Chapter 6

6 Colposcopic Findings

6.1 Normal Colposcopic Appearances

6.1.1 Original Squamous Epithelium

Like other normal superficial squamous epithelia, the native, original squamous epithelium of the uterine cervix is smooth and uninterrupted by gland openings (Fig. 6.1). This sets it apart from normal squamous epithelium that has arisen through metaplasia. More detailed observation of a surface covered by epithelium of metaplastic origin shows gland (crypt) openings and retention cysts, which indicate that the area was originally occupied by columnar epithelium (Figs. 6.2 and 6.3a–c). The original squamous epithelium during the reproductive period displays a reddish color that can vary from pale to intense pink during the various phases of the menstrual cycle. It stains deep brown with iodine, reflecting its glycogen content (Fig. 6.3c).

The so-called portio rugata is seen especially during adolescence. The cervix is dome-shaped, with a dimple-like os but can expand distally to resemble a mushroom (Fig. 6.4). Sometimes the surface looks like a cockscomb (Fig. 6.5a, b). This is probably an incidental finding without clinical relevance.

6.1.2 Atrophic Squamous Epithelium

After menopause, in the absence of estrogen, the squamous epithelium becomes thin and devoid of glycogen, and the stromal blood supply diminishes. These changes result in a pale epithelium that can show a fine network of capillaries (Fig. 6.6a). The epithelial thinning and loss of glycogen are patchy, resulting in a stippled appearance with iodine because of its irregular uptake (Fig. 6.6b). In older women, the epithelium assumes a uniform light brown to yellow color as a result of complete loss of glycogen (Fig. 6.7). The thin epithelial covering is fragile and makes the terminal vessels vulnerable to minor trauma, which can result in erosions and subepithelial hemorrhages (Fig. 6.8).

6.1.3 Ectopy (Columnar Epithelium)

Ideally, the original squamocolumnar junction (SCJ) is situated at the external os. Depending on the size, shape, and patulosity of the external os, varying portions of the canal may be visible. In patulous cervices, the architecture of endocervical mucosa can be seen clearly (Fig. 6.9).

In adolescents and young women, the columnar epithelium is frequently situated on the ectocervix at some distance from the external os. This is referred to as ectopy. In cases of marked eversion of the endocervical mucosa, its rugose architecture becomes evident (Figs. 6.10–6.12a, b).

Fig. 6.1 Original squamous epithelium in a woman of reproductive age. The surface is completely smooth and displays a fresh reddish color.

Fig. 6.2 (a) Ectopy before application of acetic acid. The gland openings at the 10 o’clock position indicate earlier transformation. (b) After application of iodine. The columnar epithelium does not stain; it is merely discolored by the thin film covering it. The demarcation from the deep brown original squamous epithelium is indistinct.

Ectopy appears classically as a “red patch” (Fig. 6.2a). Grossly, it may look suspicious to the inexperienced examiner. More detailed colposcopic examination shows its unique papillary architecture, which identifies its real nature. Ectopy does not stain with iodine (Fig. 6.2b).

Ectopy is usually covered by mucus secreted by the columnar epithelium. Acetic acid helps to remove the mucus (see Chapter 3), revealing the distinctive papillary structure. Acetic acid also causes the tissue to swell, throwing the mucosal architecture into sharp relief and giving the papillae a grapelike appearance. The intense red of the red patch changes to pink or whitish (Figs. 6.3 and 6.13).

The SCJ is usually sharp and step-like (Figs. 6.2, 6.9, and 6.13). Careful inspection often reveals a slender, white margin and gland openings, which indicates the initiation of transformation (Figs. 6.3, 6.11, and 6.14). It is important to pay close attention to the margins of ectopy so as not to overlook significant colposcopic lesions.

Ectopic columnar epithelium is less resilient and more vulnerable to trauma than squamous epithelium. It is subject to contact bleeding at speculum examination (contact bleeding should also make the examiner consider the possibility of cancer). Although neoplastic papillary fronds tend to be coarse and irregular, they can be mistaken for benign changes.

The influence of exogenous and endogenous sex steroids on the transformation of the columnar epithelium has been studied longitudinally (Fig. 6.15a–d). Estrogen-containing oral contraceptives appear to have a positive and enhancing effect on ectopy, and women who discontinue contraceptives show transformation in a relatively brief time (Fig. 6.16a, b).

6.1.4 Transformation Zone

The transformation zone (TZ) can appear as a nonspecific red area. Sometimes there is a fine vascular pattern (Fig. 6.17a). Application of acetic acid turns the previously red epithelium grayish white. Within the TZ are openings of cervical glands (crypts) and small islands of residual columnar epithelium. The demarcation from the original squamous epithelium is indistinct (Fig. 6.17b).

