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Abnormal colposcopic findings
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Most of abnormal colposcopic findings develop after the application of an aqueous 3-5% solution of Acetic acid. Impregnation of the cervix with acetic acid solution allows a clear visualization of the cervical epithelium. The mucus is dissolved and within one minute a strict contrast between the normal mucosa (remains unaltered) and any metaplasia or epithelial abnormality (becomes acetowhite) is fully developed, making possible their accurate direct visualization.
Abnormal colposcopic findings can be manifested in a variety of patterns including: leukoplakia, acetowhite epithelium and abnormal vascular patterns (mosaic, punctations, atypical vessels.
(2011 IFCPC colposcopic terminology of the cervix)
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Abnormal Pap smear
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Any PAP smear containing cells that are not within the normal limits (WNL). The degree of this abnormality varies from mild to severe, and the main goal of the PAP test is to accurately detect and correctly interpret these abnormalities
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Abnormal Transformation zone
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Transformation zone (TZ) is the area on the cervix where metaplasia takes place. In colposcopy, it is essential to assess whether Transformation zone is normal or abnormal. Abnormal Transformation zone is presented by variety of epithelial and vascular changes which can be seen as abnormal (atypical) colposcopic findings. Colposcopy evaluates this zone for evidence of neoplasia which is a result of changes in epithelial thickness, nuclear density and vascular proliferation. Over 90% of cervical neoplasia (CIN and invasive cancer) arises from within the transformation zone.
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Abnormal vessels
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In normal TZ blood vessels are usually not visible. Any visible vessels should alert the colposcopist for careful evaluation, whether their appearance is normal or abnormal. Normal vessels could be seen above Nabothian cysts. Vessels should be graded atypical when their branching pattern is not tree-like (from larger to smaller), when they present with highly different shapes and show anastomosis.
Abnormal (atypical) vessels deviate from the normal vascular pattern and appear as irregular in shape with an abrupt and interrupted course and vessels appearing as commas, corkscrew capillaries or spaghetti-like forms. Abnormal vessels are considered a key mark of invasion, however, some benign conditions may display atypical vascular pattern (diabetes, systemic diseases, vasculitis, chronic cervicitis). Each of these conditions requires thorough examination. The frequency of atypical vessels usually increases in parallel with the severity of the lesion, being most common in invasive carcinoma.
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.
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Acanthosis
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Acanthosis is an end result of any process leading in thickening of the epithelium. Acanthosis (epithelial thickening) is a salient feature of all flat HPV lesions (flat condyloma) of the genital system, readily detectable on both colposcopic examination and on light microscopy
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Accuracy of the test
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Acuracy of the test is the agreement between the test and the gold standard. In case of colposcopy, accuracy is the agreement between colposcopy and histology. Test accuracy is measured using calculations for sensitivity, specificity, positive- and negative predictive value.
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Acetic Acid
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An aqueous solution of Acetic acid in 3-5% concentration is commonly used before the colposcopic examination. Acetic acid dissolves mucous in 15-20 seconds allowing a clear visualization of the details and accentuates atypical areas (white epithelium, punctation, mosaic and atypical vessels) by inducing intracelluar dehydration and coagulation of protein. Within one minute, a strict contrast between the normal mucosa (remains unaltered) and any metaplasia or epithelial abnormality (becomes acetowhite) is fully developed, making possible their accurate direct visualization.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.
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Acetowhite epithelium
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Acetowhite lesions comprise a wide variety of both benign (metaplasia), premalignant (CIN) and malignant lesions and therefore it is not a specific diagnostic colposcopic pattern. In case of precancer/cancer, the intensity of the acetowhite staining correlates with the severity of the lesion.
Acetowhite (or white) 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.
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Adenocarcinoma of the cervix
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Adenocarcinoma is the one of the two main histological types of cervical cancer, arising from the glandular tissue of the endocervix. A large number of different histological subtypes of cervical adenocarcinoma exist, some with substantial prognostic implications (see: WHO histologic classification)
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Adequate colposcopy
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Colposcopic examination is adequate if the whole cervix is accessible and if the entire Transformation zone together with SCJ can be visualized.
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Aided visual inspection (AVI)
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A method of examination of the cervix in a dark room after application of 3-5% acetic acid to detect aceto-white areas, using illumination provided by a chemiluminescent light source in the upper blade of the vaginal speculum (speculoscopy). Sensitivity and specificity appear to be comparable to that of VIA. However, in view of the additional resources needed, it is an unlikely option as a primary screening test in developing countries.
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AGUS
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Atypical glandular cells of undetermined significance (AGUS) is the term introduced by the Bethesda System (TBS) to denote a condition where the interpreter of the PAP test cannot determine for sure the significance of the abnormal glandular cells in the smear. Recent data suggest that AGUS is a manifestation of a significant glandular abnormality more frequently than ASCUS designates a significant squamous cell lesion.
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AIN
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Anal Intraepithelial Neoplasia (AIN) is a term used to grade the cancer precursor lesions of the anus. AIN lesions are divided into three grades of severity; AIN I, II and III. Like in other anogenital squamous cell cancer, HPV involvement in AIN and anal cancer is firmly documented, being most common in women who have precancer lesions at other genital sites (CIN, VIN, VAIN) as well as in HIV-infected males.
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AIS
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Adenocarcinoma in situ is the immediate precursor of cervical adenocarcinoma. AIS was first described in 1953, but its acceptance as a separate entity took some time. Precursor lesions for cervical adenocarcinoma (Glandular cevical intraepithelial neoplasia-GCIN) are currently classified in two grades: low-grade GCIN and high-grade GCIN. The latter are equivalent to AIS, whereas low-grade glandular precancer lesions comprise all lesions with less severe atypia than AIS.
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Anal wart
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Anal wart is condyloma in the anus. Anal warts are typically exophytic type of Condyloma acuminatum, but also flat HPV lesions do occur in the parianal region and in the anal canal. Most frequent in immunocompromised individuals as well as in male homosexuals.
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Angiokeratoma
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Angiokeratoma is the most frequent vascular tumor of the vulva. Indeed, vulva is the predilection site of these benign vascular lesions of the skin. The lesion is most common in women between 20-40 years of age, and the most frequent site is the labium major.
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ASCUS
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Atypical squamous cells of undetermined significance (ASCUS) is a term introduced by the Bethesda System (TBS) to denote a condition where the interpreter of the PAP test cannot determine for sure the significance of the abnormal cells in the smear. This category of smears has significantly increased by the introduction of TBS, and currently consists some 10-25% of the smears in some laboratories. ASCUS is a heterogeneous category including both benign, reactive and premalignant cellular changes, and as such a significant source of cost increase in the PAP test screening, while being an equivocal diagnosis that needs to be confirmed by other diagnostic methods (triage of the patient). The currently used Bethesda terminology devides ASC-US to ASC-US and ASC-H (see The Bethesda cytologic system 2014).
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Atrophic squamous epithelium
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Atrophic changes result from low estrogen levels characteristic of the menopausal patient. The appearance of atrophia is 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.
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Atypical glandular cells
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see AGUS
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Atypical metaplasia
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Atypical metaplasia is an epithelial change also known as atypical reserve cell hyperplasia. This term should be reserved only for the thin metaplastic epithelium that shows cellular atypia from the very beginning. This change is regarded by some to represent the earliest manifestation in the development of a CIN lesion.
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Audit
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A quality assurance measure. Audit of colposcopy is considered an essential element of the quality assurance aiming to continuous improvement of colposcopy service. To be efficient, audit must be systematic and include standards (see below) of quality against which the performance of the colposcopy can be compared and changes implemented in cases of sub-optimal performance.
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Basal membrane (BM)
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Basal (basement) membrane (BM) is an anatomic structure between the epithelium and its underlying connective tissue stroma. Epithelial cells are attached to BM through different matrix proteins and receptors, communicating the interactions and signalling between these two structures. The main constituents of the BM include collagen IV and laminin, which are helpul in its specific visualization using specific antibodies and immunohistochemical techniques.
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The Bethesda System (TBS)
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The Bethesda System is a reporting system for cervical or vaginal cytologic diagnoses introduced by the National Cancer Institute (USA) in 1988, revised in 1991 and updated in 2001. The Bethesda system (TBS) was introduced to establish uniform terminology and standardize diagnostic reports. In addition, it introduced a standardized approach for reporting if an individual specimen is adequate for evaluation. Not less important, providing uniform terminology, Bethesda system provides guidance for clinical management.
To achieve its goals, this classification essentially describes three types of findings: 1) Within normal limits (as described cytologically). 2) Atypical squamous cells of undetermined significance (ASCUS). 3) Cellular changes suggesting; a) a low-grade squamous intraepithelial lesion (LSIL) or b) a high-grade squamous intraepithelial lesion (HSIL). Further sub-classifications relate to HPV, glandular abnormalities, and squamous metaplastic components. This system has also attempted to limit the number of inconclusive diagnoses by creating the ASCUS grouping which includes those inconclusive smears in which a distinction cannot be made between CIN and unusual reactive changes. Before the introduction of TBS, such smears were estimated to account for between 3% and 10% of screened women. After a few years of experience with TBS in practice, however, the ASCUS and AGUS problem has exploded, such smears currently representing the outrageous 20-25% of all cervical smears.
During the past decade there has been substantial change in the realm of cervical cancer screening, which, coupled with the experience gained with liquid-based technologies, automation, biomarkers, and other advances, led to consideration of another update which was published in 2014. (See:The 2014 Bethesda System and Bethesda Atlas, Third edition (Nayar R, Wilbur DC (Eds). The Bethesda System for Reporting Cervical Cytology. Definitions, Criteria, and Explanatory Notes . Springer, 2015)
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Biopsy
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A sampling of a piece of tissue for histopathological examination. Biopsy from the uterine cervix is taken by using a small punch under direct colposcopy control (directed punch biopsy). Another option is an excisional biopsy, performed either using a small scalpel (which requires suturation of the borders) or loop electroexcision.
