Gynaecological Pathology Flashcards
Approach to female genital tract problems
Developmental abnormalities Hormonal or functional disturbances Complications of pregnancy - MUST R/O! Infection/ inflammation Tumours Miscellaneous e.g. trauma, physical, chemical, iatrogenic
Common presentations
Pain - related to menstruation? sexual activity?
Bleeding - related to menstruation?
Per vaginal discharge
Mass (pelvic, abdomen, adnexal)
Infections: causes
Lower tract = vulva, vagina, cervix
Upper tract = uterus, fallopian tubes, ovary
Sexually transmitted
- -> chlamydia trachomatis (MC), n. gonorrhea –> LT and UT (PID)
- -> HPV, HSV2, Trichomonas vaginalis –> LT only
Non-sexually transmitted
- -> candidiasis (LT only)
- -> bacterial e.g. TB, E.coli –> LT and UT (PID)
Pelvic Inflammatory Disease: pathogenesis, clinical presentations, complications, chronic PID causes
Pathogenesis
- ascending infection spreading from vulva/vagina to upper tract structures (endometrium relatively spared but can still be affected)
- haematogenous spread
Clinical presentations
- pelvic pain, adnexal (tubes/ovaries) tenderness
- tubo-ovarian abscess/ suppurative inflammation
- vaginal discharge
- fever
Complications
- IO
- peritonitis
- bacteraemia
- infertility (if tubes/ ovaries affected)
Chronic PID
- post-partum or post-abortion
- IUCD
- TB
Pre-malignant neoplasms of cervix: pathogenesis and disease course
Pathogenesis
- HPV necessary but not sufficient –> tropism for immature basal squamous cells –> attack through epithelial breaks –> high concentration of immature metaplastic squamous cells at transformation zone (between glandular endocervix and squamous ectocervix)
- HPV 16/18 as high risk prototypes; HPV 6/11 as low risk prototypes
HPV 16/18:
HPV E6 and E7 onco-proteins –> promotes degradation of p53 and active Rb –> prevent cell cycle arrest –> increase risk of progression to cancer
Course:
- high rate of infections among young women –> 80% transient and regress; 20% progress to LSIL
- of the 20% LSIL –> 80% regress and 20% progress to HSIL in 6-10 yrs
- of the HSIL –> 20% progress to invasive cancer in 5-10 yrs
Pre-malignant neoplasms of cervix: squamous intraepithelial lesion definition, morphology, grading
Presence of KOILOCYTES due to cytopathic effect of HPV and absence of invasion (within basement membrane)
Morphology of koilocytes
- nuclear ATYPIA with ENLARGED, BI-NUCLEATED nuclei (HYPERCHROMATIC and COARSE CHROMATIN)
- PERINUCLEAR HALO
- CONDENSED CYTOPLASMIC MEMBRANE
Low grade (LSIL) = HPV infection/condylomas or CIN I
- koilocytes and dysplasia confined to lower 1/3 epthelium
- a/w low risk HPV
High grade (HSIL) = CIN II or CIN III
- koilocytes >1/3 (in middle third) in CIN II
- > 2/3 (span all layers), more atypia/mitosis/disorder and less koilocytes in CIN III
- a/w high risk HPV
Cervical carcinoma types and screening tests/protocols, prevention
Carcinoma
- squamous cell most common –> irregular nests and tongues with desmoplastic reaction
- adenocarcinoma
- spread down and out (cervix –> vagina –> lateral walls –> bladder and ureter etc)
Screening
- main aim is to detect SIL (especially HSIL) before progression to carcinoma –> can perform local LEEP excision or cone biopsy
- generally for >25 yrs old
- (21-29 pap every 3 yrs; 30-65 cotesting every 5 yrs)
Tests:
- pap smear/test = CYTOLOGY TEST using wooden speculum or plastic brush to SCREEN FOR MALIGNANCY at cervical TRANSFORMATION ZONE
- -> presence of metaplastic squamous cells or columnar cells = proper sampling
- -> Bethesda reporting system (LSIL, HSIL, ASC-US)
- HPV DNA test
- -> used in some countries as primary screening for >30 yrs females
- -> co-testing with pap smear possible
- -> in PWH: reflex testing if pap smear result is ASC-US; if LSIL/HSIL then directly refer to colposcopy clinic for excision!
