SM_215b: Pathology of the Cervix, Vagina, and Vulva Flashcards
Describe cervical maturation
Cervical maturation
- Cervix has squamous and glandular components
- At menarche, the hormonal milieu causes the glandular component to evert to the ectocervix
- Inflammation and irritation then causes this exposed glandular epithelium to be replaced with squamous epithelium (metaplasia)
This is ____
This is ectocervix (squamous mucosa)
This is ____
This is endocervix (glandular mucosa)
This is ____
This is transformation zone
____ is initially glandular but becomes squamous after menarche due to hormonal factors, inflammation, and irritation
Cervical transformational zone is initially glandular but becomes squamous after menarche due to hormonal factors, inflammation, and irritation
Cervical transformational zone has ____ that is vulnerable to ____
Cervical transformational zone has metaplastic squamous epithelium that is vulnerable to HPV infection
Risk factors for cervical cancer are ____, ____, ____, and ____
Risk factors for cervical cancer are multiple sexual partners, early initiation of sexual activity, high parity, and smoking
Describe histology of cervical squamous cell carcinoma
Cervical squamous cell carcinoma
- Neoplastic cells breach basement membrane
- Keratinization
- Intracellular bridges
Describe histology of cervical adenocarcinoma
Cervical adenocarcinoma
- Gland formation, mucin production
____ is most common form of cervical cancer
Squamous cell carcinoma is most common form of cervical cancer
- Pap test is good at detecting
- Histologic features: keratinization, intracellular bridges
____ is the precursor to invasive squamous carcinoma
Squamous dysplasia (cervical intraepithelial neoplasia) is the precursor to invasive squamous carcinoma
- CIN I, II, and III
Most cases of mild cervical dysplasia harbor ____ as do almost all cases of moderate / severe dysplasia and invasive carcinoma
Most cases of mild cervical dysplasia harbor high risk HPV as do almost all cases of moderate / severe dysplasia and invasive carcinoma
- Squamous dysplasia is 100x more common than invasive carcinoma
- Most cases of dysplasia will spontaneously resolve
- It takes years to progress from low grade squamous intraepithelial lesion to high grade squamous intraepithelial lesion to invasive carcinoma
Pap smears are first offered at age ____ with routine follow-up every ____
Pap smears are first offered at age 21 with routine follow-up every 3 years
- Long progression time from dysplasia to carcinoma
- Most lesions spontaneously regress
____ are cells infected with HPV
Koilocytes are cells infected with HPV
Describe mild dysplasia (LSIL)
Mild dysplasia (LSIL)
- Koilocytes: cells showing effect of HPV infection
- Dysplastic cells in lower 1/3 of epithelium
Moderate dysplasia (HSIL) involves dysplastic cells in ____
Moderate dysplasia (HSIL) involves dysplastic cells in middle third of epithelium
Severe dysplasia (HSIL) involves dysplastic cells in ____
Severe dysplasia (HSIL) involves dysplastic cells in upper third to full thickness
Moderate and severe cervical dysplasia (HSIL) involve ____
Moderate and severe cervical dysplasia (HSIL) involve dysplastic cells extending to the mid and upper third of the epithelium
p53 is responsible for ____ and ____
p53 is responsible for
- Detecting and repairing DNA damage
- Arresting cell growth while this happens
- Sending cell to apoptosis if damage is significant
Describe effect of E6 oncoprotein
E6 oncoprrotein
- E6 binds to p53
- Sends p53 for degradation via ubiquitination
- Cell accumulates DNA damage and continues cell growth without apoptosis
- Neoplasia
Describe function of Rb
Rb (retinoblastoma protein)
- Normally bound to transcription factor E2F so E2F is inactive
- Once Rb is phosphorylated by cyclin D / CDK4, E2F detaches and can get to work to promote cell growth
Describe effect of E7 oncoprotein
E7 oncoprotein
- E7 binds to Rb-E2F complex and splits it