Biopsy is the gold standard in the evaluation of the performance of all other diagnostic tests (like colposcopy, cervicography, HPV testing, etc) in the detection of cervical cancer and its precursors. Due to the inherent complexity of the transformation zone (TZ), the correlation between colposcopic biopsy and cone biopsy is far from perfect, which is important to realise in all diagnostic work.
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Bowenoid papulosis
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Bowenoid papulosis (BP) closely resembles its extragenital counterpart, Bowen's diaease (BD). By definition, BD is an intraepithelial neoplasia corresponding to CIS, characterized by a full-thickness disorganization of the epithelial cell polarity, hyperchromatic nuclei and large number of abnormal mitotic figures. Compared with classical BD, BP usually shows a lesser degree of epithelial atypia.
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Carcinoma in situ
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An intraepithelial lesion of the most severe grade, the immediate precursor of true carcinoma. CIS represents the most severe category of the dysplasia/CIS nomenclature used to classify the precancer lesions. This nomenclature was later replaced by Cervical intraepithelial neoplasia (CIN) terminology which combines severe dysplasia and Carcinoma in situ into the single entity CIN 3. As precursor lesion for cervical cancer, Carcinoma in situ (previously FIGO stage 0) was excluded from the latest FIGO classification of invasive cervical cancer (FIGO 2009).
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Cervical cancer
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Cervical cancer is the second most frequent malignancy in women world wide and number one cause of death from cancer in the developing countries. This term refers to all histological types of epithelial cervical malignancies, unless otherwise specified. Annually some 450.000 new cases of cervical cancer are detected, and over 200.000 women lives are lost due to this disease. In principle, cervical cancer is a preventable disease as demonstrated by the most successful organised screening programmes based on early detection of cancer precursor lesions (CIN) by the PAP smear.
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Cervical cautherisation
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Cautherisation is a locally destructive treatment used to eradicate different cervical lesions by electric cautery or diathermy. The technique was in widespread use in the 1960's, when commonly practised in the treatment of cervical erosions (ectropion).
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Cervical glands
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Cervical glands are branching invaginations (crypts) of mucus secreting collumnar epithelium into the cervical stroma. Crypts are elongated, covered with the same epithelium as well as branching tunnels and epithelium lining the cervical canal on the surface. Although often called glands, their structure has no real structure of a gland, because there is no evident in the way that leads to the acinus. They have connection to the inner surface of endocervical canal and empty viscous alkaline mucus into the lumen.
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Cervicitis
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Cervicitis (inflammation) may be the result of physical and chemical trauma or infection. It is characterized by hyperemia and a vascular pattern which is colposcopically similar to punctations. However, these inflammatory punctations are not present on white basis, but on hyperemic, red surface. In acute cervicitis collections of inflammatory cells below the epithelium may be seen as red spots described as "strawberry like" appearance.
After repeated inflammation and tissue necrosis, the lesions are repaired and necrotic tissue is eliminated. The newly formed epithelium has numerous vessels, and connective tissue proliferation results in fibrosis of varying extent. In clinical practice, this condition is described as chronic cervicitis.
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CIN
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CIN is the abbreviation for Cervical Intraepithelial Neoplasia, a terminology used to classify cervical cancer precursors, introduced in the late 1960's. Three categories of CIN exist, known as CIN 1, CIN 2 and CIN 3. The advantage of the CIN classification is that it clumps together the severe dysplasia and carcinoma in situ lesions, the distinction of which is highly arbitrary and poorly reproducible.
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 1 (mild dysplasia) to CIS (carcinoma in-situ).
There are characteristic colposcopic, cytologic and histologic findings associated with 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 1 or mild dysplasia represents atypical cells with increased nuclear to cytoplasmic ratio and hyperchromatic nuclei present in the lower third of the epithelial layer from the basement membrane.
CIN 2 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 thirds to 2/3 of the epithelium.
CIN 3 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.
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Cold coagulation
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Cold coagulation is the method that has been widely used in the treatment of cervical cancer precursors. The instrument (Semm cold coagulator) was introduced into gynaelocologic practice in 1966. The name comes from the fact that the recommended temperature is much less (120-160F below the boiling temperature) as compared with that (400-1500F) used in electrocauterization. The method is based on the use of thermoprobes heating the tissue to 120C and resulting in boiling of the treated tissue. A thermocoagulation of 30 seconds at 120C usually results in the depth of destruction of at least 4mm within the cervix.
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Collins test
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Collins test is a test used in the examination of the vulva on colposcopy. In Collins test, toluidine blue is used to demarcate the vulvar lesions. Toluidine blue (supravital staining) is a nuclear staing fixing the nuclei of superficial cells when applied in vivo. All foci of nuclear activity will retain the colour and become stained. Unfortunately, the test is not specific enough to make distinction between benign and precancer lesions.
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Colposcopy
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Colposcopy is a medical diagnostic procedure to examine an illuminated, magnified view of the cervix and the tissues of the vagina and vulva. Colposcopic examination involves the use of a magnifying instrument to examine the epithelium and vasculature of the uterine cervix for the purpose of detecting neoplasia and identifying abnormal tissue for biopsy.
To understand how preinvasive cervical lesions can be detected by colposcopy, the basic knowledge of the histology and biology of the cervix it is essential. Most of abnormal (atypical) colposcopic findings develop after the application of an aqueous 3-5% solution of Acetic acid.
Variations in the quality and quantity of atypical colposcopic findings help in differentiating cervical intraepithelial neoplasia (CIN) from physiological, benign, inflammatory, infective and reactive changes. CIN exhibits certain morphologic features that can be identified during a colposcopic exam. These features quantitatively and qualitatively differ related to the histological grade of the lesion.
Colposcopy is an essential triage method for the management of women with abnormal cytology. It allows identification, localisation and delineation of preinvasive lesions of the cervix. Colposcopy has changed the management of CIN, enabling directed biopsy to confirm the diagnosis, exclude the invasion and cosequently to allow more conservative techniques to be applied. It must be performed prior to any treatment of CIN. Today, colposcopy is not only the tool to evaluate the abnormal cervical smear. It has an irreplaceable role in the follow-up, as well.
Colposcopy has its advantages, but also its limitations.
Advantages of colposcopy:
- non-invasive,
- repeatable,
- high accuracy in detecting CIN 2+,
- exact localization of atypical lesion,
- can be applied not only to cervix,
- enables diagnostics of different benign conditions and
- essential for management (treatment & follow-up).
Limitations of colposcopy:
- not a screening method,
- subjectivity,
- low specificity, particularly for low-grade CIN,
- the more severe the lesion, the higher the specificity and
- requires specific training, accreditation and quality control.
Colposcopy requires long-term experience to acquire and expertise in colposcopic pattern recognition. It should never be forgotten that the primary goal of the colposcopist is to ensure that the invasive disease is not missed. This goal can be acheived only if colposcopy is performed by trained and experienced colposcopists, who audit their work and keep their colposcopic assesment and colposcopically directed treatment with internationally agreed standards.
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Colposcope
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The Colposcope is a binocular, low-magnification (7x to 30x) microscope with a light source which allowes a magnified and stereoscopic viewing of the cervix through a speculum. It is also used to visualize the cervix, vagina and vulva. It often contains an integrated camera for photographic documentation of colposcopic findings. The original instrument was developed by Hans Hinselmann already in 1925, but gained popularity as a diagnostic tool in Western Europe and Americas only during the past two-three decades.
In the simplest form, the colposcope was a binocular instrument mounted on a stand. The modern colposcope is a microscope providing illuminated magnification of the cervix ranging from 6x to 40x. Resolution is more pure with the highest magnifications, and those of 10x to 16x are generally used. In its modern setting, the instrument can be attached to the wall, ceiling or actual colposcopy couch. The colposcope lens has a focal length ranging between 200mm and 300mm, and occasionally less, i.e. 125mm (to be used with the saline technique to demonstrate the vascular patterns). The instrument is a binocular with eye-piece lenses capable of 6x to 12x magnification. Different accessories (tilting mechanism, fine focus, side arm for SLR- or video camera) are an integral part of the modern colposcope. Not infrequently, another attachment includes the green filter, used to improved visualisation of the blood vessels.
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Colposcopic score
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Colposcopic score (index) is a grading system used to evaluate the severity of the colposcopic abnormalities. A number of scoring systems have been introduced (e.g. Coppleson & Pixley, Reid) during the past decades. The classical five criteria included in such scoring systems include: thickness, colour, surface contour, vascular atypia and iodine staining. More recently, the type of peripheral margin has replaced the opacity and surface contour in the newly introduced scoring systems. Each of the criteria will be assigned a scoring of 0, 1 or 2, ending up with the maximum score of 8. Ideally, colposcopic scoring should allow categorising the colposcopic pattern as normal, insignificant and clinically significant ones. In most cases, however, biopsy is mandatory to establish the correct diagnosis.
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Collumnar epithelium
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Collumnar epithelium is the second main type of epithelium in the uterine cervix. The entire endocervical canal and the endocervical glands are covered by single columnar epithelium. In the squamo-columnar junction, the two epithelia (columnar and squamous) are in contact with each other.
Histologically, these single-layered columnar cells have a connective tissue core through which runs an afferent and efferent loop of terminal capillaries.
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, due to the absence of glycogen.
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Condyloma
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Condyloma is a common name used to denote all epithelial lesions in the genital system induced by Humanpapilomavirus (HPV). The term Condyloma is derived from the Antiqity, when it was described to be a particularly common genital lesion known as a venereal or genital wart. In 1976 it was realized that HPV is also the causal etiological agent of other morphological types of lesions, distinct from the usual exophytic condyloma: subclinical lesions presented as flat condyloma and microcondyloma.
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 condyloma acuminatum are caused by certain subtypes of HPV. 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.
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Congenital anomaly
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Congenital abnormalities of the cervix are relatively rare conditions calculated that and occur as one of the following problems: failure of fusion of the MŸllerian ducts during embriological development which results in a duplicated (two cervices) or septated cervix, congenital agenesis or dysgenesis or abnormalities related to In utero exposure to DES.
