DNA-cytometric diagnosis of prospective malignancy in borderline lesions of the uterine cervix

Interactive DNA cytometry was used for the diagnosis of prospective malignancy in 48 smears with borderline lesions (mild and moderate dysplasias) of the uterine cervix. In addition, 183 smears with benign squamous epithelia, 38 with carcinoma in situ and 7 with invasive squamous carcinoma were also measured. Nuclear Feulgen-DNA measurements were performed using various methods, and the resulting data were analyzed by an algorithm for a DNA-cytophotometric diagnosis of malignancy. The results were compared with the data on follow-up and subsequent histologic studies in these cases. There was no false-positive diagnosis in the 183 benign smears and only 1 false-negative diagnosis in the 76 histologically proven squamous-cell carcinomas, which yields a specificity of 100% and a sensitivity of 98.6%. The sensitivity for the detection of subsequent histologically proven malignancy in cases with cytologically mild or moderate dysplasia amounted to 97%. In 13 borderline cases, there was a mean interval of 21 months between the taking of the cytologic smear on which the DNA diagnosis of malignancy was made and the date on which the histologic confirmation of malignancy was made. In 17% of the cytologically dysplastic cases, the DNA diagnosis of malignancy was not verified by subsequent histologic investigation. These results indicate that interactive DNA cytometry is able to detect prospective malignancy in smears from borderline lesions of the uterine cervix with a high sensitivity.     

DNA flow cytometry of pleural effusions. Comparison with pathology for the diagnosis of malignancy

A study was undertaken to determine the potential value of DNA flow cytometry (FCM) for the diagnosis of malignancy in pleural effusions and to compare its results with those of traditional cytomorphology. Forty-one pleural fluids from 37 patients were evaluated by DNA FCM and routine cytologic techniques. Of the 41 pleural fluids, 29 (70.7%) demonstrated an abnormal DNA content by FCM. Two of the 29 pleural fluids had been originally diagnosed as benign by cytology. Cytologic review of these two cases showed no abnormal cells; therefore, there were no false-negative cases based on cytology. In 12 (29.3%) of the 41 fluids, DNA FCM and cytologic evaluation both indicated benign processes. Our preliminary observations indicate that FCM is an accurate and reliable technique that may be of aid in the diagnosis of malignant effusions. The technique may prove to be of special value in the differential diagnosis of reactive mesothelial cells versus malignant mesothelioma as well as for following patients who receive chemotherapy for malignant pleural effusions. DNA FCM may also complement cytomorphologic diagnoses in other serous, exfoliative or aspiration material.     

Role of biliary brush cytology in primary sclerosing cholangitis

OBJECTIVE: To assess the role of brush cytology in the routine evaluation of patients with primary sclerosing cholangitis (PSC). STUDY DESIGN: From January 1995 to June 2000, 64 brush cytology specimens were obtained from 21 patients who had at least one cytologic sample obtained during endoscopic retrograde cholangiography. All patients had a diagnosis of primary sclerosing cholangitis. Cases were classified as benign, atypical or malignant according to major cytologic criteria (nuclear contour and chromatin irregularities) and minor cytologic criteria (polarity, cellularity, nuclear enlargement, mitosis, increased nuclear/cytoplasmic ratio) used by us to diagnose biliary brush cytology. Follow-up was available in all cases. RESULTS: Diagnoses were benign (13), atypical (5) and malignant (3) on cytology. Follow-up of the 13 benign cases showed bile duct stones (2), gallbladder adenocarcinoma at cholecystectomy (1), ascending cholangitis (1) and clinically/cytologically by benign follow-up (9). Five of 13 benign cases had subsequent liver transplantation for liver failure, with explants showing changes of primary sclerosing cholangitis. Of the 3 malignant cases, 1 had carcinoma in situ on biopsy, with the explanted liver showing high grade dysplasia; the second patient had cholangiocarcinoma on explant; and the third had hepatocellular carcinoma on liver five needle aspiration. The 5 patients with atypical cytology were reclassified on review as reactive (3) and atypical not otherwise specified (2). Follow-up showed benign disease in 3 of 3 atypical cases reclassified as reactive; 2 of 2 reclassified as atypical not otherwise specified showed low grade dysplasia in the explant. CONCLUSION: The overall incidence of malignancy was low (3 of 21) in patients with PSC. Bile duct brushing is a sensitive method of detecting neoplasia in the setting of PSC when well-defined cytologic criteria are applied.     

