Premature rupture of membranes

Morphological basis of colposcopy
Natural history of the cervical epithelia
        The essential target of colposcopic examination is the lining layer of the vagina, cervix and lower endocervical canal. The most conspicuous item of the lining is of course its epithelial covering and in the region under notice there are three epithelial types to be found, original squamous, original columnar, and metaplastic squamous, a derivative of the columnar.

The original epithelia
        The embryological basis of the original epithelia is provided by the lining layers of the mullerian duct and of the urogenital sinus. Original stratified squamous epithelium develops from the sinus epithelium, whereas a mucus?secreting columnar epithelium develops from the mullerian duct.

Metqplastic epithelium
        Almost all cervices show evidence of transformation of columnar epithelium to squamous; at some stage of their life history. The transformation is known as metaplasia to the histologists and the area involved is appropriately known as the transformation zone (TZ) to the colposcopist. The transformation zone is the most conspicuous structure seen on colposcopic examinat ion.

Topogr
        The limits of the transformation zone are thus capable of precise definition. The caudal limit is the site of the original squamocolumnar junction and the cephalic limit, the junction between the metaplastic transformed and columnar epithelia, the new squamocolumnar junction. When this band of new epithelium is seen in its entirety, that is with columnar epithelium on its cranial end, the colposcopic examination is termed satisfacto to distinguish it from a condition where columnar epithelium is not seen cranially and the new metaplastic squamous epithelium extends out of sight into the canal. In the latter case the colposcopic examination is termed unsatisfactory

Dynamic aspects and maturity
        The metaplastic process may span all epochs from intrauterine to senescence. It is especially active prior to birth, at the menarche and during and after the first pregnancy.

Typical or atypical metaplasia 
        Atypical metaplasia occurs in place of physiological metaplasia & insidiously the typical transformation zone becomes the atypical transformation zone. The atypical process behaves in corresponding fashion to the physiological process in that it seems capable of varying degrees of progression towards an end point, frank invasive cancer, with varying periods of arrest at intermediate stages, cervical intraepithehial neoplasia (CIN) of various grades.

Basis of colposcopic appearances

        The colposcopic image hinges on three basic characteristics, the olm of the epithelium, the surface conto of the epithelium and the arrangements of the terminal vascular bed, the angioarchitecture.

        The occlusion of the bright red aspect of the cervical stroma by the development of a multilayered epithelium is evidently responsible for the pallor of immature metaplastic epithelium. With increasing maturity and associated differentiation the physiologic metaplastic epithelium becomes less pale.

        If on the other hand the epithelium becomes less rather than more differentiated it becomes whiter after its contact with acetic acid. This whiteness, evidently due to increased nuclear and cellular density combined with an increased meshwork of keratin filaments, is marked where metaplasia has become atypical and acetowhite epithelium is a feature, although not pathognomonic, of this atypical change.

        Often in acetowhite epithelium, intraepithelial vessels are absent. In this case the opacity of the nucleardense epithelium prevents the observer from seeing subepithelial vessels, so that the epithelium is seen as white. Sometimes intraepithelial vascular arrangements are sufficiently characteristic as to warrant names for some atypical appearances. Thus when the capillaries are studded through the epithelium and seen end on as red points, the term punctation is used. Equally common is a system of capillaries in a wall?like structure which subdivides blocks of tissues, honeycomb fashion, the so?called mosaic. Combinations of these appearances occur. Uncommonly there is an exaggeration of the vascular pattern such that vessels appear on or near the surface of the epithelium. These horizontal vessels show bizarre variations of caliber and of branching and are termed atypical vessels. These striking vessels are usually indicative of invasion. The tumor angiogenic factor seems to play an important part in this new vessel formation. At times white patches can be seen with the unaided eye which are termed leukoplakia. These are due to a thick keratin covering which may overlie both histologically normal and atypical epithelium. When the atypical growth process is sufficiently exuberant surface irregularities appear, culminating in conspicuous ridging and folding, the so?called microexaphydia or mountain?range appearance of invasive cancer.