Prevention
- HPV vaccine (bivalent, quadrivalent or 9-valent)
- -> vaccinated women still need to be screened as in normal female population
Colposcopy: procedure, area examined
Examine cervix, vagina and vulva (lower tract)
Apply acetowhite solution to view vascular patterns and better highlight the area of pathology for biopsy
Differential diagnosis of abnormal uterine bleeding
DEPENDS ON AGE GROUP
Pregnancy related
- ectopic pregnancy, spontaneous abortion, hydatidiform mole
Non pregnancy related
- organic lesions
- -> local MC e.g. polyps, endometrial hyperplasia, endometrial carcinoma (and adenomyosis, leiomyoma in reproductive age)
- -> local others e.g. infection, PID, IUCD
–> systemic: bleeding disorders, endocrine disorders
Prepuberty: precocious puberty (hypothalamic, pituitary, ovarian origin)
Adolescence: bleeding disorders, anovulatory cycle
Reproductive: PREGNANCY related, organic lesions listed above, dysfunctional uterine bleeding (anovulatory and ovulatory)
Peri and post menopausal: ORGANIC lesions (polyp, hyperplasia, CA), dysfunctional uterine bleeding for perimenopausal (anovulatory)/ endometrial atrophy for postmenopausal
Dysfunctional uterine bleeding: types and causes, treatment
Most common cause of abnormal uterine bleeding in reproductive and perimenopausal women
Diagnosis by exclusion!
Anovulatory (MC)
- hormonal imbalance (MC)
- endocrine disorders e.g. thyroid, adrenal, pituitary
- ovarian lesions e.g. PCOS, estrogen producing tumour
- metabolic e.g. obesity, severe malnutrition
Ovulatory (reproductive)
- mid-cycle - transient estrogen decline
- late-cycle - progresterone deficiency i.e. inadequate luteal phase
Treatment
- assess severity and treat any Fe def anaemia
- mid cycle estrogen or late cycle progestogen
- reassurance
Examination of uterine cavity
Hysteroscopy and guided biopsy Pipelle sampling (bride sampling)
Endometrial hyperplasia: nature, risk factors, morphology
Pre-malignant lesion
- increased proliferation of endometrial glands relative to stroma
- 20% a/w PTEN mutation
Due to increased estrogen levels
- obesity, failed ovulation (perimenopause), estrogen producing ovarian tumours, prolonged estrogen replacement therapy
Morphology
- without atypia (simple/complex) = low risk
- simple/complex with atypia = 20-25% risk of developing endometrioid carcinoma
Endometrial carcinoma: prevalence, types (age, risk factors, histological types, precursor, genetics, behaviour), clinical presentations, grading and staging
Most common cancer in female genital tract
Low mortality
Type 1 (more common)
- 55-65 yrs old
- Risk factors: UNOPPOSED ESTROGEN e.g. obesity; HT, DM, infertility, familial syndromes e.g. lynch
- morphology: ENDOMETRIOID (resemble normal endometrium; 80% of CA), adenocarcinoma
- precursor: ENDOMETRIAL HYPERPLASIA
- genetic aberrations: PTEN (20%), MMR genes (lynch)
- behaviour and prognosis: indolent, good prognosis
Type 2
- 65-75 yrs old
- risk factors: not related to estrogen
- morphology: SEROUS (15%)
- precursor: serous endometrial intraepithelial CA, background of endometrial atrophy
- genetics: TP53 (90%)
- behaviour: aggressive - more extrauterine extension, poor prognosis
Clinical presentation:
- post-menopausal bleeding (90%) –> present early hence good prognosis overall
Grading and staging
- grading based on degree of differentiation (I-III) – SEROUS CA IS HIGH GRADE BY DEFINITION
- TNM or FIGO staging
- -> I = 90% 5 yr survival; II = 30-50%; III = 20%
Endometriosis and Adenomyosis: definition, clinical features
