Flat in situ carcinoma of the bladder: cytological examination of urine in diagnosis, follow up, and assessment of response to chemotherapy.

Urine cytology was performed for the diagnosis and follow up of flat carcinoma in situ (CIS) of the bladder in a series of 35 patients without associated or previous bladder tumours. Ninety six per cent had positive or suspicious cytology at initial presentation. There were no false positive reports. Cytological diagnosis of malignancy was made before biopsy in 24 patients: CIS in voided urine presents as flat sheets of five to 15 cells with features of high grade malignancy. Development of tumour during follow up was suggested by the appearance of large thick sheets and clusters of 30 or more malignant cells which were large and pleomorphic in high grade tumours and relatively small and closely cohesive in low grade tumours. Eleven of 13 patients with these clusters had bladder or ureteric tumours and two had malignant disease in the prostate. Negative cytological results in the presence of degenerative changes caused by chemotherapy was an unreliable indicator of response to chemotherapy, and there were five patients with false negative reports during treatment, of whom three had developed tumour. Persistence of malignant cells with features similar to those seen in the urine before treatment reliably predicted failure to respond to chemotherapy.

Diagnosis of metastases from testicular germ cell tumours using fine needle aspiration cytology.

The cytological features of testicular germ cell tumours were established in smears from 15 freshly resected tumours. These features were applied to the fine needle aspiration cytology diagnosis of metastases in 27 patients referred for chemotherapy. There were 16 positive reports in 32 aspirates of which 13 were taken before chemotherapy and three in patients with residual or new masses after chemotherapy. Teratomas and typical seminomas showed certain characteristic morphological features in cytological preparations which when present in fine needle aspiration cytology material enabled tumour types to be diagnosed. Spermatocytic and anaplastic seminoma were not represented in this series. It is unlikely that these could be distinguished from malignant teratoma undifferentiated (MTU) in the fine needle aspiration cytology material. Metastases from carcinomatous areas in MTU and malignant teratoma intermediate (MTI) may not be distinguishable in fine needle aspiration cytology material from metastatic adenocarcinoma or undifferentiated carcinoma from a different primary site. Positive cytological findings are of value to the oncologist in the management of patients with metastases from testicular germ cell tumours; negative cytology does not exclude the presence of viable tumour. The sampling of small foci of viable tumour in large necrotic masses persisting after chemotherapy is a problem for radiologists, cytologists, and histopathologists. This paper does not advocate the use of fine needle aspiration cytology for the diagnosis of primary testicular tumour.

Tissue culture model of transitional cell carcinoma: characterization of twenty-two human urothelial cell lines.

Twenty-two continuous cell lines derived from normal and neoplastic urothelium, maintained under identical culture conditions, were characterized in terms of isozyme phenotype, tumorigenicity, and xenograft morphology following xenotransplantation to nude mice, cytological appearance, in vitro growth rate, labelling index, and colony-forming efficiency, in parallel with separate studies of in vitro drug sensitivities and monoclonal antibody reactivities. Three groups were identified: (a) distinct lines with differing isozyme patterns, a broad spectrum of growth characteristics, and xenograft morphologies similar to the histopathology of the parent tumors after periods of up to 17 yr following establishment in vitro; (b) cross-contaminated sublines (maintained separately in different laboratories for periods of up to 10 yr), with identical isozyme patterns and similar growth characteristics, but differing markedly in tumorigenicity and xenograft morphology; and (c) lines derived from normal urothelium which were nontumorigenic and had an isozyme pattern usually only encountered in untransformed cells. These data indicate that cell lines representative of human transitional cell carcinomas can be selected on the basis of xenograft morphology and isozyme patterns, and that a panel of lines derived from normal and neoplastic urothelium could provide a model system to study the biology and treatment of this disease.

Transitional carcinoma of the upper urinary tract: a histological and cytopathological study.

A histological and cytopathological study of 54 patients with transitional carcinoma of the upper urinary tract was undertaken. There were 17 patients with grade 1 tumours, 35 with grades 2 or 3, and two with carcinoma in situ. Only 16 had non-invasive tumours. A preoperative cytological diagnosis of tumour was made in 67% of the group as a whole and in 75% of patients with grade 2 or 3 tumours. Seventy per cent of voided urines and 80% of ileal conduit urines were positive for tumour. Cytological grading correlated with histology in 12 of 14 grade 1 tumours and 26 of 35 grade 2 or 3 tumours, with seven assigned grade 1. Two cases of pelvicalycine carcinoma in situ were graded 3 by cytology. Cytological investigation by those experienced in urinary cytology has an important diagnostic contribution to make in transitional carcinoma of the upper urinary tract.

Methotrexate, cisplatin and carboplatin as single agents and in combination for metastatic bladder cancer.

A review of 78 previously untreated patients with bidimensionally measurable metastatic bladder cancer who were entered into a series of studies of cytotoxic chemotherapy has shown that complete response occurred in 1 of 23 patients receiving methotrexate, none of 15 receiving cisplatin, none of 20 receiving the platinum analogue carboplatin and 3 (2 with histological confirmation) of 20 receiving methotrexate in combination with cisplatin. WHO/UICC performance status 3 and 4, though a prediction of lower response, did not provide a means for excluding patients who might benefit from chemotherapy. Studies using serial cytology showed that 5 of 8 responders according to standard criteria had complete loss of malignant cells from the urine compared with none of 10 non-responders and there was a suggestion that duration of response was longer in those whose urine was negative for malignant cells than in those which remained positive.

The value of fine needle aspiration cytology in the management of metastatic germ cell tumours.

Review of 19 patients with advanced metastatic malignant teratomas has revealed five serious complications possibly related to the surgical biopsy procedure, three of which led to the patient's death. Preliminary results from a small series of patients diagnosed by fine needle aspiration (FNA) cytology suggest that this procedure is a reliable alternative method for diagnosing these patients. In addition, when used after chemotherapy this procedure may save patients with residual malignancy from having to undergo post-treatment surgical staging. However, the absence of malignant cells in the aspirate cannot exclude malignancy because of the focal distribution of residual tumour in these masses.

Urinary cytology in inverted papilloma of the lower urinary tract.

Urinary cytology is reported in six cases of inverted papilloma of the bladder. Abnormal features were found in five of the six cases. These were essentially an increase in the number of single or small clusters of degenerate transitional cells. As their cytologic features fell within the range of normal but degenerate transitional epithelium, a diagnosis of transitional cell tumor was not possible in these cases. Histologic features suggest that the desquamating cells may be derived from the surface epithelium of the papilloma, the underlying cords and trabeculae, or from the adjacent transitional epithelium.