Diagnostic significance of "severe dysplasia" in sputum cytology

The diagnostic significance of a cytologic diagnosis of "severe dysplasia" on sputum samples was assessed. In a group of 46 patients with diagnoses of severe dysplasia, follow-up showed no malignancy of the lung in 25 patients (54%) and a malignant process in 21 patients (46%). These groups were compared to 52 patients with correct negative and 202 patients with correct positive sputum diagnoses. Of the patient characteristics investigated, age, previous sputum production, vital capacity and low forced expiratory volume were not significantly related to a sputum cytodiagnosis of severe dysplasia. In contrast, severe dyspnea showed a significantly higher frequency in patients with a sputum cytodiagnosis of severe dysplasia, but without an underlying malignant lung process. Follow-up disclosed a malignant tumor in 10 of 13 patients with disease; the presence of severely dysplastic cells in sputum specimens from such patients should be considered a warning signal for an underlying malignant lung process. Since severe dysplasia should be considered a premalignant epithelial lesion, patients with sputum cytodiagnoses of severe dysplasia should undergo bronchoscopy, with multiple bronchial brushings of all areas showing suspicious mucosal changes, together with segmental bronchial washings. In case a malignant process cannot be located, sputum examinations should be repeated at three-month intervals.     

Rapid diagnostic DNA cytometry with an automatic microscope and a TV image-analysis system

A TV-based image-analysis system (Leitz TAS plus) combined with a Leitz automatic microscope was used for rapid DNA cytometry for diagnostic purposes. Malignant or suspicious cells found by the cytopathologists in conventionally stained smears were automatically relocated and measured. A program for automatic detection and measurement of nuclear DNA content was developed. DNA data are processed by an algorithm for the diagnosis and grading of malignancy. This diagnostic procedure is performed in real time and yields highly reproducible results. With this equipment, diagnostic DNA cytometry may be introduced in the routine cytology laboratory. Our mode of application does not replace the cytopathologist, but assists him or her in cases of doubtful diagnosis and in the grading of malignant tumors.     

O‐6RESPECTIVE ROLES OF FINE NEEDLE ASPIRATION CYTOLOGY AND CORE BIOPSY IN DIAGNOSIS OF SYMPTOMATIC BREAST LESIONS

Introduction: To evaluate and compare the respective roles of fine needle aspiration cytology and core biopsy for diagnosis of symptomatic breast lesions. Methods: Retrospective study on 589 breast fine needle aspiration cytology (FNAC) cases and 88 core biopsies (CB) with no associated FNAC, performed between January and December 2004. A computer database was searched for initial results, subsequent investigations and outcomes. Results: Of the cases that had FNAC performed as an initial investigation, the final diagnosis was reached by FNAC alone in 81.8% of cases. Of these, 59.2% were benign, 6.1% malignant and 2.4% remaining suspicious with 14.1% inadequate samples. There were 31 cases reported as suspicious (C3/C4) on FNAC, of these 14% of C3 and all of C4 were malignant on CB. Of the 86 cases that had both FNAC and CB, CB improved on the FNAC diagnosis of malignancy in 19.8% of cases, half of which were considered inadequate on FNAC. The positive predictive value of malignant cases was 100%, and the negative predictive value 98%. The absolute sensitivity of FNAC in this study was 65% and complete sensitivity 72%. The false negative rate was 8% and false positive rate 0%. The diagnosis of 88 CB without FNAC showed 37.5% to be malignant and 60.2% as benign, with 2.3% as inadequate biopsies. Discussion: FNAC remains the first line investigation in symptomatic breast lesions. Its best use is in the diagnosis of benign disease which constitutes over two thirds of patients in our practice. In suspicious and clinically malignant lesions, it is complemented by CB which may provide additional information relevant to management. In conclusion, the majority benign findings in our patients who had CB without prior FNAC, does not justify the use of CB as a first line investigation. CB is indicated in cases of inadequate or suboptimal FNAC. The continuous use of suspicious categories (C3/C4) in breast cytology is justified by the subsequent outcomes, both benign and malignant.     

An audit of 'equivocal' (C3) and 'suspicious' (C4) categories in fine needle aspiration cytology of the breast

