Cervical and Vaginal Cytology - Cibas

Question 1

Current Cervical Cancer Screening Recommendations

Answer 1

Less than 21: No screening irrespective of sexual activity.
21-29: q3 years with cytology alone
30-65: q3 years with cytology alone OR q5 years with HR-HPV assay
Discontinuation: Age >65 with adequate prior screening, no history of CIN2 or higher
Screening after total hysterectomy:Not recommended IF no history of CIN2 or higher

Question 2

Pap patient instructions

Answer 2

Not during menses, >5 days after menstruation stops
Do not use tampons, birth control foams, jellies, or vaginal creams or douches for 2-3 days prior to the test.
No sexual intercourse for 2 days prior to the test.

Question 3

Lower uterine segment sampling

Answer 3

If the brushing is taken from too deep into the endocervix, it may sample the lower uterine segment.

Normal endometrium may resemble a high-grade squamous intraepithelial lesion or adenocarcinoma in situ, making this a common diagnostic pitfall.

Question 4

Test characteristics of a cervical Pap smear

Answer 4

Sensitivity 47%
Specificity 95%

Question 5

Most common false-positive culprits in diagnosis of cervical cancer

Answer 5

1. Benign squamous atypia in a granular pseudonecrotic background
2. Reparative changes
3. Keratinizing HSILs

Question 6

“Satisfactory” vs “Unsatisfactory” for evaluation in a Pap smear

Answer 6

“Satisfactory”
* A satisfactory squamous component is present (5,000 for liquid based, 8,000 for conventional)
* The presence/absence of endocervical/transformation zone is noted.
* Obscuring elements (inflammation, blood, drying artifact, etc) may be mentioned only if 50-75% of epithelial cells are obscured.

“Unsatisfactory” - a reason must be specified
* Lack of patient identification
* Unacceptable specimen (ex, slide broken beyond repair)
* Insufficient squamous component
* Obscuring elements covering more than 75% of epithelial cells

For the last two, you should write “Specimen processed and examined, but unsatisfactory for evaluation of an epithelial abnormality because ___.

Question 7

Cases with borderline unsatisfactory cellularity

Answer 7

Spot counting is used to evaluate these specimens:

Count a minimum of 10 fields along a diameter including the center of the slide. Compare this number to standardized tables, taking into account:
* The objective
* The eyepiece field number
* The diameter of the circle containing cellular material
* The type of preparation

Question 8

If a Pap is read as unsatisfactory, the clinical recommendation is. . .

Answer 8

To repeat within 2-4 months

Question 9

General categorization system within the 2001 Bethesda classification

Answer 9

1. Negative for intraepithelial lesion or malignancy
2. Epithelial cell abnormality
3. Other (non-epithelial malignancy present OR benign appearing endometrial cells in women >40 yeras of age)

Question 10

Reporting for a normal Pap

Answer 10

(Statement of adequacy)

Negative for intraepithelial lesion or malignancy.

Question 11

Answer 11

Superficial cells

Question 12

Answer 12

Intermediate cells

May be binucleated or even multinucleated.

Question 13

Answer 13

Parabasal cells

Question 14

Answer 14

Basal cells

Question 15

Answer 15

Squamous metaplastic cells

Common form of metaplasia, unique to the transformation zone.

Question 16

Answer 16

Endocervical glandular cells

Often arranged in cohesive sheets, sometimes oriented such that you can see a mucinous cap with a cup-shaped nucleus.

Question 17

Answer 17

Endometrial glandular cells

Common featuers: Balls of small cells, isolated small cells, scant cytoplasm, dark nucleus, nuclear molding, nuclear fragmentation. Balls of endometrial cells often contain neutrophils and are often “packed so tightly you cannot see inside.”

Endometrial cells are significantly smaller than HSIL cells. They MAY display mitoses, but not atypical mitoses.

Beware: Bare intermediate cell nuclei may be the size of endometrial cells. So, to avoid misinterpretation, always make sure that a cell has some cytoplasm before you call it an endometrial cell.

Question 18

Immature epithelium sampling

Answer 18

Typically, you are going to see mostly superficial and intermediate cells.

But, if you sample near the transformation zone, you will see more squamous metaplastic cells, parabasal cells, and basal cells.

You can also see more parabasal and basal cells in a atrophic epithelium, such as from a post-menopausal woman, pre-menarche individual, Turner syndrome patient, or patient s/p BSO.

Question 19

Answer 19

Transitional cell metaplasia

Key features: coffee-bean nuclei, wrinkled nuclei, small perinuclear halos (glycogenation), often streaming in one direction.

Often seen in the setting of atrophy.

Question 20

Answer 20

Hyperkeratosis

Question 21

Answer 21

Tubal metaplasia

Benign finding of the endocervical epithelium.

Question 22

Follicular cervicitis

Answer 22

This is the diagnosis when you see numerous lymphocytes and plasma cells.

Biopsy of these sites displays lymphoid follicle formation.

