Pap Smear Interpretation

The Cervix

The cervix is located at the top of the vagina. It is the opening to the uterus and is composed of dense connective tissue. It has very little smooth muscle in it, compared to the rest of the uterus, which is almost entirely smooth muscle.

The cervix is visualized by placing a speculum in the vagina. At the top of the vagina is a smooth, pink, firm structure with an opening (the os) in the center, which leads to the uterus.

The Pap Smear

In the 1940's, Dr. Papanicolaou developed a technique for sampling the cells of the cervix (Pap smear) to screen patients for cancer of the cervix. This technique has proven to be very effective at not only detecting cancer, but the pre-cancerous, reversible changes that lead to cancer.

While not originally designed to detect anything other than cancer, the Pap smear has proven useful in identifying other, unsuspected problems.

So useful has the Pap smear become, it is considered an essential part of women's health care. It is typically performed annually in sexually-active women of childbearing age, although there are some important exceptions.

Because the Pap smear is a screening test, it can have both false positive and false negative results. For this reason, it is important to have the test performed regularly (annually in the military services). It is not likely that the Pap smear will miss an important lesion time after time.

Pap smears are best performed in a stable, garrison situation because of the time it takes to send out the smear, have it read, get the result back, and perform any follow-up care that is needed. The actual obtaining of a Pap smear can be done almost anywhere (at sea, in the air, in the field), but getting the results back and further treatment performed in these operational settings can be difficult or impossible.

Dysplasia

Dysplasia means that the skin of the cervix is growing faster than it should.

Cervical skin cells are produced at the bottom of the skin (basal layer). As they reproduce, the daughter cells are pushed up towards the surface of the skin. As they rise through the skin layer, they mature, becoming flat and pancake-like (as opposed to round and plump). Their nuclei initially become larger and darker. If these daughter cells reach the surface of the skin before they are fully mature, a Pap smear will reveal some immature cells and "dysplasia" is said to exist. 

There are degrees of dysplasia: mild, moderate, and severe. None of this is cancer, but the next step beyond severe dysplasia is invasive cancer of the cervix. For this reason, any degree of dysplasia is of some concern, but the more advanced the dysplasia, the greater the concern.

Mild Dysplasia

Mild dysplasia means the skin cells of the cervix are reproducing slightly more quickly than normal. The cells are slightly more plump than they should be and have larger, darker nuclei. This is not cancer, but does have some pre-malignant potential in some women. Other phrases that describe mild dysplasia include:

• LGSIL (Low-grade Squamous Intraepithelial Lesion)

• CIN I (Cervical Intraepithelial Neoplasia, Grade 1)

Many factors contribute the development of mild dysplasia, but infection with HPV, (Human Papilloma Virus) is probably the most important. Smoking tobacco products and an impaired immune system also may contribute to this.

Mild dysplasia can come and go, being present on a woman's cervix (and Pap smear) at one time and not another.

Of all women who develop mild dysplasia of the cervix, about 10% will, if untreated, slowly progress through the various degrees of dysplasia and ultimately develop invasive cancer of the cervix. The rest will either remain unchanged or regress back to normal.

Because so many cases of mild dysplasia regress, It is common for women who develop a single Pap smear showing mild dysplasia to be watched over time with the Pap smear being repeated in 6 months. If the dysplasia persists or worsens, further evaluation is undertaken. If the Pap returns to normal, the woman's cervix is followed, sometimes with more frequent Pap smears.

Other physicians feel that the cervix should be evaluated with colposcopy with even a single dysplastic Pap smear. Their reasoning is that while many of the Pap smears revert to normal in 6 months, the abnormality will often re-appear at a later, less convenient time. They also reason that many women will feel anxiety over simply observing the abnormality over time and not investigating it right away. Operational circumstances may well dictate the approach that needs to be followed.

For women who have previously been evaluated with colposcopy and found to have dysplasia, the appearance of mild dysplasia on a subsequent Pap smear is not particularly alarming. Whether to re-colposcope them and the timing of such a re-evaluation must be individualized, based on the operational circumstances, the patient's history, risk factors, the degree of abnormality in the past and intervening Pap smear results. It is best to consult with an experienced colposcopist or gynecologist before making a final decision.

