Cervical squamous and glandular intraepithelial neoplasia: Identification and current management approaches. Professor Emeritus. Department of Obstetrics and Gynaecology. The University of Western Ontario.

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Cervical squamous and glandular intraepithelial neoplasia: Identification and current management approaches. Professor Emeritus. Department of Obstetrics and Gynaecology.

The University of Western Ontario. London, Ontario, Canada. Certain types of human papillomaviruses HPV are associated with squamous intraepithelial lesions and cancer and these are termed high-risk.

HPV type 16 is detected in approximately half of the high-grade squamous intraepithelial lesions and cancer. Because of the high rate of spontaneous regression of low-grade squamous lesions, follow-up by cytology, colposcopy and possible biopsy appears preferable.

Due to the higher rate of progression to malignancy of the high-grade lesions conservative treatment is recommended. One of the most common reasons for persistence relates to the human immunodeficiency virus. Adenocarcinoma in situ is an uncommon disorder and not well identified by cytologic sampling or colposcopic inspection. The diagnosis is made by cone biopsy, the specimen having negative margins for disease. Hysterectomy is the treatment procedure of choice unless fertility is an issue.

Excisional methods particularly electrosurgical loop can interfere with accurate histological interpretation in some cases of both squamous disease and adenocarcinoma in situ. Key words: squamous intraepithelial neoplasia; adenocarcinoma in situ ; conservative treatment. Clinical and subclinical human papillomavirus HPV infections are among the most common sexually transmitted diseases today.

At least 40 types infect the female and male anogenital tracts producing a spectrum of lesions ranging from genital condyloma to invasive cancer. Based on their association with benign lesions, high-grade precursor lesions and invasive cancer, the anogenital HPV types can be classified into non-oncogenic and oncogenic risk categories. Low or non-oncogenic risk viruses include types 6,11,42,43,44 and they are associated with condylomata and some cases of low grade squamous intraepithelial lesions CIN I but rarely if ever invasive cancer.

In these cases an intraepithelial lesion does not develop and the virus clears in 6 to 8 months. This suggests that HPV typing may be useful in predicting the likelihood of progression and the necessity of treating.

Any advancement in lesion grade requires treatment. Such candidates are usually young and nulliparous. Currently many investigators advocate electrosurgical loop excision for ectocervical high-grade squamous intraepithelial lesions. Most are office procedures and some require brief anesthesia. All ablative procedures rely on adequate colposcopic evaluation and correlation to assure that invasive cancer is not missed.

The purported advantage of routine excision of colposcopically defined high-grade squamous intraepithelial neoplasia is that a specimen or specimens is always available. However, the following questions apply: a is the specimen s always interpretable? At colposcopic examination one determines whether the examination is satisfactory or not and formulates a colposcopic impression.

After the correlation process has been completed, the colposcopist must determine what the patient needs next.

Is it: a referral to a gynecologic oncologist for staging; b diagnostic excision conization ; c conservative local treatment, or d follow-up? The indications for ablative methods or loop excision are: a cytology, colposcopy, and pathology must correlate to establish an accurate tissue diagnosis; b the entire transformation zone must be colposcopically defined; c the colposcopist must be certain from the qualitative assessment of the transformation zone that no invasive cancer is present; d the intraepithelial lesion must occupy the ectocervix with no extension into the endocervical canal, and e preferably the patient is not pregnant.

In contrast excisional procedures are required when: a discrepancies exist between cytology, colposcopy and histology; b significant lesions are located in the endocervical canal and require tissue for histological sampling; c cytology or colposcopy suggests possible invasive carcinoma that has not been proven by colposcopically directed biopsy; d colposcopic biopsy indicates microinvasive squamous disease or adenocarcinoma in situ , or e when colposcopy is unsatisfactory.

Laser excision or electrosurgical needle excision, removing a cylindrical specimen, with the apex of the specimen being cut with a scalpel or scissors creating no thermal effect produces a good quality specimen in the author's experience.

Then appropriate operative techniques can be applied to remove or destroy it Figure 2. Treatment, especially by excisional methods, can cause symptomatic stenosis with canal narrowing, although this is an infrequent complication. The most common patient symptom is severe dysmenorrhea. Narrowing can lead to difficulty in obtaining satisfactory cytology.

When thermal energy is used, heat may interfere with accurate histological interpretation. Some investigators found loop specimens in general difficult to interpret due to the thermal artifact and fragmentation. This interfered with margin assessment and grading of the lesion. Regardless of the method of treatment persistent disease occurs. After ablative methods it is usually identified at the first visit by colposcopy using acetic acid and iodine staining and including cytology.