From the point of colposcopy is necessary to think of those congenital malformations of the uterus which are two of the cervix. The association of a double uterus with bilateral synchronous premalignant and malignant cervical changes is even more uncommon. Usually in these cases the disease is developing on the cervix, which belongs to the vagina, which is more often functional. If both cervical (in one or two separate vagina) exposed to HPV infection, it can be expected that both may be at risk for developing the diseas
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Congenital transformation zone
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Congenital metaplasia is a form of squamous metaplasia that is seen in about 5% of women. It is difficult to understand the cause of its existence and is often not recognized examination. During embryogenesis cuboid vaginal epithelium is replaced by squamous epithelium. It is thought that this process begins at the caudal (lower) end of the urogenital sinus. If the conversion from cuboidal to squamous cells which goes upwards stops at a certain height of the vagina or on the periphery of the cervix, cuboid epithelium is subjected to the process of squamous metaplasia.
This type of transformation zone is developed during intrauterine life and before puberty. This is why these congenital fields, which are not exposed to mutagens during active metaplasia, have a minimal risk of neoplastic change.
The changes are primarily confined to the cervix, but in 4% of women epithelium of this type may be extended to the vagina, usually front and rear. Fields of congenital transformation can be different in size, from small around the cervical canal to those which fully spread to the upper vagina. Colposcopic picture varies from subtle findings (mosaic, punctations or AW epithelium) to dramatic images of atypical epithelium, usually resistant to glicogenation.
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Conization
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Conization is an operation introduced in the early 1960's as an alternative to hysterectomy in the treatment of cervical cancer precursor lesions. Originally made blindly (without colposcopy) by cold knife, cone biopsies were large and not infrequently induced different complications (abortion, infertility, scarring). Modern techniques such as laser or LLETZ, currently more often performed, result in less scaring and better functional recovery of the cervix. More important, after these techniques SCJ remains visible during colposcopic examination.
The aim of this operative procedure is the excision of the entire transformation zone with an extension into the endocervical canal to remove the entire lesion. The request for more safe and precise procedures (i.e. smaller cones) paved the way to the more widespread use of colposcopy. At present, conization is invariably made under colposcopic control.
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Cryotherapy
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Cryotherapy is another method used for the treatment of CIN, based on freezing of the lesion by application of special cryoprobes. In this technique, anesthesia is not usually required. The equipment consists of a hand-held probe terminating in the hollow tip which can be changed to match the size of the cervix. The cryoprobe tip is cooled by gas and when hold against the area of treatment, results in the local destruction of the lesion by freezing and cell death.
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Cytobrush
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Cytobrush is an instrument used in sampling of endocervical cells for cytological examination. The instrument is a small brush introduced into the endocervical canal and rotated 360 degrees to obtain cells from the entire circumference. A variety of different models with different brand names are commercially available, showing little difference in their performance. Cytobrush is also used to sample the cellular material for HPV testing, e.g. in Hybrid Capture II test, where the sampling kit includes a small cytobrush
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Cytology
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The discipline that examines the cellular (instead of tissue) samples taken from different mucosal sites, cervix and vagina included. Also called clinical cytolog
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Cytopathic effect
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Cytopathic effect (CPE) is a characterisrtic and specific effect of a virus on the infected target cell. Among gyneacological infections, two pertinent examples include Herpes simplex virus (HSV) and Human papillomavirus (HPV). CPEs of these two viruses are completely different and specific enough to enable the correct diagnosis in the exfoliated cells in the PAP smear.
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Decidual reaction
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Decidual reaction is an alteration characteristic to pregnancy. Apart from the endometrium of pregnancy, decidual reaction is encountered in the stroma of the uterine cervix as well, where it can appear in different types of manifestations on colposcopic examination.
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Decidual polip
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During pregnancy the cervical stroma frequently undergoes focal decidual change and this reaction may be so extensive as to form a polypoid protrusion of the cercical stroma known as decidual polyp. The decidual change is typically subepithelial in location, often disrupting the overlying epithelium. The histologic appearance may be misinterpreted as carcinoma since decidual stromal cells have large nuclei, prominent nucleoli and abundant cytoplasm, imparting an epitheloid appearance.
The risk of abortion and preterm delivery associated with polypectomy during pregnancy is greater in patients with decidual polyps, because injury to the endometrial mucosa and/or inflammation may affect the endometrium. Therefore it is safer not to remove cervical polyps during pregnancy, except in cases in which the polyps are suspected to be malignant. Decidual polyps observed early in pregnany usually spontaneously disappear through the process of necrosis.
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DES (diethyl stylbestrol)
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DES (dyethyl stylbestrol) is a synthetic oestrogenic compound prescribed for pregnant women between 1938 to early 1970's in the misbelief that it prevented miscarriages and premature labor. It was subsequently documented that DES had significant side effects. 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.
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Dyskariosis
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Dyskariosis is a term used in cytology to define morphologically altered cells derived from a cancer precursor lesion or invasive cancer. The main criteria of dyskaryosis is the enlarged nuclear:cytoplasmic ratio. This ratio increases in parallel with the increasing dyskaryosis when the lesion progresses towards an invasive disease. This is manifested by 1) an increase in the nucler size, and 2) decrease in the size of the cell, inevitably leading to increased nucler:cytoplasmic ratio. Accordingly, mildly dyskaryotic cells are usually larger than more severely dyskaryotic cells in the smears.
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Dysplasia
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Dysplasia is an epithelial abnormality that by definition represents a precancerous lesion. Dysplasia is defined by light microscopic examination of the biopsy (not cell sample), and graded into three grades of severity; mild, moderate and severe dysplasia. The concept of dysplasia-carcinoma in situ was the first classification used to categorise the process of cervical carcinogenesis, and this term has subsequently gained a widespread use in the common language of histopathology.
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Ectropion (cervical ectopy)
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Ectropion (cervical ectopy) is the presence of columnar endocervical epithelium on the exocervix. In normal situation, the squamo-columnar junction (SCJ) is situated at the external os, whereas in ectropion, the SCJ is located outside the external os, on the exocervical site. Ectropion is extremely common among women in adolescence and during pregnancy. The dynamic and physiological process of metaplasia gradually contributes to the fact that the SCJ moves higher towards the endocervix in parallel with the increasing age
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Edge definition
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An important aspect of colposcopic examination is looking at the margins of the lesion. It could give an important clue about possible severity of the lesion. While low-grade lesions usually have ill-defined margins, merging with the surrounding normal epithelium, imperceptibly, the edge definition comes sharper with increasing severity of the lesion. In high-grade lesions there may be more than one border within the abnormal TZ (inner borders), demarcating lesions with different severity from each other (i.e. low-grade CIN from high-grade CIN).
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Electrocoagulation
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Electrocoagulation is a simple and effective method which has been extensively used in the treatment of CIN lesions. The equipment is relatively inexpensive, consisting of a standard diathermy delivery unit producing 40-45W. A needle electrode is used to perform a series of radial cuts to 2-3mm beyond the iodine-negative areas, followed by segmentation of the cervix further down to 5-7mm. The segments are removed by using a ball electrode, resulting in a conical crater at least 7mm deep.
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Endocervical curettage
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Endocervical curettage is another important and powerful diagnostic tool in the assessment of cervical cancer precursors. Not infrequently, the lesions extending to or seating deep in the endocervical canal are not detected in colposcopic biopsy. In cases of discrepant findings in the PAP test (high-grade) and biopsy (negative or equivocal), endocervical curettage is frequently practised to solve the puzzle. Cone biopsy is an optional tool in such cases. Endocervical curettage is frequently needed to disclose cervical adenocarcinoma and its precursor lesions (AIS, CGIN).
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Endocervical Speculum
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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.
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Endometriosis
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Endometriosis is the presence of endometrial tissue in locations outside of the uterus, including the cervix. Although the exact pathogenesis of endometriosis in the cervix remains speculative, implantation of the endometrial tissue is the most likely mechanism. On colposcopy, endometriosis may appear as an ulcer or a cyst.
Though rarely seen under the colposcope, when identified, it appears as a focal area of hemorrhage or a blue-domed cyst.
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Endophytic condyloma
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Another morphologically distinct entity caused by HPV in the uterine cervix. This lesion is also known as inverted condyloma, characterised by an in-depth penetration (not true invasion) into the underlying stroma or glandular openings. This flat-surfaced lesions is otherwise similar to flat condyloma, with all the typical cytopahic effect of HPV readily discernible.
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Erosion
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Erosion is a common lesion in the cervix. Depending on the size, the lesion can be called erosion or ulcer. Both erosions and ulcers can arise spontaneously, but normal epithelium is less vulnerable than abnormal epithelium or atrophic epithelium.
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European Federation of Colposcopy (EFC)
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European Federation of Colposcopy (EFC) was founded in 1999. The Founder President was Joe Jordan from U.K. and the first Secretary was Renzo Barasso from France. EFC held its first congress in Rhodes in November 2000
Objectives of EFC are:
- To promote the best possible standards of Colposcopy in Europe.
- To agree Minimal Standards of Training for Colposcopy in Europe.
- To agree Minimum Standards for Treatment of CIN in Europe.
- To support the International Federation for Cervical Pathology and Colposcopy (IFCPC) in its aims to promote colposcopy worldwide.
EFC web site: www.e-f-c.org
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Excisional technique
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Excision is a joint name for all techniques of CIN treatment, where the lesion is removed as a whole (intact block) instead of local destruction.
- Indications for excision are:
- unsatisfactory colposcopic examination,
- large lesions,
- non-correlating cytology & colposcopy and
- recurrent disease
Colposcopy is essential in planning the treatment and choosing the method that should be used. There is no obviously superior conservative surgical technique for treating and eradicating cervical CIN. This means that both ablative and excisional techniques have nearly the same outcome. However, excision is preferred by many colposcopists because of better histopathological assessment.
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False negative
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False negative PAP smear, colposcopic or histopathological examination incorrectly interpreted and reported as normal, despite the fact that a pathological process exists.
