Female repro (FGT) pathology Flashcards
1
Q
Abnormal endometrial cycles: Dysfunctional Uterine Bleeding (DUB)
A
- Unopposed estrogen effect
- Exogenous progesterone effect
- Inadequate luteal phase
- Persistent luteal phase
2
Q
Inadequate luteal phase
A
- Irregular ripening
- Inadequate corpus luteum – (↓ progesterone)
- Poorly developed secretory endometrium
- Breaks down irregularly (DUB)
- Bx: Poor and immature secretory glands
- Low Progesterone, FSH, LH
- Sx of infertility
3
Q
Persistent luteal phase
A
- If C.L. continues to secrete low levels of progesterone – protracted and irregular shedding.
- Periods regular but bleeding excessive and prolonged (10 – 14 days)
- Bx. – persistent secretory even after 5 days of menstruation.
4
Q
Endometriosis
A
- Occurrence of endometrial tissue at a site other than the lining of uterine activity.
- Adenomyosis (Endometrosis interna) – myometrium > 3mm
- diffuse, focal (adenomyoma)
- Extrauterine–ovary,tubes,parametrium,gut serosa, umbilicus
- Laparotomy or Caesarian scars
- Rarely lung, pleura, bones.
Structure
- glands, stroma
- – discolored nodules; large, blood-filled cysts; adhesions
- cyclical bleeding (less in extrauterine)
- hemosiderin, fibrosis
- chocolate cysts ovary
- fallopian tubal scars – infertility
Pathogenesis
- metaplasia of celomic epithelium
- retrograde flow through FT
- vascular dissemination
Sx
- Reproductive phase of life
- Asymptomatic
- Pain
- severe Dysmenorrhea (uterus may be retroverted), menorrhagia, infertility
- Cyclical bleeding – urinary tract, rectum, umbilicus, surgical scars
- Fibrosis – infertility (tubes), intestinal obstruction
- risk of anatomical based lesions:
- tubal pregnancy,
- urinary obstruction,
- carcinoma if ovary involvement (Pathoma)
- Regression following pregnancy, oral contraceptives
5
Q
Endometritis
A
Cyclical shedding of endometrium (no foot hold)
Acute
- postpartum (puerperal sepsis), offensive lochia (foul smelling)
- Ascending gonococcal
- Pyometrum (obstruction of os by neoplasm, fibrosis)
- Sx: fever, abnormal uterine bleeding, and pelvic pain (Pathoma)
Chronic
- nonspecific chronic inflammation
- characterized by plasma cells
- Causes: IUD, retained products of conception, chronic PID (chlamydia), and tb
- Sx: abnl uterine bleeding, pelvic pain, and infertility
6
Q
A
Endometrial hyperplasia
- Excess unopposed estrogen effect
- Perimenopausal metrorrhagia
- Simple cystic, complex with/without atypia
- Reversible with progesterone therapy
- Atypia, Carcinoma in situ, endometrial carcinoma
- Look for source of estrogen – (ovary, adrenals, HRT )
Simple cystic hyperplasia
- no back to back gland
Complex endometrial hyperplasia
- shortened cycle
- cribriform pattern
- back to back glands
CRITERIA FOR ATYPICAL HYPERPLASIA -> most important predictor for carcinoma
Nuclear enlargement (2-3 times of RBC)
- Pleomorphism
- Vesicular change
- Chromatin irregularity
- Loss of polarity
- Prominent nucleoli
- Cellular stratification
Note: Carcinoma cannot be excluded so implicated rx include:
- progesterone therapy
- surgical excision
7
Q
Endometrial polyp
A
- Perimenopausal, 0.5 – 3 cm
- Extreme response to hyperplasia -> protrusion of endometrium
- Asymptomatic, or metrorrhagia
- Malignant transformation very rare
