Binary (Bethesda) system for cervical precursor lesions: A histologic perspective

Abstract

In the half century following Papanicolaou's observation that cervical carcinomas were not only preceded by precursor lesions but could be detected by cytologic screening, ' investigators have proposed a multitude of histologic/cytologic terms for these precursor lesions, have devised methods for their identification and removal in the outpatient setting, and have identified a potential causative agent (the human papillomavirus). The first major histologic classification in recent memory was proposed in 1962 by the International Committee on Histologic Terminology for Lesions of the Uterine Cervix and was predicated on the assumption that an undifferentiated intraepithelial neoplasm (carcinoma in situ, CIS) was a biologically distinct process. Lesions exhibiting less extreme alterations were variably termed dysplasia or "borderline" lesions. During this era, treatment options were limited largely to cone biopsy or hysterectomy, and a strict histologic definition of what constituted a precursor was considered desirable both to accomplish the removal of significant precursors and to avoid potentially unnecessary surgery. Over the ensuing decade, several observations by investigators have challenged the concept that dysplasia and CIS were distinguishable as separate entities: 1) dysplasia and CIS shared similar chromosomal derangements; 2) so-called mature forms of CIS-lesions overlapping with the higher grades of dysplasia-were about as much at risk of progressing to invasive carcinoma as classic CIS;4 3) the risk of CIS lesions in women with dysplasia was 20-fold that of the general population: 5*6 4) a follow-up of mild-to-moderate dysplasia disclosed CIS or worse in 40% of subsequent smears;5 and 5 ) the pro- jected incidence of invasive carcinoma in a population with a cytologic diagnosis of dysplasia was as much as 100-fold higher than that with documented normal smears. These and other observations provided the impetus for a classification system which merged the entities of dysplasia and CIS into one, i.e., cervical intraepithelial neoplasia (CIN). ' Coincidentally, colposcopy evolved as a practical method to identify lesions, punch biopsy replaced cone biopsy to define lesions histologically, and cautery, cryotherapy, and laser and, eventually, loop excision became available to remove most CIN lesions in the office setting. 's9 Inasmuch as triagehherapy became simplified by the advent of colposcopy and outpatient removal, management of cervical precursor lesions became based upon the identification of any abnormality within the spectrum of CIN. This philosophy has been encouraged in part by the legal system, which highlighted cases of invasive carcinoma occurring in association with mild Papanicolaou smear abnormalities, and the general assumption that when invasive carcinomas were missed, it was due to a failure to pursue a compulsive triage of precursor lesion identification and removal. l o Superimposed upon the emerging philosophy that all potential precursors should be removed was the discovery of papi...