Colposcopy Case File

Colposcopy Case File

Eugene C. Toy, MD, Konrad P. Harms, MD, Keith O. Reeves, MD, Cristo Papasakelariou, MD, FACOG

Case 38

A 24-year-old G1P0 woman at 26 weeks’ gestation presents to your clinic for routine prenatal care. Upon reviewing her laboratory results from her initial visit, she is found to have an abnormal Pap smear. The Pap smear demonstrated low-grade squamous intraepithelial lesion (LSIL). The patient is brought back to clinic for colposcopy which revealed no lesions.

➤ What is your next step of management?

➤ Was the referral for colposcopy warranted?

➤ How does a colposcopic examination in pregnancy differ from that in a nonpregnant patient?

ANSWERS TO CASE 38:

Colposcopy

Summary: A 24-year-old G1P0 woman at 26 weeks’ gestation with abnormal Pap smear demonstrating LSIL and subsequent normal colposcopy.

➤ Next step in management: Repeat Pap in 6 and 12 months.

➤ Referral for colposcopy warranted: Yes.

➤ Colposcopy in pregnancy: More conservative; goal is to rule out invasive disease with follow-up after delivery; no endocervical curettage (ECC) should be performed during pregnancy.

ANALYSIS

Objectives

1. List the criteria of an adequate colposcopic examination.
2. Describe the different colposcopic features of dysplasia.
3. Describe common pitfalls of colposcopy and how to avoid them.
4. Become familiar with how pregnancy affects colposcopy.

Considerations

This is a 24-year-old pregnant woman at 26 weeks’ gestation with cervical dysplasia noted on Pap smear. The finding of cervical dyplasia is not uncommon in pregnancy. Her access to prenatal care may be the first time in which cervical cancer screening is done. The management of cervical dysplasia does not change appreciably in pregnancy. Patients with LSIL and high-grade squamous intraepithelial lesion (HSIL) still require a colposcopy for further evaluation. The method in which a colposcopy is performed is not any different from that in a nonpregnant state, except that an ECC is contraindicated in pregnancy. Colposcopic examination during pregnancy can be challenging due to the increased vasculature and hormonal changes to the cervix. Acetic acid and Lugol solution can both be applied to the cervix with no risk to the pregnancy. Biopsies should only be performed in areas of suspected advanced disease. All minor colposcopic changes should await further evaluation after pregnancy. The goal in pregnancy is to rule out invasive carcinoma. Treatment of dysplasia can take place after the pregnancy is completed. In addition, it is not too uncommon for the dysplastic cells to regress/slough off after delivery. For this patient, no lesions were seen on colposcopy and she can be reevaluated in 6 months.

APPROACH TO

Colposcopy

DEFINITIONS

TRANSFORMATION ZONE: The area located between the original squamous epithelium and columnar epithelium.

ACETOWHITE EPITHELIUM: Areas of high nuclear activity which appear white. The more dense/pearl the epithelium appears, the higher the grade lesion.

PUNCTATION: Focal area with capillaries appearing like dots. The coarser the punctation, the higher the grade lesion.

MOSAIC: Focal appearance in which the capillaries appear to surround abnormal areas as tiles. A higher-grade lesion will be found to have a coarser, wider, and more irregular mosaic.

ATYPICAL VESSELS: Focal area in which vessels appear horizontal with irregular caliber and branching (appearing like commas, cork screw, etc.). The finding of atypical vessels is suggestive of invasive cancer.

CLINICAL APPROACH

Prenatal care provides many opportunities to screen for important conditions which could affect both the mother and fetus. One important screening test is the Pap smear. Cervical dysplasia occurs in 1% of childbearing women who are screened annually, and 2% to 8% of all pregnant women will have an abnormal Pap smear. The incidence of cervical neoplasia (including carcinoma in situ [CIS] and invasive carcinoma) in the pregnant population is estimated to be 1.5 to 12/100,000 pregnancies. Although patients with cervical neoplasia often are asymptomatic, common signs/symptoms of invasive cancer are often attributed to pregnancy changes when a patient is pregnant. Fortunately, if cervical cancer is detected, it is often in the preinvasive or early invasive stage.