The process of transformation characteristically begins at the SCJ. The flat epithelial margin around the periphery of an ectopy can be distinguished from the original squamous as well as columnar epithelium by its variable color and by the presence of gland openings (Figs. 6.2, 6.6, and 6.18–6.20).

The surface contour of an ectopy changes as transformation takes place. The papillae become coarse and fused, resulting in only slight fissuring of the surface. These changes signify the initiation of squamous metaplasia. Fields of metaplastic epithelium within a TZ may vary widely in their maturation, easily verifiable by application of iodine (the Schiller’s test), which is a sensitive indicator of epithelial maturity (Fig. 6.20b).

The topographic progression of transformation can be haphazard, and its stage of development can vary markedly from one part of the periphery to another. Islands of squamous epithelium can appear in a sea of columnar epithelium; these must have arisen by metaplasia (Figs. 6.15a–d, 6.16a, b, and 6.19). The metaplastic epithelium can form tongues or fingerlike processes that interdigitate with intact columnar epithelium (Fig. 6.21). Even when most of an ectopy is fully transformed, small islands of columnar epithelium can remain; this appearance is referred to as TZ with ectopic residuals (Fig. 6.22). Longitudinal study of the TZ over years is particularly informative (Figs. 6.15 and 6.16).

The transformation of an ectopy from columnar to squamous epithelium does not always proceed to completion. Areas of the newly formed squamous epithelium can be fully mature, whereas other parts of an ectopy can remain columnar for long periods (Fig. 6.23). The new SCJ is again situated at the external os. Squamous epithelium of metaplastic origin can be distinguished from original squamous epithelium by the presence of gland openings, more prominent vessels (Fig. 6.24), or retention cysts (Fig. 6.25). Undulations from numerous retention cysts (nabothian follicles), with long vessels coursing over their surface, are also characteristic (Fig. 6.26). The vasculature in such cases is so typical that the presence of deep-seated and otherwise invisible cysts can be easily inferred (Figs. 6.132 and 6.133).

Fig. 6.3 Small red area on the anterior and posterior lip of the external os. (a) Before application of acetic acid. (b) After application of 3% acetic acid. (c) After application of iodine. The columnar epithelium does not stain. The transformation zone at the margins is identifiable by the incomplete staining of the new squamous cell epithelium.

Fig. 6.4 The portio rugata in a 29-year-old woman. Squamocolumnar junction not visible (type III transformation zone). (This image is provided courtesy of O. Baader.)

Fig. 6.5 (a) Original squamous epithelium. Cockscomb-like lesion on the anterior lip and fornix in a 17-year-old girl. The polypoid contour around the external os is suggested only by the shallow notches. (b) Surprising stippling effect of iodine. Only the posterior lip shows typical uniform mahogany-brown staining. (This image is provided courtesy of O. Baader.)

Fig. 6.6 (a) Atrophic squamous epithelium in a postmenopausal woman. Fine blood vessels shine through the thin epithelium, which appears pale pink to yellowish. (b) The same cervix after application of iodine. The characteristic stippled appearance is due to focal glycogen retention.

Fig. 6.7 The loss of glycogen is uniform in the atrophic epithelium of an older woman, resulting in homogeneous yellow staining with iodine.

Fig. 6.8 With advancing age, the squamous epithelium becomes fragile. Subepithelial hemorrhages may appear during vaginal examination. Note the fine vessels that run toward the os.

Fig. 6.9 The original squamocolumnar junction of this gaping cervix is most distinct. The anterior lip displays a thin rim of transformation zone. The rugose structure of the endocervical mucosa is clearly seen.

Fig. 6.10 Eversion of the endocervical mucosa (ectopy), with its rugose architecture thrown into sharp relief.

Fig. 6.11 Apparent eversion (ectopy) of a cervix with a patulous os resulting from wide separation of the speculum. A thin rim of transformation zone is visible near the junction with the original squamous epithelium.

Fig. 6.12 (a) Ectopy with a thin rim of transformation zone (TZ) in a 14-year-old. (b) After 2 years, the transformation is more advanced. Squamocolumnar junction fully visible (type 1 TZ). (This image is provided courtesy of O. Baader.)

Fig. 6.13 Typical appearance of ectopy after application of acetic acid. The grapelike structure is unmistakable. Note the whitish rim of transformation zone at the periphery.

Fig. 6.14 Ectopy with a slim margin of transformation at the periphery in a 29-year-old nullipara (type 1 transformation zone). (This image is provided courtesy of O. Baader.)

