Cervical and Vulval Pathology Flashcards
What are condyloma acuminatum?
Genital warts
What is LSIL?
The tissue that covers your cervix is made up of squamous cells. Low-grade squamous intraepithelial lesion (LSIL) is a common abnormal result on a Pap test. It’s also known as mild dysplasia. LSIL means that your cervical cells show mild abnormalities.
Are genital warts a form of LSIL?
Yes
Different shapes of genital warts?
- Exophytic - Flat - Papillary - Occasionally inverted
What is HPV?
HPV is the name of a very common group of viruses. They do not cause any problems in most people, but some types can cause genital warts or cancer.
What is CIN?
Cervical intraepithelial neoplasia (CIN) is a precancerous condition in which abnormal cells grow on the surface of the cervix (not cancer but may become cancer)
What are the risk factors of CIN for females?
- HPV infection
- First coitus <17 yrs age
- Multiple sexual partners
- Long term OCP use
- Early first pregnancy
- High parity
- Low socio-economic status
- STD’s: Herpes, gonorrhea, chlamydia
- Smoking
- Immunosuppression, including HIV seropositivity
What is the most important risk factor for CIN in females?
HPV infection
What are the risk factors of HPV for males?
- Penile warts
- Multiple sexual partners
- Cervical cancer (or CIN) in previous partner
What are the 2 types of HPV?
- Cancer causing types (high risk)
- Non-cancer causing types (low risk)
What are the low risk HPVs?
HPV 6 and HPV 11
What are the high risk HPVs?
HPV 16 and HPV 18
What can the non-cancer causing types of HPV cause?
90% of anogenital warts
What can the cancer causing types of HPV cause?
>75% of cervical cancer >50% of vaginal and vulvar cancer
What is the purpose of the cervical screening programme (NHSCSP)?
To reduce the incidence of, and mortality from, cervical cancer through a systematic, quality assured population-based screening programme for eligible women.
When are females first invited for a cervical screening?
25
How frequently are women screened between the ages of 25-49?
Every 3 years
How frequently are women screened between the ages of 50-64?
Every 5 years
How frequently are women screened between the ages of 65+?
Not had cervical screening since 50yrs of age OR follow up of recent abnormal cytology sample.
What does the NHSCSP screen for?
Primary human papillomavirus (HPV)
How does the NHSCSP work?
Liquid based cytology to detect abnormalities of cervix.
If abnormalities are found during the NHSCSP, what is the patient referred for?
Colposcopy to diagnose cervical intraepithelial neoplasia (CIN) and to differentiate high-grade lesions from low-grade abnormalities.
When did the HPV vaccination in England begin?
Sep 2008 for girls 12-13 years
What 2 vaccines are given for HPV?
- Cervarix (HPV types 16/18) : 2008 - 2012
- Gardasil (HPV types 6/11/16/18) : since Sep 2012
What HPV types does Gardasil target?
Low AND high risk HPV types (6/11/16/18)
Is the HPV vaccine offered to boys?
Yes - ages 12-13
What has been the major recent change in primary HPV screening?
Primary hr-HPV testing has replaced primary cytology (2019)
What does hr-HPV stand for?
High risk HPV
Why has hr-HPV testing replaced primary cytology (smear)?
Evidence shows HPV testing is a better way of identifying women at risk of cervical cancer than the cytology (smear) test that examines cells under a microscope.
What is a colposcopy?
A colposcopy is a simple procedure used to look at the cervix. It’s often done if cervical screening finds abnormal cells in your cervix.
What is the transformation zone (TZ)?
Area between original and new SCJ (squamous columnar junction) where the columnar epithelium has been and/or is being replaced by new metaplastic squamous epithelium
What is the SCJ?
The squamo-columnar junction (SCJ) of the cervix refers to a transitional area between squamous epithelium of the vagina and the columnar epithelium of the endocervix.
How does the SCJ change with age?
This shifts in location through age from being more external to internal.
What is the TZ prone to?
