Anal Cytology and High-Resolution Anoscopy

Introduction

The cervix is used as a model for anal

human papilloma virus (HPV)-associated disease based on similar anatomy

and pathophysiology. Both the cervix and anus consist of squamous

epithelium, which abuts columnar epithelium inducing squamous

metaplasia. These areas undergoing squamous metaplasia are most

susceptible to abnormal changes caused by HPV. The same strains of HPV

found in the female genital tract are found in the anal canal of women

and men. They induce the same range of disease in the anus as in the

cervix, vagina, and vulva.

Anal disease is classified with similar

cytology and histology taxonomies as the cervix, although in the anus,

squamous intraepithelial lesions (SIL) is often called anal

intraepithelial neoplasia (AIN) grades I, II, and III. High-grade AIN

(HGAIN) is considered to be the precursor lesion to anal squamous cell

cancer (SCC), and as such, screening procedures used for the cervix

including cytology and colposcopy have been adapted for screening of

anal HPV-associated disease. Sensitivity and specificity of anal

cytology are similar to cervical cytology, and liquid-based cytology has

been shown to improve quality of samples. As a screening test for anal

cancer, anal cytology has been shown to be cost-effective. In the anal

canal, colposcopy is called high-resolution anoscopy (HRA). Colposcopy

techniques and terminology have been validated for anal canal

disease.

Figure 1 View Original Figure 1 View Original

There are several principles of

screening when using anal cytology and HRA. Anal cytology is used for

identification of populations and individuals with HPV-associated

diseases through cytology screening programs. HRA is used for detection

of lesions, histologic diagnosis of disease, and treatment of disease,

specifically HGAIN and prevention of cancer development. It is also used

for early detection of nonsymptomatic cancer.

Before an anal cytology exam or HRA,

instruct the patient to avoid douching, enemas, or insertion of anything

per rectum 24 hours prior to the procedure. Obtain relevant history,

including current anal symptoms such as pruritus, bleeding, and pain.

Determine prior history of anal or perianal condyloma and whether

treatments were surgical or office based. Also determine prior history

of any anal abnormalities such as fissures, fistula, abscesses, or

hemorrhoids requiring intervention. Ask about any prior treatments that

may have caused scarring or other alterations in the normal anal mucosa

such as abscess lancing, fistula repairs, or hemorrhoidectomies. Obtain

informed consent with explanation of the procedures to be performed.

Equipment

Much of the equipment is similar to

that used for cervical examinations. Most gynecology or dysplasia

practices have these supplies without significant additional cost for

performing these procedures. A procedure tray for examination includes

the following:

Figure 2 View Original Figure 2 View Original

Figure 3 View Original Figure 3 View Original

  • Cytology liquid medium (or conventional slide with fixative solution)
  • Dacron swab
  • Anoscope (disposable or sterilized metal)
  • 3% acetic Acid
  • Nonsterile cotton swabs
  • Nonsterile Scopettes
  • Nonsterile 4 4 gauze pads
  • Lugol solution
  • K-Y Jelly mixed with 1% to 5% " lidocaine gel

For intra-anal biopsies, the

following additional equipment is needed:

  • Monsel solution or silver nitrate sticks
  • Formalin
  • Baby-Tischler punch biopsy or endoscopy forceps

For perianal biopsies the

following additional equipment is needed:

  • 1% to 5% " lidocaine gel/cream
  • 1% " lidocaine with epinephrine and sodium bicarbonate (2 mL per 10 cc of lidocaine)
  • Small pick-up forceps
  • 30-gauge needle
  • 22-gauge needle
  • 1-cc syringe

Colposcope

The following specifications are

recommended for colposcopes intended for HRA:

  • Double objective lens with magnification up to 25 to 40
  • Oculars that magnify 10 to 20
  • Angled eye pieces, as the straight-on view is ergonomically difficult for HRA
  • Side-swing arm to brace clinician 's arm while holding the anoscope for long periods
  • Green filter for evaluation of vascular changes

Figure 4 View Original Figure 4 View Original

Indications

Populations to screen include the

following:

  • HIV-seropositive individuals
  • Immune-compromised individuals (organ transplant recipients, autoimmune diseases)
  • HIV-seronegative women with a history of anal or perianal warts, genital high-grade SIL (HSIL), or cancer
  • HIV-seronegative men who have sex with men with a history of anal or perianal warts or prior receptive anal intercourse

Contraindications

  • There is no contraindication for cytology screening or HRA, although patients who have recently undergone anal procedures such as hemorrhoidectomy, fistula repair, or fulguration of anal warts should defer examination until healed.
  • Biopsy should be deferred in patients with platelets <65,000 or in patients who are neutropenic or who are on anticoagulant therapies.

The Procedure

Step 1

The anatomy of the anus is

depicted.

