Pathology

NOMENCLATURE OF PRECANCEROUS SQUAMOUS LESIONS OF CERVIX

NOMENCLATURE OF PRECANCEROUS SQUAMOUS LESIONS OF CERVIX

The nomenclature of precancerous lesions of the cervix has undergone several changes. in the past four decades. No classification is free of drawbacks and universally accepted. However, attempts are being made to bring about a uniformity of terminology which can be interpreted and understood by the colposcopists, cytologists and the histopathologists.

Reagan et al. (1953) introduced the term “dysplasia” for atypical hyperplasia of cervical epithelium.Later Reagan et al. (1957) divided dysplasia into four categories of mild, moderate and severe dysplasia for early lesions depending upon the severity and “carcinoma-in-situ” (CIS) for lesions that showed alteration of full thickness of epithelium.P This nomenclature was widely accepted and recommended by WHO (1973).60 However, this classification implied that dysplastic lesions were not premalignant; only CIS meant preneoplasia, indicating two separate processes. Therefore, it did not convey the concept of continuum of change in carcinogenesis according to our present understanding. It also created problems in patient management since sometimes dysplasias were not treated.

Cervical intraepithelial neoplasia (CIN) is a more appropriate terminology. It is subdivided into CIN 1, CIN Il and CIN III according to the severity of cellular alterations.V This terminology has been widely accepted around the world but has its drawbacks because neither all early lesions are premalignant nor all advanced lesions progress to neoplasia. Some object to the term “neoplasia” as a given lesion at a given time may not be neoplastic and may have only neoplastic potential. “Neoplasia” also has sinister connotation and scares the patients.

For these reasons another nomenclature was developed in 1988 at a meeting convened at the National Cancer Institute (NCI) in Bethesda’? where it was decided to delete the word “neoplasia” and replace it with the term “lesion”. This was called the Bethesda System (TBS) and was modified again in 199] .43 The entire spectrum of abnormalities from earliest to advanced lesions were included and were called Squamous Intraepithelial Lesions (SIL). Since many clinical and laboratory studies advoc~ted the two tier system of classification, SIL was divided into Low-grade SIL and High-grade SIL depending on the severity of cellular alterations. Low-grade SIL includes HPV changes, koilocytoatypia, condyloma, CIN 1. High-grade SIL includes qN Il, III and CIS.

Since CIN classification is well founded and accepted by most of the laboratories, Richart in 1990 acknowledging the concept of two tier system divided CIN into Low-grade CIN and High-grade CIN. Koss in 1992 devised yet another classification of precancerous lesions into Early Borderline Lesions for minimal changes and Well Developed Borderline Lesions for more advanced changes.

NOMENCLATURE OF PRECANCEROUS GLANDULAR LESIONS OF CERVIX

An increase in the incidence of adenocarcinoma of the cervix in young women below the age of 35 years in the last three decades has aroused an interest in precancerous glandular lesions of cervix. Helper et al. in 1952 for the first time described glandular lesions showing highly atypical endocervical glands adjacent to frankly invasive adenocarcinoma of cervix, Friedell and Makay in 1953 also found two similar cases and coined the term Adenocarcinoma-in-situ (AIS) for these abnormalities. However, subsequently it became apparent that not all cases had severe enough abnormalities to be labelled as AIS. Cases with less severe cellular abnormality have been called endocervicaldysplasia, 11 Endocervical glandular dysplasia (EGD) and atypical hyperplasia.Pc Brown
and Wells (1986) divided EGD into low grade and high grade EGD depending upon the severity of cellular alterations’”. Jaworsky (1990) however does not advocate the subdivision.P Gloor and Hurlimann (1986) on the analogy of squamous lesions classified abnormal glandular lesions as Cervical Intraepithelial Glandular Neoplasia (CIGN) and divided into three grades of I, Il and III depending upon the severity of cytologic abnormality and mitotic activity.” CIGN I and Il corresponded to atypical hyperplasia and CIGN III corresponded to AIS: Since there is no conclusive evidence based on scientific data to show that CIGN I and Il are truly neoplastic lesions and progress to invasive adenocarcinoma, Kurman et aJ. (1992) prefer to use the term Atypical Endocervical Hyperplasia for these lesions.

NATURAL HISTORY OF PREMALIGNANT LESIONS

Natural history of precancerous lesions is considered a dynamic process characterized by progression, persistence or regression. Several epidemiological studies have now established that high grade lesions are more likely to progress to invasive cancer than low grade lesions over a period of 5-15 years.t? Oster (1993) in his review using life table analysis found that for CIN I the likelihood of regression was 57%, of persistence 32%, of progression to CIN III 11 % and to invasive cancer 1 %49. Comparable figures for CIN Il are 43%, 35%, 22%, 5%; and for CIN Ill, 32% regress, 56% persist and 12% progress to invasive cancer. It is important however to note that it is not a must that all low grade lesions progress through high grade lesions to invasive cancer since many low grade CIN lesions may progress to cancer without intervening stages of II-III and many high risk lesions arise de novo .

The risk factors for the development of precancerous lesions are similar to those implicated in the carcinogenesis of invasive cancer, namely early age at marriage, multiple partners, promiscuity, smoking, tobacco chewing, oral contraceptives and genital infections particularly human papilloma virus infection.

HPV infectum has received much attention in the last two decades and the detection of HPV DNA in lesions has become an important adjunct to diagnosis of precancerous lesions.F It has been documented in many studies that the majority of low grade lesions are associated with low risk HPV 6, 11 and high grade lesions show high risk HPV types 16, 18, 30, 33, 35. HPV subtyping in abnormal Pap smears can be used in management of cases. The role of HPV infection in carcinogenesis has been dealt with in a separate chapter.