Effects of human papillomavirus (HPV) infection
        Increasing recognition of the incidence of HPV and the colposcopic disorders it causes makes it necessary to include a new section in colposcopic morphology. In topographic terms viral infection does not respect limits imposed by the transformation zone and may occur within the original squamous epithelium. Neoplastic potential is most often confined to lesions within the transformation zone. In structural terms the key colposcopic features are expressed in keratin and blood vessel distribution. The former is manifest as variation of the whiteness of the epithelium from low grades of acetowhite, often with reflective shine, to very high grades such as to produce a thick keratin pile on the surface. Such exuberance of keratin synthesis, with different effects on the stromal papillae, results in characteristic surface changes from the subclinical micropapilliferous and microconvoluted (brain?like) configurations up to the exophytic of the clinical condyloma. The blood vessel alterations induced by the virus can be conspicuous. There may be no true demarcation between wart?characteristic vessels and those of obvious precancerous lesions.

        Recording of colposcopic findings. The format adopted tends to vary with the individual or individual institutions. The report is best made in writing, sketching the cervix on a diagram.

        Classification - The International colposcopic terminology

A. Normal colposcopic findings - Original squamous epithelium, Columnar epithelium, Normal transformation zone .

B. Abnormal colposcopicfindings

1. Within the transformation zone
Acetowhjte epithelium - Flat, Micropapillary or microconvoluted
Punctation, Mosaic, Leukoplakia, Iodine negative, Atypical vessels

2. Outside the transformation zone, e.g. ectocervix, vagina
Acetowhite epithelium - Flat, Micropapillary or microconvoluted Punctation, Mosaic, Leukoplakia, Iodine negative, Atypical vessels C. Colposcopically suspect invasive carcinoma D. Unsatisfactory colposcopy Squarnocolumnar junction not visible, Severe inflammation or severe atrophy, Cervix not visible E. Miscellaneous findings Nonacetowhite micropapillary surface, Exophytic condyloma, Inflammation Atrophy, Ulcer, Others Indicate minor or major change Minor changes ? Acetowhite epithelium, Fine mosaic, Fine punctation, Thin leukoplakia Major changes ? Dense acetowhite epithelium, Coarse mosaic, Coarse punctation, Thick leukoplakia Atypical vessels, Erosion (Ratified by the International Federation of Cervical Pathology and Colposcopy, in 1990, Rome, Italy.)

Colposcopic Appearances
Original squamous epithelium
         This epithelium is of uniform pink color and contrasts with the red of columnar epithelium. In the postmenopausal era the epithelium becomes paler. Its surface is smooth and its vascular patterns inconspicuous as looped capillaries or a fine network.
Columnar epithelium

        The color is dark red since each single cell column produces a lens?Re view of the underlying stromal blood vessels. These finger?like processes contain one or more capillary loops and are often vested with tenacious mucus. The thinness of the epithelium and vascularity leads to ease of contact bleeding.

Typical transformation zone
        The villous configuration of the preexisting columnar epithelium is gradually lost until the surface becomes flat. The pallor of this immature epithelium contrasts with the red color of the previous columnar epithelium. In the well developed transformation zone the epithelium becomes thicker and loses its pallor as it matures.

Atypical colposcopic appearances
         Preneoplastic lesions tend to be confined to the transformation zone. In contrast SPI is not so characteristically limited and may transgress the original squamocolumnar junction onto the original squamous epithelium of the cervix and sometimes extend further caudally to involve vagina. SPI can also transgress cranially to produce lesions within columnar epithelium. In other patients precisely defined asymmetric, map?like areas of acetowhitening are seen within the original squamous epithelium.

        Acetowhite epithelium The basic feature of the atypical transformation zone is ephemeral white or white?gray, clear cut areas with or without an obvious keratin covering and with or without conspicuous alterations of the capillary bed. This appearance persists for several minutes. The rate of color change may be slow especially with the shiny reflective change seen in many minor lesions (e.g. SPI). There is a general correspondence between the degrees of whiteness and the grade of the histological abnormality. The less shiny and the more opaque the lesion the more likely is there to be significant CIN.

        Leukoplakia (keratosis). White keratotic elevations, extensive or patchy, apparent to the naked eye are termed leukoplakia to distinguish them from acetowhite epithelium. Leukoplakia within the transformation zone may reflect either benign HPV infection or CIN. Leukoplakia is also seen in original squamous epithelium where it has no clinical significance or is due to HPV infection.

        Punctation. This term is applied to the presence of a fine stippling within the epithelium produced by the end?on view of intraepithelial capillaries closely spaced with grid?like patterns. In more pronounced punctation there is an increase in caliber and spacing and in most pronounced exarnples there is even greater dilatation and spacing with irregular intervals.