- Causes: side effect of tamoxifen (Pathoma)
8
Q
A
Endometrial carcinoma
- gland constitute more than 50% of stroma
- glands extend into myometrium
- 55 – 65 years
- endometrial carcinoma: old
- cervical carcinoma: Young
- Unopposed estrogen effect
- Preceded by:
- hyperplasia -> endometrioid histo
- sporadic -> serous/papillary w no evident precursor lesion & assoc w p53 mutation (Pathoma)
- Obesity, diabetes, hypertension, nulliparous
- Post menopausal bleeding
- Endometrial biopsy for diagnosis
Pathogenesis
- Polypoid fungating mass in the cavity
- Asymmetric enlargement of uterus
- Back to back glands
Spread
- local, myometrium, cervix, vagina, rectum
- peritoneal
- lymphatic – iliac, paraaortic
- blood – lung, liver
9
Q
Malignant mixed Mullerian tumor
(Mixed mesodermal tumor)
A
- admixture of carcinoma and sarcoma
- >55years
- From residual Mullerian
- mosodermal cells in endometrium
- Large, fleshy mass, hemorrhage, necrosis
- Epithelial and mesenchymal (leio, rhabdo, chondro, osteo)
- Poor prognosis
10
Q
Leiomyoma
A
- no nuclear atypia
- no evidence of necrosis
- whirled and criss-cross appearance of smooth muscle
- estrogen-dependent
- Common (25%), benign smooth muscle tumor
- 20 – 40 years, estrogen dependant growth -> premenopausal women
- (regress with menopause)
- Multiple – subserous, intramural, submucous
- Circumscribed, whorled white nodules
- Resemble normal smooth muscle, fibrosis (fibroid)
- No malignant potential
11
Q
Leiomyosarcoma
A
- Rare, de novo and not from leiomyoma
- Older women, post menopausal bleed
- Large, bulky single lesion, hemorrhage, necrosis
- Hypercellular with atypia
- > 10 mitosis/10 high powered fieled (h.p.f.)
- Poor prognosis
12
Q
Uterine bleeding - Possibilities
A
- Abortion
- DUB
- Endometriosis
- Chronic endometritis
- Endometrial hyperplasia, polyp, carcinoma
- Leiomyoma
13
Q
Acute vs. chronic cervicitis
A
Acute
- Endocervix (not erosion)
- Gonococcal, Chlamydia, Candida,
- Trichomonas, Herpes
- Post partum, Post D and C
- Purulent vaginal discharge
Chronic
- Non-specific,incidental
- Lymphocytes and plasma cells normally present in wall
- Granularity,thickening
- Retention (Nabothian) cysts -> dilated endocervical cysts filled w mucin
14
Q
A
Squamous metaplasia
- physiological condition
- Non-specificresponse to irritation
- No malignant potential
- upward migration of ectocervix (squamous)
- endocervix: columnar
- transitional zone
- nuclear: cytoplasm ratio nl
- no loss of polarity
- no polychromasia
- no mitotic figures
15
Q
Endocervical polyp
A
- Pre-menopausal
- Hyperplastic glands, vascularity, edema, inflammation
- No malignant potential
16
Q
Condyloma accuminatum
A
Condyloma accuminatum aka Anogenital warts
- eptihelial hyperplasia
- koilocytosis (arrows)
- perinuclear halo
- hyperkeratosis
- STD usually caused by HPV low risk
- Papillomatous, koilocytes, HPV 6,11 (low risk -> no malignant potential)
- Inactivate tumor suppressor genes p53, RpB and activate cyclinE, leading to uncontrolled proliferation
Etiopath:
- CPE -> koilocytosis
- rarely progress to carcinoma with LR HPV
Sx: painless warts -> mostly itching and burning in vulvar region
DDx: Condyloma latum: plaque-like lesion due to syphillitic infection
17
Q
A
CIN I to III -> still reversible!