Oncogenic effects of HPV –> is the site of CIN development
What is the site of CIN development?
Transformation zone
Describe difference in obtaining cells between a female in her reproductive age and a female in her menopausal age
- Transformation zone cells can be obtained from surface of cervix
- Endocervical brush needed to sample the endocervical cells due to SCJ moving higher up
What is liquid based cytology?
A new method of preparing cervical samples for cytological examination. It involves making a suspension of cells from the sample and this is used to produce a thin layer of cells on a slide.
Pap smear appearances
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What is CIN1?
Low grade dysplasia
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What is CIN2 and CIN3?
High grade dysplasia
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Natural progression of HPV infection
Progression of normal cells after the HPV infection from CIN1 –> CIN2 –> CIN3 –> invasive malignancy (carcinoma)
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What is dyskaryosis?
Dyskaryosis means abnormal nucleus and refers to the abnormal epithelial cell which may be found in cervical sample. It is graded from low to high grade based on degree of abnormality.
New vs old protocol for cervical screening?
Old: only referred for HPV testing if displayed dyskaryosis, referred straight to colposcopy if high grade dyskaryosis
New: primarily tested for HR-HPV test
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What are precursor lesions in the cervix? How are they identified?
- CIN
- Asymptomatic lesions
- Identified in cytology then referred to colposcopy
- They can then be identified by visual examination after 3-5% acetic acid application
LSIL vs HSIL?
HSIL is an acronym for high grade squamous intraepithelial lesion, and LSIL means low grade squamous intraepithelial lesion
What are the morphological features of CIN1?
- Maturation is seen in upper 2/3 of epithelium.
- Some degree of nuclear abnormality full thickness epithelium; more in basal 1/3rd
- Normal MF’s may be increased; abnormal mitosis supports diagnosis
N.B. to call anything CIN you have to have presence of nuclear abnormality
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Morphological features of CIN II?
- Cytoplasmic maturation is seen in upper 1/3 of epithelium.
- Nuclear atypia more marked than CIN1
- MF’s increased; atypical mitosis common.
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Morphological features of CIN III?
- Maturation may be absent or confined only to superficial layers.
- Nuclear atypia is severe, through full epithelial thickness.
- MF’s are seen at all levels of epithelium.
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Describe dyskaryosis in CIN 1?
LSIL –> low grade CIN –> mild dysplasia/dyskaryosis
Describe dyskaryosis in CIN 2?
High grade CIN –> HSIL –> moderate dysplasia/dyskaryosis
Describe dyskaryosis in CIN 3?
High grade CIN –> HSIL –> severe dysplasia/dyskaryosis
What is p16? What is it used as a diagnostic marker of?
p16 is a tumor suppressor protein –> Block positive p16 expression is a sensitive and specific diagnostic marker of a transforming HRHPV infection
Where would you expect to see positive p16?
In cervical squamous lesions, p16 is positive in most high-grade cervical intraepithelial neoplasia (CIN) and in some cases of low-grade CIN
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What is the % of CIN I that a) regress b) progress to cancer?
a) 60% regression
b) <1% progression to cancer
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Treatment of CIN?
A large loop excision of the transformation zone (LLETZ) is the most common way of removing cervical tissue to treat pre-cancerous changes of the cervix.
ALSO CALLED Loop electrosurgical excision procedure (LEEP) –> This technique uses a small, electrically charged wire loop to remove tissue (transformation zone).
These samples are then analysed.
Describe stage 1 (T1) of cervical squamous carcinoma. What can stage 1 be subdivided into?
Tumour is confined to the cervix. Can be subdivided into 1a and 1b.
How can stage T1a of cervical squamous carcinoma be diagnosed? How about T1b?
- T1a - Only by microscopy
- T1b - Clinically visible lesion
What can T1a of cervical carcinoma then be subdivided into? What causes this differentiation?
T1a1 and T1a2 –> difference in stromal invasion and horizontal spread
Describe basement membrane in stage 1a1 or 1a2 tumours
Absence of sharply defined basement membrane
Staging of cervical cancer
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What is CGIN?