An audit of 'equivocal' (C3) and 'suspicious' (C4) categories in fine needle aspiration cytology of the breast
We have audited the frequency of use and outcome of the 'equivocal/atypia probably benign' (C3) and 'suspicious of malignancy' (C4) category for breast cytology in our Unit. A total of 14 935 cytological specimens were reported by at least one of the three pathologists with a special interest in breast pathology, according to five categories of the NHSBSP guidelines for cytology reporting, 1992; 3.7% (555 cases) and 3.9% (587 cases) of cases were classified as equivocal (C3) and suspicious (C4), respectively, giving a total rate (C3 + C4) of 7.6%. Of the C3 cases, 68% were subsequently benign and 32% were malignant. Of the C4 cases, 19% were subsequently benign and 81% malignant. The commonest benign lesions in both categories were fibroadenomas (7.6% of C3 and 19.8% of C4), fibrocystic change (14.3% of C3 and 12.5% of C4), radial scars (6.2% of C3 and 10.4% of C4) and papillomas (6.2% of C3 and 6.3% of C4). Of the malignant lesions (particularly those classified as C3), a high proportion were low grade or special type cancers. The categories of atypia probably benign (C3) and suspicious of malignancy (C4) in breast cytology provide a strategy for classification of problematic or uncertain cases; this maintains the predictive value of the benign (C2) and malignant (C5) categories, and allows separation of these difficult cases into clinically useful groups with differing probabilities of malignancy.     

Abrasive bronchial brushing cytology. A preliminary study of 200 specimens for the diagnosis of neoplastic and nonneoplastic bronchopulmonary lesions

Two hundred subjects with chronic respiratory symptoms with a suspicion of malignancy were selected for bronchial brushing cytology. Prior sputum examination had shown malignant squamous cells in two cases only. The cytologic appearances of the brushing smears were divided into five categories: 41 (20.5%) smears with positively malignant cells; 20 (10%) smears predominantly showing chronic inflammatory features; 31 (15.5%) smears with mainly acute inflammatory changes; 60 (30%) smears with normal cytologic features; and 48 (24%) smears unsatisfactory for cytologic interpretation. Thirteen patients with a positive cytology had a positive tissue biopsy for malignancy. Among the group with chronic inflammatory changes, acid-fast bacilli were identified in nine cases, and one smear showed frank tuberculous granuloma. In the unsatisfactory group, two cases showed malignant cells in the postbrushing sputum. There was one false-negative report for malignancy in the entire study. This study confirms the sensitivity and accuracy of bronchial brushing cytology in the diagnosis of various bronchopulmonary lesions, especially malignancy and pulmonary tuberculosis, in India.     

Early diagnosis of mesothelioma in serous effusions using AgNOR analysis

OBJECTIVE: To compare the results of conventional cytology, DNA image cytometry, immunocytochemistry and argyrophilic nucleolar organizer region (AgNOR) analysis for the diagnosis of malignant cells in serous effusions. STUDY DESIGN: One hundred twenty effusions, 40 with carcinoses, 40 with malignant mesotheliomas and 40 without tumor cells on follow-up were studied by conventional cytology and three adjunctive methods. RESULTS: Unequivocal tumor cells were detected in 92.5% of effusions due to carcinoses and in 45% due to mesotheliomas. Applying immunocytochemistry with BerEP-4 positivity and DNA image cytometry with aneuploidy as a marker revealed 100% of carcinoses and 71.7% of mesotheliomas. Applying the experimentally found thresholds of 2.5 AgNORs as "satellites" and 4.5 AgNORs as "satellites and clusters" together as mean values per nucleus resulted in a 95% correct rate of mesothelioma and 100% rate of carcinoma cell identification without false positive diagnoses. CONCLUSION: AgNOR analysis may be a useful adjunct to other methods in the routine diagnosis of malignant serous effusions. It seems to be the most sensitive method in early cytologic diagnosis of mesotheliomas in effusions. Seventy-three percent of malignant mesotheliomas were diagnosed cytologically at first on effusions. Forty-seven percent of patients with malignant mesotheliomas were identified at the early tumor stage T1 N0 M0.     

DNA aneuploidy as a specific marker of neoplastic cells in FNAB of the thyroid

OBJECTIVE: To investigate whether DNA image cytometry (ICM) could be of value in the specific identification of neoplastic cells in cytologic specimens of the thyroid. STUDY DESIGN: FNABs of thyroid from 162 patients with different benign and neoplastic diseases were investigated. Nuclear DNA content in thyroid cells was measured after Feulgen staining using a TV image analysis system. Data were correlated with clinical and histologic patient follow-up. The occurrence of abnormal DNA stemlines was used as a marker for aneuploidy and thus for neoplasia. RESULTS: None of the 89 cases without tumor cells revealed DNA aneuploidy. An abnormal DNA stemline was found in 55% of histologically proven benign thyroid tumors (follicular or oncocytic adenomas) and in 59.5% of malignant tumors. The positive predictive value of DNA aneuploidy in FNABs of the thyroid for neoplasms was 100%. The negative predictive value of DNA nonaneuploidy for the prediction of tumor-free histologic or clinical follow-up was 79.4%. CONCLUSION: DNA image cytometry may be helpful in the specific identification of neoplastic follicular cells. DNA ICM on FNABs of the thyroid is an additional tool to achieve early identification of patients with nodular lesions of the thyroid that have to be operated on. DNA euploidy excludes the presence of neither malignancy nor neoplasia.     

