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Cytological Changes Preceding Cervical Cancer 27828 Clin Pathol 1994;47:278-279 Cytological changes preceding cervical cancer J H Robertson, B Woodend, H Elliott J Clin Pathol: first published as 10.1136/jcp.47.3.278 on 1 March 1994. Downloaded from Abstract invasive disease. However, recent studies of Cervical smears were reviewed from 62 cervical intraepithelial neoplasia (CIN), the women who developed squamous carci- histological counterpart of dyskaryosis, cast noma of the cervix up to 18 years later. doubt on this concept of the evolution of The findings indicate that the prevention cancer. 1 of cervical cancer by screening depends To investigate the relation between carci- very largely on the detection of severe noma and dyskaryosis we report a study dyskaryosis. In this series there was no based on 62 women with cervical cancer, evidence that mild dyskaryosis was a describing the cytology of positive smears forerunner of invasive disease. Cytology taken up to 18 years before diagnosis of the during the evolution of squamous disease. carcinoma is not characterised by a dyskaryosis which progressively in- creases in severity. Instead the findings Methods support new concepts that cervical can- Most of these 62 patients had been given cer generally arises from an aggressive false negative smear reports by a number of CIN 3 lesion widely present in the cervix, laboratories at varying intervals before the and in our series, established years development of carcinoma. The method of before invasion occurs. It would be more tracing the patients and their smears has been useful to report cytology as showing described before.3 The present study also either a low or high grade abnormality includes patients who had positive smear rather than distinguishing between dif- reports but who were lost to follow up and ferent degrees of dyskaryosis. later presented with invasive cancer. Only patients with fully invasive tumours were (7 Clin Pathol 1 994;47:278-279) studied, microinvasive disease being excluded, as were smears taken less than one year before diagnosis. Some of the patients http://jcp.bmj.com/ Varied patterns of dyskaryosis are encoun- were found to have had more than one smear, tered during cervical cancer screening. The but we describe here only the findings in the relation of these to squamous carcinoma of earliest smear showing any abnormality. Of the cervix remains uncertain, this being the 62 patients, 60 had squamous and two Department of especially so for mild dyskaryosis.1 The Cytopathology, Belfast adenosquamous carcinoma, their ages rang- City Hospital, Belfast uncertainty about mild dyskaryosis is com- ing from 27 to 74 years, 12 being less than 35 BT9 7AD pounded by the difficulty cytologists have years of age at the time of diagnosis of the on October 2, 2021 by guest. Protected copyright. J H Robertson in distinguishing it from the cellular cancer. B Woodend changes H Elliott of papillomavirus (HPV) infection.2 The Almost all of the smears were reviewed by of Correspondence to: grading dyskaryosis into mild, moderate, or the authors, the remainder by the original Dr J H Robertson severe suggests an epithelial lesion which pathologist. Initially, they were examined by Accepted for publication progresses in severity, eventually resulting in the first two authors (JHR, BW) 7 September 1993 indepen- dently to determine if dyskaryosis was present, and its degree. Evidence of papillo- mavirus infection was also noted. They were then 14- _ Severe dyskaryosis re-examined, with control smears by the Dyskaryosis, probably severe third author (HE) who at that time was 12- iJ Moderate dyskaryosis unconnected with the study and unaware of E3 HPV infection the patients' histories. The final opinion was reached by consensus among the reviewers. w8 El 10 Results Z A The figure illustrates the findings on review of the 62 smears taken from these patients at intervals over a period of 18 years before the diagnosis of carcinoma. In 51 of the smears 1 2 3 4 5 6 7 8 9 10 11 12 15 18 there was unequivocal severe dyskaryosis Years before diagnosis even many years before the cancer was diag- Results of review of cervical smears from 62 patients who subsequently developed nosed. In six smears the dyskaryosis was more carcinoma of the cervix. difficult to grade because fewer dyskaryotic Cytological changes preceding cervical cancer 279 cells were present and interpretation was hin- treatment