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.
The transformation zone is the area of actively maturing epithelium between the present squamocolumnar junction (SCJ) and the original squamous epithelium. This zone is composed of the intermingling of squamous and columnar epithelium. Squamous metaplasia, islands of columnar epithelium, gland openings and Nabothian cysts may be identified. This is shown schematically in the card SCJ Diagram.
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.
Atypical Transformation Zone
Over 90% of cervical neoplasia (CIN and invasive cancer) arises from within the
transformation zone. Colposcopy evaluates this zone for evidence of neoplasia
which is a result of changes in epithelial thickness, nuclear density and vascular proliferation. These changes can be manifested in a variety of patterns including:
epithelium and abnormal vascular patterns.
Original Squamous Epithelium
Squamous epithelium derived from the evolution of columnar cells to squamous
during the first 18-20 weeks of fetal age.
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.
(due to Trichomonas)
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.
Acetic Acid Solution
Acetic acid dissolves mucous and accentuates atypical areas (white epithelium,
punctation, mosaic and atypical vessels) by inducing intracelluar dehydration and coagulation
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.
From the examiner's perspective
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.
Speculum in use
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.
Atrophic changes result from low estrogen levels characteristic of the menopausal
patient. The appearance is that of a typically smooth and thin epithelium. This results in
blood vessels being more readily visible and trauma easily incurred. These changes are
reversible with the use of exogenous hormonal therapy.
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 normal physiologic process by which columnar epithelium evolves into
squamous epithelium. The outermost border is the original squamocolumnar junction (SCJ)
while the innermost border is the present SCJ. This occurs under the effect of several factors including, hormonal stimulation, low pH and trauma.
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.
Gland openings are the persistent appearance of the opening of the endocervical
gland ducts on the squamous epithelial surface of the transformation zone.
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.
Pap test was introduced as a cervical screening test in 1943 by
Dr. George Papanicolaou for whom it is named. It is the evaluation of exfoliated
cells which when stained and examined microscopically, exhibit changes consistent
with a variety of abnormalities including CIN and invasive cancer.
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.
Endometriosis in relation to colposcopy
Endometriosis is the presence of endometrial tissue in locations outside of the
uterus. Though rarely seen under the colposcope, when identified, it appears as a focal
area of hemorrhage or a blue-domed cyst.
Diethylstilbestrol (DES) is a non-steroidal, synthetic estrogen used extensively
from 1940-1971 for complications of pregnancy. When taken antenatally (during the first 20
weeks of pregnancy), the female offspring may exhibit a variety of changes that include
anatomic deformities, histologic abnormalities and colposcopic changes which can affect the
vagina, cervix and uterus.
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.
The presence of columnar epithelium in the vaginal fornices or vagina. When
identified, antenatal exposure to DES should be considered.
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.
CIN - Cervical intraepithelial neoplasia
Cervical intraepithelial neoplasia (CIN) refers to a spectrum of abnormalities of
the surface epithelium. The spectrum includes epithelial changes in the transformation zone
ranging from CIN I (mild dysplasia) to CIS (carcinoma in-situ).
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: Mild Dysplasia
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: Moderate Dysplasia
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: Severe Dysplasia
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.