        Mosaic. Here fine vessels form lines or partitions between blocks of acetowhite epithelium often regular in size and shape. More extensive grades show increasing irregularity in the epithelial blocks marked out by septa with coarser more conspicuous vessels and an overall increase in intercapillary distance.

        Vessels with warty characteristics. Vessels with warty characteristics may be disposed vertical or horizontal to the plane of the epithelium. The former resemble hairpin capillary loops of uniform vessel caliber and have a punctate?like appearance. The latter produce ill?defined mosaic?like patterns, with less complete boundaries than true mosaic.

        Atypical vessels. An exaggeration of the vascular abnormalities may occur as the lesion becomes more severe in type. They demonstrate gross variation in caliber and course with bizarre irregular branching grading into the specific appearances of the vessels of frank cancer.

        Surface configuration changes. The colposcope may reveal micropapill projections (the so?called asperities) occurring in acetowhite areas of the transformation zone and within HPV?infected areas outside the transformation zone. Sometimes the accent is on microconvolutions much broader than the micropapillary structures. These brain?like epithelial derangements usually contain a variety of mosaictype vascular arrangement. A further striking and most significant alteration takes the form of microexop Such small protuberances or excresences may herald the onset of or indicate early invasive disease. Grading of atypical (abnormal) colposcopic appearances

        Grade I (inignficant. not suspicious . Acetowhite epithelium, usually shiny or semitransparent, borders not necessarily sharp, with or without fine?caliber vessels, often with ill?defined patterns; absence of atypical vessels; small intercapillary distance.

        Grade II (sigaidcant. suspicious . Acetowhite epithelium of greater opacity with sharp borders; with or without dilated caliber, regularly shaped vessels; defined patterns; absence of atypical vessels; usually increased intercapillary distance.

        Grade HI (highly significant, highly suspicious . Very white or gray opaque epithelium; sharply bordered; dilated caliber, irregularly shaped, often coiled, occasionally atypical vessels; increased but variable intercapillary distance; and sometimes irregular surface contour ?microexophytic epithelium.

        In Grade I appearances the histologic appearances overlap from metaplastic epithelium (both immature and mature, the so?called abnormal or acanthotic epithelium) to SPI and CIN 1. In Grade 11, the findings are more prone to be CIN 2?3 while in Grade 111, CIN 3 or early invasion can be expected. The latter diagnosis is probable in the presence of atypical vessels and microexophytia.

        A new and less subjective approach to the problem of predicting histologic diagnosis in the presence of HPV, especially with the minor lesions, is a scoring system constructed by Reid and colleagues in 1984 and modified in 1985. Four colposcopic signs, margin (including surface contour and topography), color,vessels and iodine res " ponse are graded into three objective categories. In general the more wart?like the lesion the lower the score. Combining these four individual signs the colposcopic index was 97% correct in forecasting either SPI or lower grade dysplasia, or CIN 3.

        Atypical colposcopic appearances of doubtful or physiological significance Colposcapically suspect overt carcinoma Overt cancer may be colposcopically recognized in the absence of its classical signs by the better lighting and magnification afforded by the colposcope. This entity, known as the colposcopically suspect overt carcinoma, whilst rare, is obvious after acetic acid application, with its striking raised edge, irregular surface contour, the so?called 'mountain range' appearance, and even more striking bizarre blood vessels which show marked alterations in shape, size, caliber, direction and arrangement.

Overt carcinoma
         All features described in the previous entity become exaggerated when clinically recognized invasive cancer is present. The surface contour is irregular with nodulation and ulceration. Thin?walled bizarre blood vessels show sudden variation in caliber, often with gross dilatation, and are frequently unbranched for long courses. Contact bleeding is frequent.

Adenocarcinoma and adenocarcinoma in situ (AIS)
        The colposcopic appearances of invasive squamous cell carcinoma and invasive adenocarcinoma may be similar although subtle differences are usually evident. In the latter villous surface configurations may resemble normal columnar epithelium but there is usually gross distortion, fusion and bridging of the villi and presence of atypical vessels. In AIS, villous outgrowths are present which closely mimic the surface configuration of normal columnar epithelium. The distinguishing feature of the villi, which are often fas_td, after the application of acetic acid is their striking white col . AIS lesions are frequently within view of the colposcope, may be multifocal and often coexist with CIN.

Miscellaneous colposcopic appearances
        Condyloina. These exophytic structures may be present both in the cervical transformation zone and original squamous epithelium. Accompanying lesions of similar morphology are often found on the vagina and vulva.