of severe dyskaryosis and, to a dered by inflammatory changes. It was con- lesser extent, of moderate dyskaryosis. The sidered by the reviewers, however, that in predominance of severe dyskaryosis even in each smear the dyskaryosis was probably smears taken many years before the cancer severe. Dyskaryosis of moderate degree was develops is also difficult to reconcile with J Clin Pathol: first published as 10.1136/jcp.47.3.278 on 1 March 1994. Downloaded from present in the smears of four patients. No CIN lesions which gradually progress in instance of mild dyskaryosis was found. severity. This correlates with recent histologi- Only one smear showed the changes of cal studies which have found that severely HPV infection without associated dyskary- dyskaryotic smears are associated with exten- osis. In view of the current prevalence of sive CIN 3 lesions in the cervix. It was found HPV infection the smears were re-examined that squamous carcinoma arises from these to determine whether evidence of it had been rather than from the smaller CIN 3 lesions overlooked in the presence of dyskaryosis, but which are sometimes associated with mildly it could not be detected in any of the other dyskaryotic smears.'7 It was considered that smears. these pre-cancers arise not from progression of low grade CIN, but from expansion of a high grade lesion. Our cytological findings are Discussion in keeping with the evolution of squamous In these patients there was a predominance of carcinoma in this manner. They suggest that severe dyskaryosis in smears taken up to 18 the phase of expansion of aggressive CIN years before the diagnosis of carcinoma. In lesions often occurs many years before inva- contrast, we found little or no evidence of sive disease arises. If these findings are con- HPV infection or mild dyskaryosis. As noted finned it would be more logical to report by others,4 it was difficult to compare our cervical smear abnormalities as being either of results with some previous studies because of low or high grade as in the Bethesda system,6 variable nomenclature. Paterson et al (1984)5 rather than to distinguish between different described 34 smears taken up to eight years degrees of dyskaryosis and HPV infection as before a carcinoma as containing either is the current practice. malignant cells, cells suspicious of malig- We are grateful to all the pathologists who submitted or nancy, or severe dyskaryosis. No mention was reviewed cervical smears for this study. made of mild dyskaryosis or HPV infection. Stanbridge et al (1992)4 included in their study 43 smears taken up to 10 years before 1 Tidbury P, Singer A, Jenkins D. CIN 3: The role of lesion diagnosis of fully invasive carcinoma. Six size in invasion. BrJ Obstet Gynaecol 1992;99:583-6. 2 Richart RM, Wright TC. Controversies in the manage- showed mild dyskaryosis or evidence of HPV ment of low-grade cervical intraepithelial neoplasia. infection. These were all found in younger Cancer 1993;71:1413-20. 3 Robertson JH, Woodend B. Negative cytology preceding women, however, many of whom had smears cervical cancer: causes and prevention. J Clin Pathol 1994;47:700-2. taken while attending maternity clinics and at http://jcp.bmj.com/ 4 Stanbridge CM, Suleman BA, Persad RV, El-Khatib S. an age when these mild abnormalities are A cervical smear review in women developing cervical most common. Of those who developed car- carcinoma with particular reference to age, false negative cytology and the histologic type of the cinoma when over 40 years of age, all except carcinoma. IntJ Gynecol Cancer 1992;2:92-100. one, whose dyskaryosis was difficult to grade, 5 Paterson MEL, Peel KR, Joslin CAF. Cervical smear histories of 500 women with invasive cervical cancer in showed evidence of a high grade abnormality Yorkshire. Br MedJ7 1984;289:896-8. as in the Bethesda classification.6 6 National Cancer Institute Workshop, Bethesda (1989). The 1988 Bethesda system for reporting cervical/vaginal Our study suggests that mild dyskaryosis in diagnoses. Acta Cytol 1989;33:567-71. on October 2, 2021 by guest. Protected copyright. a cervical smear must be a very rare forerun- 7 Jarmulowicz MR, Jenkins D, Barton SE, Goodall AL, Hollingworth A, Singer A. Cytological status and lesion ner of invasive disease. The prevention of cer- size: a further dimension in cervical neoplasia. Br J vical cancer depends on the detection and Obstet Gynaecol 1989;96:1061-6..
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