Ch. 1 - Cervical & Vaginal Cytology

Question 1

At what age should pap screening begin, or stop?

Answer 1

Start at age 21 (regardless of age of sexual initiation).

Stop after age 65, if no history of CIN-2 or worse.

Question 2

What high-risk patients benefit from increased pap screening?

Answer 2

Immunocompromised patients (eg, screen HIV+ yearly), DES-exposed patients, and patients with history of abnormal paps.

Question 3

What percentage of women get regular pap testing?

Answer 3

90%

Question 4

What is the annual incidence (and mortality) of cervical cancer?

Answer 4

About 12,000 new cases per year, with 4,000 deaths per year.

Question 5

What instructions should patients follow prior to pap smear? What instructions should the collecting OB/GYN follow?

Answer 5

Patients: Schedule pap outside of menstrual periods. Avoid sex, tampons, foams, douches etc 2 days prior to sampling.

Clinicians: Minimize gel, remove mucous before sampling, and collect prior to application of acetic acid or Lugol’s iodine.

Question 6

Distinguish between liquid-based and conventional cytologic preparations of cervical paps.

Answer 6

Conventional smear: Literally smearing of spatula & brush onto slide.

Liquid-based: Spatula/brush placed in methanol fixative (lyses red cells) and processed by machine (ThinPrep vs SurePath). Accepted as superior to conventional paps.

Question 7

Describe how the Thinprep imaging system assists the cytotechnologist in review cervical pap smears.

Answer 7

Coverslipped slides are scanned, with 22 FOVs with high optical density (likely to be full of cells) flagged for cytotech review. This results in the cytotech only needing to review 25% of the slide area.

Question 8

What is the approximate sensitivity and specificity of the pap test?

Answer 8

Sensitivity: ~50%
Specificity: ~95%

Question 9

Compare and contrast the Papanicolaou, Dysplasia, and SIL (Bethesda) systems of reporting.

Answer 9

Papanicolaou: Classes I (definitely benign) - V (definitely malignant)
Dysplasia: CIN 1-3
SIL: LSIL (CIN-1) & HSIL (CIN-2/3)

Question 10

Compare and contrast LSIL/HSIL in terms of their clinical significance.

Answer 10

LSILs likely represent transient HPV infections that carry little risk for oncogenesis.

HSILs are associated with persistent viral infection with a significant risk of progression.

Question 11

Under the Bethesda system, what is required for adequacy on cervical pap test?

Answer 11

Presence of squames (>5000 cells on the slide, approximately 3+ squames per 20x field). Endocervical glandular cells are actually not required.

Question 12

What are the three choices of general categorization under the Bethesda system?

Answer 12

NILM (includes presence of organisms, other non-neoplastic changes)
Epithelial cell abnormalities (includes squamous and glandular abnormalities)
Other (eg. Endometrial cells in a >40yo woman)

Question 13

What percentages of paps will be NILM?

Answer 13

90%

Question 14

Compare and contrast the appearance of superficial and intermediate cervical squamous cells.

Answer 14

Superficial: Small 5-6um pyknotic nucleus with pink keratinized cytoplasm.

Intermediate: 8um diameter nucleus with finely granular chromatin. May be multinucleated! Glycogenated cytoplasm.

Question 15

In what states may parabasal and basal cells be abundant on cervical paps?

How do they appear?

Answer 15

In squamous atrophy (low-estrogen states) and in squamous metaplasia (common).

Look for sheets of immature cells, maybe syncytium-like or arranged like stepping stones.

Question 16

Compare the morphology of hyperkeratosis and parakeratosis.

Answer 16

Hyperkeratosis: Presence of anucleate squames.
Parakeratosis: Orangeophilic superficial cells which may be arranged in whorls.

Question 17

Describe the appearance of endocervical cells.

Answer 17

Eccentric nucleus with finely granular chromatin and abundant vacuolated cytoplasm. Often found in strips or honeycomb sheets.

Question 18

Describe the appearance of tubal metaplasia, and transitional cell metaplasia.

Answer 18

Tubal: Presence of cilia (or terminal bars)
Transitional: Coffee-bean nuclei (grooves) and perinuclear halos

Question 19

Describe the appearance of exfoliated endometrial cells.

Answer 19

Small dark cells with scant cytoplasm and frequent fragmentation/apoptosis, usually arranged in clusters/balls.

Question 20

What is the significance of exfoliated endometrial cells in a cervical pap?

Answer 20

They are reportable only in women >40yo. In younger women, they likely just represent normal shedding (present during first 12d of cycle).

Question 21

What is the significance of various inflammatory cells in cervical pap?

