hemorrhagic luteal cyst
Bleeding into corpus luteum.
Can cause “mass” within ovary.
Follicular cysts
Due to degeneration of follicle.
Most women have some.
Polycystic Ovarian Disease
Characterized by increased LH and low FSH.
LH:FSH >2
Many follicular cysts in the ovary.
High LH –> high androgen production –> hirusitism and estrone creation in androgen –> feedback inhibition of FSH –> no stimulation of follicle –> degeneration and formation of follicular cyst
Classical presentation:
Obese young woman with infertility, oligomenorrhea, and hirusitism
- Some patients have insulin resistance
- High circulating estrone levels increase risk for enodmeterial carcinoma
Surface epithelial ovarian tumors
MC type of ovarian tumor
Derived from coelomic epithelium that lines ovary
Two MC subtypes are serous tumors and mucninous tumors. Both are usually cystic.
Can be endometrioid (usually carcinoma) and can have separate endometrioid carcinoma in endometrioid
Can be Brenner tumor (cells resemble urothelium)
Surface tumors present late.
Vague abdominal sx (pain, fullness). Signs of compression/urinary frequency.
Poor prognosis
*Epithelial carcinomas tend to spread locally especially to the perioneum (omental caking)
CA-125 is useful serum marker to monitor treatment response and screen for recurrence
Cystadenoma
Benign tumor of ovary.
Composed of a single cyst w/ simple, flat lining
Most commonly in premenopausal women (30-40yrs. old)
Can be serous or mucinous based on fluid present and histology.
Cystadenocarcinoma
Composed of complex cysts with thick, shaggy lining.
MC arises in post menopausal women (60-70 years old)
Cells invade into CT of cyst wall.
Can be serous or mucinous based on fluid present and histology.
BRCA1 mutation carriers have increased risk for serous carcinoma of the ovary and fallopian tube (can prophylactically remove)
Borderline tumors
Features between benign and malignant tumors
Better prognosis, but still have metastasis capability.
Germ cell tumors
2nd MC ovarian tumor (15%)
Usually occur in women of reproductive age (15-30)
Tumor subtypes mimic tissues normally produced in germ cells
Cystic teratoma
Germ cell tumor that resembles fetus. 2-3 three layers present
MC germ cell tumor in females.
Bilateral in 10%
Benign
Presence of immature tissue (MC is neuroectoderm) or somatic malignancy (i.e. squamous cell carcionma of skin of teratoma) indicates malignant potential
Struma ovarii is a cystic teratoma composed primarily of thyroid tissue.
Embryonal carcinoma
Composed of large primative cells.
Aggressive with early metastasis
Endodermal Sinus Tumor
aka Yolk Sac Tumor
Malignant
MC germ cell tumor in children
Serum AFP is often elevated
Schiller-Duval (glomeruloid) bodies are seen on histology.
Dysgerminoma
Composed of large cells with clear cytoplasm and central nuclei (oocyte)
MC malignant germ cell tumor
Testicular counterpart is seminoma
Good prognosis; responds to radiotherapy
Serum LDH is seen in serum.
Choriocarcinoma
Germ cell tumor of placental orgin
Malignant proliferation of trophopblasts and synctiotrophoblasts w/o villi
Small, hemorrhagic tumor with early hematogenous spread ( cells are programmed to find blood vessels)
Can cause many metastasis with a small primary tumor.
High B-hcg
Poor response to chemotherapy
May also arise from complication of gestation (complete molar pregnancy; abortion; complete pregnancy) or as a spontaneous germ cell tumor. Gestation pathway responds well to chemotherapy.
Struma Ovarii
cystic teratoma composed primarily of thyroid tissue.
Sex cord stromal tumors
Tumors that resemble sex-cord stroma tissues of ovary
Granulosa-theca cell tumor
Neoplasm of granulosa and theca cells
Often produce estrogen
Presents with signs of estrogen excess (Sx vary with age)
Sertoli-Leydig Cell tumor
Sertoli cells form tubules
Leydig cells contain characteristic Reinke crystals
May produce androgen –> hirsutism or virilization
Fibroma
Benign tumor of fibroblasts.