Fig. 6.15 Longitudinal follow-up of a 20-year-old woman beginning oral contraception (OC). (a) Before starting OC, there is ectopy with a slim margin of transformation (type 1 transformation zone [TZ]). (b) After several months of OC, the ectopy has assumed a strongly coarse papillary appearance. (c) At this point, the woman has resumed OC after a vaginal delivery. The ectopy is again apparent. (d) The woman received an intrauterine contraceptive device 9 months later and discontinued OC. Three months later, the ectopy has been rapidly transformed (type 1 TZ). (This image is provided courtesy of O. Baader.)

Fig. 6.16 Transformation of marked ectopy with discontinuation of oral contraception (OC). (a) Marked ectopy with coarse papillae in a woman with 4 years of OC. (b) Only 1 year after discontinued OC (and intrauterine device insertion), there is advanced transformation of the ectopy (type 1 TZ). (This image is provided courtesy of O. Baader.)

Fig. 6.17 (a) Transformation zone (TZ) before the application of acetic acid. There are small, unremarkable vessels at the edge of the reddish area on the posterior lip of the cervix. (b) After application of acetic acid, the previously reddish epithelium is grayish white. Gland openings and small islands of residual columnar epithelium are signs of the TZ.

Fig. 6.18 Step-like border between the grapelike structure of the glandular epithelium (ectopy) and the squamous epithelium of the transformation zone. Note the gland openings at the periphery of the squamous epithelium, indicating completed transformation at the edge of the previously larger ectopic area.

Fig. 6.19 Transformation zone. Here, too, the process begins peripherally and spreads toward the center in an irregular manner. Note the smooth surface in spite of the incomplete transformation. There are numerous gland openings.

Fig. 6.20 (a) Transformation zone. Centrally, within this ectopy, the villi become plumper and fuse to eventually form a flat surface. (b) The same patient after application of iodine. The transformed epithelium is mature and contains glycogen. Gland openings are well displayed. The central part does not take up iodine, which merely covers it like a veil.

Fig. 6.21 Fingerlike processes of metaplastic epithelium extend centrally from the periphery and interdigitate with islands of columnar epithelium. The transformation involves only the anterior lip.

Fig. 6.22 Transformation zone with residual islands of grapelike columnar epithelium on the anterior lip.

Fig. 6.23 Partial transformation. The transformation zone on the anterior lip takes up only a small portion of the ectopy, which is largely unchanged, apart from enlargement and fusion of its papillae.

Fig. 6.24 Well-established transformation zone. Although the color of the new squamous epithelium is hardly distinguishable from that of the original, the border of the transformation is marked by fine blood vessels. The new squamocolumnar junction is abrupt.

Fig. 6.25 Nabothian follicles covered by smooth squamous epithelium. They are the only indicators of earlier transformation. Blood vessels characteristically run over the surface of the retention cyst on the right.

Fig. 6.26 Nabothian follicles in an established transformation zone. The long, regularly branching blood vessels that shine through the attenuated epithelium are typical.

6.2 Abnormal Colposcopic Findings

6.2.1 Acetowhite Epithelium

These criteria do not always signify the development of atypical epithelium. Transformation can also result in a metaplastic epithelium with only slight keratinization and no elongated stromal papillae and thus will not appear colposcopically as keratosis, punctation, or mosaic. Compared with original squamous epithelium, metaplastic epithelium undergoes a more distinct color change with acetic acid, and its junction with original squamous epithelium is sharply defined (Fig. 6.27). In spite of these differences, it is not always possible to distinguish colposcopically between metaplastic epithelium and squamous intraepithelial lesion (SIL). Even the whitish epithelium of high-grade SIL (HSIL) may be only discrete (thin acetowhite epithelium) so that it can be difficult to distinguish from a normal TZ (Fig. 6.28).

There may be subtle hints of the presence of white epithelium before application of acetic acid. Any shade of red other than the fresh red of the normal TZ should be viewed with suspicion. Grayish red tones, which give the TZ an opaque appearance, and yellow shades, which are probably due to marked inflammatory infiltration of the stroma (Figs. 6.29 and 6.30a), are particularly worrisome. In such cases, acetic acid usually induces a distinct white color change and reveals sharp borders (Figs. 6.29b and 6.30b). A rich vascular bed suggests unusual transformation but is not pathognomonic of epithelial atypia (Fig. 6.31).