Answer 21

Neutrophils: Seen in nearly all specimens, increased in injury/infection.
Lymphocytes/plasma cells: May indicate follicular cervicitis.
Histiocytes: Expected, insignificant.

Question 22

What is the appearance and significance of trophoblastic cells in cervical pap?

Answer 22

Can be seen in pregnant women; look for multinucleated cells with irregular chromatin which stain for bhCG and hPL. Does NOT indicate impending abortion.

Question 23

What is the appearance of lactobacilli, and when are they most prominent?

Answer 23

G+ rod-shaped bacteria, which are more prominent in the luteal phase (as epithelium sheds more readily).

Question 24

What organism is responsible for bacterial vaginosis? How many clue cells are required for diagnosis?

Answer 24

Gardnerella vaginalis, but many organisms can cause the condition. Need >20% clue cells.

Question 25

Describe the morphology of Trichomonas infection.

Answer 25

Look for 15-30um long pear-shaped flagellar organisms with eccentric nuclei and granular cytoplasm. Also look for Leptothrix (filamentous long bacterium).

Question 26

Describe the benign endocervical changes seen in pregnancy and with OCP use.

Answer 26

Pregnancy: Increases in size, in line with Arias-Stella reaction.

OCP use: Microglandular hyperplasia (nuclear enlargement and cytoplasmic vacuolization)

Question 27

What changes are seen in IUD use?

Answer 27

Abundant vacuolization of cells and isolated small round dark cells. Unknown histogenesis.

Question 28

What are the high-risk serovars of HPV? What oncogenic proteins do they express?

Answer 28

There are many, but 16 and 18 are the most significant. They express E6 (inhibits p53) and E7 (inhibits Rb).

Question 29

How many paps will be called LSIL? What percentage of LSIL will advance?

Answer 29

2.5% of all Pap specimens. 20% will advance to HSIL.

Question 30

What are the morphologic features of LSIL?

Answer 30

Increased nuclear enlargement with moderate variation in size and shape. Look for koilocytes (sharply defined perinuclear cytoplasmic cavity with a dense rim of cytoplasm).

Question 31

What are the morphologic features of HSIL?

Answer 31

Increased N:C ratio with actually smaller cells overall than in LSIL (much less cytoplasm). May be present as individual cells of syncytium-like clusters.

Question 32

What is the recommended management of LSIL? HSIL? SQC?

Answer 32

LSIL can be serially biopsied. HSIL requires LEEP and endocervical assessment. (both OK to wait until end of a current pregnancy). SQC requires trachelectomy vs hysterectomy (simple vs radical)

Question 33

What are the morphologic feature of squamous cell carcinoma?

Answer 33

Extreme nuclear atypia and N:C ratio. Tumor diathesis (blood and necrotic debris).

Question 34

What quality metrics should be observed to avoid diagnosing ASC too frequently?

Answer 34

Keep to < 5% of Pap diagnoses and keep ratio of ASC:SIL < 3.0

Question 35

What is the role of the ASC-H diagnosis?

Answer 35

Meant to convey high suspicion for specifically HSIL. Usually applies to cases resembling atypical squamous metaplasia.

Question 36

What is the appearance of endocervical adenocarcinoma in situ?

Answer 36

Look for columnar cells arranged in strips or rosettes with feathering. as well as the usual hyperchromasia.

Question 37

What are the morphologic subtypes of endocervical adenocarcinoma

Answer 37

Mucinous (includes intestinal, signet-ring, minimal deviation, and villoglandular)
Adenosquamous
Clear cell
Transitional cell, serous (rare)

Question 38

What is the appearance of mucinous adenocarcinoma? What about villoglandular and minimal deviation subtypes?

Answer 38

Columnar cells with abundant foamy cytoplasm and basal nucleus. Villoglandular & Minimal deviation have little atypia and are often undercalled.

Question 39

What is the morphologic appearance of endometrial adenocarcinoma? Distinguish between endometrioid and serous/clear cell.

Answer 39

Endometrioid may look underwhelming with hyperchromasia, prominent nucleolus, and interestingly intracytoplasmic neutrophils.

Serous/clear cell are obviously malignant with a horrendous necrotic background and psammoma bodies.

Question 40

What conditions may fall under AGC?

Answer 40

Atypical endocervical cells (includes OCP effect, pregnancy, polyp, etc) and atypical endometrial cells (hormonal, endometritis, hyperplasia, polyps).

Question 41

What rare malignant neoplasms (besides SQC and adeno) should be considered in a cervical pap?

Answer 41

Small cell carcinoma (nuclear molding)
Malignant melanoma (melanin, nucleolus)
Lymphoma (irregular large lymphocytes)
MMMT (biphasic cell population)
Local spread ovarian, endometrial, colon and bladder.