Cervical glandular intra-epithelial neoplasia: an abnormality of the glandular cells. It’s much less common that CIN, but it’s similar. It’s a pre-cancerous abnormality.
What are the 2 categories of glandular neoplasia?
- L-CGIN: not reported
- H-CGIN - corresponds to AIS (adenocarcinoma in-situ)
Where does CGIN usually occur?
At or close to TZ
What do glandular cells show dring CGIN?
Glandular cells show mucin depletion, nuclear stratification, atypia, hyperchromasia, MF’s and apoptosis (non-luminal aspect of the gland).
Can involve both surface and crypt epithelium.
What are the positive stains for CGIN?
- p16
- Ki67 increased
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What is Ki67?
The expression of Ki67 is strongly associated with tumor cell proliferation and growth, and is widely used in routine pathological investigation as a proliferation marker.
What is an adenocarcinoma?
Cancer that begins in glandular (secretory) cells.
Where is the tumour confined to in stage 1 of an early invasive adenocarcinoma?
T1: Tumour confined to the cervix
Describe invasive glandular / adenocarcinoma
- Obvious infiltrative pattern.
- Architectural complexity despite absence of obvious destructive invasion or stromal response.
- Buds with squamoid appearance emanating from glands involved with CGIN.
What are some other types of cervical tumours?
- Adenosquamous carcinoma
- Adenoid basal carcinoma
- Adenoid cystic carcinoma
- Neuroendocrine tumours
- Metastatic lesions
What is VIN?
Vulvar intraepithelial neoplasia, also known as VIN, is a non-invasive squamous lesion and precursor of squamous cell carcinoma (SCC) of the vulva.
What are the 2 main types of VIN?
- uVIN: usual type / undifferentiated
- dVIN: differentiated type
How is uVIN graded?
Graded 1-3 (similar to CIN)
What is uVIN related to?
HPV
Who is uVIN more common in?
Younger women (<40)
How is dVIN graded?
Not graded
Is dVIN HPV related?
No
Who is dVIN more common in?
Older women
What is the recurrence of uVIN related to?
- Recurs after local Rx in 50% cases.
- Recurrence correlated to smoking, multifocality and positive margins.
How often is progression of uVIN to SCC seen?
- Progression to SCC in 5-6% of treated women
- Progression to SCC in 10-15% of untreated women
Who is spontaneous regression of uVIN most likely in?
Pregnant or post partum women
Does dVIN carry a greater or lesser risk of a progression to invasive SCC?
Greater risk of progression: 1/3 of dVIN lesions progressed and within a short period (mean 28 months).
What is vulval squamous cell carcinoma associated with?
- Associated with VIN (msot common)
- Can also be associated with inflammatory dermatosis like Lichen sclerosus.
What is a multifocal lesion?
A lesion arising from or having many locations
Where is the tumour confined to in stage 1 of vulval carcinoma?
Tumour confined to the vulva: split into 1a and 1b depending on stromal invasion and size
What is Paget’s disease of the vulva (extramammary)?
- Paget’s disease of the vulva is an unusual kind of skin cancer (1% of vulval cancers) that arises from glandular cells
- Pruritus (itch); burning; eczematous patch
- Mean age - 7th decade
- This disease appears as a red, velvety area with white islands of tissue on the vulva. At times it may be pink, and occasionally there are moist, oozing ulcerations that bleed easily.
What else must you look for in Paget’s disease of the vulva?
30% patients have synchronous or metachronous internal carcinoma, most commonly of breast or genitourinary system.
Other types of vulval tumours?
- Adenocarcinoma
- Basal cell carcinoma
- Merkel cell tumour
- Malignant melanoma
- Sarcomas
- Metastasis
What conditions can dVIN be related to?
Chronic inflammatory diseases –> Lichen sclerosus
Which types of HPV cause 90% of genital warts?
HPV6 & HPV11