Genitourinary Pathology

Cervical Screening and Pathology

• Embryology: primordial germ cells from the yolk sac migrate into urogenital ridge.
- Mullerian duct derived from coelomic lining epithelium
- Urogential sinus gives the vestibule of external genitalia and lower vagina while mullerian duct gives fallopian tubes, uterus and upper vagina
• Pathology of uterine corpus:
- Uterine bleeding
- Endometrial hyperplasia
- Endometrial polyps
- Benign tumours (leiomyoma or fibroid)
- Malignant tumours (adenocarcinoma and leiomyosarcoma)
• Endometrial adenocarcinoma:
- Occurs with perimenopausal and postmenopausal women
- Aetiology: increased level of estrogen due to obesity or hormone replacement therapy and late menopause
- Presents with vaginal bleeding and endometrial hyperplasia
• Pathology of vagina:
- Infections (candida, trichomonas, gardnerella)
- Cysts such as inclusion cysts and mesonephric duct remnants
- Vaginal intraepithelial neoplasia caused by HPV
- Invasive squamous cell carcinoma
- Malignant melanoma
• Pathology of the vulva:
- Infections by gonococcus, candida, hperes virus
- Cysts such as Bartholin’s cyst and epidermal inclusion cyst
- Warts (usually not in the cervix)
- Vulvar intraepithelial neoplasia
- Invasive squamous cell carcinoma
- Malignant melanoma
• Vulvar intraepithelial neoplasia: precursor lesion of invasive squamous cell carcinoma of the vulva
- Associated with HPV infection or intraepithelial neoplasia at other sites of the genital tract, e.g. cervix (CIN)
- Symptoms: asymptomatic or local itchiness (pruritis)
- Lesions are multifocal and can be red or white, raised or flat
• Squamous cell carcinoma of vulva:
- Younger woman: high rate of cervical/vaginal neoplasia and HPV associated. Carinoma is warty or basaloid.
- Older women: no associated with VIN and HPV but associated with vulvar dermatoses. Different background to younger with p53 mutation mostly.
• Pathology of cervix:
- Acute and chronic cervicitis caused by gonococci, chlamydia, muycoplasma and herpes II infection
- Endocervical polyps (common in woman with irregular bleeding and removal only)
- Intraepithelial and invasive neoplasia (squamous and glandular)
• Cervical cancer: behaves like a STD
- More common in women with multiple sexual partners
- Absent in virgins
- Incidence increases with number of partners and age at first intercourse
- Relationship with sex: high correlation of cervical and penile cancer in terms of distribution, and number of sex partners.
• Causality of cervical carcinoma: caused by a sexually transmitted virus, the human papilloma virus. Develops after a long preinvasive stage.
- Incidence and mortality is significantly reduced by cervical cancer screening
- Prognosis: worsen with stage as cancer spread to bladder and uterus and gains access to ureter to spread laterally.
- HPV: type 6 and 11 causes warts (6, 11, 16, 18, 33, 35 infect genital tract). Infection is able to be cleared however in older people, low immunity and immunosuppressant leads to persistent infection.
• Process of infection by HPV:
- DNA virus gains entry to epithelial cells via disruption
- Outcomes: HPV remains latent/replicates to form tumours (warts)/integrated into host cell and transforms cell into cancer cell. Difficult to predict these outcomes.
- However progression to invasive cancer is uncommon (5-10% if untreated)
• Multiple genital tract neoplasia: high risk invasion suffers pre-mutations and loss of normal epithelium, gains malignancy.
- Cervix: CIN invasive carcinoma, CIN 3 suffers no mutation at all.
- Vagina: VAIN invasive carcinoma
- Vulva: VIN invasive carcinoma
- Perianal region: PAIN invasive carcinoma
• Prevention of cervical cancer:
- Primary: education, delay sexual intercourse, barrier method of contraception, prophylactic vaccine. Mature cervix is more prone and prevention of dysplasia important from 16 to 18.
- Secondary: antriviral agents, vaccine to prevent HPV progression, improve cervical cancer screening.
• Screening: examination of asymptomatic people in order to classify them as likely or unlikely to have the disease tested for.
- Programmes introduce to reduce community burden of cancer by screening some individuals
- Lack of luxury of multiple information systems – single tests
- Involve a prediction for the future
• Screening guidelines:
- Importance with known history and recognizable early stage
- Beneficial early treatment
- Suitable test
- Treatment available
- Benefit outweighs harm
- Cost-effective
• Cervical smears: swap is taken between the squamous epithelium covering the ectocervix and the endocervix with the columnar epithelium. Sample of the top layer of cells is taken
- Ayres spatula
- Cytobrush
• Cervical screening:
- Low sensitivity but high specificity. Single smear does not guarantee result (must be regular)
- Long preinvasive stage
- False negatives: low chance of cancer obscured by neutrophils etc. Error when examination (so a tiring process)
• Elements of successful cervical cancer
- Ensuring sexually active and previously sexually women have regular smears
- Good sampling and specimen preparation
- High quality laboratories
- Appropriate treatment and follow up