Endometriosis = presence of endometrial tissue (gland +/- stroma) outside the uterus Adenomyosis = presence deep in the myometrium
Endometriosis
- **ovaries, tubes, pouch of Douglas, bladder, rectum
- oestrogen dependent
- clinical features based on area of abnormality
- -> PELVIC PAIN, DYSMENORRHEA, dyspareunia, dysuria/haematuria, pain on defecation/PR bleed
- -> abnormal cyclic bleeding (premenstrual spotting, menorrhagia)
- -> GI disturbance - bowel adhesion or IO
- -> increased risk of ectopic pregnancy; infertility
- -> endometriotic cysts if ovaries involved (chocolate cyst)
- -> increased risk of endometrioid malignancy
Adenomyosis
- also responds to hormones –> cyclic bleeding –> causes pressure build up in myometrium with reactive hypertrophy and thickened walls –> pain in menses
Gross features: commonly see spotty haemorrhage
Leiomyoma and Leiomyosarcoma: nature, prevalence, clinical features of leiomyoma, morphology, diagnostic features of leiomyosarcoma
Leiomyoma
- benign smooth muscle neoplasm
- most common gynaecological tumour (30-50% of REPRODUCTIVE women; estrogen dependent)
- may be asymptomatic
- clinical presentations: abnormal PV bleed, urinary frequency or difficulty, constipation, sudden pain (if blood supply disrupted e.g. too large or torsion of stalk), impaired fertility, pregnancy complications e.g. abortion, foetal malpresentation, uterine inertia and post-partum haemorrhage
- morphology: sharply circumscribed firm mass, WHORLED SURFACE, often multiple scattered (intramural, submucosal, subserosal which can become stalked)
Leiomyosarcoma
- usually arise de novo
- solitary, post-menopausal (opposite of leiomyoma)
- invasive +/- metastatic
- diagnostic features (2 out of 3): significant cytological atypia, high mitotic activity, tumour necrosis
- smooth muscle tumour of undetermined significance has better prognosis but still need FU
Polyps
Endocervical or endometrial
- benign polypoid masses protuding through mucosa
- smooth glistening surface with underlying cystically dilated spaces
- oedematous stroma
- may bleed but no malignant potential
Endometrial polyp more common in reproductive age
Ovaries: endometriotic cysts
Haemorrhage and pressure buildup from endometriosis causes cyst formation
“Chocolate cyst” due to colour
Endometrioid epithelium –> endometrial stroma underneath –> fresh clot indicating recent haemorrhage –> siderophages indicating old haemorrhage
Ovarian cystic lesions
Generally, many ovarian lesions associated with cyst formation (both benign and malignant)
Physiological/functional cysts
- follicular cyst, luteal cyst
Pathological cysts
- polycystic ovarian disease, endometriotic cyst, cyst tumours
Ovarian tumours: clinical presentations, risk factors, tumour markers
Presentations
- mostly PRESENT LATE due to non-functional nature of tumours and deep-seated location of ovaries –> only detect mass or pain when very large/cause GI or urinary symptoms
- non-specific constitutional symptoms
- hormonal symptoms only for sex-cord stromal tumours e.g. endometrial hyperplasia, abnormal PV bleed, hirsutism
Risk factors
- age, infertility, nulliparity
- endometriosis
- hereditary ovarian syndromes e.g. BRCA mutation, lynch syndrome
Tumour markers (diagnosis, treatment response and recurrence)
- CA125 for epithelial carcinoma (especially serous type)
- AFP for yolk sac tumour, beta-hCG for choriocarcinoma
Classification of ovarian tumours
Epithelial
- benign, borderline, malignant
- serous, mucinous, endometrioid, clear cell etc.