The management of cervical dysplasia in pregnancy is similar to, but less aggressive than in nonpregnant women. In general, the management is conservative with the ultimate goal of ruling out an invasive malignancy. Treatment for cervical intraepithelial neoplasia (CIN) is generally delayed due to the potential serious complications with therapy, minimal risk of disease progression, high rate of spontaneous disease resolution, and high rate of incomplete excision. In this case, a pregnant patient with LSIL should be evaluated with a colposcopy. Her colposcopy can be performed in a similar fashion to a nonpregnant patient, except for the fact that an ECC should not be done and cervical biopsy performed only if invasive disease is suspected. In the presence of this patient’s normal colposcopy, a repeat Pap can be performed postpartum.

Studies have suggested a higher CIN regression rate than that of a non pregnant patient.1-3 The regression rate is likely increased due to several factors. The local inflammatory reaction and increased shedding and turnover of the cervical epithelium stimulated by cervical trauma (dilation) may improve regression rates. In addition, the extensive metaplasia and cell turnover in the cervix during pregnancy may also contribute to the higher rate of regression. Studies are conflicting as to whether a vaginal delivery yields higher regression compared to a cesarean delivery. Although some studies have suggested a higher rate of regression after a vaginal delivery, the mode of delivery should be made based on obstetrical indications.

Colposcopy

Colposcopy is a method of visually examining the cervix, vagina, and vulva for intraepithelial neoplasia and early invasive carcinoma. It uses an external white light source under magnification to highlight abnormal changes of the tissue (Figure 38–1). Changes in the relationship between the epithelium and stroma with exposure to external light allow the colposcopist to identify potential lesions. As light passes through the colorless epithelium, it is either absorbed or reflected by the underlying stroma (which appears red). The thickness and optical density of the epithelium along with vascularity of the underlying stroma determine the amount of reflected light seen under magnification. When acetic acid is applied to the cervix, surface cells undergo cytoplasmic dehydration. This dimunition of cytoplasm results in more reflected light that appears white on colposcope. When the nuclear to cytoplasm ratio is high (dysplasia/cancer), more reflected light is noted, thus producing the acetowhite change (Figure 38–2). When acetic acid is applied to the columnar epithelium, most of the light is absorbed and little is reflected due to the high mucin content rendering the endocervix highly transparent. Thus, the endocervix appears dark pink to red in color with grapelike appearance (Figures 38–3 and 38–4 for examples of LSIL and HSIL). Punctation, mosaicism, and atypical vessels are seen as stromal vessels have traversed the stroma and lie close to the epithelium. (Figure 38–5 shows mosaic epithelium consistent with HSIL.) When vessel changes occur within the acetowhite epithelium, an underlying neoplastic process should be suspected. Atypical vessels are highly suggestive of advanced neoplasia as new vessels are formed under the influence of tumor angiogenic factor. Iodine can also be applied to the cervix to highlight changes in the epithelium. Normal squamous cells will stain brown due to the abundant glycogen content in the cytoplasm. The cytoplasmic glycogen absorbs the iodine, resulting in brown color. Cells with limited cytoplasmic glycogen (neoplasia, estrogen-deficient states, and inflammation) will not stain as darkly.

Figure 38–1. Colposcope reveals a binocular magnifying device used to magnify the image of the cervix. (Reproduced, with permission, from DeCherney AH, Nathan L, Goodwin TM, et al. Current Diagnosis & Treatment: Obstetrics & Gynecology, 10th ed. New York: McGraw-Hill 2007:534.)

The majority of neoplasia occurs in the transformation zone of the cervix. This area lies between the original squamocolumnar junction and the new squamocolumnar junction. For a colposcopy to be considered adequate, two criteria must be met: (1) the entire transformation zone must be visualized and, (2) if a lesion is present, it must be seen completely. The original squamocolumnar junction is often difficult to visualize due to the metaplasia which has occurred. Therefore, visualization of the new squamocolumnar junction in its entirety is considered a satisfactory colposcopy. When the colposcopy is considered inadequate, a diagnostic cone biopsy is recommended. Other indications for a diagnostic cone are positive endocervical curettings, Pap/colpo discrepancy, and suspected microinvasive disease.

