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S3B3 Pathology > Cervical Pathology & The Pap Smear > Flashcards

Cervical Pathology & The Pap Smear Flashcards

1
Q

What type of epithelium lines the endocervix, ectocervix & tranformation zone?

A
  • endocervix
    • mucus, secreting columnar cells
  • ectocervix
    • mature squamous cell continuous with vaginal lining
  • transformation zone
    • squamous-columnar junction
    • location varies with age & hormonal influence
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2
Q

What is squamous metaplasia & how is it related to cervical cancer?

A

replacement of columnar epithelium with squamous cells

immature squamous cells of transformation zone are most susceptible to HPV, so this area is most susceptible to lesions/cancer

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3
Q

What part of the cervix is most susceptible to squamous dysplasia & cancer?

A

transformation zone

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4
Q

What is the significance of lactobacilli in the vagina?

A

produce lactic acid & keep pH < 4.5, which suppresses the growth of pathogenic organisms

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5
Q

Overgrowth of bacteria can cause what issues in the female reproductive tract?

A

vaginitis / cervicitis

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6
Q

What condition is likely based on the histological slides from a PAP smear?

A

Cervicitis

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7
Q

What condition is shown on the provided image?

A

Endocervical Polyp

small, sessile “bumps” to large polyploid masses protruding through external os

it can appear pink b/c it is very vascular

smalls

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8
Q

The provided slide is a microscopic sample of what condition?

A

Endocervical Polyp

  • prominent vascularity
  • loose, fibromyxoid stroma covered with muco-secreting endocervical glands
  • stroma may show edema
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9
Q

What are the High Risk HPV strains?

A

16 (60% cervical cancers)

18 (10% cervical cancers)

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10
Q

What are the low risk HPV strains?

A

6

11

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11
Q

90% of HPV infections clear within what time frame?

A

2 years

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12
Q

HPV infects what type of cells?

A

immature basal cells of squamous epithelium in areas of epithelial breaks or squamo/columnar junctions (transformation zone)

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13
Q

What are the two most important HPV proteins in the pathogenesis of cervical neoplasia?

A

E6

E7

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14
Q

What do E6 and E7 do?

A

inactivate crucial cell cycle proteins

  • genetic instability
  • mutations
  • malignant progression
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15
Q

Describe the interaction between E6 and p53 inside infected cells? This has what impact on the cell?

A

E6 binds to p53 & causes it degradation

  • unchecked cellular cycling - uncontrolled proliferation
  • anti-apoptotic effect - chromosomal instability
  • stimulate mitotic activity via regulating Src tyrosine kinases
  • upregulate telomerase expression

proliferation of genetically unstable infected cells

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16
Q

What is the role of p53 in a healthy cell?

A

inhibitor of cell growth - controlling transition from G0G1 to S phase

tumor suppressor - preventing cell growth after chromosomal damage

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17
Q

How are HPV infected cell immortalized?

A

E6 upregulates telomerase expression

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18
Q

Describe the interaction between E7 and p53.

A

sensitizes wild-type p53 cells to undergo apoptosis & exerts an anti-apoptotic effect in cells with mutated p53

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19
Q

How does E7 interact with Rb? This has what impact on infected cells?

A

E7 binds to activated retinoblastoma (Rb) protein & promotes its degradation, removing its antiproliferative effect

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20
Q

What is the role of Rb in an uninfected cell?

A

Retinoblastoma (Rb) protein, when active, binds and inhibits E2F transcription factors that regulate genes required for cells to pass through the G1/S cell cycle checkpoint

Rb has an antiproliferative effect on the cell cycle

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21
Q

How does E7 interact with p21 and p27? This has what impact on infected cells?

A

E7 binds & inhibits p21 and p27 (cyclin-dependent kinase inhibitors)

  • enhances cell cycle progression
  • impairs the ability of the cells to repair DNA damage
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22
Q

What are the similarities & differences between Dysplasia and Carcinoma in situ in the cervix?

A

Similarities

  • occur at transformation zone
  • associated with HPV 16 & 18

Differences

  • Dysplasia
    • disordered growth & maturation beginning at basal layer & extending upward
    • nuclei hyperchromatic w/ irregular outlines
  • Carcinoma in situ
    • full-thickness dysplasia with no maturation & no invasion
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23
Q

Which Cervical Intraepithelial Neoplasia levels are considered high grade & which are considered low grade?

A
  • Low grade (LSIL)
    • CIN I
  • High grade (HSIL)
    • CIN II
    • CIN III
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24
Q

LSIL is associated with what variable?

A

productive HPV infection with a high level of viral replication (usually high risk HPV)

25
Q

Is LSIL treated as a pre-malignant condition?

A

no, it is not becauseSCC does not directly arise from it, only from HSIL

  • 60% LSIL regress
  • 30% persist
  • 10% progress to HSIL
26
Q

HSIL is associated with what variable?

A

progressive deregulation of the cell cycle

lower rate of viral replication than LSIL

100% are associated with high risk HPV (usually type 16)

27
Q

Is HSIL treated as a pre-malignant condition?

A

yes, all are treated as high risk for progression to carcinoma

  • 30% regress
  • 60% persist
  • 10% progress to carcinoma
28
Q

What condition is depicted by the special stain on the provided slide?

A

HSIL

p16 stain

strong & fairly confluent positive brown staining of both cytoplasm and nuclei

29
Q

What is the function of p16?

A

a tumor suppressor protein that inhibits cyclin D-dependent protein kinases CDK4 and CDK6, which helps to maintain Rb in its active state

30
Q

Why do HPV cells express high levels of p16?