Question 23

Cytolysis

Answer 23

Pattern of the luteal phase of the menstrual cycle, characterized by bare intermediate cell nuclei, fragments of squamous cytoplasm, and abundant lactobacilli.

Question 24

Answer 24

Macrophages on Pap

Nonspecific.

Question 25

Answer 25

"Cockleburrs" Most commonly associated with pregnancy, though not entirely specific.

Question 26

Answer 26

Cornflaking artifact Air bubbles trapped on superficial squamous cells. Can be reversed by returning the slide through xylene -> alcohol -> water, restaining, and re-coverslipping.

Question 27

Answer 27

Clue cell Seen in bacterial vaginosis, but not entierly specific for BV. >20% clue cells increases the specificity, but this is not perfect either.

Question 28

Answer 28

Trichomonas vaginalis Small, pear-shaped cell, pale oval nucles, and faint red granules.

Question 29

Answer 29

Actinomyces They are uncommon inhabitants of the cervix and vagina, most often associated with a foreign body, usually an IUD.

Question 30

Answer 30

Herpes simplex virus 3 M's: **M**ultinucleation, **m**olding of nuclei, **m**argination of chromatin Sometimes with eosinophilic intranuclear inclusions.

Question 31

Answer 31

Cytomegalovirus Features: Mononuclear cells, markedly enlarged, basophilic intranuclear inclusions, small granular cytoplasmic inclusions

Question 32

Answer 32

Entamoeba histolytica Organisms have a small, eccentrically placed nucleus and abundant vacuolated cytoplasm. Erythrophagocytosis is common.

Question 33

"Simple nuclear enlargement"

Answer 33

Reactive change which may occur in cervical squamous cells, particularly perimenopausally. Nuclei are enlarged up to 1.5-2x normal intermediate cell size. Since this change is characteristically perimenopausal, sometimes these are called "PM cells."

Question 34

Answer 34

Reactive endocervical cells, sometimes seen in "microglandular hyperplasia," a benign reactive condition sometimes confused for adenocarcinoma.

Question 35

Answer 35

Repairative changes Often signed out as "ASC-US, with features of atypical repair" Result from injury to the cervical epithelium and proliferation of reserve cells. Morphologic characteristics are: * Cohesive, flat sheets * Streaming appearance * Large nuclei with marked size variation * Large nucleoli (sometimes irregular in shape) * Pale chromatin * Mitoses

Question 36

Answer 36

Radiation change Multinucleation and size variation is common. At first glance, it may look like Herpes. However, it lacks the ground glass nuclear appearance and Cowdry A type inclusions. A "two-tone" staining (blue and pink) may also be seen.

Question 37

Answer 37

IUD Cytologic Effect Often seen as a combiation of small, dark cells with scant cytoplasm and cells with large vacuoles. Generally read as "Benign" If they are especially numerous or atypical in appearance, reading the biopsy as "Atypical glandular cells" or "Atypical squamous cells" may be warranted.

Question 38

If it's got cilia. . .

Answer 38

. . . it's benign.

Question 39

Sequellae of intrauterine diethylstilbestrol exposure

Answer 39

1. Excess mucinous glands in the vagina 2. Excess endometrial-type epithelium in the vagina 3. Increased risk of clear cell carcinoma of the vagina

Question 40

Progression rate of LSIL

Answer 40

50% of LSILs will regress completely. Only 0.15% progress to invasive cancer. HSILs are much less likely to regress and more likely to progress.

Question 41

Answer 41

Koilocytic LSIL You know these guys. Crisp-bordered, angular perinuclear halo, mild nuclear enlargement, and frequent binucleation.

Question 42

Answer 42

Non-koilocytic LSIL Intermediate-sized cells. Nuclei are significantly enlarged with mild hyperchromasia and nuclear contour irregularities. May be keratinizing.

Question 43

Answer 43

Orangophilic keratin pearls. May be seen in LSIL or keratinizing SCC, but may just be benign keratin pearls. This does not tell you the diagnosis, but is a clue that you should be looking closely at the involved cells.

Question 44

Rate of patients with HSIL who test positive for high risk HPV

Answer 44

97%

Question 45

Answer 45

HSIL Usually parabasal-sized cells with significant nuclear atypia (large nuclei, irregular nuclear contour, marked hyperchromasia, marked chromatin coarseness). Often they have contour abnormalities but only mild to moderate hyperchromasia. May be present as individual cells or as clusters with indistinct borders (syncytium-like clusters). May be keratinizing. Divided into small cell (10%), intermediate (70%), and large cell (20%)

Question 46

ASC-H

Answer 46

**A**typical **s**quamous **c**ells, cannot exclude **H**SIL

Question 47

When to favor AIS over HSIL

Answer 47

Generally speaking, you should favor HSIL unless: * There is clear columnary differentiation * There is feathering or rosette formation

Question 48

When to favor SCC over HSIL

Answer 48

Generally speaking, you should favor HSIL unless: * There are prominent nucleoli * There are necrotic debris

Question 49

Using IHC in Pap smear evaluation

Answer 49

**p16**: Highlights HPV-infected cells (in this circumstance) **Ki-67**: For proliferation index **p63**: Tells you whether the cells you are seeing have squamous differentiation (distinguishes squamous from glandular, when that distinction is difficult by morphology alone)

Question 50

ASC-US

Answer 50

Atypical squamous cells of uncertain significance Typically called when there is atrophic cervical epithelium with atypia that cannot confidently be distinguished from HSIL.