Treatment of mild dysplasia may be cryosurgery (freezing the part of the cervix containing the dysplastic cells and destroying those cells). Other approaches include vaporizing the dysplastic cells with a laser, or shaving them off with an electrified wire (LEEP). Sometimes, the mild dysplasia is not treated at all, but the patient is closely watched instead. If the dysplasia advances to a more severe stage, treatment can be undertaken at that later time. But for women in low-risk situations whose cervical lesion does not advance, surgery can sometimes be avoided.

Moderate Dysplasia

Moderate dysplasia means the skin of the cervix is growing faster than it should and has progressed beyond the mild stage. A biopsy of the cervix would show immature basal cells growing partway through to the surface of the skin, without significant maturation.

Moderate dysplasia is important because there is a much greater risk that these changes will advance, if untreated, into invasive cervical cancer. For that reason, moderate dysplasia is known as a "high grade" lesion, or "high grade squamous intra-epithelial lesion" (HGSIL). Another synonym for this condition is "CIN II" (Cervical Intra-epithelial Neoplasia Grade II).

Moderate dysplasia on a Pap smear usually indicates that further study of the cervix with colposcopy is needed. If moderate dysplasia is confirmed, then it is usually treated. Treatments might include cryosurgery, LEEP, or laser. Following treatment, frequent Pap smears are usually obtained as follow-up to make sure that if there is a recurrence (about 10% chance), that the recurrence is promptly diagnosed and further treatment performed.

Severe Dysplasia

Severe dysplasia means that the skin of the cervix is growing so rapidly that the immature basal cells extend completely through the skin thickness to the surface with any maturation. This is evidenced on the Pap smear as many completely immature cells appearing on the slide. This condition, a high grade intraepithelial problem, is also known as "CIN III." (Cervical Intraepithelial Neoplasia, Grade III), or "carcinoma-in-situ."

This is not cancer, but the only reason it isn't cancer is because the immature cells have not started growing (invading) beneath the epithelium into the underlying tissues. Because it is only one step away from invasive cancer, this is a very dangerous condition requiring treatment.

Treatment might consist of eliminating the dysplastic cells by freezing them (cryosurgery), vaporizing them (laser), or shaving them off with an electrified wire loop (LEEP). In some circumstances, more extensive surgery in the form of a cervical cone biopsy is required to eliminate the problem.

Carcinoma in situ

This is not cancer, but is considered a pre-cancerous problem. Carcinoma in situ means:

• There are abnormal cells extending the full thickness of the skin.

• These cells individually look just like cancer cells.

• If the cells were invading through the basement membrane into the underlying tissues, they would be considered cancer.

• Because they have not invaded through the basement membrane, they are, by definition, not cancer.

Carcinoma in situ is considered by many authorities to be clinically equivalent  to severe dysplasia, or CIN III. It should be promptly and carefully evaluated by a qualified health care provider.

Treatment might consist of eliminating the abnormal cells by freezing them (cryosurgery), vaporizing them (laser), or shaving them off with an electrified wire loop (LEEP). In some circumstances, more extensive surgery in the form of a cervical cone biopsy is required to eliminate the problem.

Hysterectomy is generally not necessary, but under unusual circumstances might be the best treatment of choice.

Invasive Cancer of the Cervix

Cancer of the cervix is among the more common forms of cancer affecting the reproductive organs. It is locally invasive into neighboring tissues, blood vessels, lymph channels and lymph nodes. In its' advanced stages it can be difficult to treat and may prove fatal.

Prior to developing cancer of the cervix, there is usually a period of pre-cancerous (and reversible) change, known as dysplasia. This can be detected by Pap smears, and is the basis for periodic screening with Pap smears.

Depending on the stage or degree of invasion, cancer of the cervix may be treated with local excision, hysterectomy, radical hysterectomy, radiation, and chemotherapy.