Germ cell tumours
- dysgerminoma, teratoma, yolk sac tumour, choriocarcinoma
Sex-cord stromal tumours
- fibroma, granulosa cell tumour, sertoli-leydig cell tumour
Metastasis
- mullerian origin or extra-mullerian
Epithelial ovarian tumours: age group, classification, histological types and features, caution when diagnosing mucinous tumours
Generally occurs in adults
Benign
- e.g. cystadenoma
- around 30-40 yrs old
- (psammoma bodies)
Borderline
- low malignant potential
- presence of cytological and architectural atypia but no stromal or lymphovascular invasion
- excellent prognosis if confined within ovaries (stage Ia)
Malignant
- carcinoma
- serous type most common –> can be low grade or high grade
- older post-menopausal women
Morphology
- serous type most common, usually forms papillary structures
- mucinous type can have heterogenous areas of benign and borderline and malignant cytology
Caution when diagnosing mucinous ovarian tumour!!
- always check the appendix for any primary mucinous cystadenocarcinoma that has metastasised!
Germ cell tumours: age group, tumour markers, types (benign/malignant, response to chemoRT)
Mostly children and adolescent (except teratoma which occurs at all ages)
AFP/hCG may be elevated
All malignant except mature teratoma
Dysgerminoma
- most common malignant GCT
- mostly solid, “potato tumour”
- responsive to chemoRT
Yolk sac tumour
- children or young female
- responsive to chemotherapy
- very high AFP
Teratoma
- ALL AGES
- mostly cystic; trilineage cells
- mature teratoma = BENIGN –> but may turn malignant in later life or can be mixed tumour with other malignant GCT
- immature teratoma = malignant; grade by amount of primitive neuroepithelial tissue
Choriocarcinoma
- increase hCG
- unresponsive to chemotherapy – fatal
Sex-cord stromal tumours: age group, types (nature, hormonal secretion)
Fibroma
- benign but possible torsion if stalked
- SOLID white mass
- bland uniform spindle cells
Granulosa cell tumour
- malignant but indolent
- bimodal (some juvenile, some post-menopausal)
- estrogen secreting –> a/w endometrial hyperplasia
- tendency to recur late so need long term FU
Metastasis to ovaries: suspicion, gross appearance, possible origins
More likely if bilateral lesions
Mushroom-like capsular deposits
Mullerian origin e.g. uterus, contralateral ovary
Extra-mullerian
- breast, GI tract, pancreas
- e.g. Krukenberg tumour from diffuse type adenoCA stomach
General investigations for ovarian tumours (staging)
Peritoneal washing to obtain cytology
Check contralateral ovary
Peritoneal LN sampling
(check appendix)
DDx for solid ovarian tumour
Fibroma
Metastasis
Fallopian tube disorders
Most common: inflammation (PID) –> suppurative salpingitis, TB salpingitis, tubo-ovarian abscess (rare)
Tubal pregnancy –> emergency if rupture!
