|Stephen C. Rubin, MD and Ivor Benjamin, MD|
|University of Pennsylvania Cancer Center|
| Last Modified: December 19, 2003
Morphologically there are two types of squamocolumnar junctions (SCJ). The original SCJ is the border where the original squamous epithelium meets the outermost limit of the developing transformation zone. The present SCJ is the innermost border where the maturing squamous metaplasia meets the mucous secreting columnar epithelium.
Over 90% of neoplasia arises from within the transformation zone. Therefore, a colposcopic evaluation of the cervix is not considered adequate unless the transformation is seen in its entirety.
The precise location of the transformation zone varies in relation to the exo and endocervix. This is related to the age of the patient and the degree of squamous metaplasia.
A variety of instruments are available which are specifically designed for directed biopsy of abnormal areas seen grossly or through the colposcope. Another commonly used intstrument during colposcopy, albeit not for biopsy, is the endocervical speculum.
Cervicitis is a non-specific, inflammatory response to a variety of both infectious and non-infectious agents. It is characterized by hyperemia and a vascular pattern sometimes confused with punctation under the colposcope. In contrast to punctation, changes of cervicitis extend well beyond the transformation zone.
Red-free filters (green or blue) create a contrast between blood vessels and their background. This allows for enhanced evaluation of blood vessel architecture as demonstrated below.
This effect peaks approximately 2 minutes after application and fades within 5 minutes. Therefore, acetic acid may need to be reapplied several times during the exam.
Lugol's solution is composed of iodine and potassium iodide in water. It stains the glycogen in mature squamous epithelium a dark brown color. Consequently, areas devoid of glycogen such as immature squamous eptithelium, columnar epithelium, cervicitis, erosion and neoplasia will be non-staining.
The application of Lugol's solution to the cervix is known as the Schiller Test.
The Colposcope is a binocular, low-magnification (7x to 30x) microscope with a light source which is used to visualize the cervix, vagina and vulva. It often contains an integrated camera for photographic documentation of colposcopic findings.
Malignant epithelium with increased metabolic need is accompanied by proliferation of blood vessels. This vascular growth is not symmetric and is often associated with progressively smaller blood vessels. With invasive cancer these vessels can make sharp angulations with either cork-screw, hockey-stick or spaghetti-like patterns. The distance between vessels is often increased resulting in bizarre patterns.
Visualization of the entire transformation zone is mandatory for colposcopic evaluation of the cervix to be considered adequate. At times, the zone is within the endocervical canal. The endocervical speculum is specifically designed to allow for better evaluation in such cases.
It is important to remember that atrophy can result in cytologic changes that mimic high-grade abnormalities (CIN or invasive cancer). It is therefore, important to inform the cytologist of the patient's age and hormonal status.
This term refers to a white plaque visible without magnification and without the application of acetic acid. It is usually elevated from surrounding surfaces with a sharp border and Lugol's non-staining. Histologically, this lesion would reveal hyperkeratosis.
Though leukoplakia in and of itself is not pathologic, an underlying more significant lesion may be present.
Through the colposcope, columnar epithelium appears as a grape-like, mucous secreting three-dimensional structure. Its reddened appearance is secondary to the proximity of blood vessels to the surface. This pattern is best visualized after the application of acetic acid and is Lugol's non-staining.
Histologically, these single-layered columnar cells have a connective tissue core through which runs an afferent and efferent loop of terminal capillaries.
The transformation zone is the area in which squamous metaplasia is actively ocurring and is the most common site for the development of CIN or invasive cancer.
Through the colposcope there is a pattern of a combination of squamous and columnar epithelium. Gland openings and Nabothian cysts may be evident.
Histologically, in the early stages of this process, immature squamous cells push up columnar cells. Eventually, the columnar cells degenerate and there is differentiation into immature and eventually mature squamous epithelum.
Nabothian cysts are inclusions or entrapments of mucous from secreting columnar villae under the developing squamous epithelial surface. The capillaries in such areas are often dilated, but have a normal branching architecture.
Condyloma (acuminatum) are exophytic, warty lesions caused by human papilloma virus infection (HPV). These lesions are often multi-focal and can be located both within and outside of the transformation zone.
It is currently believed that certain subtypes of HPV cause condyloma as described above. Other subtypes, however, are associated with flat condyloma which appear to be part of the etiology of high grade intraepithelial neoplasia and perhaps invasive cancer.
Some infections with HPV are subclinical and are manifested by subtle abnormalities under the colposcope, such as minimally raised, whitened epithelium.
The anatomic abnormalities include cockscomb cervix, cervical collar, pseudopolyp, loss of pars, cervical hypoplasia, vaginal constriction ring and transverse septum. In addition, there are a variety of benign changes of the uterus including T-shaped, (with or without a small cavity) which may result in obstetrical complications.
Histologically, DES exposure in utero has been shown to result in vaginal adenosis. One in a thousand cases of DES exposure result in clear-cell adenocarcinoma.
Colposcopically,there is often a widened transformation zone which with advancing age becomes covered with metaplastic epithelium. During the process of progessive squamous metaplasia, a mosaic pattern or punctation may be seen. However, these changes are rarely associated with CIN, in contrast to the significance to these findings in the non- DES patient.
White (or acetowhite) epithelium refers to the whitened appearance of an area under the colposcope after the application of acetic acid. In contrast to leukoplakia, white epithelium is visible only after the application of acetic acid because it represents epithelium with increased nuclear density. White epithelium is sometimes associated with intraepithelial neoplasia (CIN) and therefore, should be biopsied.
There are three characteristic abnormal vascular patterns found on colposcopic examination. They are mosaic, punctation and atypical vessels.
A vascular change of interconnecting vessels resulting in a cobble-stone or honey- comb surface appearance through the colposcope. This pattern is often associated with CIN and mandates biopsy.
It is a zone of red dots representing stromal papillae and blood vessel loops reaching to the surface epithelium. When this pattern is identified through the colposcope, biopsy is indicated since this pattern may reflect blood vessel changes of neoplasia.
There are characteristic colposcopic, cytologic and histologic findings associated with each grade of CIN.
These findings will be illustrated for each grade of CIN.
Cytologic aberrations seen in CIN include: hyperchromaticity, abnormal chromatin distribution, increased nuclear to cytoplasmic ratio and nuclear pleomorphism. These abnormalities may be seen in exfoliated cells in a Pap smear or in a histologic slide from a biopsy specimen.
Histologically, CIN grading is based upon the proportion of the surface epithelium composed of undifferentiated cells characteristic of the basal layer. Increasing grade is associated with a progressive loss of epithelial maturation.
CIN I or mild dysplasia represents atypical cells with increased nuclear to cytoplasmic ratio and hyperchromatic nuclei present in the lower /3 of the epithelial layer from the basement membrane.
CIN II or moderate dysplasia shows further progression of the nuclear abnormalities with greater involvement of the epithelial thickness. In CIN II, immature basaloid cells occupy the lower /3 to 2/3 of the epithelium.
CIN III or severe dysplasia represents almost total involvement of the epithelium with only one or two layers of mature cells remaining at the surface. When the entire epithelium is involved, the term CIS is applicable.
Histology With all levels of CIN the basement membrane of the epithelium remains intact. Once the membrane is violated, invasive cancer is diagnosed. With very early invasion the term microinvasion applies.