Adenocarcinoma of the Cervix

While most cancer of the cervix comes from the squamous cells making up the exterior skin, there is an occasional cancer that arises from the mucous-producing cells which line the endocervical canal leading up into the uterus. This is called "adenocarcinoma" as opposed to "squamous cell carcinoma."

Because adenocarcinoma may not appear on the Pap smear if just a spatula is used, the brush part of the Pap smear is particularly important. It is the brushing of the endocervical canal which is most likely to detect the presence of adenocarcinoma of the cervix.

Visible Lesions on the Cervix

Whenever a visible lesion or abnormality is seen on the cervix that cannot be positively identified visually, it should be biopsied.

Waiting for the results of a Pap smear and obtaining a biopsy only if the Pap is abnormal can be a mistake, since the Pap smear is only a screening test and has both false positives and false negatives. Even in the presence of gross cancer of the cervix, a Pap smear may occasionally be falsely reassuring.

If there is a visible abnormality that you cannot identify as innocent, biopsy is usually the wisest course.

Colposcopy

A technique of viewing the cervix to determine the source of abnormal cells. It consists of:

• Soaking the cervix with vinegar (acetic acid).

• Looking with binocular magnification (6-10x).

• Using a red-free light (blue or green).
  ...and frequently...

• Taking small biopsies of the cervix.

Colposcopy is the first step in the evaluation of significant abnormalities on a Pap smear. It may be recommended by the cytologist after reviewing a Pap for which there are some significant clinical concerns.

These images show a cervix with mild dysplasia. The first image is as the cervix initially appeared and looks normal. The second image is after treatment with acetic acid. The "aceto-white" areas (areas of abnormality) are clearly visible.

Actinomycosis

This fungus is occasionally identified on Pap smear and for the most part is an incidental finding, posing no threat to the patient.

Its' clinical significance controversial. IUD users sometimes (rarely) develop pelvic abscesses with this organism inside. For that reason, some physicians have recommended removal of the IUD in asymptomatic patients if Actinomyces are present. Others disagree, believing that removal of the IUD in patients with no symptoms is an over-reaction to a very small chance of a problem.

Atrophy

This is an expected finding in menopausal women not taking estrogen replacement therapy.

• If this is the only abnormal finding and the patient has no symptoms, it can be safely ignored.

• If the patient complains of vaginal dryness, irritation, painful intercourse, vaginal discharge, odor, or other symptoms, then the Pap finding of atrophic vaginitis is helpful in determining the cause.

• If the Pap smear has other abnormalities, treating the patient for 2-3 weeks with Premarin 0.625 mg PO daily and then repeating the Pap will often result in the other abnormality disappearing.

Atypical Squamous Cells of Undetermined Significance (ASCUS)

ASCUS (Atypical Squamous Cells of Undetermined Significance) is the way the cytologist tells you that there is something on the patient's Pap smear that is not perfectly normal, but they can't tell with any certainty what it is or whether it is significant.

ASCUS smears are handled differently in different circumstances:

• If this is the first time any abnormality has been found on the patient's Pap smears, some gynecologists recommend colposcopy, while others recommend simply treating any coincidental infection (if present) and repeating the Pap in 6 months. Should the abnormality persist, then colposcopy is usually recommended.

• If the patient has previously been evaluated for an abnormal Pap and found to have either mild dysplasia or HPV changes, the occurrence of an occasional ASCUS smear is not surprising and is often considered normal for that person. In higher risk circumstances, further colposcopy is sometimes undertaken to re-evaluate the cervix.

• A patient with (1) a past history of cervical dysplasia, who (2) has had many normal Pap smears following treatment, and who (3) develops ASCUS should probably be re-evaluated colposcopically if she has not had that procedure done recently, as this could represent the beginning of a new problem.

Usually, evaluation of an ASCUS smear is not an emergency and can await completion of operational commitments.

Candida (Monilia, Yeast)

This fungus is occasionally identified on Pap smear and for the most part is an incidental finding, posing no threat to the patient.

If the patient is experiencing symptoms (itching, burning, or cheesy discharge), then she should be treated for a yeast infection.

If the Pap smear shows...