Pathology of Ovary, Tubes and Uterus

• Pelvic inflammatory disease: condition worsens after it passes upwards to the pelvis
- Symptoms: pelvic pain, adnexal tenderness, fever and vaginal discharge
- Infection: Gonococci, chlamydia, enteric bacteria (these can be asymptomatic)
- Acute suppurative salpingitis (fallopian tube sticking together)
- Salpingo-oophoritis
- Tubo-ovarian abscess (abscess between ovaries), pyosalpinx (inflammation process with dissociated of connective tissue into watery substance with pus)
- Hydrosalpinx (fluid and pus accumulation)
- Peritonitis, intestinal obstruction (adhesion), bacteremia, infertility
• Endometriosis:
- Endometrial glands or stroma outside the uterus (sites adjacent to peritoneal, vagina and rectum, ovary, tubes and ligaments)
- Important clinical condition affecting young women in third/fourth decades
- Complications: infertility, dysmenorrhoea (painful menstruation) and pelvic pain
• Causes of endometriosis:
- Regurgitation and retrograde menstruation through the fallopian tubes into the peritoneal cavity
- Metaplastic theory – arise from coelomic epithelium
- Dissemination of vasculature (pelvic vein) and lymphatics through the pleura cavity.
• Ovarian endometriosis: complications
- Foci respond to cyclical hormonal stimulation with periodic bleeding
- Ovarian surface deposits (causes adhesions and stop movement between ovarian tube and ovary)
- Ovarian stroma deposits (chocolate cysts due to bleeding into the ovary)
- Relationship with endometrioid ovarian tumours due to inflammation and
• Pathology of the fallopian tubes:
- Inflammation with PID
- Ectopic pregnancy (risk increases with gestation)
- Elderly women
- Poor prognosis
- Have watery vaginal discharge
• Ectopic pregnancy: implantations of the zygote in any site other than normal uterine location
- 90% occurs in tubes. Post surgery or ruptured appendix contribute to risk
- Consequences: zygote invades into walls, increase size and result in tubal rupture with intraperitoneal haemorrhage causing severe abdominal pain. This is a medical emergency
- Complications; PID with chronic salpingitis, peritubal adhesions and endometriosis
• Ovarian pathology:
- PID
- Functional cysts: simple cysts that occurs with normal menstruation
- Polycystics ovarian disease
- Endometriosis
- Ovarian tumour
• Polycystic ovarian disease: numerous cystic follicles or follicular cysts. The ovaries is enlarged and the smooth white external surface is dottedwith numerous subcortical cysts
- Complications: infertility with oligomenorrhoea, persistent anovulation, obesity and hirsutism (excessive hair growth due to increased level of androgen)
• Ovarian tumours: common tumours in women, both benign and malignant
- Symptoms: lower abdominal pain, abdominal enlargement, GI complaints, urinary frequency and dysuria
- Ascites occurs with malignant tumours
- Malignancy increases with age
- Pathogenesis: reduced risk with oral contraception and high parity while increased risk with low parity, hormone replacement therapy, familial and BRACA1 and 2 mutation
• Classification of ovarian tumours:
- Surface epithelial-stromal tumours, serous/mucinous/endometrioid tumours
- Germ cell tumour such as teratoma, dysgeminoma, yolk sac tumour (usually benign)
- Sex cord-stromal tumours
- Metastatic tumours
• Surface epithelial-stroma tumours:
- Each of the three different types represent mullerian differentiations of tubal (serous), endometrial (endometrioid) and cervical (mucinous) lines
- These vary in size and bilateral
- Cystic and likelihood of malignancy increases with amount of solid epithelial growth
- Histology: serous have p53 alteration, mucinous have KRAS (stayed with mucin) and endometrioid have PTEN, genetic lesion.
• Germ cell tumours:
- 95% are benign cystic teratomas (dermatoid cyst – mixture of keratin, gut, teeth, fat and gums)
- Pain and abdominal mass
- Mature or immature (multipotential as it is derived from embryo)
• Sex cord-stromal tumours:
- Derived from ovarian stroma undifferentiated gonadal mesenchyme gives rise to Sertoli and Leydig cells in male and granulosa and theca cells in female
- Secretes oestrogen and androgens causing feminisation or masculinisation
- Infertility in mature woman
• Metastatic tumour: bilateral and multinodular often located at surface and have extensive unusual extraovarian spread.
- Gotten from colon, stomach, breast, endometrium, lymphoma and leukaemia
- Appendix, pancreas and billary tract mimic borderline mucinous tumours.
• Pathology of the peritoneum:
- Peritonitis caused by (chemical, rupture of biliary systems, acute haemorrhagic pancreatitis, rupture of viscus, e.g. appendix, peptic ulcer and diverticulum)
- Mesenteric cyst or pseudocysts
- Tumours such as mesothelioma and primary peritoneal carcinoma