Figure 38–2. The cervix shows changes to become white in color due to the addition of 5% acetic acid. (Reproduced, with permission, from Schorge JO, Schaffer JI, Halvorson LM, et al. Williams Gynecology. New York: McGraw-Hill, 2008:631.)

Figure 38–3. Low-grade squamous intraepithelial neoplasia after adding 5% acetic acid. (Reproduced, with permission, from Schorge JO, Schaffer JI, Halvorson LM, et al. Williams Gynecology. New York: McGraw-Hill, 2008:926.)

Figure 38–4. High-grade squamous intraepithelial neoplasia after adding 5% acetic acid. (Reproduced, with permission, from Schorge JO, Schaffer JI, Halvorson LM, et al. Williams Gynecology. New York: McGraw-Hill, 2008:632.)

Figure 38–5. Mosaicism is seen on the cervix indicative of high-grade CIN. (Reproduced, with permission, from Schorge JO, Schaffer JI, Halvorson LM, et al. Williams Gynecology. New York: McGraw-Hill, 2008:632.)

When trying to interpret the colposcopic lesions and predict histology, various colposcopic findings need to be assessed. High-grade lesions are often found to have dull gray or oyster white color with the application of acetic acid. In addition, the acetowhite changes occur rapidly after the application of acetic acid and persist longer than that of lower-grade lesions. High-grade lesions also have irregular surface contours and well-demarcated borders. The finding of atypical vessels within the well-demarcated lesion is also suspicious for advance neoplasia. Several grading systems (Reid Index) have been developed to provide a structured approach for systematically assessing the severity of cervical neoplasia. Despite the use of grading systems, current research suggests a poor correlation between the colposcopic impression and subsequent histology. The sensitivity of colposcopy for CIN 3 has been reported to be between 54% and 85%. Findings from the ALTS (ASCUS-LSIL Triage Study) trial also revealed poor intraobserver agreement in the assessment of colposcopy. Recent studies have also determined that timing of the colposcopy (in regard to menses) is not a significant factor. The sensitivity may also be affected by the thickness of the epithelium covering the lesions (the thinner the epithelium over the lesion, the less abnormal and less likely to be biopsied). To increase sensitivity, studies have shown that random biopsies may increase the detection by 37.4% and another 5.5% with an ECC. At present, with more sensitive screening tests, more pressure is being put on the colposcopist to identify early lesions not previously known to exist. New studies are underway to improve colposcopic detection.

A colposcopy performed during pregnancy requires an understanding of the normal gestational physiologic changes of the cervix. It is important to make sure that the pathologist is aware of the pregnancy state as the physiology of pregnancy alters cellular morphology. Because of increased pelvic congestion, vaginal wall protrusion and redundancy may affect visualization at the time of colposcopy. Other challenges to colposcopy when pregnant include increased friability from eversion of endocervix, an enlarged cervix, cervical distortion form fetal head, early effacement, and poor visualization from mucus plug. Because of eversion of endocervix, after 20 weeks’ gestation, almost all colposcopies will be adequate. Acetowhite and vessel changes are similar to those of the nonpregnant state.

Comprehension Questions

38.1 When does eversion of the endocervix take place in a primigravid patient?

A. End of first trimester

B. End of second trimester

C. End of third trimester

D. After delivery

38.2 Which of the following is true?

A. Lugol solution is more sensitive than acetic acid.

B. Lugol solution stains areas of dysplasia.

C. Vaginal atrophy would cause Lugol solution to not stain.

D. Lugol solution stains area of cervical trauma darker.

38.3 The performance of an ECC with colposcopy (in a nonpregnant patient) increases the sensitivity by what percentage?

A. 1%

B. 5%

C. 10%

D. Has not been shown to increase sensitivity

ANSWERS

38.1 A. Endocervical eversion occurs after the first trimester during a patient’s first pregnancy as compared to the last trimester in multigravid patient.

38.2 C. Lugol solution nonstaining lesions can be caused by inflammation, atrophy, trauma, in addition to dyplasia, making it less sensitive than acetic acid.

38.3 B. Studies have shown that adding an ECC with colposcopy increases the sensivity by approximately 5% and should be considered on all nonpregnant colposcopies.