Associated with pleural effusion and ascites in osme patients (Meigs syndrome)
Meigs syndrome
Fibroma of ovary that causes pleural effusion and ascites
Kruckenberg tumor
Mucinous carcinoma that metastasizes to both ovaries.
MC is diffuse type gastric adenocarcinoma (signet-ring cell).
Can come from lobular carcinoma of breast or colon.
Mucinous tumor of ovary –> must ddx vs. surface mucous tumor –> key is unilateral (primary) vs. bilateral (metastasis)
Pseudomyxoma peritonei
Abundant mucin in peritoneum –> Jelly Belly
Clasically seen in mucinous carcinoma of appendix.
Often metastsizes to the ovary.
Ectopic Pregnancy
Implantation of fertilized ovum at site other than uterine wall
MC site is lumen of fallopian tube
Key risk factor is scarring
Classic presentation: Lower quadrant abdominal pain weeks after missed period. Surgical emergency
Sponatneous abortion
Miscarriage of ferus (20 weeks before gestation)
Common; occurs in up to 1/4th of recognizable pregnancies
Presents as vaginal bleeding, cramp-like pain, and passage of fetal tissue.
Usually due to chromosomal anomolies.
Other causes include hypercoaguable state (lupus), congenital infection, and exposure to teratogens (esp. within 0-3 weeks)
Placenta previa
Placenta implants in lower uterine segment and covers surgical os.
Needs C-section
Placental abruption
Placental separates from decidua prior to delivery
Common cause of still birth
Presents with third trimester bleeding and fetal insufficiency.
Blood on the maternal suface on gross
Placenta Accreta
Improper implantation of placenta into myometrium with little or no intervening decidua
Presents with difficult delivery of the placenta and post-partum bleeding
Often requires hysterectomy.
Preeclampsia
Pregnancy induced HTN, proteinuria, and edema; arises in 3rd trimester
Due to abnormality of maternal-fetal vascular interface in placenta
Fibrinoid necrosis of vessels of placenta.
Can progress to ecclampsia or HELLP
Ecclampsia
Preeclampsia with seizures
HELLP
Preeclampsia with thrombotic microangiopathy inolving liver
Hemolysis, Elevated Liver enzymes, Low platelets.
Schistocytes
Sudden Infant Death Syndrome
Death of a healthy infant (1 month to 1 year) without cause
Infants usually expire during sleep
Risk factors include sleeping on stomach, smoking in household, and prematurity.
Hydatidiform mole
Abnormal conception characterized by swollen and edematous villi with prolifereation of trophoblasts
Uterus expands as if normal pregnancy is present. (bigger than normal and B-hcg is higher than expected)
Woman will begin to pass grape-like masses in early 2nd trimester.
With prenatal care dx by routine ultrasound in the early first trimester. Fetal heart tones are absent and “snow-storm” appearance on ultrasound.
Classified as complete or patial
Rx: is D&C
B-hcg monitored to ensure adequate mole removal and to screen for development of choriocarcinoma
Partial mole
Genetics: Normal ovum fertilized by two sperm (or one sperm that dublicates its chromosomes) ; 69 chromosomes
Fetal tissue is present
Villous edema: some villi are hyropic and some are normal
Trophoblastic proliferation: Focal proliferation present around hydropic villi
Risk for choriocarcinoma: minimal
Complete mole
Completely from dad
Genetic: Empty ovum fertilized by two sperm (or one sperm that duplicates chromosomes); 46 chromosomes
Fetal tissue: Absent
Villous edema: Most villi are hyropic
Trophoblastic proliferation: diffuse, circumferential proliferation around hydropic villi
Risk for choriocarcinoma: 2-3%
B-hcg is much higher (synctiotrophoblasts make B-hcg)
