Gynae + testicular pathology Flashcards
What is the epithelium type of the cervix?
- endocervix lined by columnar (glandular) epithelium
- ectocervix lined by squamous epithelium
the two types of cells meet at the squamocolumnar junction
How does the cervix histology change during puberty and pregnancy?
During puberty and pregnancy, hormonally-induced eversion of cervix occurs: lower pH of vagina results in formation of a physiological transformation zone (TZ):
- the columnar epithelium undergoes physiological metaplasia to tougher + more resistant squamous epithelium
Following the physiological metaplasia, what other changes can occur in the transformation zone?
- cells undergoing metaplasia are predisposed to develop dysplasia
- so it is in transformation zone that virtually all cervical dysplasia arises
- in the cervix, the agent inducing dysplasia is HPV
- dysplasia occuring in the cervix is called cervical intraepithelial neoplasia (CIN) - usually asymptomatic
- left untreated, CIN may progress to invasive squamous cell carcinoma
How likely is CIN progression to invasive carcinoma?
- ~ 11% of CIN 1 will progress to CIN 3 (other 89% stays as CIN 1 or regresses)
- ~ 12% of CIN 3 will progress to invasive cancer (other 88% stay as CIN 3 or regresses)
What is the major risk factor for development of CIN and cervical cancer?
- persistent HPV infection
- over 99.5% of cervical cancers associated w/ high risk of HPV infection
- more than 130 HPV genotypes identified
- sexually transmitted
HPV infections of the genital tract have been subclassified into those associated w/ benign (low risk) and malignant (high risk) genital tract disease.
What are the high risk subtypes?
- HPV types 16 + 18
- associated w/ 70% of cervical cancers
What are the low-risk HPV subtypes?
- HPV types 6 + 11
- subtypes associated w/ anogenital warts (condyloma acuminata) but not CIN and cervical cancer
What is the pathophysiology of the HPV virus and how it infects?
- HPV viral DNA integrates into host cell DNA in the cervical squamous epithelium
- the virus preferentially infects cells in the TZ since these cells are undergoing metaplasia and altered gene expression
- the viral E6 + E7 gene products interact with and inhibit tumour suppressor gene products: P53 and retinoblastoma protein
- these proteins are important for cell cycle control + apoptosis
- inactivation of these genes -> uncontrolled cell proliferation
- HPV is a prerequisite for cervical cancer but only small proportion of HPV infections progress to either high-grade CIN or cancer
- progression to malignancy requires one or more cofactors eg. smoking, immunosuppression
Cervical cancer is the most common cause of cancer in women aged 18-35yrs. How does cervical cancer usually present?
- vaginal bleeding
- most commonly post-coital bleeding
- post-coital bleeding is due to cervical cancer until proven otherwise
- there may be an offensive vaginal discharge
- pain is not an early feature
- speculum exam usually reveals an ulcer or a mass on cervix
Following examination, what investigations can be carried out for suspected cervical cancer?
- biopsy -> to confirm diagnosis, give the type and grade
- staging -> examination under anaesthesia, abdo/pelvis CT
- staged using FIGO system
NB. a smear is a screening test for asymptomatic women and so is not appropriate in a symptomatic woman
What is the pathology/type of most cervical cancers?
- invasive squamous cell carcinomas (80%)
- precursor lesion is CIN
What are the remaining 20% of cervical cancers?
- adenocarcinomas
- arising from endocervical epithelium in cervix
- high risk HPV also important in causing cervical adenocarcinoma
- precursor lesion is CGIN (cervical glandular intraepithelial neoplasia)
CGIN beyond scope of T year syllabus
Describe the cervical screening programme
- to detect + treat premalignant lesions (ie. CIN)
- therefore to reduce incidence + mortality of squamous cell carcinoma
- cervical smears are basis of programme
- women screened every 3 years from 25-49yrs and every 5yrs from 50-64yrs
- test involves opening up vagina w/ speculum and using a brush to take sample of cells from the transformation zone
- the brush, where cells are lodged, rinsed directly into preservative fluid
- this is sent to cytology lab for prep as a slide
- stained slides scrutinised for squamous epithelial cells showing dyskaryosis
What is dyskaryosis?
- refers to abnormalities of the cell nucleus
- eg an irregular shape, an increased size
- term that is only used in cervical smear reports
- dyskaryosis is graded depending on severity of nuclear abnormalities:
- low grade - mild
- high grade - moderate or severe
What is the difference between dyskaryosis and CIN regarding terminology?
- dyskaryosis - diagnosis rendered on cervical smear (screening)
- CIN - diagnosis only rendered on cervical biopsy (gold-standard)
A smear showing dyskaryosis is a good predictor of the presence of CIN in the cervix. What dyskaryosis grades correlate with the level of CIN?
- low grade (mild) dyskaryosis - CIN 1
- high grade (mod) dyskaryosis - CIN 2
- high grade (severe) dyskaryosis - CIN 3
These are all PREDICTIONS - like all screening tests, the cervical smear is not perfect + sometimes is wrong. A definite diagnosis of CIN can only be made on biopsy (or LLETZ) taken at colposcopy.