• Significant inflammation, or

• Reactive changes, or

• Reparative changes, or

• Class II or Class IIA category, 

...then some physicians favor treating the yeast infection (which makes the Pap smear easier to read) and then following up with another Pap smear. Other physicians feel that is not necessary so long as the patient continues to come in annually for a Pap smear. Any abnormality not seen because of an obscuring yeast infection, they reason, will be seen at the next Pap smear.

If you are preparing to investigate a more serious abnormality with colposcopy, then it is probably worthwhile treating the yeast to try to reduce the confusing picture of inflammation that may be present.

If the Pap smear is otherwise normal and the patient without symptoms, Candida appearing on the Pap smear can be safely ignored and the Pap repeated, as usual, in 1 year.

Chlamydia

Chlamydia is a common sexually-transmitted illness. It can be found in 5-20% of asymptomatic women, depending on their sexual history. In the majority of cases, it causes no problems, but in some patients, it causes:

• PID (pelvic inflammatory disease)

• Infertility

• Cervicitis

Whenever chlamydia is suggested on a Pap smear, consider one of the following approaches:

• Assume chlamydia is present, treat with Doxycycline (or erythromycin or Azithromycin), and then perform a chlamydia culture to insure it has been eradicated, or

• Bring the patient in for a chlamydia culture. If positive, treat with Doxycycline (or erythromycin or Azithromycin). If negative, ignore.

CIN (Cervical Intraepithelial Neoplasia)

CIN (Cervical Intraepithelial Neoplasia) is an older term that describes the process of dysplasia. There are degrees of CIN:

• CIN I is equivalent to mild dysplasia and low grade SIL (Squamous Intraepithelial Lesion)

• CIN II is equivalent to moderate dysplasia and represents a high grade SIL

• CIN III is equivalent to severe dysplasia, carcinoma-in-situ, and is a high grade SIL.

Coccoid Bacteria

The presence of these bacteria on an otherwise normal Pap smear is of no consequence.

If the Pap shows inflammation sufficient to obscure the reading and the cytologist asks for an earlier-than-normal repeat Pap, many physicians will treat the patient with a broad-spectrum antibiotic suitable for strep and anaerobic bacteria (Flagyl, Amoxicillin, etc.) before repeating the smear. Others will simply repeat the smear at a somewhat earlier than normal time.

If the Pap is otherwise normal, but the patient complains of symptoms of vaginal discharge, bad odor or irritation, the presence of coccoid bacteria on the Pap smear is sometimes used as the basis for treatment using broad-spectrum antibiotics effective against strep and anaerobes.

In the absence of symptoms or other abnormality on the Pap, the presence of coccoid bacteria is not considered clinically significant and needs no treatment.

Condyloma

An abnormality in the appearance of the cells of the skin of the cervix which suggests the presence of condyloma (venereal warts). Condyloma are not by themselves dangerous, but require further investigation, because:

• Condyloma are caused by HPV, the same virus which is associated with cervical dysplasia and cancer of the cervix.

• The Pap changes which suggest condyloma have basically the same clinical significance as the changes suggesting low grade intraepithelial lesions (LGSIL), CIN I, and mild dysplasia.

Patients demonstrating condyloma on their Pap smears who previously had normal Paps are ideally evaluated with colposcopy and cervical biopsies to determine the precise diagnosis, extent of the problem, and rule out other, more significant illness. If operational requirements make prompt evaluation difficult or dangerous, colposcopy can usually be safely delayed for weeks to a few months.

Drying Artifact

The Pap smear must be sprayed with cytology fixative immediately (within seconds) of spreading the smear on the glass slide. The slide should be soaked so that the fixative will begin to fall off the slide if it is tilted (don't tilt it to see as you may lose some cells).

Many physicians avoid the problem of drying by leaving the speculum in place while they obtain their specimen, spread it on the slide and immediately fix it with spray.

If you are temporarily out of cytologic fixative, hair-spray is an acceptable alternative.

Endocervical Cells not Present

The presence of endocervical cells on a Pap smear is an indication that the smear included sampling of the cervical canal and, by inference, the squamo-columnar junction. If endocervical cells are not seen, it may mean:

• You did not sample high enough in the cervical canal.