        Vaginocervicifis. Inflammatory lesions are characterized by prominent alterations in the epithelial capillaries which are coiled, dilated and sometimes duplicated. They may occur in punctate-like or mosaic-like patterns not unlike those present in intraepithelial neoplasia. Differentiation of the two conditions which is facilitated with increasing experience is usually possible. Such appearances, typical of Trichomonas and Neisserian infections, are often of such intensity as to render discernment of an associated serious lesion difficult.

        Ulcers. These can arise from trauma, chemical agents or from microbial origin such as herpes genitalis, syphilitic and tuberculous infection.

        True erosion. Of importance in the interpretation of significance of true erosion is the epithelium at the edge. Most often the edge of such lesions is of normal appearance. If one sees an edge beset with acetowhite epithelium, punctation and so forth, the lesion probably represents loss of the fragile epithelium of intraepithelial neoplasia.

        Atrophic cervicifis (estrogen deficient cervicids). The atrophic epithelium is predictably thin and fragile and upon instrumentation is prone to bleed in the form of petechiae. These changes are usually reversed by estrogen therapy.

        Post-irradiation change The white appearance of the irradiated cervix is beset with bizarre?appearing blood vessels assuming unusual patterns, which may be difficult to differentiate from the atypical vessels of malignant disease.

        Polyps. Polyps can assume appearances characteristic of either columnar epithelium, typical and atypical transformation zone or their combinations.

PLACE OF COLPOSCOPY
Aids localization of the lesion
        CIN lesions almost always occur within the transformation zone which is usually visible in its entirety with or without the use of the cervical speculum. Six states are possible in colposcopic assessment of an abnormal smear report: (i) The lesion is focal and can be seen in its entirety. (ii) The lesion's upper limit is not seen as it disappears into the canal. Such unsatisfactory colposcopic examinations are significantly increased in women aged over 40 years and may exceed 50% of examinations in the postmenopausal woman. (air) The lesion may extend to the vagina. (iv) No lesion is visible. (v) Adequate opinion is prejudiced in the presence of severe acute inflammatory changes. (vi) Concurrent lesions on vagina and/or vulva and/or anus are evident.

Aid in selection of biopsy type
        In the absence of a colposcopy service, biopsy is more rigorously proscribed; conization is recommended. On the other hand, where colposcopy is used the type and size of biopsy such as punch, cone or wedge is adapted to the lesion with great precision. The cone biopsy rate falls sharply in favor of an increase in the rate of the smaller colposcopically directed punch biopsy. Some authorities supplement colposcopically directed biopsy with the use of endocervical curettage. Alternatively the cervical canal can be further evaluated by use of the endocervical brush (cytobrush) ) technique.

Aid in management of abnormal smear in pregnancy
        By reducing the incidence of conization. Aid in selection of treatment for early invasive cancer
The recognition of the colposcopically overt carcinoma. Aid in selection of treatment for CIN and SPI
        There tend to be less hysterectomies, more therapeutic conizations and a distinct trend towards local physical destruction of lesions.

Aid in identification and management of vaginal extension of intraepithelial neoplasia
        The occasional presence of the transformation zone on the vaginal wall may be followed by the appearance of an intraepithelial lesion in this unusual site.

Aid in follow-up of women treated for early invasive carcinoma and intraepithelial neoplasia
        In women treated by the methods of physical destruction, colposcopy is obligatory in their follow?up. After treatment of lesions by conization and hysterectomy, colposcopy is indicated during the first year of the follow?up period or thereafter in the event of an abnormality in the smear report. Colposcopy is also mandatory for prospective follow?up of women with SPI and/or CIN I being observed instead of treated. Spontaneous regression has been noted colposcopically.

Reduction in unnecessary biopsy
        Many clinicians still biopsy red areas seen by the naked eye on the cervix despite the fact that many such areas turn out to be columnar epithelium. A glance through the colposcope usually shows the normality of such conditions and so avoids unnecessary interference.

Aid in research
        A less recognized role for colposcopy is as an aid to clinical and basic research. Great strides in the understanding of cervical carcinogenesis and indeed carcinogenesis in general have been instigated in this way.

        Ref. Coppleson M & Pixley EC Colposcopy of Cervir. In Gynecologic Oncology. By Coppleson M, et al. 2'd ad. Churchill Livingstone, New York 1992, pp. 297-323