Ca Prostate – Clinical and Pathology

• Anatomy of prostate: divided into three zones
- Central zone: surrounds the ejaculatory ducts does not contribute to benign prostatic hyperplasia or cancer
- Peripheral zone: gives rise to carcinoma and palpated anteriorly in a rectal exam (asymptomatic until late on in the disease)
- Transitional zone: includes the periurethral glands between the verumontanum and bladder neck (area of benign prostatic hyperplasia which can increase urethral resistance and result in symptomatic outflow obstruction)
• Prostate cancer:
- Epidemiology: up to 50% of men over age of 50 have prostate cancer.
- Found at autopsy but does not cause the patient clinical problems
- However prostate cancer that progress to cause clinical problems (in rectal examination) and produce abnormal PSA values is fatal
- Aetiology: unknown causes but androgen, diet and environmental factors are important.
- Features: prostate cancer is extremely infiltrative and not discrete.
• Diagnosis:
- Prostate specific antigen: glycoprotein of low molecular weight synthesised by normal prostatic epithelial cells (function of liquefy sperm coagulum). Elevated level of this antigen can be detected in circulating blood for men with prostate cancer as cancer cell invades the blood. However this method is only 60% specific as high PSA level also indicate UTI, prostatitis and instrumentation.
- Digital rectal examination: palpation of the prostate for masses *these are often advanced and incurable)
- Trans-rectal ultrasound: not a reliable tool but used to guide needle biopsy to prostate
• Clinical presentation of prostate cancer:
- Urinary obstruction and frequent urinary tract infection
- When prostate cancer invades from peripheral zone to transitional zone, disease is incurable.
• Progression of cancer: spreads to seminal vesicle, and pelvic organs causing pain
- Post renal failure if urethra blocked off
- Tumour capable of wrapping around nerves and spread through the capsule along the nerve. Cancer invasion leads to impotence as nerves is essential for erection
• Grading of tumour: The Gleason grading system is the common one and based on architectural pattern of the tumour rather than cellular features.
- Overall grading is by the sum of the grades for the most prevalent and the second most prevalent patterns.
• Staging: TMN system is used for stage.
- T1 tumours are not palapable
- T1a and T1a diagnosed after prostatectomy while T1c is detected on raised serum PSA
- T1b and T1c tumour have faster rate of progression than T1a so are treated often
- T2a and b tumours are detected by rectal examination
- T3, 4 and N1 and M1 tumours are presently incurable by any form of current treatment
• Treatment of prostate cancer:
- Radical prostatectomy: for early stage prostate cancer treatment and finding out the stage. Radical radiotherapy has similar results but stage remains unknown. Surgery leads to higher impotence and incontinence rate while radiotherapy is associated with frequent bowel and bladder problems
- Hormonal therapy: used for incurable local/metastatic disease, and ablation of androgens is by surgical castration or androgen receptor blocker.
• Carcinoma in bladder: arise in urothelium and most common in bladder and second most common in calyx. Develops from flattened urothelium to papillary and invasive carcinoma leading to haemoturia i.e. fragile papilla breaks off and bleeds
- Flat carcinoma in situ and multiple nodules.
- Complications: tumours blocking off the urinary channel can cause hypertrophy of bladder muscles.
• Treatment of carcinoma of bladder:
- Transurethral resection
- BCG used to stimulate immune system to kill cancer
- Cytotoxic agent instilled in bladder to destroy cancer
- Cystectomy: removal of bladder complete when cancer goes to detrusor muscles. Attach ureter to skin and collect urine in a bag.

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