SM_215b: Pathology of the Cervix, Vagina, and Vulva Flashcards by Nathan Shlobin

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)

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This is ____

This is ectocervix (squamous mucosa)

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This is ____

This is endocervix (glandular mucosa)

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This is ____

This is transformation zone

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____ 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

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Cervical transformational zone has ____ that is vulnerable to ____

Cervical transformational zone has metaplastic squamous epithelium that is vulnerable to HPV infection

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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

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Describe histology of cervical squamous cell carcinoma

Cervical squamous cell carcinoma

Neoplastic cells breach basement membrane
Keratinization
Intracellular bridges

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Describe histology of cervical adenocarcinoma

Cervical adenocarcinoma

Gland formation, mucin production

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____ 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

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____ is the precursor to invasive squamous carcinoma

Squamous dysplasia (cervical intraepithelial neoplasia) is the precursor to invasive squamous carcinoma

CIN I, II, and III

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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

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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

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____ are cells infected with HPV

Koilocytes are cells infected with HPV

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Describe mild dysplasia (LSIL)

Mild dysplasia (LSIL)

Koilocytes: cells showing effect of HPV infection
Dysplastic cells in lower 1/3 of epithelium

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Moderate dysplasia (HSIL) involves dysplastic cells in ____

Moderate dysplasia (HSIL) involves dysplastic cells in middle third of epithelium

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Severe dysplasia (HSIL) involves dysplastic cells in ____

Severe dysplasia (HSIL) involves dysplastic cells in upper third to full thickness

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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

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HPV infection and LSIL are ____

HPV infection and LSIL are extremely common and usually transient

High risk HPV is HPV ____ and tends to ____

High risk HPV is HPV 16 and 18 and tends to integrate into host chromosomes

18 is associated with adenocarcinoma

Low risk HPV is HPV ____ and is associated with ____

Low risk HPV is HPV 6 and 11 and is associated with warts

Does not integrate into genome, present as episome

HPV oncoproteins are ____ and ____

HPV oncoproteins are E6 and E7

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 1. E7 binds to Rb-E2F complex and splits it 2. E2F is free to accelerate cell growth free of internal regulation 3. E2F removes a negative feedback loop on p16 4. Negative feedback for CDK 4/6 and cyclin D is turned on in an attempt to slow down the madness 5. 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

\_\_\_ is what classifies an HPV serotype as high risk or low risk

Affinity of E6 or E7 to respective targets to is what classifies an HPV serotype as high risk or low risk

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

Describe vulvar pathology

Vulvar pathology * Condyloma * Lichen simplex chronicus * Lichen sclerosus * Vulvar cancer: squamous cell carcinoma, Paget's disease

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

Genital herpes is caused by ____ and presents as \_\_\_\_

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

Syphilis is caused by \_\_\_

Syphilis is caused by Treponema pallidum (corkscrew shaped spirochete)

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)