• Your sampling was fine, but the cytologist didn't recognize the cells.

Some physicians feel that any Pap without endocervical cells should be repeated. However, studies have demonstrated that Paps without endocervical cells are still very effective in detecting abnormalities.

Pap smears obtained at a 6-week postpartum visit often do not have endocervical cells present.

If your Pap smears consistently show "no endocervical cells," you may wish to review your basic Pap smear technique to be sure you are taking a high enough sample.

Endometrial Cells are Present

This indicates that endometrial cells, normally located inside the uterus, have been shed and are appearing at the mouth of the cervix.

This is a normal finding in women of childbearing age, particularly if they are close to starting or just finishing their menstrual period. Menopausal women taking estrogen replacement therapy may also normally show a few endometrial cells on their Pap smears from time to time.

In menopausal women not taking estrogen replacement therapy, the presence of endometrial cells is an abnormal finding and should be followed up with an endometrial biopsy to try to determine the reason for the presence of these cells.

Estrogen Effect

Estrogen has a predictable effect on the cells of the cervix and the absence or presence of estrogen can be determined on the Pap smear.

In women of childbearing age, or menopausal women taking estrogen replacement therapy, the Pap would be expected to show an "estrogen effect," and its' absence would be a curiosity, though probably not dangerous.

In menopausal women not taking estrogen replacement therapy, the presence of detectable "estrogen effect" would suggest some non-ovarian source of estrogen and the long-term effects of unopposed estrogen should be considered.

Gardnerella

The presence of Gardnerella on an otherwise normal Pap smear in a patient without symptoms is of no consequence.

If the Pap shows inflammation sufficient to obscure the reading and the cytologist asks for an earlier-than-normal repeat Pap, many physicians will treat the patient with Flagyl before repeating the smear. Others will simply repeat the smear at a somewhat earlier-than-normal time.

Herpes

If the Pap smear demonstrates giant cells with intranuclear inclusions, the cytologist may report "possible herpes virus."

In the asymptomatic patient with an otherwise normal Pap smear, this is of no clinical significance. Some physicians will bring the patient back for a herpes culture (if her history is negative for herpes), while others will ignore this finding.

If the Pap shows significant degrees of inflammation, the presence of herpes virus may explain the inflammation. A follow-up Pap avoiding any time of herpes recurrence may give more reliable information. In patients suspected of having herpes, a herpes culture is ideal for confirming the diagnosis. If such a culture is unavailable, scraping an active lesion and preparing a Pap smear from the secretions can be useful. In this case, the cytologist looks carefully for herpes-related microscopic findings.

HPV

An abnormality in the appearance of the cells of the skin of the cervix which suggests but does not confirm the presence of human papilloma virus (HPV).

This finding is often based on the presence of "koilocytes," having enlarged nuclei, surrounded by a clear "halo" of cytoplasm. Koilocytes often (but not invariably) point to the presence of virus in the cells.

Patients demonstrating these changes who previously had normal Paps are ideally evaluated with colposcopy and cervical biopsies to determine the presence or absence of HPV, although such evaluation can usually safely wait for weeks to a few months if necessary because of operational requirements.

Inadequate Smear

This means the quality of the Pap smear is not adequate to give a reliable interpretation. The smear may be inadequate because:

• An insufficient number of cells were present.

• The slide had too many RBCs on it.

• The slide had too many WBCs on it.

• The cells had dried out before fixative was applied to the slide.

An inadequate smear should be repeated, using good technique and fixing the slide with appropriate spray immediately after the cells are smeared on the glass. Before repeating the Pap, you may want to treat any infection that is present (to eliminate the WBCs) and make sure the patient is not on her period (to eliminate the RBCs).

Inconclusive Smear

This usually means that there are either too few cells to be certain of the diagnosis, or there are confusing findings and the cytologist is warning you not to rely too strongly on this smear.

It is wise to repeat "inconclusive" smears. Before repeating the Pap, treat any infection that may be present, avoid her menstrual flow, get a good, representative sample, and apply the fixative immediately.