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Fibroepythelial polyp
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Fibroepythelial polyp is a benign lesion frequently found in the vulva. Also known as skin tag. This solitary lesion is composed of connective tissue stalk covered by squamous epithelium that can be atrophic or acanthotic. The etiology of this innocent lesion is unknown.
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Flat condyloma
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Flat condyloma is a morphological manifestation of HPV infection, distinct from the exophytic Condyloma acuminatum or genital wart. The association of flat condylomas with HPV was described only in 1976, while realizing that the similar cytopathic effects (CPE, i.e. koilocytosis) of this virus are shared by both type of lesions.
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GCIN
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Glandular Cervical Intraepithelial Neoplasia (GCIN) is a precursor lesions for cervical adenocarcinoma. Currently, two grades of GCIN are differentiated; low-grade and high-grade. The latter are equivalent to adenocarcinoma in situ (AIS), whereas low-grade GCIN denote all lesions with less severe atypia than AIS.
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Gartner's cyst
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A Gartner's cyst (sometimes incorrectly referred to as vaginal inclusion cyst) is a benign vaginal cystic lesion that arises from the vestigial remnant of a mesonephric duct or Gartner's duct. This duct is present during embryonal life, but most often disappears after birth. If parts of the duct remain, they may collect fluid and develop into a vaginal wall cyst later in life.
Gartner's cyst is typically small asymptomatic cysts that occur along the lateral walls of the vagina, following the course of the duct. It can, however, enlarge to substantial proportions and be mistaken for urethral diverticulum or other structures.
There is a small association between Gartner's duct cysts and metanephric urinary anomalies, such as ectopic ureter & ipsilateral renal hypoplasia.
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Genital wart
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The term used to denote exophytic Condylomata acuminata. Flat condylomas are not usually called genital warts. Synonym is venereal wart.
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Giant condyloma
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Giant condyloma is also known as Buschke-Löwenstein tumor. Giant condylomas are extensive lesions with a distinct histological pattern where exophytic papillary structures are intermingled with downgrowth of an acanthotic epithelium into the underlying connective tissue. Criteria of malignancy should be absent in genuine giant condylomas, whereas Buschke-Löwenstein tumors resemble more closely the verrucous carcinoma in their histological appearance and clinical behavior
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Gland openings
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Gland openings are the persistent appearance of the opening of the endocervical gland ducts on the squamous epithelial surface of the transformation zone.
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Glandular neoplasia
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Glandular neoplasia ia a common name to all tumours arising from the glandular tissues. In the cervix, glandular neoplasia refers to both benign, premalignant and malignant tumours of the endocervical glandular tissue.
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Grading of colposopic finding
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Ideally, colposcopic examination should allow categorizing abnormal colposcopic pattern as low grade or high grade colposcopic finding
Grading of colposcopic findings takes into account:
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Granulation tissue
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Granulation tissue is the overgrowth which appears as a reddish accumulation of tissue, usually localized at the suture line after surgical interventions. Histology is identical with granulation tissue elsewhere, composed of proliferating small capillaries embedded in a loose connective tissue containing an extensive inflammatory cell infiltrate.
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Green filter
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Green filter is an attachment used in the colposcope for improved visualisation of the blood vessels. Green filter is used in context with saline colposcopy, where higher magnifications (x25) are used to inspect the details of capillaries, resulting in enhanced visibility of the vessels.
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Guidelines
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Guidelines are systematic recommendations for an optimal performance of a test or other procedure, given for the users to select
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Herpes simplex infection (HSV)
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HSV (Herpes simplex virus) is a causative agent of genital herpes. Two types of HSV exist (HSV1 and HSV2). Genital lesions are usually caused by HSV2, with a minority of infections caused by HSV1. Before the HPV era, HSV was the suspected etiological agent of cervical carcinoma, but no firm evidence to substantiate this concept has been obtained despite intense studies during the 1960's and 1970's.
Typical symptoms of genital herpes are itching and sensitivity of the mucous membranes. The disease is presented with painful ulceration of the vulva and lower vagina, but when changes affect the cervix, is usually painless and can be found only by examination or colposcopy. In addition to pain, generalized weakness can occur during primary infection.
Epithelial changes can be easily recognized colposcopy. Infection begins in the parabasal cells of squamous epithelium. It usually develops as a small group of vesicles (3-5 mm in diameter). Thin vesicles that can be seen in the initial infection at the cervix do not last as long as the ones on vulva. They are quickly sprayed, leaving a few superficial circular ulcers with a red halo. Vesicles often merge and after their splash an ulcer may appear. On the ectocervix greater and deeper ulcers than those normally seen on the vulva are more likely to develop. On the base of the ulcerations there is a necrotizing exudate. Later, the exudate detaches, leaving large inflammatory areas that colposcopically may look atypical, even suspicious to invasive cancer.
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High grade squamous intraepithelial lesion (H-SIL)
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High-grade squamous intraepithelial lesion (HSIL) is one of the categories of cellular abnormalities introduced by TBS. HSIL usually represents cells derived from severe epithelial abnormalities, known as cervical cancer precursors (CIN 2 and CIN 3). These are commonly called as high-grade abnormalities as well.
Colposcopic features suggestive of high- grade disease (major changes) are:
- A generally smooth surface with sharp outer border
- Dense acetowhite change, may be oyster white whuch appears early and is slow to resolve
- Iodine negativity
- Coarse punctation and wide irregular mosaic of different s
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Human Papilloma virus (HPV)
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The single most important human tumour virus, inducing both benign epithelial proliferations (warts and papillomas) as well as premalignant and malignant epithelial lesions at different body sites. For some reason, female genital tract seems to be particularly vulnerable. More than 140 different HPV types are currently distinguished, categorised into low- and high-risk types, according to their biological significance. The high-risk types are the single most important etiological agents of cervical carcinoma. HPV involvement has been firmly documented in squamous cell carcinomas at other genital sites as well, including those of the vagina, vulva, anus and penis. Recognition of the association of HPV with genital cancer has revolutionized the research, diagnosis and management of these lesions during the past 25 years. HPV typing by modern molecular diagnostic tools is a frequently used method of triaging the woman with equivocal PAP smear or colposcopy.
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HPV test
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Detection of Human papillomavirus genome (DNA or RNA) in the biopsies or cellular samples taken for that purpose from the cervix or elsewhere in the genital system. A wide variety of different molecular techniques exist for HPV testing and type-specific analysis. These technique vary in their sensitivity and technical performance, and only few are suitable for large-scale clinical use e.g. in organised population-based screening
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Hystiocytosis of the cervix
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Langerhans cell histiocytosis (LCH, histiocytosis X) of the female genital organs is a very rare disease. It can affect the vulva, vagina, cervix, endometrium and ovary. Although LCH of the genital organs can occur at any age, it is most common in young adults.
In case cervix is affected, it is enlarged, pink, with an uneven surface. Similar, uneven changes can be observed in the vaults of the vagina. By palpation cervix is firm and painless. Colposcopically, lesions from 5 to 20 mm in diameter, diffusely distributed and covered squamous epithelium can be seen at the ectocervix. They are described as yellowish, elevated areas which give an impression of subepithelial infiltration. Vascularization of the areas of changes is increased, but typical. On the surface of these changes, true erosion of epithelium can be seen, which is a result of necrosis.
Clinically LCH may resemble either the primary neoplasia, or various inflammatory lesions. The diagnosis is made only by histological examination of tissue samples by light microscopy, immunohistochemistry and electron microscopy. Histologically, the differential diagnosis is important to exclude venereal and other inflammatory diseases.
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IFCPC - International Federation of Cervical Pathology and Colposcopy
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The International Federation for Cervical Pathology and Colposcopy (IFCPC) was founded in Mar del Plata Argentina in 1972.
The main goals of the Federation are to:
- stimulate basic and applied research and the exchange of knowledge in the field cervical pathology and colposcopy
- stimulate the creation of national societies;
- contribute to the standardization of terminology and evaluation of diagnosticbnd therapeutic procedures in the field of cervical pathology and colposcopy; hold World Congresses at regular intervals, each held successively in a different country;
- take part in and, where possible, sponsor regional or national congresses organized by affiliated societies;
- where possible, to help co-ordinate the dates of conferences which are relevant to the field of cervical pathology and colposcopy;
- collaborate with affiliated societies whenever joint scientific action is appropriate; and,
nurture international and regional collaborative efforts related to training or research in cervical pathology and colposcopy.
Web site of the Federation is: www.ifcpc.org
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IFCPC colposcopic nomenclature
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In the attempt to facilitate international communication related to colposcopic terminology, International Federation of Colposcopy and Pathology of the Cervix has formed a Committee for nomenclature, which adopted the first terminology in 1981.
With the improvement of knowledge and the use of the first terminology in practice, it became clear that it did not satisfy all requirements of colposcopy. It was felt that the old terminology was not appropriate any more, to describe all colposcopic appearances in the broad category of atypical Transformation Zone. This lead to the development of international nomenclature in colposcopy, which was approved by IFCPC during the 8th world congress in Rome, in 1990. This classification was used for more than two decades. It was based on the fact that most of CIN lesions develop in the Transformation zone. It also recognized abnormal colposcopic pictures, such as HPV changes, often appearing in original squamous epithelium and having small or no neoplastic potential.
However, this classification has also not been ideal and was replaced by new Colposcopic terminology of the Cervix, Vagina and Vulva was adopted during the 14th World congress of the International Federation of Colposcopy and Cervical Pathology which was held in Rio de Janeiro, Brasil from 4-7, July 2011.
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Immature squamous metaplasia
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Metaplasia is usually categorized as immature and mature metaplasia. On colposcopic examination, this dynamic process of squamous metaplasia can be clearly observed and followed-up from initial changes visible on the top of the columnar epithelium papillae to the stage of immature squamous epithelium
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Inadequate colposcopy
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Inadequate colposcopic examination is the one where the cervix is not accessible or when the entire cervix, including Transformation zone and SCJ can not be visualized. Cervix can not be reached in case of vaginal stenosis caused by neoplasia, irradiation, severe atrophy, previous surgery on the lower genital organs, due to pelvic tumors or congenital malformations (septum) and some dermatologic diseases such as Lichen planus. Colposcopic examination is also inadequate if the cervix is obscured by discharge or the blood.