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Step 2

The anus is composed of

squamous epithelium. The rectum or colon is columnar epithelium. The

anal canal is mucosa lined, and the anal margin is epidermal. The

proximal end of the anal canal begins at the junction of the ani

muscle and external anal sphincter and extends to the anal verge. It

is 2 to 4 cm in length and is shorter in women compared with that

found in men. The distal end of the anal canal is the dentate line,

which is approximately equivalent to the original squamocolumnar

junction (SCJ) in colposcopic terminology. The dentate line is

considered to be a "fixed " anatomic zone, whereas the

anal transformation zone (AnTZ) is dynamic and undergoing squamous

metaplasia. The AnTZ is the current SCJ. The anal margin begins at

the verge and represents the transition from mucosal to epidermal

epithelium and extends to the perianal skin.

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Step 3

By consensus, perianal skin

is considered to extend approximately 5 cm from the anal margin.

Areas for screening include the SCJ, AnTZ, anal canal, verge,

margin, and perianal skin.

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Performing Anal Cytology

Step 1

The anal cytology

specimen should be performed first to provide the highest yield

of cells. Gently separate the buttocks. The patient can hold his

or her right cheek to facilitate the view.

  • PITFALL: There must be no lubrication prior to obtaining a cytology sample, as the lubricant may interfere with the processing and interpretation of the sample.

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Step 2

Insert a moistened

Dacron swab approximately 3 to 4 cm into the anus to assure

sampling of cells from the AnTZ. If initial resistance is

encountered, change the position of the swab and reinsert.

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Step 3

Remove the swab in a

circular motion in order to sample cells from all aspects of the

anal canal. Apply pressure so that the swab bends while slowly

removing it. Count slowly to ten as you remove it. Preserve

quickly on slides or in liquid medium. Fewer cells exfoliate

from the anal canal than the cervix, and it is easier to get

air-dried artifacts.

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Performing High-Resolution Anoscopy

Step 1

Assist the patient

into one of the following positions: left lateral, lithotomy if

also performing cervical exam (but most women prefer to switch

to left lateral for the HRA), or prone (if overhead colposcope

is available). In the left lateral and prone positions, the

patient should be as close to the bottom edge of the table as

possible to facilitate focusing the colposcope.

Step 2

Be clear and

consistent in describing location of lesions and the position

used. The "anal clock " is different from the

"gynecologic clock. " In the prone position,

posterior is 12:00, while in the lithotomy position, it is 6:00.

When referring patients for follow-up to anal surgeons, it is

helpful to use anatomic descriptors (posterior, anterior, left

or right lateral) in place of or in addition to the

"clock " positions.

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Step 3

Obtain a cytology

specimen if needed (new patients or those referred with abnormal

cytology specimens >3 months old). Lubricate the anal

canal with K-Y Jelly mixed with 1% to

5% " lidocaine. Perform a digital rectal exam,

and palpate for warts, masses, ulcerations, fissures, and focal

areas of discomfort or pain. The presence of hard and fixed

lesions should increase your index of suspicion for cancer,

since these are not the usual presentation of hemorrhoids and

warts.

Step 3 View Original Step 3 View Original

Step 4

Insert the anoscope,

and remove the obturator.

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Step 5

Insert a cotton swab

wrapped in gauze that has been soaked in acetic acid.

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Step 6

Remove the anoscope,

leaving the cotton swab " wrapped gauze pad inside. Soak

for 1 to 2 minutes.

Step 6 View Original Step 6 View Original

Step 7

Remove the gauze,

and reinsert the anoscope. Observe through the colposcope while

slowly removing the anoscope until the AnTZ comes into

focus.

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Step 8

Continue to apply

acetic acid with Scopettes or cotton swabs during the exam.

Using cotton swabs to manipulate the folds, hemorrhoids, or

prolapsing mucosa as well as adjusting the anoscope will help to

view all aspects of the AnTZ. In most cases, the entire AnTZ

should be seen, and the exam will be considered satisfactory.

Continue withdrawing the anoscope until the entire canal has

been observed.

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Step 9

The AnTZ is seen

here as a thin acetowhite line between the mature squamous and

immature columnar epithelium. Early metaplasia can be seen as

the columnar epithelium begins to coalesce adjacent to the SCJ.

Acetic acid distinguishes anal squamous epithelium from colon

columnar epithelium. Squamous epithelium will generally appear

lighter and pinker in color, while columnar epithelium is darker

and redder.

Step 9 View Original Step 9 View Original

Step 10

Lugol application

may help determine areas of abnormality. Normal glycogenated

squamous epithelium stains dark mahogany. Abnormal lesions lack

glycogen and have a partial stain or no stain. Care must be

taken to differentiate areas that do not pick up Lugol staining,

such as columnar epithelium, scar tissue, and skin. In this

case, a lesion can be seen, which is better delineated than with

acetic acid alone.