A

E7 oncoprotein inactivates Rb and leads to overexpression of p16

31
Q

Doe LISL stain positive or negative on a p16 stain?

A

negative

32
Q

What is the most common cervical carcinoma?

A

squamous cell carcinoma (80%)

33
Q

What is the biggest risk factor for developing cervical carcinoma?

A

HPV infection

34
Q

What is the typical age of presentation of cervical carcinoma?

A

45yr

35
Q

What pathology is shown in the provided gross sample?

A

Invasive Squamous Cell Carcinoma of the Cervix

(superficially invasive tumors are not grossly visible, except via colonoscopy or application of acetic acid)

36
Q

The histological samples are examples of what pathology?

A

Squamous Cell Carcinoma of the Cervix

  • Left
    • small nest of invasive cells breaking through the basement membrane
  • Right
    • nests & tongues of malignant squamous epithelium
    • may or may not produce keratin
37
Q

What pathology is shown in the provided histological sample?

A

Adenocarcinoma

  • Left: In situ
    • pseudostratified, hyperchromatic nuclei
  • Right: invasive
    • proliferation of glands
    • large, hyperchromatic nuclei, nuclear stratification & decreased cytoplasmic mucin
38
Q

How does cervical SCC spread?

A

direct extension to contiguous tissues & via lymphatic/vascular invasion

39
Q

What is the most successful cancer screening test ever developed?

A

Pap smear

40
Q

How does the Pap smear help detect cancer?

A

most cervical cancers arise from precursor lesions and take years to develop

these lesions shed cells that may be detected on cytological examination

41
Q

What are the two types of Pap smear processing?

A
  • Traditional
    • cells are immediately smeared on glass slide & sprayed with fixative
  • Liquid
    • cells placed into vial of liquid fixative that is spun down onto a slide
42
Q

How is the physical collection of the pap smear performed?

A

transformation zone is circumferentially sampled with a “broom”, spatula or brush

43
Q

What is the the specificity of the Pap smear? What variable contributes to this specificity?

A

70%

reactive conditions may mimic dysplasia

44
Q

What is the the sensitivity of the Pap smear? What variable contributes to this specificity?

A

80%

  • dysplastic cells may be missed or not present
  • Issues with pap smear
    • poor sampling
    • obscuring blood or inflammation
    • air-dry artifact with traditional smears
    • thick or poorly prepared traditional smears
45
Q

What are the three major advantages of the liquid-based processing method of a Pap smear?

What is the disadvantage

A
  • Advantages
    • morphology is better - easier to read (higher sensitivity)
    • sample can also be used for molecular methods of testing
    • residual material in vial can be used to prepare cell blocks & special stains
  • Disadvantages
    • expensive
46
Q

The provided microscopic slide of a pap smear is an example of normal, LISIL or HSIL? How do you know?

A

Normal

  • abundant cytoplasm & small, round/oval nuclei
  • basal epithelial cells are smaller with relatively larger nuclei
47
Q

The provided microscopic slide of a pap smear is an example of normal, LISIL or HSIL? How do you know?

A

HSIL

  • cells are smaller than LSIL, have less cytoplasm but bigger nuclei
  • higher nuclear: cytoplasm ratio
48
Q

The provided microscopic slide of a pap smear is an example of normal, LISIL or HSIL? How do you know?

A

LSIL

  • with koilocytes
  • cell may be multinucleated & nuclei are hyperchromatic with irregular nuclear membranes
  • higher nuclear:cytoplasm ratio than normal
49
Q

What pathology is characteristic of the cells shown on the provided slides?

A

Squamous Cell Carcinoma

  • Left
    • keratinizing SCC in inflammatory background
    • cells are large, pleomorphic, have large, hyperchromatic nuclei & red cytoplasm
  • Right
    • non-keratinizing SCC in bloody background
    • cells smaller than keratinizing SCC
    • higher N:C ratio
50
Q

What pathology is characteristic of the cells shown on the provided slides?

A

Adenocarcinoma

  • Left: in situ
  • Right: invasive

clusters of crowded, atypical glandular cells with high N:C ratio, nuclear hyperchromasia & prominent nucleoli

51
Q

When should someone get their first pap smear?

A

at 21 yrs or within 3 years of onset of sexual activity

52
Q

At what intervals should someone get Pap smears?

A

every 3 years until 30 yrs

After 30

  • If (-) high risk HPV
    • sceened every 3-5 yrs
  • If (+) high risk HPV
    • screen every 6-12 months

After 65, no more screening indicated if adequate prior screening

53
Q

What are the next steps after an abnormal cytology is noted on a pap smear?

A

perform colposcopic examination of the cervix and vagina to identify & biopsy the lesion

54
Q

What is the treatment for HSIL?

A
  • Superficial excision
    • cold knife cone
    • Loop electrosurgical excision (LEEP)
    • Lasar ablation
    • cryotherapy
55
Q

What is the treatment for LSIL?

A

usually treated conservatively but doctors may perform local ablation

56
Q

What are the steps to the colposcopic procedure?

A
  1. acetic acid is applied to the cervix & vagina
  2. mucosa is examine with a strong light & magnifying glass
  3. abnormal epithelium appears as white spots
  4. any aceto-white areas are biopsied
57
Q

What demographic is recommended to receive the HPV shot?

A

all girls & boys age 11-12

young men & women up to 45 yrs

58
Q

All 3 HPV vaccines protect against what two types? What additional types are covered by ⅔ vaccines?

A
  • All 3
    • 16 & 18
  • ⅔
    • 6 & 11

S3B3 Pathology (6 decks)

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