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Inadequate smear
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Any smear considered unsuitable for reliable diagnosis. The reason can be a sampling error or error in specimen preparation.
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Inner border sign
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Inner border (inner demarcation) is a rare colposcopic phenomenon but highly specific for CIN 2 or 3 in young women (usually younger than 35 years). It is a sharp acido-white (dull, oyster white area) demarcation within a less opaque AW area. The peripheral area represents an earlier, minor grade change, the central area being the subsequent evolution of a High grade CIN at the advancing edge of the new squam-ocolumnar junction (SCJ) with aging.
In 70% of women with inner border, CIN 2 or 3 is confirmed histologically. The sensitivity of the colposcopic sign inner border for detection of CIN 2 or 3 is 20%, and the specificity was 97%. There was no significant association between inner border and any high-risk HPV type.
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Intercapillary distance
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An important criteria in colposcopic assessment of lesion severity. Fine and coarse vascular patterns are distinguished, and the intercapillary distance increases with the increasing severity of the lesions.
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Inter-observer variability
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The same as reproducibility. In colposcopy, inter-observer variation is substantial, and has been subject to serious attention only relatively recently.
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Interpretation error
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An error made by the cytopatholigist in interpreting the cytological finding. Such an error may be mild (one grade deviation) or severe, when a significant abnormality is erroneously interpreted as normal. Similar errors can also occur while interpreting the coloscopic patterns or cervical biopsies by the colposcopist and pathologist, respectively.
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Invasive carcinoma of the Cervix
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Histologically, 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. 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.
Colposcopic features suggestive of invasive cancer are:
- Irregular surface, erosion or ulceration
- Dense acetowhite change
- Wide irregular punctation and mosaic
- Atypical vessels
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ISSVD
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ISSVD is an acronym for International Society for the Study of Vulvar Disease. This Society has launched the latest terminology of vulvar diseases that has gained wide acceptance worldwide.
The main aims of the Society are :
- to promote international communication among gynecologists, pathologists, dermatologists, and related disciplines, and to establish international agreement on terminology and definitions of vulvovaginal diseases.
- to promote clinical investigation, basic research, and dissemination of knowledge in this field.
ISSVD website: www.isvvd.org
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Keratoacanthoma
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Keratoacanthoma is squamous cell lesion of the skin, commonly encountered in sun-exposed areas in middle aged or elderly people. Also found in the vulva, bearing close resemblance to squamous cell carcinoma both in gross appearance and on light microscopy. Etiology remains speculative, but HPV involvement has been suspected. Spontaneous regression is not uncommon.
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Koilocyte
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A characteristic and specific cytopathic effect (CPE) of HPV in the infected squamous cells. Described for the first time in 1956 by Koss et al., koilocytes were firmly associated with HPV infections twenty years later (Meisels et al and Purola et al. 1976). True koilocytes are intermediate layer keratinocytes with characteristic perinuclear vacuolization (halo) and varying degrees of nuclear atypia. Cells without nuclear atypia and minor cytoplasmic vacuolization should not be diagnosed as koilocytes indicative of HPV infection.
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Large Loop Excision of the Transformation Zone (LLETZ)
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The technique of Large loop excision of the transformation zone (LLETZ) was introduced in 1989 by Prendiville, who used large diathermy loops for taking biopsies large enough to result in complete treatment of the cervical lesions. The technique has all the advantages of a minimally invasive conservative therapies and the added value of obtaining large tissue blocks for histopathological assessment. The equipment consists of both cutting and coagulation facilities, used with a single device called the loop. In current devices, a wide variety of loop designs and sizes are available, making the instrument applicable to any anatomic variants of the cervix. In addition, two basically different loops can be selected; the one made of a thin flexible wire or the one with more rigid thick wire. The use of these two options necessitates a different touch of the operator and both have their advantages and disadvantages. Finally, after removal of the loop specimen, the defect must be carefully cauterized using the second device of the instrument; the ball-headed cautery.
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Laser vaporization
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A technique of treating cervical cancer precursors that became increasingly popular since the mid 1970's. Medical applications of laser (light amplification by stimulated emission of radiation) developed quickly since their introduction, and currently play a key role in many fields of medicine. CO2-laser is the most widely used modality in the treatment of CIN. It is equivalent or superior to cryotherapy and electrocoagulation in its efficacy, and favourable competes also with LLETZ as an optional tool in the local destruction of CIN lesions. When used as a locally destructive treatment, the laser beam of 1.5 to 2mm is commonly used, resulting in instant vaporization of the tissue at the focal point of the beam.
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Laser conization
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Laser conization is an optional modality of using laser as an excisional tool in the treatment of cervical cancer precursors. The facility to reduce the spot size and thus increase the power density of the beam gives the surgeon a highly accurate instrument for precise cutting of the cervix. In contrast to laser vaporization, the spot size used in laser conization is 1mm or less.
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Latent HPV infection
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By definition, a latent viral infection depicts only the situations where viral genome is detected in clinically and morphologically normal epithelium. In latent HPV infections, viral DNA can be found without any signs of CPE (cytopathic effects) of the virus.
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Leukoplakia
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The term Leukoplakia refers to a white plaque visible without magnification and without (before) the application of Acetic acid. It is usually elevated from surrounding surfaces with a sharp border and Lugol's non-staining. Leukoplakia is a clinical term, not a histopathological entity. Histologically, such an epithelium usually presents with a thick layer of hyperkeratosis or parakeratosis. Though leukoplakia in and of itself is not pathologic, it may cover a serious underlying pathology.
Leukoplakia may be seen in:
- HPV infection
- Keratinizing CIN
- Keratinizing cancer
- Chrinic trauma
- Post irradiation
- Immature metaplasia
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Lichen planus
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Lichen planus (LP) is a relatively common inflammatory dermatosis that often affects mucosa of the mouth. The disease can be confined to vulva only, but more frequently the vulva is affected as a part of more generalised disease. This idiopathic or sometimes drug-induced condition can have an auto-immune basis.
In the past not much was known about vulvo-vaginal localization of the disease, which led to an underestimation of the problem and delay in diagnosis and treatment.
Vulvar lesions consist of clearly limited, whitish deposits that are the source of itching of varying intensity. Typical lesions in the submucosal areas are purple, polygonal papules with flat surfaces, sometimes slightly hyperkeratotic. Pronounced erythema and erosion are associated with burning, pain dyspareunia and post-coital bleeding. Erosions can affect large areas and in most cases are surrounded with a delicate, almost lacy epithelial lesions that are important diagnostic aid. Lesions tend to disappear after a few weeks or months, often leaving typical post-inflammatory pigmentation.
Vulvar lesions can be accompanied with vaginal lesions, which are painful and hemorrhagic, causing desquamative vagintis that can lead to the formation of adhesions and stenosis which makes sexual intercourse impossible.
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Lichen sclerosis (LS)
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Lichen sclerosis (LS) is an inflammatory dermatosis affecting any site of the skin. One of the predilection sites is vulva, where this chronic disease can cause significant morbidity. Etiology is unknown, but there seems to be a genetic susceptibility and a link with autoimmune mechanisms. No firm evidence of HPV involvement has been obtained.
The affected tissue is reversibly atrophic and has normal maturation potential. It was shown that normal skin graft transplanted to diseased skin is transformed into LS and that skin graft taken from the full thickness vulval LS transplanted to normal skin, becomes normal.
Initially LS is asymptomatic and clinical finding is minimal. Clitoral edema with subsequent phimosis may be an early sign of the disease. In the beginning small, flat, polygonal shape white to ivory colored papules appear. These changes are shiny and transparent and may be slightly eritematous. Later they coalesce making plaques that could be seen together with atrophy. This epidermal atrophy gives to the fully developed lesions a parchment- like, wrinkled appearance. Sometimes, as the consequence of rubbing and scratching epithelium may become lichenificated. Palor of such areas is often striking. When constant pruritus is present heamorrhagic bulae, purpura or petechias may result from scratching. Sclerosis leads to loss of elasticity and fissuring. LS may affect not only the skin but mucosa as well. In these cases mucosa becomes white, often with haemorrhagies, telangiectases and bullae. The vagina itself is not involved but stenosis of the orifice occurs which may ultimately leave only a pinhole meatus which makes intercourse impossible. In advanced cases the vulvar contures dissapear and labia are lost. Whole field is shiny, waxy and speckled. Adhesions are further complication, although they are infrequent except on clitoris. In such cases separation of fused tissue is possible, but readhesions readily occur.
The frequency and the significance of the association of LS and vulvar malignancy has been debated over many decades. There has long been concern over the malignant potential of Lichen sclerosus but there is no definite proof that LS is precancerous condition. LS may exist alone be complicated by other distrophic conditions with malignant potentital in which cases planocellular carcinoma can develop later.
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Liquid based cytology (LBC)
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Liquid based cytology (LBC) is a technique of collecting and preparing the PAP smear. Under optimal conditions, no cells are lost and a regular monolayer of evenly distributed cells is obtained on the slide. Different modifications of liquid-based cytology are commercially available, and have been extensively tested in comparison with the conventional PAP test during the past several years. When the disadvantages due to increased costs can be solved, liquid-based cytology can be anticipated to gain more widespread popularity than achieved until today.
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Local destructive treatment
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A common name to all treatment modalities of cervical cancer precursors, where the lesion is not excised but destroyed locally by using cryotherapy, cold coagulation, electrodiathermy or laser vaporization.
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Loop electroexcision procedure (LEEP)
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Loop electrosurgical excision procedure (LEEP) is the name used in the US for LLETZ. Both terms denote an identical procedure- see LLETZ.
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Low grade squamous intraepithelial lesion (L-SIL)
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Low-grade squamous intraepithelial lesion (LSIL) is another category of squamous cell abnormality introduced by TBS. LSIL usually represents cells derived from mild epithelial abnormalities, consistent with mild dysplasia.
