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a_GYNGU > 11/3- Lab 1: HPV and Pap Smears > Flashcards

11/3- Lab 1: HPV and Pap Smears Flashcards

1
Q

Cervical cancer is the #__ cause of cancer deaths

A

Cervical cancer is the #20 cause of cancer deaths

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2
Q

What is the epidemiology of cervical cancer?

  • Highest rate of diagnosis in what ages
  • Median age at diagnosis
  • Highest in what population
A
  • Highest rate of diagnosis in 35-44 yo
  • Median age at diagnosis = 49 yo
  • Highest incidence in Hispanics
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3
Q

What are the 2 different ways to obtain a cervical vaginal smear?

A

1. Conventional

  • Instrument samples both ecto and endocervix; spread on a slide

2. Liquid based cytology

  • Same method, but spatula is placed in liquid fixative and sent to pathology where a monolayer circle slide is produced
  • Benefits:
  • Machines are used to initially screened slides and this produces uniform, thin sheet
  • Allows quick molecular testing for HPV genotypes
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4
Q

What tissue is sampled in pap smear?

  • Describe the different types
A

The transformation zone

  • Where the normal columnar mucous-secreting endocervical cells transform into squamous epithelial cells lining ectocervix
  • Most cancers arise here
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5
Q

Why is the transformation zone screened so heavily?

A

It has metaplastic squamous cells predisposed to HPV infection

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6
Q

How does the transformation zone change with age/other health conditions?

A

The transformation zone is higher in the endocervical canal for young women and those who have not been pregnant

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7
Q

What is seen here?

A

Normal squamous cells (ectocervix)

  • May be “intermediate” or “superficial”
  • As the squamous epithelium matures, the nucleus becomes smaller and darker; cytoplasm becomes translucent
  • Nucleus of intermediate cell = size gaze for dysplasias
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8
Q

What is seen here?

A

Normal columnar epithelial (endocervical) cells

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9
Q

What is seen here?

A

Atrophic smear from post-menopausal (estrogen deficient) woman (could also be seen if breast-feeding or if tumor present)

  • Not many mature squamous epithelial cells
  • More parabasal cells
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10
Q

Case 1)

  • 25 yo woman, G1P0, 12 wks pregnant
  • Chief complaint: vaginal itching and thick white “cottage cheese” discharge
  • What is the diagnosis?
A

Candida infection

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11
Q

Describe Candida infection

  • Speculum/colposcopic view
  • Discharge
  • Symptomic infections
A
  • Thick, curd-like discharge
  • Symptomatic patients complain of severe pruritus and thick white vaginal discharge

Symptomic infections:

  • Diabetes mellitus
  • Antibiotics
  • Pregnancy
  • Immunocompromised states
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12
Q

How does Candida infection appear cytologically?

A
  • Smears may show numerous neutrophils
  • Epithelial cell clusters arranged around pseudohyphae in a “Shish kebab” look
  • Pseudohyphae of Candida love glycogen that is found abundantly in squamous epithelial cells (why they are so closely associated)
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13
Q

What is seen here?

A

Candida infection

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14
Q

Case 2)

  • 32 yo woman
  • Chief complaint: copious yellow discharge
  • Exam findings include “strawberry cervix” and abundant yellow discharge
  • What is the diagnosis?
A

Trichomonas infection

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15
Q

Describe a Trichomonas infection

  • How common
  • Discharge
  • Exam findings
A
  • 15% of STD clinics
  • Frothy, copious discharge
  • Discharge is often malodorous, with a greenish-yellow color
  • “Strawberry cervix”: vascular congestion
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16
Q

What causes Trichomonas vaginalis?

  • How does it appear on cytology?
A
  • Flagellate protozoan
  • T vaginalis are oval or pear shaped and have a small green nucleus and green cytoplasm with red granules
  • Flagella is difficult to visualize in PAP smear
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17
Q

How does Trichomonas vaginalis appear cytologically?

A
  • T vaginalis are oval or pear shaped and have a small green nucleus and green cytoplasm with red granules
  • Flagella is difficult to visualize in PAP smears
  • Smears often show mixed inflammation (lymphocytes and neutrophils)
18
Q

What is seen here?

A

Trichomonas vaginalis infection

19
Q

What is seen here?

A

Trichomonas vaginalis infection

20
Q

Case 3)

  • 20 yo woman in for routine Pap smear
  • Social/GYN history includes menses at 12 years, first intercourse at 16 years; 5 lifetime partners and no tobacco use
  • What are some red flags for cervical dysplasia in this history?
A
  • Early age of intercourse (16 yo)
  • 5 lifetime partners
21
Q

How do we make the diagnosis of low grade squamous intraepithelial lesion (LSIL) on a pap smear?

