Terminology of the BSCC, European Community and the Bethesda system: the boundary between low‐grade and high‐grade cytology

Field: Medicine (Health Sciences)

The Bethesda system (TBS) is used in so much of the world that it has gone a long way towards standardizing the terminology of cervical cytology.1 The EU Guidelines for Quality Assurance in Cervical Cancer Screening recommend that all systems should use the framework of TBS2 and the British Society for Clinical Cytology (BSCC) proposes to move closer towards that system.3 Atypical squamous cells (ASC) and atypical glandular cells (AGC), known as borderline in the BSCC system, are categories used for the uncertain divide between normal and abnormal that exists in any screening process. However, it appears to us that neither TBS nor the BSCC revised terminology have dealt satisfactorily with the indistinct boundary between low-grade and high-grade squamous intraepithelial lesions (LSIL and HSIL). Blanks,4 in an editorial published along with the BSCC revised terminology,3 drew attention to the potential for misclassification of intermediate cases in any 2-tier classification. This is clinically relevant with a classification that attempts to separate two very different entities – potentially reversible low-grade lesions and high-grade precancerous lesions warranting immediate investigation and treatment. Two articles from different perspectives in this issue5,6 demonstrate that this is an issue that needs to be clarified. Hunter et al analyse both the morphological features and histological outcome of cases described as LSIL, cannot exclude HSIL (LSIL-H) and compare them with ASC, cannot exclude HSIL (ASC-H).5 The outcome in terms of positive predictive value (PPV) for CIN2 or worse was similar to ASC-H and the classification and regression tree analysis (CART) demonstrated that high nuclear/cytoplasmic ratio was the morphological feature most predictive of a high-grade histological outcome in both entities. Nevertheless, there were distinct qualitative differences between LSIL-H and ASC-H. The former includes cases with “unequivocal features of LSIL with rare cells suggesting HSIL” while ASC-H is a sub-group of ASC, which is defined as category in which there is genuine doubt as to whether the changes are reactive or neoplastic. Thus ASC-H should exclude cases with unequivocal features of LSIL; it should also exclude “dysplasia with borderline nuclear cytoplasmic ratio”, which is another feature of LSIL-H mentioned by Hunter et al. TBS recognizes cases intermediate between HSIL and LSIL and describes them as SIL without explaining on which side of the fence they should reside. Traditionally, the BSCC includes cases of dyskaryosis, grade uncertain with moderate dyskaryosis, which would place them with high-grade dyskaryosis in the revised classification. Nayar and Solomon, in a letter in the December issue of Cytopathology, indicated that intermediate cases should be classified with HSIL.7 However, Hunter et al refer to a growing number of articles using the category LSIL-H. They very reasonably point out that although the outcome is similar to ASC-H the PPV is significantly higher than for LSIL and lower than for HSIL. In other words, they describe an intermediate category that has emerged for the very reason that was so eloquently illustrated by Blanks;4 an average-sized man could equally well be classified with individuals suffering from achondroplasia as from acromegaly. There has to be some way of describing the intermediate group and it would help if we could agree as to whether it should effectively be included with LSIL or HSIL. This seems particularly relevant now that the European Community has agreed to use TBS as the framework for their diverse classification systems, many of which use a 3-tier system.2 How much does this intermediate group matter in clinical practice? Part 2 of the EU guidelines on clinical management of abnormal cytology6 recommends that in cases with high-grade cytology not confirmed at colposcopy “the TZ (transformation zone) should be excised in its entirety; this should be combined with an endocervical curettage.” While the guidelines recommend review of the cytology and say that “ideally, all cases with discrepant high-grade cytology, colposcopy or histology findings should be discussed in a multi-disciplinary forum to optimise management” it is understandable that cytologists would want to preserve their PPV for high-grade dyskaryosis and perhaps could do so by identifying intermediate cases in which the changes were less certain. Should we simply retain the distinction between moderate and severe dyskaryosis as allowed in the EU guidelines? Prendiville, in an editorial accompanying the article on the revised BSCC terminology believes that the moderate category should be retained to allow triage and potentially more conservative management in some women with high-grade cytology.8 It is likely that most of the intermediate cases described by Hunter et al would be classified in the UK as moderate (or ungraded) dyskaryosis rather than severe; with that option available such cases are less likely to be classified as mild dyskaryosis (equivalent to LSIL-H). There is no doubt that the outcome is very different for moderate and severe dyskaryosis. During 2007-08 in England as a whole, an outcome of CIN1 or less was found in 32.2% of women referred for colposcopy with moderate dyskaryosis compared with 12.0% with severe while CIN3 (which is at greater risk than CIN2 of progressing to invasive cancer) was found in 33.5% with moderate dyskaryosis compared with 70.1% with severe (Figure 1). Percentage colposcopy outcomes by referral smear (data from 2007/8 KC61 part C2 return for all laboratories in England). The main reason for the BSCC recommending a 2-tier system was that most cytologists find it difficult to divide high-grade cytology into two categories and are conscious of the poor reproducibility of moderate dyskaryosis, which is equally likely to predict CIN2 as CIN3 (Figure 1). The great advantage of the revised BSCC classification would be the convenience of using the term high-grade dyskaryosis for the majority of cases in which HSIL was undoubtedly present and in which the differential diagnosis was between moderate and severe. In our view, what is needed is a term or category to describe cases that are described by Hunter et al as LSIL-H; but we would prefer it to be a sub-group of HSIL that indicates a lower risk of progression to invasive cancer. Perhaps a slight modification of the definition of moderate dyskaryosis would be enough; to do away with the idea that we can measure nuclear/cytoplasmic ratio with such accuracy and to identify cases that only just make it into that category (and favour CIN2 rather than CIN3) or that contain a small population of high-grade dyskaryosis in a background of low-grade. That would allow us to maintain a clinically useful PPV for the majority of cases and would help colposcopists to decide when they should consider carrying out excisional treatment on women with high-grade cytology that is not confirmed at colposcopy. We are grateful to Roger Blanks of the Cancer Screening Evaluation Unit for providing Figure 1.