Question 51

HSIL management

Answer 51

If 24 or younger or pregnant, follow-up Pap smear. If >/= 25 and not pregnant: LEEP or colposcopy with endocervical assessment

Question 52

When to call "SIL, grade cannot be determined"

Answer 52

* Few dysplastic cells * Extensive cytolysis * LSIL with a small number of equivocal HSIL cells * Extensively keratinized SIL, without definitive HSIL

Question 53

When to call "HSIL, with features suggestive of invasive carcinoma"

Answer 53

HSIL with marked nuclear abnormalities and pleomorphism.

Question 54

Answer 54

**Squamous cell carcinoma** HSIL plus the following features: * **Macronuclei** * **Irregular chromatin distribution** * **"Tumor diathesis"** (here meaning abundant granular, amorphous precipitate with nuclear debris and red blood cells) * **"Tadpoles/Cercariform cells"** and **"Fiber cells"** (keratinizing-type only)

Question 55

DDx for tumor diathesis

Answer 55

Could be seen in the context of atrophic smears or heavy menstrual bleeding. However, if you see it in the context of tadpole cells/fiber cells/abundant atypical keratinized cells, it is diagnostic of SCC.

Question 56

Behcet's in Pap smears

Answer 56

**A well known mimic of SCC** You should hesitate to make the call if the patient has a history of Behcet's.

Question 57

What proportion of patients with ASC-US go on to have a diagnosis of HSIL on repeat biopsy?

Answer 57

10-20%

Question 58

Management of ASC-US

Answer 58

Usually reflex HPV testing. If that is positive, proceed to colposcopy with directed biopsy.

Question 59

Answer 59

Adenocarcinoma in-situ Features: * Hyperchromatic crowded groups of cells * Glandular differentiation * Columnar cells * Strips and rosettes * "Feathering" * Neoplastic nuclear features * Hyperchromasia * Crowding, stratification * Inconspicuous nucleoli * Apoptoses * Mitoses * Usually lacking prominent nucleoli * Absence of a tumor diathesis (which would make it invasive)

Question 60

Answer 60

Invasive adenocarcinoma Generally very similar to AIS features, but with tumor diathesis, large and round nuclei, prominent nucleoli, and abundant cytoplasm

Question 61

Answer 61

This one is tricky. **Minimal deviation adenocarcinoma of the cervix.** Think of this as the best differentiated carcinoma ever. But, it still invades and metastasizes. Just. . . always be aware of this one. On Pap smear there may be no way to tell they are neoplastic, but they may come as larger chunks. This is just one of those diagnoses that Pap smears are not good at picking up.

Question 62

Answer 62

Endometrial adenocarcinoma, endometrioid-type. Looks similar to IUD effect, but the nuclear features are higher grade.

Question 63

If a patient presents with primary adenocarcinoma of the vagina, the first question you should ask is. . .

Answer 63

Were they ever exposed to diethylstilbestrol?

Question 64

In the cervix, you should always be aware that reactive conditions often display more __ than carcinoma.

Answer 64

In the cervix, you should always be aware that reactive conditions often display more **heterogeneity** than carcinoma.

Question 65

Answer 65

Melanoma The coarsely granular melanin pigment is the giveaway.

Question 66

Answer 66

Small cell carcinoma Classical features are all there: **many** small cells with hyperchromatic nuclei, nuclear molding, scant cytoplasm, numerous mitoses, and lots of smear artifact.

Question 67

"Endometrial cells in women older than 45 years of age"

Answer 67

Benign-appearing endometrial cells in a post-menopausal woman may be suggestive of endometrial cancer. But, a patient's menopausal status is not always indicated in the chart, and even when it is may not be accurate. So, you should word your report like this: "Satisfactory for evaluation. Endometrial cells, cytologically benign, in a woman greater than or equal to 45 years of age. Negative for squamous intraepithelial lesion. Note: Endometrial cells after age 40, particularly out of phase or after menopause, may be associated with benign endometrium, hormonal alterations, and less commonly, endometrial abnormalities. Clinical correlation is recommended."

Question 68

Quick rules for adequacy

Answer 68

* At least 5,000 cells for fluid specimen, 8,000 for conventional * At least 10 endovervical or squamous metaplastic cells (quality indicator) * IF IT HAS ANYTHING ABNORMAL, IT IS AUTOMATICALLY ADEQUATE AND REPORTABLE