Colposcopic features suggestive of low grade disease (minor changes) are:
- A smooth surface with an irregular outer border
- Slight acetowhite change slow to appear and quick to dissapear
- Mild, often speckled iodine partial posivitity
- Fine punctation and fine regular mosaic
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Lugol's solution
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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.
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Major grade colposcopic finding
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Based on severity and combination of these features, all atypical findings on the cervix can be divided to Grade 1 (G1) lesions, which indicates histologically less severe lesion (CIN1/L-SIL) and Grade 2 (G2) which is usually appearance of the higher grade lesion (CIN 2 and 3/H-SIL).
Colposcopic features suggestive of Grade 2 (major grade findings) are:
- a generally smooth surface with sharp outer border,
- dense acetowhite change, may be oyster white appears early slow to resolve,
- coarse punctation and wide irregular mosaic of different size,
- iodine negativity
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Melanoma of the cervix
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Primary melanomas of the uterine cervix are rare tumors representing less than 2% of cases of melanoma affecting the female genital system. In general prognosis is poor and unpredictable.
Due to rarity of the tumor, it is difficult to define typical colposcopical presentation. The lesion may be flat or elevated (nodular or polypoid), dark blue or brown colored, but it is definitely unusual and attracts attention. The definitive diagnosis is made by biopsy.
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Melanoma of the vulva
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Although rarely seen, Melanoma accounts for 10% of all malignant disease of the vulva. Melanoma of the vulva does not occur in girls before puberty, but after that period their frequency increases gradually and is the highest in the sixth and seventh decade. As in other parts of the body Melanoma can be developed from pre-existing nevus or may arise de novo from intra-epidermal melanocytes.
Medical history is usually brief, lasting from a few weeks to 8 months, although symptoms can be present for more than a year. In the beginning, nodule which may bleed, burning or itching are present. Many women notice change in appearance of vulvar nevi present long before. Typically the lesions are brown to blue-black, but a small percentage is amelanocytic and microscopically resembles the squamous cell carcinoma. Localization can be different, but generally the changes are centrally positioned on the small lips and clitoris.
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Metaplasia
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When exposed to the acid vaginal environment, columnar epithelium undergoes the process of metaplasia. Metaplasia is a physiological and benign process whereby one type of epithelium is replaced by another. In the uterine cervix, squamous metaplasia is taking place in the transformation zone (TZ), where glandular epithelium is gradually replaced by mature squamous epithelium. This occurs under the effect of several factors including, hormonal stimulation, low pH and trauma. It starts from the original Squamo-columnar junction (which is the peripheral border of ectopia) and advances towards the external opening. Metaplasia causes SCJ to gradually moves higher towards the endocervix, in parallel with the increasing age. Transformation zone is the area on the cervix where metaplasia takes place.
Metaplasia is a normal, physiologic, irreversible process initiated by acid vaginal environment which stimulates reserve cells positioned on the basal membrane of columnar epithelium to differentiate not to columnar but to the squamosus type. Metaplasia is the most critical period for the onset of cervical abnormalities, because the immature metaplastic cells are susceptible to the effects of carcinogens Metaplastic process is usually categorised as immature and mature metaplasia. On colposcopic examination, this dynamic process of squamous metaplasia can be clearly observed and distinguished by three stages. The latter represent mature metaplastic squamous epithelium.
Through the colposcope there is a pattern of a combination of squamous and columnar epithelium. Islands of collumnar 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.
Colposcopic features suggestive of metaplastic changes
- A smooth surface with fine, uniform-caliber vessels
- Mild acetowhite change
- Negative or partial positivity with Lugol's iodine
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Microcolpohysteroscopy (MHC)
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This technique was introduced in 1980 by Hamou as a valuable adjunct to colposcopy and PAP test. The Hamou microcolpohysteroscope is an endoscope, 4mm in diameter, 25cm in length and provided with 90° field angle and 30° forward oblique scope. This enables the use of the instrument in a panoramic or contact mode with different magnifications, applied to examination of the ectocervical surface cells and endocervix.
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Microglandular hyperplasia
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Microglandular hyperplasia is a peculiar type of reactive change in the endocervical glandular tissue, usually manifested by progestogenic stimulation. Microglandular hyperplasia is also common during pregnancy, and if extensive, can give rise to a polypoid mass in the endocervical os, detectable on colposcopy.
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Microinvasive carcinoma
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Microinvasive carcinoma is an early invasive cervical carcinoma. During the past several decades, the criteria of microinvasive carcinoma have been highly variable, the current classification being introduced by FIGO in 1994. Accordingly, microinvasive carcinoma is graded into stage IA1 and IA2, according to the depth of invasion and the lesion diameter. Stage IA1 lesions represent early invasive disease with stromal invasion less than 3mm and no wider than 7mm, and stage IA2 are lesions with invasion deeper than 3mm but less than 5mm and no wider than 7mm.
Colposcopic signs of microinvasion are:
- Yellow discoloration
- Ulceration
- Thickened areas
- Nodularity
- Abnormal vascularity
- Rapid increase in size
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Minor grade colposcopic finding
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Based on severity and combination of these features, all atypical findings on the cervix can be divided to Grade 1 (G1) lesions, which indicates histologically less severe lesion (CIN1/L-SIL) and Grade 2 (G2) which is usually appearance of the higher grade lesion (CIN 2 and 3/H-SIL).
Colposcopic features suggestive of Grade 1 lesions (minor grade findings) include:
- a smooth surface with an irregular outer border
- slight acetowhite change slow to appear and quick to disappear
- fine punctation and fine regular mosaic and
- mild, often speckled iodine partial posivitity
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Moluscum contagiosum
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Molluscum contagiosum is a common viral lesion of the skin, also encountered in the vulva. This benign tumor is induced by MCV (molluscum contagiosum virus), belonging to the Poxvirus family and present as two types: MCV1 and MCV2. On gross appearance, mollusca bear some resemblance to HPV lesions and basal cell carcinoma.
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Mosaic
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Mosaic is a characteristic colposcopic pattern, where the underlying small blood vessels become visible on colposcopic examination in a pattern resembling a mosaic. This pattern is almost invariably associated with a cancer precursor, and grading the mosaic as regular, irregular and coarse bears some correlation with the severity of the lesion.
Mosaic reflects the islands of squamous epithelium, encircled by blood vessels in a basket-like arrangement. Grading the mosaic as regular, irregular and coarse bears some correlation with the severity of the lesion.
Mosaic can be seen in:
- Inflammation
- Rapidly growing metaplastic epithelium
- CIN
- Invasive squamous cancer
- Recurrence of cervical cancer
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Nabothian cysts
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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.
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Necrosis
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If the inflammation affects the stroma, the final phase of desquamation may be ulceration, which is most often seen in prolonged or severe inflammation. Sometimes it can occur early. The superficial epithelium disappears. Interstitial liquid from the connective tissue exudates and coagulates on the surface producing fibrinogen-purulent exudate. Necrosis of the connective tissue can be deep. If there is no actual loss of tissue, it is partially filled with a thick fibrinous-purulent exudate, forming adherent yellow-white membrane. The ulcers are generally surrounded by a narrow rim, which can be raised.
Typically, these lesions heal quickly, without sequelae and scars. Subsequent healing of significant lesions cause fibrosis. Blood vessels are dilated and surrounded by infiltrates of histiocytes, plasma cells and polimorfonulear cells. Enlarged capillaries directed perpendicular to the edge of the ulceration can be seen. The whole appearance may be similar to invasive cancer.
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Negative predictive value (NPV)
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The proportion of true negative tests out of all tests suggesting a negative result (true negatives/true negatives + false negatives). For colposcopy, the NPV in the selected group is around 95%, but in the random population, NPV of colposcopy is up to 99%.
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Negative smear
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Any PAP smear containing only normal cells
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Original squamous epithelium
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Original squamous epithelium is the squamous epithelium originally covering the exocervix. It is derived from the evolution of columnar cells to squamous cells during the first 18-20 weeks of fetal age.
Original squamous epithelium and original columnar epithelium meet in the squamo-columnar junction (SCJ), known as the original squamo-columnar junction (OSCJ), which is the linear junction between the columnar and squamous epithelium present at birth (fetal junction). This OSCJ should be distinguished from the new or active squamo-columnar junction (NSCJ) that is the meeting line of the metaplastic (mostly immature) squamous- and the columnar epithelium.
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Original Squamocollumnar junction
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The original SCJ is the border where the original squamous epithelium meets the outermost limit of the developing transformation zone.
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Papanicolaou classification
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Papanicolaou classification is the first classification developed to grade these cellular abnormalities in the PAP smear, based on the use of 5 classes (from normal to invasive carcinoma). Although commonly replaced by more updated classifications, the traditional Papanicolaou classification still has its place in cytological diagnosis, being used in different modifications e.g. in many European countries.
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Papanicoulaou test (PAP test)
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The Pap test was introduced as a cervical screening test in 1943 by Dr. George Nicholaus Papanicolaou, a Greek pathologist. The test is based on the genuine idea that cells scraped from the epithelium closely reflect in their morphology the underlying pathological process and thus can be used for diagnosis of the latter. Cell samples are taken separately from the endocervix (using cytobrush) and ectocervix, and smeared either on a single slide or on two separate glass slides. In some countries, a third sample is taken from the vaginal fornix and usually smeared on the single slide together with the two other samples.
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.
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Papilloma
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Papilloma is the joint name to describe epithelial proliferations originating from squamos epithelium and presenting with a papillary morphology. The typical example is squamous cell papilloma, which can be solitary or multifocal lesion, characteriyed by exophytic cauliflower-like proliferation where acanthotic epithelium is overlying connective tissue papillae. These lesions are entirely benign and are not necessarily induced by HPV infection.
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Papullosis
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Papulosis is a HPV-associated lesion in the external genitalia of both sexes. Papulosis is an elevated papular focus of an acanthotic epithelium, not exhibiting, however, the exophytic papillary structures typical to condyloma acuminatum. In many cases, a slightly elevated, shallow, papillomatous countour can be detected. In cases where intense melanin pigmentation is present in the basal cells, the lesion is brown or even black in color, and can be called pigmented papulosis.