The best diagnostic criterion is the acetic acid test. The more marked and the more rapid the color change and the greater the swelling, the greater the likelihood of epithelial atypia (dense acetowhite epithelium; Figs. 6.30b, 6.32, and 6.33). However, the spectrum of color changes is wide (Figs. 6.34 and 6.35a).

Fig. 6.27 (a) Regularly branching blood vessels in a reddish yellow, colposcopically abnormal lesion before application of acetic acid. (b) Acetic acid suppresses the vascular pattern but brings out a sharply demarcated fine mosaic with a distinct change in color tone. Histology showed metaplastic epithelium.

Fig. 6.28 (a) Characteristic appearance of thin acetowhite epithelium, distinguished from the normal transformation zone only by numerous cuffed gland openings. Histology showed low-grade squamous intraepithelial lesion (LSIL) (CIN 1). (b) Application of iodine (Schiller’s test) reveals a variegated appearance resulting from the admixture of LSIL and fully mature brown squamous epithelium.

Fig. 6.29 (a) Before application of acetic acid, the white epithelium shows indistinct red tones. Several nabothian follicles shine through the reddish surface. (b) The white change is produced by acetic acid. Some gland openings are cuffed. The lesion between the 11 o’clock and 12 o’clock positions is due to glandular involvement. Histology showed LSIL (CIN 1).

Fig. 6.30 (a) Pronounced red transformation zone, sharply demarcated from the original squamous epithelium. (b) Patchy appearance after application of acetic acid. Between the coarse and irregular white patches, there are reddish areas with cuffed gland openings and solid epithelial pegs in the glands. Histology showed HSIL (CIN 3).

Fig. 6.31 Transformation zone with suspicious vessels on the posterior lip. Histology showed HSIL (CIN 3).

Fig. 6.32 Dense acetowhite epithelium after application of acetic acid. There are only isolated gland openings. Histology showed HSIL (CIN 3).

Fig. 6.33 Dense acetowhite epithelium with numerous cuffed gland openings. Histology showed HSIL (CIN 3).

Fig. 6.34 Dense acetowhite epithelium on the posterior lip and on the anterior lip between 12 o’clock and 3 o’clock and between 9 o’clock and 10 o’clock positions. Histologically, the acetowhite epithelium was HSIL (CIN 3), whereas the pale pink area on the anterior lip was metaplastic epithelium.

Fig. 6.35 (a) Dense acetowhite epithelium involving the entire posterior lip as well as the external os between 11 o’clock and 1 o’clock positions. Note the whiteness of the epithelium and the gland openings, some of which are cuffed. Histology showed HSIL (CIN 3). (b) After iodine staining, the pathologic epithelium clearly stands out against the fully mature squamous epithelium in the transformation zone.

6.2.2 Atypical Transformation Zone

6.2.3 Mosaic

Fine mosaic, like fine punctation, occurs in sharply demarcated areas in the plane of the superficial epithelium. The appearance of such an area before application of acetic acid can be nonspecific and can remind one of a relatively vascular TZ, which, however, is usually devoid of gland openings or cysts (Figs. 6.27 and 6.36–6.42). A distinct color change to gray-white occurs with acetic acid application, and the margins become sharp. The blood vessels become less conspicuous (Fig. 6.27b). The whole area remains in the same plane as before. The mosaic pattern is delineated by the fine network of pale red lines. Such an area may not display the mosaic pattern throughout its entirety; in places, the surface may be uniform and flat because the epithelium is not supported by elongated stromal papillae.

It can be difficult to classify mosaic as fine or coarse (Figs. 6.39 and 6.42). Intermediate forms are mostly caused by low-grade squamous intraepithelial lesion (LSIL), which may also produce various forms of punctation, depending on the degree of atypia and epithelial architecture.

Coarse Mosaic

Coarse mosaic is characterized by greater irregularity of the mosaic pattern. The network of fissures is more pronounced and intensely red. The furrows are more widely spaced, and the epithelial cobbles between them are bigger and more variable in shape than in the fine form (Figs. 6.38–6.41). The swelling from acetic acid makes the structures stand out (Fig. 6.41); the peak effect may take a minute to develop. The metamorphosis can be observed through the colposcope as the coarse structure of the mosaic and punctation gradually appears. In contrast, the effect of acetic acid on fine mosaic is immediate.

Gland openings and nabothian follicles are usually not found within areas of punctation or mosaic. Like leukoplakia, mosaic and punctation can also be found outside the TZ, in original squamous epithelium (Figs. 6.39, 6.43, and 6.44; see also Fig. 6.52). This is fundamental to the understanding of the morphogenesis of punctation and mosaic and epithelial atypia.