- HPV 16, 18, 31, 33, 35, 45 (high risk) -> produces E6 & E7
- HPV 6, 11, 40, 54 (low risk) (not associated with invasive carcinoma)
- Sexual activity at a young age
- Multiple sex partners
- Parity (>7)
- Chymydal infection
- Smoking
- High viral load
- Persistent SIL/HPV
CIN I (top image)
- top layers show koilocytotic change
- basal show dysplastic changes
- LSIL (Low-grade squamous intraepithelial lesion)
- – increased N:C ratio
- – pleomorphic, hyperchromatic nuclei
CIN II
- dysplastic expand to 2/3 of surface epithelium
- HSIL
CIN III
- no orientations bw top and bottom layers; severe dysplasia
- no Cytopathic effects (no koilocytic)
- HSIL
- Pre-malignant -> usually asx
- sx only appear during malignancy
18
Q
CIN – Risk Factors
A
- HPV 16, 18, 31, 33, 35, 45 (high risk)
- HPV 6, 11, 40, 54 (low risk)
- (not associated with invasive carcinoma)
- Sexual activity at a young age
- Multiple sex partners
- Parity (>7)
- Chlamydial infection
- Smoking
- High viral load
- Persistent SIL/HPV
Dx:
- Pap smear
- p16 staining for both nuclear and cytoplasm; surrogate maker for HPV
19
Q
Pap smear
A
aka cervical cytology
- Schiller test first to visualize site to take Pap smear
- alone cannot differentiate bw CIN I to III -> need biopsy
- can only differentiate bw low and high grade
- cannot detect metaplasia
- can only detect abnormal squamous cells (not adenocarcinoma) -> dysplastic
- All females should get pap smear starting at 21 for screening
Mild dysplasia (CIN I)
– increased N:C ratio
– pleomorphic, hyperchromatic nuclei
Severe dysplasia, carcinoma in situ (CIN III)
- invasive carcinoma
20
Q
Cervical Carcinoma
A
- *Gross**
- scaly, necrotic patches
- carcinoma occurs in transformation zone (seen)
Structural changes
- firm cervix (palpable barrel cervix)
- *Microscopic**
- keratin pearls
Etiopath
- Risk factor: multiple coitus, multiparity, (pathoma) smoking, immundeficiency
- Majority squamous cell / rarely adenocarcinoma
- Gradual decline due to Pap screening
- CIN, Squamous Intraepithelial lesion (cytology)
- HPV 16, 18, HSV-2? Promoter
Clinical features
- 30 – 50 years; middle-aged
- Irregular vaginal bleeding
- Postcoital bleeding
- Vaginal discharge
- Pyometra
- *Dx**
- comb biopsy: deeper biopsy
- *C&C**
- uterine infection (pyometra)
- urine stasis
- invasive cervical carcinoma
- Exophytic–necrotic fungating mass
- Ulcerative
- Infiltrative(rare)
- microinvasive carcinoma Stage IA
- Spread: confined to uterus, beyond uterus in pelvis or lower1/3of vagina, parametrium, bladder, rectum, distant mestastasis
29
Q
A
Genital herpes
Clinical image showing painful, erythematous vesicles on the mucosa or skin of female genitals.
Histological (H&E) image of vesicle (top)
Tzanck smear (bottom)
Morphology
- Primary or recurrent mucocutaneous lesions; vesicular and painful.
- Presence of intraepithelial vesicles accompanied by necrotic cellular debris, neutrophils, and cells harboring characteristic intranuclear viral inclusions (top) and Cowdry type A inclusion appears as a light purple, homogeneous intranuclear structure surrounded by a clear halo, 3M Margination, multinucleation, moulding (bottom)
Etiopath
- HSV-2 and, less commonly, HSV-1 can cause genital infections. Initial (primary) infection causes painful, erythematous, intraepithelial vesicles on the mucosa and skin of external genitalia, along with regional lymph node enlargement.
- Histology shows the vesicles of HSV infection contain necrotic cells and fused multinucleate giant cells with intranuclear inclusions (Cowdry type A).
- Infected cells commonly fuse to form multinucleate syncytia.
Virus blocks effects of interferon, prevents CD8 T-cell recognition of infected cells, escapes antibody neutralization and clearance by going into “hiding” during latent infection. - Latent infections (neurons); Viral re-activation due to stress, hormones, UV radiation
- HSV is actively shed during symptomatic period.
Sx
- Sx: dysuria, urethral discharge, local lymph node enlargement and tenderness, and systemic manifestations, such as fever, muscle aches, and headache.
- Signs and sx may last for several weeks during the primary phase of disease
C&C
- Neonatal herpes can be life-threatening and occurs in children born to mothers with genital herpes.
- Affected infants have generalized herpes, often associated with encephalitis and consequent high mortality.
35
Q
Tubal pregnancy
A
- 1% of all pregnancies
- ↑ because of PID with tubal adhesions,
- endometriosis with fibrosis is also a risk factor
- fibrosis blocks the passage of fertilized ovum (50% idiopathic)
- Lack of space, poor vasculature, limited placental size.
- Ruptures 2 – 6 weeks after fertilization.