Statistical analysis of fine needle aspiration cytology of the breast. A review of 678 cases plus 4,265 cases from the literature

Between 1979 and 1984, 678 breast fine needle aspiration (FNA) cytologic specimens were received in our laboratory; tissue follow-up was available for 159 cases (23%). The diagnoses rendered in cases with subsequent tissue study were benign (41%), insufficient (10.5%), atypical and/or suspicious for carcinoma (10.5%) and malignant (38%). Using the tissue diagnosis as the standard, there were four false-negative cytologic results and one false-positive result. Considering only cases with a definitive diagnosis of benign or malignant, the sensitivity of cytologic interpretation for diagnosing malignancy on adequate material was 94% while the specificity was 98%; the overall efficiency of the test was thus 96%. The predictive values were 98% for a positive test and 94% for a negative test. Of the total number of submitted cases, a correct and definitive diagnosis was rendered 76% of the time. Calculation of similar statistics from six other series in which the FNA cytologic diagnoses were compared with the histologic diagnoses yielded data almost identical to our findings. The high degree of uniformity in the data indicates that these statistical parameters can be used as standards for evaluating the efficiency of breast FNA cytology.     

Prediction of upper aerodigestive tract cancer by slide-based cytometry.

AIM: To evaluate slide-based cytometry in screening for and following up of carcinoma of the upper aerodigestive tract using swabs for a minimal-invasive approach. METHODS: Laser scanning cytometry (LSC) was used for multiparametric analysis of cells stained for cytokeratin and DNA to determine the DNA-index (DI) of the tumor cells. Histograms with 0.95 < DI < 1.05 and 1.9 < DI < 2.1 were defined as DNA euploid and any other DI as DNA aneuploid. After subsequent HE-staining, single cells were relocalized in order to document morphology. Conventional cytology was also performed on a subset of the slides. Routine histopathology of parallel biopsies served as gold standard in all cases. RESULTS: 115 swabs from 109 patients were obtained from the entire upper aerodigestive tract. 16 swabs were classified as insufficient for LSC. In the remaining 99 specimens, 1 benign lesion was misclassified as malignant, while 61 of the 75 malignant lesions were correctly identified. This corresponds to predictive values of 98.4% and 62.2% for the detection of malignant and benign samples by LSC. CONCLUSION: This pilot study demonstrates the validity of LSC screening for the identification of tumor malignancy in the upper aerodigestive tract from swab collected cytological material.     

Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomas

S. Schmid, M. Tinguely, P. Cione, H. Moch and B. Bode
Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomas Objective: Diagnosis of low grade non‐Hodgkin B‐cell lymphomas on cytological material may be problematic and in the past frequently required lymph node excision. We analysed our experience of the value of flow cytometry (FC) as an additional tool for the diagnosis of lymphoproliferative processes in the setting of a university cytology division with a busy fine needle cytology service. Methods: Consecutive cytological specimens with FC over a period of 3 years were retrospectively analysed and correlated with histology and follow‐up if available. FC was performed with the following antibodies: CD3, CD4, CD8, CD2, CD7, CD19, CD5, CD10, CD23, lambda and kappa chains. Results: Of 299 probes (273 fine needle aspirations and 26 fluids from 285 patients), 179 cases (60%) were diagnosed as reactive, 91 cases (30%) as malignant or suspicious and 29 cases (10%) as inconclusive. The results of histological examination of the lymph nodes were available in 41 of 91 (45%) malignant or suspicious cases and in 13 of 179 (7%) reactive cytological diagnoses. Cytologically diagnosed malignancy was confirmed in all histologically examined cases. In 12 of 13 reactive cytological cases (92%), a benign process was diagnosed histologically. In 34 of 299 cases (11%) additional molecular investigations of B‐cell clonality or specific translocations were performed. The lymphomas most frequently diagnosed were follicular lymphoma and lymphocytic lymphoma, followed by mantle cell and marginal zone lymphomas. Correlation with histology showed a sensitivity of 98% and a specificity of 100% for cytology in our series. Conclusions: FC is an important additional tool in the cytological diagnosis of lymphoproliferative disorders. The combined approach has a high diagnostic value that allows a reliable subclassification of low grade B‐cell non‐Hodgkin lymphomas.     