A
  • Compared to nuclei of intermediate cells; LSIL cell nuclei is >3x’s larger
  • Moderate variation in nuclear size and shape with occasional binucleation or multinucleation.
  • Nuclear hyperchromasia
  • The abnormal nucleus is conserved throughout the entire thickness of the squamous epithelium! (CIN I/mild dysplasia)
  • Can be picked up just by sampling surface epithelial cells
22
Q

What else is seen cytologically in low grade dysplasia (apart from nuclear changes)?

A

Koilocytes (HPV effect): squamous epithelial cells filled with HPV virus particles

  • Perinuclear halo
  • Nuclear enlargement
  • Hyperchromasia and wrinkling

As the virus particles are formed, they destroy the cytoskeleton of the cell, resulting in that wrinkling

  • Recall, these are another sign of low grade dysplasia (LSIL)
23
Q

What is seen here?

A

LSIL (low grade dysplasia)

24
Q

What is seen here?

A

LSIL on colposcopy

  • Fine mosaicism (due to irregular vascularity; high grade will have coarser mosaicism)
  • Punctuation
25
Q

What two features can be used to make the diagnosis of low grade dysplasias?

A
  • Mature squamous epithelium with enlarged nucleus (2.5-3x)
  • Koilocytes
26
Q

What are other names/classification systems of mild squamous dysplasia?

A

LSIL or CIN 1

27
Q

What are the histological features of mild squamous dysplasia (LSIL) or CIN 1?

A
  • Dysplastic changes involving the lower third of the epithelium.
  • The most superficial cells show extensive HPV changes or Koilocytes:
  • Perinuclear halo
  • Nuclear enlargement, hyperchromasia and wrinkling
28
Q

Key note on features in dysplasia/the spectrum for mild vs. high grade dysplasia

A
  • Mild dysplasia has abnormal nucleus but mature cytoplasm
  • As you progress to higher grade dysplasias, nucleus is still abnormal but now cytoplasm is less mature (less cytoplasm)
29
Q

Case 4)

  • 35 yo woman for follow up Pap smear
  • Social/GYN history: menses at 13 yrs, first intercourse at 15 yrs; 7 lifetime partners
  • Previous abnormal Pap smears
  • Positive for tobacco history
  • What’s significant in this history?
A

Many risk factors for cervical dysplasia

30
Q

High grade squamous intraepithelial lesions are also called what? What classes are included?

A

HSIL

  • Includes moderate and severe squamous dysplasia/CIS
  • CIN 2 and CIN 3 (carcinoma in situ)

(Cytologically, they are just separated mild or high grade dysplasia; this determines management)

31
Q

What is seen cytologically in high grade squamous intraepithelial lesions?

A
  • Markedly increased nuclear to cytoplasmic ratio (large nucleus and scant cytoplasm), less number of koilocytes
  • Sheds in syncytial groups and occasional single cells
  • Large hyperchromatic nuclei
32
Q

What is seen here?

A

HSIL, high grade dysplasia

  • Very abnormal nucleus
  • Very little cytoplasm (immature); very high N:C ratios
  • Syncytial groups
33
Q

What is seen here?

A

HSIL on colposcopy

  • Mosaicism (coarser; much more abnormal vasculature than mild)
34
Q

What is seen histologically in high grade dysplasia?

  • CIN 2
  • CIN 3
A
  • Dysplastic changes involve up to half of the epithelial thickness (moderate dysplasia or CIN 2)
  • Dysplastic changes involve more than half of the epithelium ( Severe dysplasia or CIN 3)
  • Dysplastic changes involve the entire thickness of the epithelium (Severe dysplasia /Carcinoma in situ or CIN 3/CIS)
35
Q

Describe the HPV life cycle

A
  • Virus infects metabolically active cells: metaplastic squamous epithelial cells
  • Low grade lesions (LSIL): replicative infections of HPV; virus NOT integrated into host DNA
  • High grade lesions (HSIL): viral DNA integrated into host DNA; result in neoplastic cells;
  • NOT concerned with replication; therefore, no koilocytes; disrupts function of Rb, p53
36
Q

What are the HPV types responsible for common warts (most often)?

A

Types 2 and 5

37
Q

What are the HPV types responsible for condyloma acuminatum (most often)?

A

Types 6 and 11

38
Q

What are the HPV types responsible for laryngeal papillomatosis (most often)?

A

Types 6 and 11

39
Q

What are the HPV types responsible for HSIL and squamous cancer (most often)?

A

Types 16, 18, 31, 33 (also 35, 39, 45, 51)

40
Q

What are the HPV types responsible for anogenital dysplasia and cancer (most often)?

A

Type 16

41
Q

Which type of HPV is the most common cancer causing strain?

A

Type 16 is the most prevalent high risk viral type

(if you add in 18, you’ve got most of them covered, 70% of cervical cancers worldwide)

a_GYNGU (17 decks)

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