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