Clinical Pearls

See Table 1-2 for definition of level of evidence and strength of recommendation

➤ Colposcopy has poor sensitivity in detecting early lesions but sensitivity can be improved by adding an ECC and random biopsy (Level A).

➤ The colposcopic finding of atypical vessels is the most consistent colposcopic finding of invasive neoplasia (Level A).

➤ Colposcopy is performed in a similar fashion during pregnancy as non pregnant but with primary goal to rule out invasive disease (Level B).

➤ In order for a colposcopy to be adequate, the transformation zone (new squamocolumnar junction) and lesion need to be seen entirely (Level C).

REFERENCES

1. Hunter MI, Monk BJ, Tewar KS. Cervical neoplasia in pregnancy. Part 1: screening and management of preinvasive disease. Am J Obstet Gynecol. 2008;199:3-9. 

2. Baliga BS. Colposcopic terminology and colposcopic appearances of the cervix. Principles and Practice of Coloposcopy. New York, NY: McGraw Hill; 2004:53-59. 

3. Broderick D, Matityahu D, Didhdhai M, Alter S. Histologic and colposcopic correlates of ASCUS Pap smears in pregnancy. J Low Genit Tract Dis. 2002;6:116-119. 

4. American College of Obstetricians and Gynecologists. Management of Abnormal Cervical Cytology and Histology. ACOG Practice Bulletin, 66.Washington DC; 2005. 

5. Baliga BS. Colposcopy in pregnancy. Principles and Practice of Coloposcopy. New York, NY: McGraw Hill; 2004:138-143. 

6. Cantor SB, Cárdenas-Turanzas M, Cox DD, et al. Accuracy of colposcopy in the diagnostic setting compared with the screennig setting. Obstet Gynecol. 2007;111:7-14. 

7. Carcopino X, Akkawi R, Conroy R, Prendiville W. Specific timing for colposcopy: Is it worthwhile? Obstet Gynecol. 2008;111:373-377. 

8. Cox JT. More questions about the accuracy of colposcopy: What does this mean for cervical cancer prevention? Obstet Gynecol. 2008;111:1266-1267. 

9. Everson JA, Stika CS, Lurain JR. Postpartum evolution of cervical squamous intraepithelial lesions with respect to the route of delivery. J Low Genit Tract Dis. 2002;6:212-217. 

10. Ferris DG, Litaker MS. Colposcopy quality control by remote review of digitized colposcopic images. Am J Obstet Gynec. 2004;191:1934-1941. 

11. Ferris DG, Litaker MS. Prediction of cervical histologic results using an abbreviated Reid colposcopic index during ALTS. Am J Obstet Gynecol. 2006;194:704-710. 

12. Jeronimo J, Schiffman M. Colposcopy at a crossroads. Am J Obstet Gynecol. 2006;195:349-353. 

13. Katz VL, Lentz GM, Lobo RA, Gershenson DM. Intraepithelial neoplasia of the lower genital tract (cervix, vulva). In: Katz VL, Lentz GM, Lobo RA, Gershenson DM. eds. Comprehensive Gynecology. 5th ed. Philadelphia, PA: Mosby; 2007:743-757. 

14. Massad LS, Jeronimo J, Schiffman M. Interobserver agreement in the assessment of components of colposcopic grading. Obstet Gynecol. 2008;111:1279-1284. 

15. Muller CY, Smith HO. Cervical neoplasia complicating pregnancy. Obstet Gynecol Clin North Am. 2005;32:533-546. 

16. Yang B, Pretorius RG, Belinson JL, Zhang X, Burchette R, Qiao Y. False negative colposcopy is associated with thinner cervical intraepithelial neoplasia 2 and 3. Gynecol Oncol. 2008;111:332-336. 

17. Walker JL, Wang SS, Schiffman M. Predicting absolute risk of CIN3 during postcolposcopic follow-up: results from the ASCUS LSIL Triage Study (ALTS) group. Am J Obstet Gynecol. 2006;195:341-348. 

18. Wright TC, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. J Low Genital Tract Dis. 2007;11:223-239.

HomeGynecologic Surgery Case FileColposcopy Case File