Punctation and mosaic occur in isolated fields (Figs. 6.39 and 6.43–6.45) and can coexist with other lesions (see Fig. 6.42; also see Fig. 7.20). In the latter case, the more peripherally located lesions usually represent lower-grade lesions (LSIL, CIN 1) or merely metaplastic epithelium, which was confirmed by topographic studies showing that mosaic and punctation occur more commonly outside than inside the TZ (84 vs. 16%). Histologically, mosaic and punctation outside the TZ corresponded to benign metaplastic epithelium in 70% and to CIN in only 30% of treated cases; within the TZ, the respective rates were 20 and 80%. Thus, mosaic and punctation within the TZ are more likely to represent CIN than are the same lesions outside the TZ.

Fig. 6.36 Fine mosaic, mainly on the anterior lip of the external os, after application of acetic acid. Histology showed metaplastic epithelium. The string of an intrauterine device is visible.

Fig. 6.37 (a) Indistinct lesion outside an intensely red area around the external os. Close examination shows increased vascularity on the posterior lip at the edge of the area. (b) Application of acetic acid shows an unexpectedly large, fine mosaic, mainly on the anterior lip. The whitish points in the narrow transformation zone are glands filled by squamous epithelium. Histology showed metaplastic epithelium.

Fig. 6.38 (a) Transformation zone surrounded by a semicircular area that turns whitish after the application of acetic acid and shows a fine mosaic. (b) Higher magnification shows that the mosaic is coarser and more irregular than in Figs. 6.27, 6.36, and 6.37. Histology showed LSIL (CIN 1).

Fig. 6.39 Fine to coarse mosaic outside the transformation zone involving original squamous epithelium. Histology showed HSIL (CIN 2).

Fig. 6.40 Coarse mosaic around the os. Histology showed HSIL (CIN 3).

Fig. 6.41 Coarse mosaic intermingling with coarse punctation on the posterior lip. The border to the acetowhite epithelium is sharp, corresponding to HSIL (CIN 3). The mosaic returned HSIL (CIN 2).

Fig. 6.42 Fine to coarse mosaic intermingling with fine punctation at the edge of acetowhite epithelium with cuffed gland openings and solid white points. The points correspond to HSIL (CIN 3).

Fig. 6.43 Leukoplakia outside the transformation zone, on the anterior lip of the cervix. Histology showed metaplastic epithelium.

Fig. 6.44 Slightly prominent punctation. The entire sharply demarcated area apparently lies within unaltered squamous epithelium. Histology showed HSIL (CIN 3).

6.2.4 Punctation

Fine punctation characteristically imparts delicate stippling to an otherwise circumscribed grayish white to reddish area (Fig. 6.45). When the epithelium is keratinized, the dots may appear white, but they are usually red and remain in the same plane as the surface epithelium, even after the application of acetic acid. The “dots” of fine punctation are close together (Fig. 6.46). Fine punctation is often combined with equally fine mosaic. Fine focal punctation may be due to inflammation, in which case the margins of the inflamed area appear indistinct after application of iodine (see Figs. 6.47 and 6.48b). Fine punctation can also be associated with LSIL (caused by human papillomavirus [HPV] infection). With the Schiller’s iodine test, the punctations become yellow to ocher, whereas the adjacent epithelium, as a result of the koilocytes, stains brown. This is known as iodine-positive punctation (Fig. 6.45b).

Fig. 6.45 (a) A fine punctation on the posterior lip of the cervix extends into the cervical canal. The squamocolumnar junction is not visible (type 3). (b) After application of iodine, the epithelium is stained brown. This so-called iodine-positive punctation is a sign of human papillomavirus infection. Histology showed LSIL (CIN 1) with koilocytosis.

Fig. 6.46 Leukoplakia. Punctation appears where the keratin layer has been peeled off. Histology showed keratinizing metaplastic epithelium.

Coarse punctation usually indicates HSIL. The petechiae are more pronounced, bigger, and widely separated (Figs. 6.44 and 6.49–6.51). In extreme cases, punctation resembles papillae (Fig. 6.52). With higher magnification, corkscrew capillaries can be seen in the papillae. After application of acetic acid, coarse punctation stands out from the plane of the surrounding surface epithelium (Fig. 6.49a, b). Coarse punctation may be combined with coarse mosaic. The two patterns may overlap, with intermingling of dots and fissures (Fig. 6.50).

Fig. 6.47 (a) On higher magnification, the vessels within the papillae resemble commas and antlers. Their coarseness gives the impression of atypia. (b) Condyloma. The brownish color after application of iodine indicates glycogen-containing patches within the condyloma and correlates well with the histologic picture.

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