- E2F is free to accelerate cell growth free of internal regulation
- E2F removes a negative feedback loop on p16
- Negative feedback for CDK 4/6 and cyclin D is turned on in an attempt to slow down the madness
- Accumulation and overexpression of p16 in the cell
Pathologists exploit ____ as a surrogate marker of high risk HPV infection
Pathologists exploit p16 accumulation as a surrogate marker of high risk HPV infection
Describe HPV mechanism
HPV mechanism
- E6 protein: accelerates proteolytic degradation of p53 -> no apoptosis, DNA damage accumulation, promotes cell division
- E7 protein: binds Rb protein -> promotes cell division, overexpression of p16
Pap smear is a ____ that aims to ____
Pap smear is a screening test that aims to identify dysplastic lesions for eradication before they can progress to carcinoma
- Screening test so requires a confirmatory test (colposcopy and biopsy)
- Increasingly combined with hrHPV testing b/c not 100% sensitive by itself
Cervical dysplasia / carcinoma is driven by ___ infection and generally involves the ___
Cervical dysplasia / carcinoma is driven by high risk HPV infection and generally involves the transformation zone
- HPV infection and dysplasia only rarely progress to carcinoma
- Takes many years for dysplasia to progress to carcinoma
- Pap test is not 100% sensitive and works because you repeat it and because of combination with hrHPV testing
Condyloma acuminatum is a ___ caused by ___
Condyloma acuminatum is an exophytic papillary lesion (genital wart) caused by infection with low risk HPV (6, 11)
- No considered pre-malignant
- Pathology: koilocytes, papillae (finger-like projects), epithelial thickening
Lichen sclerosus is ____ seen in ____ that most often has an ____ cause
Lichen sclerosus is whitish scaly plaques seen in older patients that most often has an autoimmune cause
- Thinning (atrophy) of the epithelium with stromal hyalinization (dense fibrosis)
- Invasive squamous cell carcinoma can occasionally arise in lichen sclerosus
Lichen simplex chronicus is ____ caused by ____
Lichen simplex chronicus is squamous cell hyperplasia caused by chronic irritation (itching)
- Can get anywhere on skin
- Hyperkeratosis also
Vulvar squamous carcinoma occurs due to two pathways: ____ and ____
Vulvar squamous carcinoma occurs due to two pathways
- Usual pathway (HPV driven): LSIL and HSIL (similar to cervix), younger women
- Differentiated pathway (associated with p53 pathway, lichen sclerosis): older women
Vulvar Paget’s disease is usually a manifestation of ____ and sometimes represents ____
Vulvar Paget’s disease is usually a manifestation of underlying neoplasm of sweat glands or skin adnexae and sometimes represents internal malignancy (colon cancer, urothelial carcinoma)
- Often presents as a crusted red vulvar or perianal lesion
Herpes simplex is characterized by the 3Ms: ____, ____, and ____
Herpes simplex is characterized by the 3Ms: multinucleation, molding, and margination
- Multinucleation: numerous nuclei
- Molding: nuclei fit and shape to one another
- Margination: chromatin is pushed to the edge of the nucleus by viral proteins
Herpex simplex often appears as ____ on histology
Herpex simplex often appears as pink nuclear inclusions (Cowdry A) on histology
Primary syphilis presents as ___
Primary syphilis presents as chancre (painless ulcer)
- Ulcerated skin / mucosa with chronic inflammation and numerous plasma cells, surrounding blood vessels
Secondary syphilis presents with ____
Secondary syphilis presents with condyloma lata (plaques and papules on genitalia, palms, soles, and vaginal / oral mucosa)
- Bacteremia highest, best stage to detect
- Chemical tests for syphilis usually positive
- Rash
Tertiary syphilis presents with ___, ___, and ___
Tertiary syphilis presents with aortitis (proximal aorta), CNS manifestations, and gummas
- Gumma: necrotic center surrounded by granulomatous reaction (histiocytes)