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Polyp
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Polyp is a benign tumor in the cervix. These benign pedunculated lesions may be visible with naked eye, while protruding from the canal. Depending on their histological composition, three types of polyps exist: mucous, fibrous and angiomatous. All polyps should be excised and submitted to histopathological examination to rule out the rare occurrence of malignant transformation (usually squamous cell carcinoma).
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Positive predictive value (PPV)
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The proportion of true positive tests out of all tests suggesting a positive result (true positives/true positives + false positives). For colposcopy, the PPV in the selected group is around 66%, but in the random population, PPV falls down to 4-5%.
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Positive smear
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Any smear containing abnormal cells or cells not within the normal limits. Positive smear is not an acceptable classification category, but must be always defined as either borderline, pre-cancerous or cancerous.
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Post treatment consequence
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If any surgical procedure on the cervix has previously been performed, the topography of the TZ can be significantly altered. The fields of metaplasia, CIN and invasive cancer in the canal or in endocervical glands can skip the destruction and remain as iatrogenic, skip lesions. They can persist on the surface of endocervical canal surrounded by glandular epithelium which proliferates over the treated field or can be covered by new squamous epithelium. Alternatively, these islands can be buried in cervical stroma, particularly if the sutures have been applied.
Reparative and healing changes themselves can mimic residual disease. Late effects of previous treatment may give confusing colposcopis picture, particularly to the less experienced colposcopist. The finding may resemble recurrent disease. As colposcopic interpretation is based on intact, unaltered transformation zone, the interpretation of postoperative changes must be very careful.
Cervical stenosis can additionally compromise colposcopic examination. In cases where SCJ is visible previous treatment does not seem to impair the ability of colposcopy to diagnose any cervical abnormality. However, there is a suggestion that the sensitivity of colposcopy to differentiate negative/low grade disease from high grade/invasion is lower in previously treated women.
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Punctation
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Punctation is a characteristic colposcopic pattern, where the underlying small blood vessels become visible on colposcopic examination as a punctate lesion. It reflects the capillaries in the stromal papillae that penetrate the epithelium and are seen end-on. This pattern is almost invariably associated with a cancer precursor (CIN) lesion, and (similarly as in mosaicism) grading the punctation as regular, irregular and coarse bears a correlation with the severity of the lesion.
Similarly to mosaic, punctations can be seen in:
- Inflammation
- Rapidly growing metaplastic epithelium
- CIN
- Invasive squamous cancer
- Recurrence of cervical cancer
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Quality Assurance (QA)
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A process building a quality control in any diagnostic (or management) system.
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Quality Control (QC)
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The set of measures designed to guarantee the accuracy of taking, preparation, interpretation and reporting of the test. Applies equally well to all diagnostic and therapeutic procedures, including the PAP test, colposcopy, LLETZ etc.
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Rag sign
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Rag sign is an opaque acetowhite area at the SCJ, mechanically abraded during either collection of the smear for cytology or HPV testing and/or applying acetic acid or Lugol's solution. In rag sign, part of the epithelium is sloughed off in a rag.
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Reactive cell changes
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Reactive cell changes (RCC) are cell changes in the PAP smear, which are benign in nature, and associated e.g. with inflammation, radiation, an intrauterine device (IUD) or due to non-specific causes. Categorization depends on classification, and practices of controlling vary from country to country.
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Referral Criteria
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Referral criteria is set of characteristics required to correctly identify the women who need a referral to colposcopy. The optimal referral criteria would lead to correct detection of clinically significant (high-grade) lesions with the minimum proportion of false negative and false positive cases (=high performance). Lately, a clear tendency towards less stringent referral criteria seems to gain favor among colposcopists.
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Recurrence of cervical cancer
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Initial colposcopical appearance of recurrent cervical cancer may be nonsignificant. This is why detailed colposcopic examination, even after irradiation my be of great importance. In general, coarse punctations and atypical vessels are typical findings. Advanced recurence is not difficult to recognize, as a exophytic or ulcerative lesion. Most often necrosis and bleeding are present.
If the patient has been irradiated before, it may be difficult to evaluate postirradiation necrosis. Serial examinations and biopsy if needed can help.
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Reserve cells
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Reserve cells are characteristic cell type in the uterine cervix also known as sub-columnar cells. The origin of these sub-columnar reserve cells is still obscure. These cells play an important role in the metaplastic process, which usually starts as a marked proliferation of the reserve cells. This initial early step of metaplasia is known as reserve cell hyperplasia, which is easily detected on the light microscopic examination of cervical biopsies from the TZ.
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Ridge sign
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Ridge (ledge) sign is an opaque lesion, growing in the SCJ, which resembles a mountain ridge. Ridge sign refers to a thick epithelium, which exhibit opaque color and lack of iodine uptake.
Colposcopic ridge sign is associated with CIN2 or CIN 3 in more than two thirds of cases, which gives high positive predictive value. Sensitivity and sensitivity of ridge sign for detection of CIN 2 or 3 is 33.1% and 93.1% respectivelly. Women with ridge sign are significantly younger than women with no ridge sign. Contrary to the inner border sign, this sign was associated with the presence of HPV 16.
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Saline colposcopy
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Saline colsposcopy is the technique pioneered by Kolstad and Koller, which soon gained wide popularity in the Scandinavian countries. A saline-soaked cotton wool ball is applied to the cervix which results in moistening of the epithelium and allows a better visualization of the underlying angioarchitecture. Higher magnifications (x25) are needed to inspect the details and use of green filter is useful while enhancing the visibility of the capillaries.
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Satisfactory colposcopy
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The colposcopic examination is not satisfactory whenever the transformation zone is not visible in full. When this is the case and the TZ is completely visualised, colposcopy is called satisfactory.
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Schiller's test
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Schiller's test is one of the key elements in the colposcopic examination. In Schiller test, a solution of iodine (Lugol's iodine solution) is applied to the cervix to visualise any epithelial abnormalities. Following the iodine application, the normal mucosa will stain mahogany brown (iodine-positive), in contrast to epithelial abnormalities (metaplasia, CIN) that stain pale or remain completely unstained (iodine-negative).
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Seborrhoic keratosis
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Seborrhoic keratosis is also known as basal cell papilloma. A very common skin lesion also encountered in the vulva. Important is the differential diagnosis to malignant melanoma, when heavily pigmented
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Sensitivity
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Sensitivity parameter of test performance. Sensitivity of the test denotes its capacity to correctly identify the true positive smears out of all smears with confirmed positive result (counted as: true positives/true positives + false negatives). The higher the sensitivity, the better is the test performance.
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Specificity
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Specificity is another key parameter of test performance. Specificity of the test denotes it capacity to correctly identify the true negative smears out of all smears with confirmed negative result (counted as: true negatives/true negatives + false positives). The higher the specificity, the better is the test performance
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SPI (Subclinical Papillomavirus Infection)
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Subclinical Papillomavirus Infection (SPI) is a term used by some authors to define HPV infections that become visible only after acetic acid application. Others prefer to designate these non-exophytic lesions as flat condylomas, to make distinction from true virological concept of subclinical infection. In the virological sense of the name, subclinical means any viral infection that does not induce clinical symptoms or signs. Accordingly, subclinical HPV infections would represent cases where HPV genome (DNA or RNA) is detected in minor lesions not fulfilling the morphological criteria of classical clinical HPV lesions (flat condylomas). The criteria of subclinical HPV infections are ill defined and not reproducible, sometimes referred to as minimal or secondary characteristics of HPV.
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Spiked condyloma
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Spiked condyloma is morphologically characteristic manifestation of HPV infection. Typical sites include the vagina where the lesions can be multiple, and vulva, where the lesions are also called microcondyloma or filamentous condyloma. Distinction should be made from vulvar micropapillomatosis, which is regarded as a physiological manifestation (analogous to penile perly papulosis) unrelated to HPV.
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Squamocollumnar junction (SCJ)
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Squamo-columnar junction (SCJ) is the meeting line between the columnar epithelium, which covers the endocervical canal, and the squamous epithelium of the exocervix. SCJ is a dynamic point, which changes its position depending on the age of women and estrogen level. In the pre-pubertal period SCJ is located in the endocervix. With the puberty, it moves distally to ectocervix and usually remains visible during the whole reproductive period. After the menopause, SCJ moves proximally and remains in the endocervical canal during the entire postmenopausal life.
Due to the metaplastic process, the SCJ is not stable; it advances inward, toward the endocervical canal forming a new junction. Morphologically there are two types of squamocolumnar junctions (SCJ). The original SCJ (OSCJ) is the border where the original squamous epithelium meets the outermost limit of the developing transformation zone. It is the linear junction between the columnar and squamous epithelium at birth (fetal junction).
The new or active squamo-columnar junction (NSCJ) is the innermost border where the maturing squamous metaplasia meets that is the meeting line of the metaplastic (mostly immature) squamous and the columnar epithelium.
SCJ is the most critical part of the cervix. Immature metaplastic cells are susceptible to the development of atypical cellular changes. The process of transformation from normal cells to atypical cells occurs under the influence of Human papillomavirus (HPV) and cofactors.
SCJ can be visualized completely, partially or can not be visualized at all. In the latter situation, colposcopic examination is considered unsatisfactory.
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Squamous cells
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The name given to the cells composing the epithelial lining of the lower genital tract (cervix, vagina, vulva).
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Squamous cell carcinoma
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Squamous cell carcinoma is the main histological type of cervical carcinoma, so named because of its origin from the squamous cells. Unless otherwise defined, the general term cervical cancer usually denotes for the squamous cell carcinoma. This important disease is subject to wide variation in incidence and mortality worldwide. In the developing countries, cervical squamous cell cancer is the second most frequent malignancy, but number one killer of all women malignancies. According to best estimates, over 450.000 new cases are detected every year, and over 200.000 women lives are lost due to this disease, which is a preventable disease if properly controlled.