When repeating an "inconclusive" Pap, it is sometimes helpful to the cytologist to obtain two slides rather than one, just to provide more material for review.

Inflammation

Inflammation merely means the cervix is irritated for some reason. In the absence of any symptoms or any other significant abnormality on the Pap, it can be safely ignored.

If inflammation is severe enough, it may interfere with the ability of the cytologist to accurately read the Pap. In such cases, it is wise to repeat the Pap at more frequent intervals (6-9 months) rather than the usual once a year.

Inflammation by itself need not be treated. If other abnormalities are identified in addition to the inflammation, you may treat the other problems and the inflammation will probably go away.

IUD Changes

These are minor changes seen on the Pap smears of some women with IUDs. It is of no clinical significance.

Koilocytosis

A distinctive abnormality in the appearance of the cells of the skin of the cervix, in which some of the nuclei are surrounded by tiny "halos."

Most commonly, these changes occur in the presence of HPV (Human Papilloma Virus) but occasionally are associated with more serious problems such a cervical dysplasia or even early malignancy.

Patients demonstrating koilocytosis who previously had normal Paps are ideally evaluated with colposcopy and cervical biopsies to determine the source of the koilocytes, although such evaluation can usually safely wait for weeks to a few months if necessary because of operational requirements.

Leptothrix

This curious bacteria is occasionally found in large numbers in the vagina and cervix. It apparently causes no harm and is not considered a pathogen. It would not be worth noting except for two characteristics:

• It can live comfortably with Trichomonas.

• It can resemble yeast on a wet mount.

It may safely be ignored.

Nuclear Atypia

An abnormality in the appearance of the nuclei of the cells of the skin of the cervix.

Most commonly, these changes occur in the presence of HPV (Human Papilloma Virus) but occasionally are associated with more serious problems such a cervical dysplasia or even early malignancy.

Patients demonstrating nuclear atypia who previously had normal Paps are ideally evaluated with colposcopy and cervical biopsies to determine the source of the atypia, although such evaluation can usually safely wait for weeks to a few months if necessary because of operational requirements.

Reparative and Reactive Changes

Changes in the skin cells of the cervix which suggest that a healing process is underway or that the cervix is reacting to the presence of a virus or bacteria.

While these changes are not dangerous, their presence often provokes gynecologists to repeat the Pap smear at a sooner-than-expected time (such as 6 months, rather than 1 year after the previous Pap). The reasons for this increased surveillance are:

• Reactive or Reparative changes make the Pap more difficult to interpret, so that the clinician cannot be as reassured by this Pap as he/she would by a Pap without these changes, and

• Distinguishing between reactive/reparative changes and early dysplasia is difficult and the Pap interpretation may be incorrect.

Other gynecologists feel that in a patient with previously normal Pap smears, the first appearance of reactive/reparative changes is not cause for alarm and they will repeat the Pap at the next annual examination. They reason that should there be an underlying dysplastic process, the progression of dysplasia is usually so slow that there is no particular advantage to repeating the smear sooner than the annual exam.

SIL (Squamous Intraepithelial Lesion)

This is a general term for dysplasia.

Low grade SIL (LGSIL) includes mild dysplasia, HPV changes, and CIN I. These are considered "low grade" because the risk of progression to malignancy is small (10% or less).

High grade SIL (HGSIL) includes moderate dysplasia, severe dysplasia, carcinoma in situ, CIN II and CIN III. These are considered "high grade" because many of them (although not all) will progress ultimately to invasive cancer of the cervix if not treated.

Squamous Metaplasia

This is an innocent finding that represents the normal squamous epithelium of the face of the cervix overgrowing the columnar epithelium of the cervical canal. Squamous metaplasia need not be treated.

Trichomonas

This microorganism is usually treated when identified on Pap smear. Trichomonas causes substantial inflammation of the cervix and makes the job of interpreting the Pap smear more difficult.

After treating the patient with Flagyl, the smear should be repeated in about 3-6 months...long enough to allow complete resolution of any lingering inflammation, but sooner than 1 year.

If there is other evidence of a significant cervical lesion (dysplasia) then the Pap may be repeated sooner after treatment.

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