Cervical and Vaginal Cytology - Cibas Flashcards
Current Cervical Cancer Screening Recommendations
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
Pap patient instructions
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.
Lower uterine segment sampling
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.
Test characteristics of a cervical Pap smear
Sensitivity 47%
Specificity 95%
Most common false-positive culprits in diagnosis of cervical cancer
- Benign squamous atypia in a granular pseudonecrotic background
- Reparative changes
- Keratinizing HSILs
“Satisfactory” vs “Unsatisfactory” for evaluation in a Pap smear
“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 ___.
Cases with borderline unsatisfactory cellularity
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
If a Pap is read as unsatisfactory, the clinical recommendation is. . .
To repeat within 2-4 months
General categorization system within the 2001 Bethesda classification
- Negative for intraepithelial lesion or malignancy
- Epithelial cell abnormality
- Other (non-epithelial malignancy present OR benign appearing endometrial cells in women >40 yeras of age)
Reporting for a normal Pap
(Statement of adequacy)
Negative for intraepithelial lesion or malignancy.
Superficial cells
Intermediate cells
May be binucleated or even multinucleated.
Parabasal cells
Basal cells
Squamous metaplastic cells
Common form of metaplasia, unique to the transformation zone.
Endocervical glandular cells
Often arranged in cohesive sheets, sometimes oriented such that you can see a mucinous cap with a cup-shaped nucleus.
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.
Immature epithelium sampling
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.
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.
Hyperkeratosis
Tubal metaplasia
Benign finding of the endocervical epithelium.
Follicular cervicitis
This is the diagnosis when you see numerous lymphocytes and plasma cells.
Biopsy of these sites displays lymphoid follicle formation.
Cytolysis
Pattern of the luteal phase of the menstrual cycle, characterized by bare intermediate cell nuclei, fragments of squamous cytoplasm, and abundant lactobacilli.
Macrophages on Pap
Nonspecific.
“Cockleburrs”
Most commonly associated with pregnancy, though not entirely specific.
Cornflaking artifact
Air bubbles trapped on superficial squamous cells. Can be reversed by returning the slide through xylene -> alcohol -> water, restaining, and re-coverslipping.
Clue cell
Seen in bacterial vaginosis, but not entierly specific for BV. >20% clue cells increases the specificity, but this is not perfect either.
Trichomonas vaginalis
Small, pear-shaped cell, pale oval nucles, and faint red granules.
Actinomyces
They are uncommon inhabitants of the cervix and vagina, most often associated with a foreign body, usually an IUD.
Herpes simplex virus
3 M’s:
Multinucleation, molding of nuclei, margination of chromatin
Sometimes with eosinophilic intranuclear inclusions.
Cytomegalovirus
Features: Mononuclear cells, markedly enlarged, basophilic intranuclear inclusions, small granular cytoplasmic inclusions
Entamoeba histolytica
Organisms have a small, eccentrically placed nucleus and abundant vacuolated cytoplasm. Erythrophagocytosis is common.
“Simple nuclear enlargement”
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.”
Reactive endocervical cells, sometimes seen in “microglandular hyperplasia,” a benign reactive condition sometimes confused for adenocarcinoma.
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
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.
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.
If it’s got cilia. . .
. . . it’s benign.
Sequellae of intrauterine diethylstilbestrol exposure
- Excess mucinous glands in the vagina
- Excess endometrial-type epithelium in the vagina
- Increased risk of clear cell carcinoma of the vagina
Progression rate of LSIL
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.
Koilocytic LSIL
You know these guys. Crisp-bordered, angular perinuclear halo, mild nuclear enlargement, and frequent binucleation.
Non-koilocytic LSIL
Intermediate-sized cells.
Nuclei are significantly enlarged with mild hyperchromasia and nuclear contour irregularities.
May be keratinizing.
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.
Rate of patients with HSIL who test positive for high risk HPV
97%
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%)
ASC-H
Atypical squamous cells, cannot exclude HSIL
When to favor AIS over HSIL
Generally speaking, you should favor HSIL unless:
* There is clear columnary differentiation
* There is feathering or rosette formation
When to favor SCC over HSIL
Generally speaking, you should favor HSIL unless:
* There are prominent nucleoli
* There are necrotic debris
Using IHC in Pap smear evaluation
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)
ASC-US
Atypical squamous cells of uncertain significance
Typically called when there is atrophic cervical epithelium with atypia that cannot confidently be distinguished from HSIL.
HSIL management
If 24 or younger or pregnant, follow-up Pap smear.
If >/= 25 and not pregnant: LEEP or colposcopy with endocervical assessment
When to call “SIL, grade cannot be determined”
- Few dysplastic cells
- Extensive cytolysis
- LSIL with a small number of equivocal HSIL cells
- Extensively keratinized SIL, without definitive HSIL
When to call “HSIL, with features suggestive of invasive carcinoma”
HSIL with marked nuclear abnormalities and pleomorphism.
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)
DDx for tumor diathesis
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.
Behcet’s in Pap smears
A well known mimic of SCC
You should hesitate to make the call if the patient has a history of Behcet’s.
What proportion of patients with ASC-US go on to have a diagnosis of HSIL on repeat biopsy?
10-20%
Management of ASC-US
Usually reflex HPV testing.
If that is positive, proceed to colposcopy with directed biopsy.
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)
Invasive adenocarcinoma
Generally very similar to AIS features, but with tumor diathesis, large and round nuclei, prominent nucleoli, and abundant cytoplasm
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.
Endometrial adenocarcinoma, endometrioid-type.
Looks similar to IUD effect, but the nuclear features are higher grade.
If a patient presents with primary adenocarcinoma of the vagina, the first question you should ask is. . .
Were they ever exposed to diethylstilbestrol?
In the cervix, you should always be aware that reactive conditions often display more __ than carcinoma.
In the cervix, you should always be aware that reactive conditions often display more heterogeneity than carcinoma.
Melanoma
The coarsely granular melanin pigment is the giveaway.
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.
“Endometrial cells in women older than 45 years of age”
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.”
Quick rules for adequacy
- 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