What is meant by ‘borderline nuclear change’?
- a reporting category which is best thought of as a holding category
- used when the pathologist is uncertain whether the smear is normal or shows dyskaryosis
- does not correspond to a particular disease process
- borderline category is necessary bc the cervical smear is an imperfect screening test which doesn’t always give a clear result
What are the national guidelines for management of abnormal cervical smears?
- high-grade dyskaryosis (mod/severe) -> refer pt to colposcopy
-
low-grade dyskaryosis (mild) -> HPV testing using PCR performed on smear sample to see if high risk HPV subtypes (16+18) are present in sample:
- high-risk HPV positive -> refer pt to colposcopy
- high-risk HPV negative -> return pt to routine recall (3-5yrs)
- borderline nuclear change managed in same way as low-grade dyskaryosis (ie HPV triage)
Why is it reasonable to “return to routine recall” if the high-risk-HPV test is negative?
- in absence of high-risk HPV, CIN is very very unlikely
- therefore it is safe to assume the ‘mild dyskaryosis’ seen in smear is actually a false positive
- reflects imperfections of the screening test
What happens at colposcopy?
- cervix exposed using a speculum
- colposcopist carefully examines cervix using colposcope
- both before and after application of acetic acid
- certain abnormal colposcopic appearances are associated w/ CIN eg. acetowhite epithelium
- however, CIN is a histological diagnosis so biopsy required to confirm diagnosis
What is the management of CIN?
- CIN 1 - observation + regular follow-up smears
-
CIN 2 + 3 - excision of transformation zone w/ cutting diathermy under local anaesthesia - ‘large loop exicison of transformaton zone’ (LLETZ)
- specimen sent to lab to be carefully examined histologically by pathologist
- pts who have had a LLETZ for CIN are offered a repeat smear + high risk-HPV testing 6 months later
What is the endometrium composed of?
- endometrial glands
- endometrial stroma
- in normal endometrium, the glands are widely spaced in the stroma
What is endometrial hyperplasia?
- increase in the number of endometrial glands relative to the endometrial stroma
- glands become more closely packed
- results in a thickening of endometrium
- can be seen at hysteroscopy or on imaging (transvaginal ultrasound)
How common is endometrial cancer?
- endometrial carcinoma = most common gynae malignancy
- most endometrial cancers (>90%) occur in women aged >50yr
- majority are adenocarcinomas arising from atypical hyperplasia
What are the gold standard investigations for post-menopausal bleeding (suspected endometrial cancer)?
- hysteroscopy and endometrial biopsy
- gynaecologist is able to visualise the endometrium + biopsy suspicious areas
- biopsy will establish diagnosis of carcinoma + also provide grade of tumour (1, 2 or 3)
- once cancer dx established, tumour needs to be staged - done by MRI, staged using FIGO system
An ovarian mass may present acutely. What one of three things might it be associated with in a patient?
- torsion of pedicle of the mass -> impairment to blood supply, initially causes ischaemia + abdominal pain. If torsion isn’t corrected, the mass will undergo infarction + patient’s clinical condition will worsen
- rupture of a cystic mass with a release of cyst contents into the peritoneal cavity -> intense pain, this is particularly associated w/ a mature cystic teratoma
- haemorrhage of a cystic mass into itself or into peritoneal cavity often causes pain, peritoneal cavity haemorrhage can be so severe as to cause hypovolaemic shock
What is the most common type of malignant ovarian tumour?
- high grade serous carcinoma (HGSC)
- on naked eye examination, HGSC may be purely solid but more commonly it has solid + cystic components
- over 90% of ovarian cancers are carcinomas (ie. tumours arising from epithelial cells)
- HGSC accounts for ~70% of all ovarian carcinomas
There are many types of germ cell tumours, they are divided into two groups. What are these two groups?
Seminoma and non-seminomatous GCTs
For T year, we only expect you to know about seminoma. You are not expected to know about the subtypes of NSGCTs but you should be aware of the existence of the NSGCT group of tumours.
Seminoma has a peak incidence in the 30-40yr age group. Where does it arise?
- type of germ cell tumour
- arises in the seminiferous tubules of testis
- remember that the seminiferous tubules are site of spermatogenesis:
- germ cell -> spermatogonia -> spermatocyte -> spermatid -> spermatozoa
What is the primary treatment for seminoma?
- radical orchidectomy
- seminoma usually spreads via lymphatics to para-aortic retroperitoneal lymph nodes; chemo to treat involved retroperitoneal nodes may be employed (if required)
What comparisons can be made between seminomas and non-seminomatous germ cell tumours?
- testicular germ cell tumours are uniquely chemo- and radiosensitive
- consequently, cure rates for these tumours are more than 80% even in those w/ metastases
- however, treatment can be less intensive when disease is diagnosed at an earlier stage
Compare and contrast the features of the most common ovarian and testicular tumours