- Embryo dies, rarely implanted in abdomen
- *Sx:**
- right iliac pain
- vaginal bleeding
- nausea
- Severe hemorrhage, shock
- Mimics acute appendicitis if right sided
- Ultrasound, absence of appropriate uterine enlargement
- Expansion of adnexa
- Peritoneal aspiration yields blood
Dx
- βhCG elevated due to pregnancy
- Once the embryo dies, βhCG drops
- ↓ βhCG leads to degeneration of corpus luteum
- Leadto↓estrogenandprogesterone
- Endometrium breaks down leading to bleeding.
- Arias Stella rxn showing endometrial glands tortuous, irregular branching and budding.
- Uterus small compared to amenorrhea
- Endometrial curettings show no chorionic villi but have hypersecretory glands
- R/O spontaneous abortion (chorionic villi)
37
Q
A
Placenta Previa: abn placental implantation, implants on LUS, internal OS, 3rd trimester
- placental overlies cervical os
38
Q
A
Abruptio Placenta:
- premature separation of placenta -> clots on maternal surface of placenta (Pathoma image below)
- ante partum hemorrhage (3rd trimester);
- shock
- DIC,
- premature labour & stillbirth.
39
Q
A
Placenta Accreta:
- occurs when all or part of the placenta attaches abnormally to the myometrium (the muscular layer of the uterine wall)
- difficult delivery & post-partum bleeding
- often requires hysterectomy
41
Q
Gestational trophoblastic disease
A
- Hydatidiform mole (Molar Pregnancy) – complete, incomplete
- Invasive mole (chorioadenoma destruens)
- Gestational choriocarcinoma
- Placental site trophoblastic tumor
- βhCG levels more important than anatomic classification (urine, serum)
Microscopic image below:
- structure to maximize surface area
- inner: cytotrophoblast
- outer: syncytiotrophoblast
42
Q
A
Hydatidiform Mole
Gross:
- swollen and edmatous villi w proliferation of trophoblasts
- grape-like masses
- *Microscopic:**
- stroma has bluish myxoid material -> degeneration of stroma
- non-uniform (circumferential) proliferation of trophoblastic cells
Etiopath
- 2 extremes of reproductive life
- Far east like South-East Asia
- Partial or complete
- ultimately resulting in deficiency of fetal blood vessel
- uterus expands as if nl pregnancy
Complete molar pregnancy (dyspermy): empty ovum;
- Genotype paternally derived chromosome
- fertilized by two sperms or a SINGLE diploid sperm
- 46XX, rarely XY
- Embryo dies early, no fetal parts seen
- 2% develop choriocarcinoma
Partial mole: triploid
- Ovum (23x) fertilized by two sperms 23 X and 23 Y
- So moles are triploid (69 XXY)
- Ovum fertilized by 2 different sperms one with X Chr and one with Y Chr- triploidy
- Embryo develops for a short period, fetal parts may be seen
- Molar changes partial, uterus minimally enlarged
- No risk of malignancy
Sx
- Amenorrhea, vomiting, pregnancy test +ve
- Uterus larger compared to amenorrhea (large for date); DDx w ectopic (where uterus is not enlarged)
- At 3 – 4 months vaginal bleeding, grape like structures; and snow storm appearance on US
- U/S – enlarged cystic placenta, absent fetus
- βhCG greatly elevated in serum, urine
- Curettage to remove the lesion
- Monitor βhCG for 2% that develop choriocarcinoma
- *Dx:**
- incr in beta-HCG (1e5 SI units)
- pregnancy sx
- *C&C**
- invasive into myometrium, lungs, brain
- bilateral thecal lutein cyst
44
Q
A
Gestational choriocarcinoma
- tumour of trophoblasts
Gross: Friable hemorrhagic mass
Microscopic:
- cytotrophoblast (pale)
- no choronic villi present
- complete anaplasia
- multi-nucleation
- 1:40,000 pregnancies, high in Asia and Africa (1:2000)
- 50% follow a mole
- 25% follow abortion
- 23% follow normal pregnancy
- 2% follow ectopic pregnancy
Etiopath
- Extensive infiltration and metastasis – lung, brain, liver
- Malignant cyto and syncitiotrophoblasts
- Hemorrhage and necrosis (bloody discharge per vagina)
- NO CHORIONIC VILLI
- βhCG elevated, confirm diagnosis by biopsy
- Chemotherapy yields good results- cure (contract w non-gestational CC which does not respond to chemo)
- Followup βhCG levels monitored