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Squamous epithelium
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Squamous epithelium is the main histological type of epithelium lining the female lower genital tract. Stratified squamous epithelium is composed of squamous cells arranged in four distinct layers, known as basal, parabasal (suprabasal), intermediate and superficial layers. CIN lesions have their origin in the basal cells, explaining their histological resemblance to basaloid cells.
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Squamous intraepithelial lesion (SIL)
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A term introduced by TBS to replace the term cervical intraepithelial neoplasia (CIN). SIL represents a precancerous condition where normal epithelial cells are replaced by abnormal cells; classified as high grade (HSIL) or low grade (LSIL).
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Stenosis
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Cervical stenosis is clinically defined as the narrowing of the external cervical opening (and/or endocervical canal) that prevents the insertion of a 2.5 mm wide dilator. In some cases, the endocervical canal may be completely closed.
Cervical stenosis may be congenital or may be caused by other factors such as surgical procedures performed on the cervix (knife cone or loop exsicion), trauma, chronic infection, atrophy of the cervix after menopause, invasive cancer or cervical irradiation.
In cases of severe stenosis, proximal obstruction may result in haematometra, hydrometra or pyometra. Cervical stenosis can also impact natural fertility by impeding the assisted fertility techniques (embryo transfer and intra-uterine insemination).
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Stroma
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The underlying connective tissue on which all epithelial structures are situated. Stroma is composed of fibrous and elastic tissues, including fibroblasts and the extracellular matrix. Reactions of the stroma have a significant impact on the colposcopic appearance of the cervix.
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Thermal damage
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Thermal damage is an artefactual damage of the wound margins induced by laser ablation or LLETZ excision of the cervical cone. It is according to the best interests of the clinician to select a technique that keeps the thermal damage of the margin to minimum. This has important implications in the histopathological assessment of the cone specimen, and particularly the involvement of the margins by the CIN lesion. In a number of studies, the thermal damage is the most minimal when LLETZ is used, even less than induced by laser ablation.
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Transformation zone
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Transformation zone (TZ) is the area on the cervix where metaplasia takes place.
Metaplasia is a 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 (active, new) SCJ.
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. 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.
The three types of the Transformation zone can be distinguished:
- Type 1 TZ: ectocervical and fully visible
- Type 2 TZ: has an endocervical component, but is fully visible
- Type 3 TZ: has an endocervical component that is not visible and may have an ectocervical component
In colposcopy, it is essential to assess whether Transformation zone is normal or abnormal. Abnormal transformation zone is presented by variety of epithelial and vascular changes which can be seen as abnormal (atypical) colposcopic findings
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Tuberculosis of the cervix
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Tuberculosis (TB) of the genital organs involves cervix in only 5-6% of the cases. The main clinical manifestation is discharge with unpleasant smell and contact bleeding.
In cervical TB, the cervix can be hypertrophic, with fine nodular surface and no visible lesions. Small nodules on both lips, with a picture mosaic, punctuation and atypical vessels, without ulceration may be present. When ulcers appear in TB, they are usually multiple, in series, like the links of a chain, with rolled and purple edges, gray center and does not bleed easily because they do not have many vascular elements. The base is typically elevated in a shape of a mushroom surrounded by even edges. Cervical TB also can resemble cancer. Diagnosis must be confirmed by histopathological examination of tissue samples obtained by biopsy.
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Ulceration
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Ulceration is the defect of epithelium and underlying stroma. It is not exclusive sign of invasion and can be seen in severe inflammation, caused either by infection or by physical or chemical trauma. The bottom can be covered with necrotic tissue or can be denuded and seen as red or pink stromal tissue
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Vaginal adenosis
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Vaginal adenosis is the presence of glandular epithelium (similar to endocervical epithelium) in the vagina. It may be located either at the surface, with the replacement of the normal squamous epithelium, or appearing in the form of the cystic glands and the crypts that secrete mucus at the mucosa of the vagina, which otherwise contains no glandular elements. Fields of adenosis, spread beyond the cervix to the vaults and down along the vaginal walls. They may be associated with TZ or appear independently.
Colposcopic examination in vaginosis shows the fields that are either pure columnar epithelium or columnar epithelium mixed with metaplastic epithelium. This epithelium is very similar to endocervical columnar epithelium with villi resembling the grapes that are seen after the application of Acetic acid. It is not stained by Iodine. As in normal columnar epithelium, the fields of adenosis can undergo the process of squamous metaplasia. During this process, the epithelium becomes acido-white in appearance, and often expresses a variety of vascular forms, especially mosaic. Blood vessels are thin and regular. As metaplasia matures, acido-white epithelium and vascular changes are disappearing and colposcopically epithelium resembles the original (native) squamous epithelium of the vagina. Distinguishing this metaplasia of the vaginal epithelium from neoplasia can be difficult.
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VAIN
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VAIN (Vaginal Intraepithelial Neoplasia) is the precursor lesions of vaginal squamous cell carcinoma. Originally, three grades of VAIN were distinguished, but more recently the division into low-grade and high-grade VAIN has gained more popularity, due to the difficulties in categorizing the intermediate (VAIN II) grade of lesions with any feasible degree of reproducibility.
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Venereal wart
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Another name for genital warts or Condylomata acuminata
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Vestibular papilomatosis
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Vulvar papillomatosis is a heavily disputed entity. These small, smooth projections found on the vulvar mucosa have been called by a variety of names, including vestibular papillae, vulvar squamous papillomatosis, micropapillomatosis labialis, benign squamous papillomatosis, and pruritic vulvar squamous papillomatosis. Some authors suggest that the lesions are HPV-associated and may be the source of vulvar symptoms, whereas others are convinced that the lesions are normal anatomic variants equivalent to pearly papules of the penis. Recent data favor the latter view.
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Video colposcope
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The latest development in the colposcope instrumentation. A video colposcope comprises a video camera and the colposcope with an electronic green filter, motorized zoom and fine focus controls, all combined in one single unit. Capture and storage of the images in digital form allows any image form of image management (processing, storage, retrieval) for documentation and e.g. teaching purposes. In parallel with the development of reasonably priced powerful computers, it can be anticipated that video colposcopy will be the technique-of-choice in the near future.
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Villus
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The basic subunit of endocervical columnar epithelium. On colposcopy, endocervix appears as bunches of small grapes 1.5 to 0.15mm in diameter, composed of several villi. Individual villi are separated by an intervillous space.
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VIN
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VIN (Vulvar Intraepithelial Neoplasia) is currently used name to denote all precancer lesions of the vulva. Analogous to cervical precancer lesions, also VIN lesions are graded into three grades of severity: VIN 1, 2 and 3. However, there is neither evidence that the VIN 1-3 morphologic spectrum reflects a biologic continuum, not that VIN 1 is a cancer precursor.
VIN 1 is an uncommon histologic finding. It constitutes o basally located cellular changes or minimal atypia. These findings are usually reactive or an HPV effect and considerable intra- and inter-observer variations in the VIN 1 diagnosis. This means that the term intraepithelial neoplasia for such benign lesion may be misleading. This is why ISSVD Vulvar Oncology Subcommittee modified terminology of Squamous Vulvar Intraepithelial Neoplasia, in 2004.
According to this classification the term VIN 1 will no longer be used. Histological changes previously encompassed within the term VIN 1 will be described either as flat condyloma or HPV effect. The use of the term atypia is discouraged. The majority of VIN lesions are categorized as VIN 2 and VIN 3. When they are combined as a single diagnostic category, good histologic agreement is obtained. Today, these two entities are referred as high grade vulvar squamous lesion- VIN. According to 2004 ISVVD terminology two categories should describe squamous VIN:
- VIN usual type (VIN 2 + VIN 3) which includes warty (condylomatous), basaloid (bowenoid) and mixed type, and
- VIN, differentiated type (VIN 3 differentiated type)
VIN usual type is HPV related in most cases and seen adjacent to approximately 30% of squamous cell carcinomas. It occurs in women younger 30 years. These lesions have a low to intermediate (2-20%) invasive potential. The role of immune system seems to be central to both progression and spontaneous regression.
VIN differentiated type has no association with HPV exposure or tobacco use. It is seen primarily in older women and is often associated with keartinizing squamous cell Ca (>95%). In some cases it is associated with Lichen sclerosus and/or Squamous cell hyperplasia.
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Visual inspection with acetic acid (VIA)
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Visual inspection with acetic acid (VIA) is the test that involves visual examination (with the naked eye) of the uterine cervix after the application of 3-5% acetic acid. It has been consistently demonstrated to have a sensitivity equivalent to that of cytological screening to detect high grade lesions. Therefore, this test should be considered as a primary screening method in settings where quality cervical cytology is not available. However, the specificity is lower than that of cervical cytology. Further evaluation is required to identify ways to improve the specificity and to reduce the number of women who suffer form adverse outcomes when VIA is coupled with immediate treatment.
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Vulvar vestibulitis
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Characteristics of vestibulitis are the patient's complaint of entry dyspareunia, discomfort at the opening of the vagina, point tenderness discovered on palpation of the gland orifice with a cotton-tipped applicator, and diffuse or focal erythema involving the vestibule and seen around the gland openings. Vulvar vestibulitis may be of acute onset or more protracted in its course with considerable discomfort completely preventing coitus. The data on the role of HPV in etiology of vulvar vestibulitis are controversial. There are authors who suggest that HPV can be an associated variable, whereas others have not found convincing evidence to support that notion.
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Vulvodynia
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Vulvodynia is a distinct entity (syndrome) characterised by non-provoked, intractable pain in the vulva. This syndrome is also known as dyesthetic or essential vulvodynia.
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Vulvoscopy
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Examination of the vulva by the colposcope. This is done as the final step in the colposcopic examination of the lower genital tract, following the examination of the cervix and the vagina. The procedure is performed after application of 5% acetic acid on the inner margins of labia minora and the vaginal introitus
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Wart
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Wart is a common name for all cutaneous squamous cell proliferations induced by HPV. Specific HPV skin types are associated with cutaneous warts, which are most frequently encountered in young children or immunocompromised patients. When present in the genital tract, proliferative HPV lesions are called genital warts or Condylomata acuminata.
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Warty
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Warty is any lesion with wart-like appearance.
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