Tumours: mostly from metastasis; distal ends may be the origin of ovarian tumours (especially in familial cases)
Gestational/Placental disorders
Infection (ascending or haematogenous spread from TORCH organisms)
Spontaneous abortion (10-15%) – either fetal cause (genetics) or maternal cause (inflammation, trauma, uterine abnormalities)
Ectopic pregnancy
Hydatidiform moles
Placental choriocarcinoma
Pre-eclampsia
Ectopic pregnancy: definition, common sites, appearance, risk factors, why is it an emergency?, long term outcome
= Foetal implantation at a site other than normal uterine locations
- 90% at tubes, other areas e.g. ovary, abdominal cavity, uterine cornu
Medical emergency! –> rupture can lead to haemoperitoneum, peritonitis and shock
Appearance: intratubal haematoma, intraperitoneal haemorrhage
Risk factors:
- PID with chronic salpingitis and scarring –> abnormal function of ciliated tubal epithelium
- peri-tubal adhesions due to appendicitis, endometritis, leiomyoma
Long term outcome:
- more prone to infertility if tube destroyed
Hydatidiform moles: nature, outcome, diagnostic histology, types (genetic, markers, risk of choriocarcinoma), treatment and surveillance
Benign tumours of chorionic villi leading to abnormal pregnancy and inevitable abortion (12-14 wks)
Diagnostic histology
- hydropic swelling of chorionic villi (vesicle-like)
- abnormal trophoblastic proliferation
Complete mole
- genetic: diploid, 46XX with both sets paternally derived
- markers: very high hCG
- risk of placental choriocarcinoma: 2/5%
- all villi abnormal, no foetal tissue
- diffuse and circumferential trophoblastic proliferation
Partial mole
- genetic: triploid, 69 XXY, extra set of paternal chromosomes
markers: elevated hCG - risk of choriocarcinoma: rare, lower than complete
- some normal villi present, some foetal tissue
- focal and slight trophoblastic proliferation
Treatment: complete removal and surveillance post-operation until hCG levels drop to zero
- if persistently high –> persistent disease or early signs of placental choriocarcinoma (need to avoid pregnancy to prevent interference with surveillance)
Placental choriocarcinoma: nature, cell types involved, causes, clinical features, response to chemotherapy
Malignant tumours composed of syncytiotrophoblast and cytotrophoblast (no chorionic villi!!)
- easily metastasise to lungs, vagina, liver, brain
Causes:
- complete mole (50%)
- spontaneous abortion (25%)
- after natural pregnancy (22%)
Clinical features:
- Extremely high hCG –> pregnancy symptoms
- PV bleed
- haemorrhagic necrotic mass
Very responsive to chemotherapy (c.f. choriocarinoma)
Pre-eclampsia (toxaemia of pregnancy): characteristic features, pathogenesis, histology, clinical features/management
Characterised by HT, proteinuria and oedema in 3rd trimester of pregnancy
Purely placenta induced –> disease gone after delivery
Pathogenesis (starts in early pregnancy)
- ABNORMAL PLACENTATION = insufficient infiltration of trophoblasts into decidua –> failed remodelling of small spiral arteries into large capacity uteroplacental vessels –> PLACENTAL ISCHAEMIA
- trigger cascade of events with placental derived factors entering maternal circulation
- ENDOTHELIAL DYSFUNCTION: due to imbalance of antiangiogenic factors (sFLT1, endoglin) –> increase vasoconstriction (ATII, TXA2) and decrease vasodilation (PGI2/E2) ==> HT
- HT (decrease PGI2) + endothelial injury = HYPERCOAGULABILITY –> DIC
Histology of decidua vessels
- fibrinoid necrosis, foamy histiocytes in endothelium, infarcts, retroplacental haemorrhages
Clinical features
- mild = HT (relieved by bedrest, balanced diet)
- moderate = HT (anti-HT drugs needed)
- severe = convulsion, coma, DIC, multi-organ failure (may need urgent C-section)
- HELLP syndrome = HA and DIC
Vulva disorders: basic anatomy, VIN (associations, nature, appearance), SCC (risk factors)
Basic anatomy
- outer = skin
- inner = mucosa
- both lined by stratified squamous epithelium
- any lesions a/w skin or mucosa can occur e.g. dermatitis, lipoma, melanoma, epidermoid cysts, basal cell CA
Vulvar intraepithelial neoplasia (VIN)
- precursor for SCC of vulva
- a/w high risk HPV (low risk HPV causes condyloma acuminata)
- also graded VIN I-III
- appearance: leukoplakia
SCC of vulva
- most common malignant tumour of vulva
- risk factors:
- -> high risk HPV (high grade VIN; risk of progression increased by smoking, immunodeficiency)
- -> non-HPV related – lichen sclerosis or squamous hyperplasia (morphology more differentiated, unifocal)
- metastasis to inguinal LN
Vaginal disorders: primary vs secondary SCC
Vaginal SCC
- primary (rare): from VAIN (also hrHPV)
- secondary more common (extension from cervical or vulvar SCC)
- metastasis to inguinal LN