If significant disease is identified, retreatment is usually necessary. The technique depends upon disease location. For excisional procedures, it is important to know whether there was an endocervical apical margin positive or an ectocervical margin positive. Others have found abnormal cytology to be an excellent predictor of residual disease. In some cases simple hysterectomy for the high-grade squamous case may still be required for the following reasons: a failed conservative management; b extensive disease involving the cervix and vagina where conservative management may be difficult; c the presence of co-existing pathology not resolved conservatively such as large fibroids, uterine prolapse, endometriosis or intractable menorrhagia; d technical difficulties in exposure; e unresolved post-conservative treatment stenosis; f definitive management of adenocarcinoma in situ ; g to control hemorrhage post-excision conization , and h cancer phobia.

This spectrum has been divided into low grade and high grade CIGN. Adenocarcinoma in situ is uncommon. Making the diagnosis of AIS by the clinician is challenging. The lesion is frequently overlooked because of the absence of clinical findings, the presence of normal cytology or cytology reflecting squamous disease and unfamiliar colposcopic patterns.

This finding suggests that cytologic studies are more accurate in identifying the squamous component than the glandular component. Basically there are three colposcopic presentations of AIS lesions. The most common colposcopic appearance is a papillary expression resembling an immature transformation zone Figure 6. Second is a flat, variegated red and white area resembling an immature transformation zone Figure 7.

The least common is one or more isolated, elevated, individual, densely acetowhite lesions overlying columnar epithelium. In mixed disease, the glandular lesion can abut the glandular lesion, be sandwiched between two squamous lesions or lie above the squamous lesion Figure 8.

AIS lesions can be small, focal and easily missed. Measurements linear length of AIS lesions the distance over the tissue surface between caudal and cephalad edges have been studied. The distance usually does not exceed 15 mm and rarely does it encompass the entire glandular epithelium. Nicklin et al found that women younger than age 36 years have a mean lesion length of 5. In contrast 9 of 17 women in the older group had lesion lengths of more than 10 mm, with a maximum of 25 mm.

The highest focus did not exceed As in squamous intraepithelial neoplasia, AIS can extend into underlying cervical crypts. Involvement averages 2. Multifocal lesions so called "skip lesions" represent foci involving different portions of the endocervical mucosa. By definition, this is when a normal radial histological section separates two areas of AIS. AIS can involve both superficial and deep crypts that are covered by metaplastic or dysplastic squamous epithelium.

AIS lesions are to be suspected when any of the following colposcopic findings are observed: a a lesion overlying columnar epithelium and not contiguous with the squamocolumnar junction; b large gland openings Figure 7 ; c papillary-like lesions Figure 6 ; d epithelial budding; e variegated red and white lesions Figure 7 , and f atypical angioarchitecture such as waste-thread-like, tendril-like, root-like Figure 8 or character-writing-like vessels and single and multiple-dot-like formations Figure 6 , the latter seen in the tips of the papillary excrescences.

The differential of similar appearing lesions is shown in Table I. The excisional procedure should attempt to account for the distribution of disease linear length, crypt involvement, and disease location.

As in squamous intraepithelial neoplasia, the configuration base and height dimensions will vary. A cylindrical shaped specimen best accounts for disease distribution Figure 9. The preferred instrument for the excisional procedure to provide the best interpretable specimen is a subject of debate.

From the pathologist's standpoint, the cold knife conization is the safest and best therapeutic modality, provided that the cone specimen is adequately sampled and the margins are free. There is general consensus that electrosurgical loop may not be the procedure of choice.

This is because electric current follows the path of least resistance into crypt mucus and thus it can potentially distort the glandular epithelium causing pseudostratification or streaming of nuclei parallel to the electric field making it difficult to histologically differentiate between in situ and invasive disease.

Cumulative studies show that positive margins are of significance due to persistent AIS in Repeat excision, producing negative margins is also recommended before a simple hysterectomy as definitive treatment. Failure to do so may result in inappropriate surgery simple hysterectomy instead of radical hysterectomy , should adenocarcinoma be found in the extirpated uterine cervix. Studies indicate that if excised specimens have negative margins then conservative management is possible in those women who desire future child bearing.

For the conservatively managed patient, follow-up management should consist of cytology, colposcopy, and endocervical curettage every four months for one year and every six months thereafter. Cervical cancer: Epidemiology, prevention, and the role of the human papillomavirus infection. Can Med Assn J ; Comparison of self-collected vaginal, vulvar and urine samples for human papillomavirus testing to detect high-grade squamous intraepithelial lesions.

Persistent genital human papillomavirus infection as a risk factor for persistent dysplasia. J Natl Cancer Inst ; Is it an alarm for recurrence? Gynecol Oncol ; Human papillomavirus is a necessary cause of invasive cancer worldwide. J Pathol ; The role of human papillomavirus in cervical adenocarcinoma carcinogenesis. Eur J Cancer ; Virchows Arch ; Guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus.

Ann Intern Med ; Incidence of cervical squamous intraepithelial lesions in HIV-infected women. JAMA ;


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