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Repro / GU > SM_215b: Pathology of the Cervix, Vagina, and Vulva > Flashcards

SM_215b: Pathology of the Cervix, Vagina, and Vulva Flashcards

1
Q

Describe cervical maturation

A

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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2
Q

This is ____

A

This is ectocervix (squamous mucosa)

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3
Q

This is ____

A

This is endocervix (glandular mucosa)

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4
Q

This is ____

A

This is transformation zone

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5
Q

____ is initially glandular but becomes squamous after menarche due to hormonal factors, inflammation, and irritation

A

Cervical transformational zone is initially glandular but becomes squamous after menarche due to hormonal factors, inflammation, and irritation

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6
Q

Cervical transformational zone has ____ that is vulnerable to ____

A

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

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7
Q

Risk factors for cervical cancer are ____, ____, ____, and ____

A

Risk factors for cervical cancer are multiple sexual partners, early initiation of sexual activity, high parity, and smoking

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8
Q

Describe histology of cervical squamous cell carcinoma

A

Cervical squamous cell carcinoma

  • Neoplastic cells breach basement membrane
  • Keratinization
  • Intracellular bridges
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9
Q

Describe histology of cervical adenocarcinoma

A

Cervical adenocarcinoma

  • Gland formation, mucin production
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10
Q

____ is most common form of cervical cancer

A

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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11
Q

____ is the precursor to invasive squamous carcinoma

A

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

  • CIN I, II, and III
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12
Q

Most cases of mild cervical dysplasia harbor ____ as do almost all cases of moderate / severe dysplasia and invasive carcinoma

A

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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13
Q

Pap smears are first offered at age ____ with routine follow-up every ____

A

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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14
Q

____ are cells infected with HPV

A

Koilocytes are cells infected with HPV

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15
Q

Describe mild dysplasia (LSIL)

A

Mild dysplasia (LSIL)

  • Koilocytes: cells showing effect of HPV infection
  • Dysplastic cells in lower 1/3 of epithelium
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16
Q

Moderate dysplasia (HSIL) involves dysplastic cells in ____

A

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

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17
Q

Severe dysplasia (HSIL) involves dysplastic cells in ____

A

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

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18
Q

Moderate and severe cervical dysplasia (HSIL) involve ____

A

Moderate and severe cervical dysplasia (HSIL) involve dysplastic cells extending to the mid and upper third of the epithelium

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19
Q

HPV infection and LSIL are ____

A

HPV infection and LSIL are extremely common and usually transient

20
Q

High risk HPV is HPV ____ and tends to ____

A

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

  • 18 is associated with adenocarcinoma
21
Q

Low risk HPV is HPV ____ and is associated with ____

A

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

  • Does not integrate into genome, present as episome
22
Q

HPV oncoproteins are ____ and ____

A

HPV oncoproteins are E6 and E7

23
Q

p53 is responsible for ____ and ____

A

p53 is responsible for

  • Detecting and repairing DNA damage
  • Arresting cell growth while this happens
  • Sending cell to apoptosis if damage is significant
24
Q

Describe effect of E6 oncoprotein

A

E6 oncoprrotein

  1. E6 binds to p53
  2. Sends p53 for degradation via ubiquitination
  3. Cell accumulates DNA damage and continues cell growth without apoptosis
  4. Neoplasia
25
Q

Describe function of Rb

A

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
26
Q

Describe effect of E7 oncoprotein

A

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
27
Q

Pathologists exploit ____ as a surrogate marker of high risk HPV infection

A

Pathologists exploit p16 accumulation as a surrogate marker of high risk HPV infection

28
Q

Describe HPV mechanism

A

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
29
Q

___ is what classifies an HPV serotype as high risk or low risk

A

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

30
Q

Pap smear is a ____ that aims to ____

A

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
32
Q

Cervical dysplasia / carcinoma is driven by ___ infection and generally involves the ___

A

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
33
Q

Describe vulvar pathology

A

Vulvar pathology

  • Condyloma
  • Lichen simplex chronicus
  • Lichen sclerosus
  • Vulvar cancer: squamous cell carcinoma, Paget’s disease
34
Q

Condyloma acuminatum is a ___ caused by ___

A

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
35
Q

Lichen sclerosus is ____ seen in ____ that most often has an ____ cause

A

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
36
Q

Lichen simplex chronicus is ____ caused by ____

A

Lichen simplex chronicus is squamous cell hyperplasia caused by chronic irritation (itching)

  • Can get anywhere on skin
  • Hyperkeratosis also
37
Q

Vulvar squamous carcinoma occurs due to two pathways: ____ and ____

A

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
38
Q

Vulvar Paget’s disease is usually a manifestation of ____ and sometimes represents ____

A

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
39
Q

Genital herpes is caused by ____ and presents as ____

40
Q

Herpes simplex is characterized by the 3Ms: ____, ____, and ____

A

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
41
Q

Herpex simplex often appears as ____ on histology

A

Herpex simplex often appears as pink nuclear inclusions (Cowdry A) on histology

42
Q

Syphilis is caused by ___

A

Syphilis is caused by Treponema pallidum (corkscrew shaped spirochete)

43
Q

Primary syphilis presents as ___

A

Primary syphilis presents as chancre (painless ulcer)

  • Ulcerated skin / mucosa with chronic inflammation and numerous plasma cells, surrounding blood vessels
44
Q

Secondary syphilis presents with ____

A

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
45
Q

Tertiary syphilis presents with ___, ___, and ___

A

Tertiary syphilis presents with aortitis (proximal aorta), CNS manifestations, and gummas

  • Gumma: necrotic center surrounded by granulomatous reaction (histiocytes)

Repro / GU (46 decks)

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