SUMMARY One hundred cases oftransitional cell carcinoma ofthe bladder were studied to determine whether squamous metaplasia and other histological features within the bladder can be of value in predicting outcome of treatment with radiotherapy. Sixty cases showed the changes of squamous metaplasia, and of this group 46 (78%) failed to respond to radiotherapy. A significant response rate of 90% was seen in the 40 tumours without squamous metaplasia.It is concluded that transitional cell carcinomas of the bladder showing squamous metaplasia are mainly resistant to radiotherapy and alternative treatment methods should be sought.The heterogeneity of invasive bladder carcinoma has prompted many studies of histological features in an attempt to relate these to prognosis.`13 Most studies have been performed on radical cystectomy specimens, and there is little information about the histological features in transurethral resection material which may be relevant to the prognosis of patients, especially those treated with radiotherapy.The presence of squamous metaplasia is well recognised in transitional cell carcinoma of the bladder,45 but its importance for prognosis is not known. It has been shown that squamous cell carcinoma of the bladder is more resistant to radiotherapy than its transitional cell counterpart,67 and this aroused our interest in the responsiveness to radiotherapy of transitional cell carcinomas showing squamous metaplasia.It has been suggested that if radioresponsiveness of the tumour could be predicted more accurately before irradiation then non-responders could be offered alternative treatment including early cystectomy. We therefore undertook a study to determine whether the histological features of invasive transitional cell carcinoma of the bladder were related to or could be used to predict the response of the tumour to radiotherapy. Material and methodsFrom the records of the departments of urology and histopathology at this hospital 111 patients with muscle invasive transitional cell carcinoma of the bladder were identified (International Union Against Cancer (UICC) and American (Jewett) classification Accepted for publication 6 October 1988 stage T2/T3).' These patients presented between 1980 and 1985 and had received radiotherapy. Six cases with invasion of the prostate (UICC stage 4) were excluded as this group is recognised as having a poor prognosis and as being resistant to radiotherapy.8 In five cases the original pathology material was unavailable, thus leaving 100 cases. The mean age of patients was 68 3 years, range 33-85. There were 78 men and 22 women.The histological sections were processed from tissue fixed in 10% formol saline by standard techniques and stained with haematoxylin and eosin. The original tumours before treatment had been reviewed independently by three pathologists (JM, RZ, SB) unaware of the clinical outcome. Between one and seven blocks of tissue were available in each case (mean 2.6).The sections were assessed for grade using the WHO classification,5 degree and...
A retrospective analysis of the prognostic value of pretreatment histology and expression of human chorionic gonadotrophin (B-hCG) was carried out in 100 invasive (T2/T3) transitional cell carcinomas of the bladder treated in a uniform manner. After transurethral resection of the tumour, all patients received a course of radical radiotherapy, with salvage cystectomy for those who failed to respond. Forty-nine of 100 patients responded to radiation; thus 51 did not. Forty-seven of 60 (78%) patients whose tumours contained areas of squamous differentiation and 22 of 29 (76%) of tumours staining positively for HCG failed to respond to radiotherapy. Twenty-two of 23 (96%) patients with tumours that had both these features did not respond to radiotherapy. The other histological features studied (grade of tumour, necrosis, inflammation, vascular invasion, and growth pattern) appeared unrelated to each other or to clinical outcome.
LondonSUMMARY A retrospective study of 15 patients with primary dysplasia of bladder urothelium was performed in an attempt to clarify some of the clinical and histopathological features. The lesion occurs predominantly in middle aged men who present with irritative bladder symptoms with or without haematuria and show no evidence of bacteriological urinary tract infection. Appearances at cystoscopy are non-specific. Thirteen patients showed no progression to carcinoma in situ after a long period of follow up, but primary dysplasia cannot be regarded as an entirely innocuous condition as the remaining two patients did develop carcinoma in situ. The grade of dysplasia on presentation bears no relation to the final outcome. Regular cytological analysis of urine seems to be the best means of follow up, and more active treatment does not seem to be justified.Over the past 30 years, following early work by Melicow and Hollowel in 1952' and Melamed, Voutsa, and Grabstald in 1962,2 interest in bladder carcinoma has focused on the early stages of tumour development. These stages included dysplasia (or "atypical hyperplasia")3 and transitional cell carcinoma in situ (CIS). Experimental studies on animals suggest that bladder cancers usually grow slowly through several stages of increasing dysplasia to invasive tumours.4In patients with overt bladder cancer or patients undergoing follow up of previously treated transitional cell carcinoma a complete search of the bladder mucosa often shows that macroscopically normal epithelium is histologically abnormal, with changes varying from minor degrees of dysplasia to CIS" This concomitant or secondary dysplasia or CIS is much more common than that found in the absence of exophytic bladder cancer-that is, primary dysplasia and primary CIS.Little is known about the clinical presentation, natural history, or incidence of primary dysplasia of the bladder. We performed a retrospective study on patients with this condition in an attempt to assess the features of primary vesical urothelial dysplasia.Accepted for publication 23 June 1988 Material and methods Cases ofbladder urothelial dysplasia were found in the files of our pathology and urology departments. Forty cases of dysplasia were identified. From this group 25 cases were excluded because the histological features were not those of dysplasia, or the patient had confirmed bladder carcinoma.Multiple mucosal biopsy specimens had been taken on each of the remaining 15 cases, the histology of which was reviewed by three pathologists without knowledge ofthe clinical history. Histological features were graded according to the criteria used by Nagy, Frable, and Murphy9: (a) Mandatory features degree of change of urothelial polarisation; presence or absence of superficial cells; variation in nuclear size; presence of nuclear crowding; degree of nuclear irregularity; chromatin structure.
The original pre-treatment histological sections from 125 patients with invasive (T2/T3) transitional cell bladder cancer treated by radical radiotherapy were studied; 63 tumours responded completely to radiation and 62 did not; 55 of 72 tumours containing areas of squamous metaplasia and 27 of 36 staining for beta-human chorionic gonadotrophin failed to respond to radiotherapy; 26 of 28 tumours showing both squamous metaplasia and beta-human chorionic gonadotrophin did not respond to radiation, whereas 40 of 45 tumours without either of these features responded. The DNA ploidy of 86 tumours in the series was measured by flow cytometry; 11 of 27 aneuploid and 30 of 59 diploid tumours responded to irradiation. Squamous metaplasia and beta-human chorionic gonadotrophin in bladder cancer indicate resistance to radiotherapy but DNA ploidy does not.
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