  • PITFALL: Review allergy to iodine during history taking. If patient has an allergic reaction to shellfish or has known allergy to iodine from prior procedures, do not use during the examination.

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Step 11

Commonly recognized

cervical lesion characteristics that help distinguish cervical

low-grade SIL (LSIL) and HSIL are also seen in anal lesions and

help guide the clinician in choosing areas for biopsy. A typical

raised low-grade AIN (LGAIN) is shown in part A and a typical

flat high-grade AIN (HGAIN) is shown in part B.

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Step 12

Biopsies are

directed at areas thought to represent the highest grade of

abnormality. Anal biopsies should be smaller than those

typically taken of the cervix using forceps no larger than 2 to

3 mm. Internal biopsies do not require anesthesia. External

biopsies require injecting a small amount of

1% " lidocaine with epinephrine buffered with sodium bicarbonate (2

cc NaHC03: 10 cc lidocaine), similar to biopsies of the vulva.

The injection can be preceded by numbing medication topically

with lidocaine gel or spray. Monsel solution or silver nitrate is used for hemostasis,

although the pressure of the anal walls will generally stop

bleeding for internal biopsies.

Step 13

Insert closed

forceps through the anoscope while looking through the

colposcope.

  • Pearl: Closing the forceps will prevent unintentional injury.

Step 13 View Original Step 13 View Original

Step 14

Once the forceps is

adjacent to the lesion, open in the direction that allows for

the forceps to grab the tissue. For some lesions, the forceps

will need to be positioned upside down.

  • PITFALL: Patients on warfarin (Coumadin) or daily aspirin may have increased bleeding with biopsy. If the platelet count is <65,000, approach the biopsy with caution or postpone until count improves. It is no longer considered necessary to provide antibiotic prophylaxis prior to biopsy in patients with history of endocarditis or otherwise at risk for heart valve disease.

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Step 15

To obtain a small

sample, the forceps should not be opened the entire width but

rather should be partially closed before closing and grabbing

the tissue. Monsel solution can be applied to the biopsy site

for hemostasis, although most small biopsy samples will

coagulate spontaneously once the anoscope is removed.

Step 15 View Original Step 15 View Original

Complications

  • Bleeding with bowel movements for several days post biopsy
  • Infection (rare)
  • Problematic bleeding (rare)

Pediatric Considerations

Since cytology screening is not

usually done until a patient has been sexually active, this procedure is

not routinely done in a pediatric population.

Postprocedure Instructions

Patients should be told to expect

slight bleeding with bowel movements for several days post biopsy. There

may be mild postprocedure pain associated with biopsy of lesions in and

around the anal canal. Rarely, a patient may require medication such as

hydrocodone.

Comfort measures include avoiding

constipation by increasing fiber in the diet during a few days following

biopsy. If the patient requires pain medications, stool softeners may be

necessary, depending on their routine bowel habits. Avoid hot and spicy

foods. Soaking in warm water will facilitate faster healing and relieve

any pain associated with biopsy. Lidocaine 1% to

5% gel/cream can be applied to perianal tissue when biopsies have

been performed.

Follow-up will depend on the results

of the cytology, histology, and the clinical indications for the

referral. See 01412520.

Triage for Anal Cytology and High-Resolution Anoscopy

Figure 5 View Original Figure 5 View Original

Coding Information and Supply Sources

View Large CPT Code Description 2007 AVERAGE 50th Percentile Fee Global Period 46600 Anoscopy $117.00 0 46606 Anoscopy with biopsy, single or multiple $244.00 0 46900 Destruct lesion(s) anus simple, chemical (e.g.,

trichloroacetic acid) $400.00 10 46916 Destruct lesion(s) anus simple, cryosurgery $424.00 10 Use a -22 modifier for use of microscope with

any of above.CPT is a registered trademark of the

American Medical Association.2008 average

50th Percentile Fees are provided courtesy of

2008 MMH-SI 's copyrighted Physicians ' Fees and

Coding Guide.

ICD-9 Codes

View Large 078.11 Anal condyloma 211.4 Benign neoplasms of the anus (AIN I or AIN II) 230.5 HGAIN (AIN III) or carcinoma in situ of the anus 239.2 Anal dysplasia (nonspecific) 154.2 Anal cancer 042 HIV

Supplies for HRA needed in

addition to standard colposcopy supplies include the following:

View Large Item Manufacturer Contact information Anoscopes Cardinal Healthcare 800-477-3800 Endoscopic forceps Fibertech Forceps 714-522-7112 Endoscopic forceps ESCO Medical Instruments 631-689-9153 Infrared coagulator Redfield Corporation http://www.redfieldcorp.com

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