Analysis of fine needle aspiration cytology of the breast: a review of 1,297 cases and correlation with histologic diagnoses

OBJECTIVE: To evaluate the accuracy of fine needle aspiration (FNA) cytology of the breast and to ascertain its usefulness. STUDY DESIGN: The authors reviewed 1,297 cases of FNA cytology of the breast which were performed at Chonnam National University Hospital from 1999 to 2002. Cytologic diagnoses were compared with histologic diagnoses in 457 cases that underwent both cytologic and histologic examination. RESULTS: Of 1,297 cases, 1,201 (92.6%) were satisfactory and 96 (7.4%) unsatisfactory. Subsequent histologic examination was performed on 291 cases (29.7%) out of 981 "benign" lesions, 28 (73.7%) of 38 "suspicious," 124 (68.1%) of 182 "malignant" and 14 (14.6%) of 96 "unsatisfactory." FNA cytology revealed 77.7% sensitivity, 99.2% specificity, 98.4% positive predictive value and 88.0% negative predictive value. Diagnostic accuracy was 91.1%. Of the 291 benign cases on cytology, 35 cases were malignancy on histology. Of the 124 cases reported as malignant, 2 were benign. Interpretive error was the leading cause of false positive diagnoses. CONCLUSION: Although FNA cytology is a useful diagnostic procedure for the evaluation of breast lesions, it should be combined with other diagnostic modalities, such as physical examination, ultrasonography and mammography.     

Exfoliative cytodiagnosis of gastric adenocarcinoma. Comparison with biopsy and endoscopy

Endoscopy complemented by directed biopsies and exfoliative cytology was performed on 593 patients with different gastric lesions. Of the 194 cases of proven adenocarcinoma of the stomach, cytology was positive for malignancy in 176 (90.7%) and yielded the highest diagnostic rate. Endoscopy correctly diagnosed 171 cases (88.1%), and biopsy had the lowest accuracy, 153 cases (78.9%). The combined use of the three techniques increased the positive diagnosis to 185 adenocarcinomas (95.4%). Only three early gastric cancers were diagnosed by the combined methods, with only cytology positive in all three cases. There were five (1.3%) false-positive cytologic reports, principally due to benign gastric ulcers. It is concluded that these techniques have a complementary function in distinguishing benign from malignant gastric lesions. Since the value of endoscopic signs is limited, biopsy and cytology should always be performed. Exfoliative cytology plays an effective diagnostic role in cancer of the gastrointestinal tract and should be used more frequently by gastroenterologists, who, however, should be aware of the risk of false-positive results.     

The gray zone in breast fine needle aspiration cytology. How to report on it?

OBJECTIVE: To study the "gray zone" in breast fine needle aspiration cytology in which an unequivocal diagnosis cannot be reached with fine needle aspiration cytology findings. STUDY DESIGN: This study compared cytology and histopathology of 72 breast lesions in which an initial cytologic diagnosis of atypia was given. RESULTS: There were 36 benign (50%) and 36 malignant (50%) histologic biopsy cases in the cytologic atypia group. Anisonucleosis, chromatin and nuclear membrane irregularity, and presence of myoepithelial cells were significantly different in benign and malignant cases. CONCLUSION: The gray zone in breast fine needle aspiration cytology is a broad spectrum that changes from proliferative fibrocystic disease to sclerosing adenosis to malignancy. Diagnosing gray zone pathology as atypical in fine needle aspiration cytology causes no delay in treatment as excisional biopsy is recommended for all equivocal cases.     

Computed tomography-guided fine needle aspiration of peripheral lung opacities. An initial diagnostic procedure?

OBJECTIVE: To evaluate the results of computed tomography (CT)-guided fine needle aspiration (FNA) cytology following negative fiberoptic bronchoscopy and sputum cytology. STUDY DESIGN: Retrospective study of 64 patients who underwent CT-guided needle aspiration of lung opacities over one year. Following a review of the CT studies, patients were selected according to image characteristics of a primary neoplasm and pleural effusion in cases with pleural lesions. The lesions were classified into three categories--intrapulmonary and peripheral pulmonary, pleuropulmonary and pleural--and were localized and aspirated under CT using a fine needle (22-23 gauge) for obtaining cellular material. Lesions diagnosed as benign on FNA cytology were followed by serial CT scans for a period of two years at six-month intervals. RESULTS: Thirty-nine of 64 (61%) lesions were diagnosed as malignant on FNA cytology and 25 of 64 (39%) as benign. There was one false negative case. There were no serious complications from the procedure. CONCLUSION: FNA under CT guidance may be applied as the initial procedure in the diagnosis of peripheral malignant pulmonary lesions, rendering a high diagnostic yield.     

Brush cytology of gastric malignancies

OBJECTIVE: To compare endoscopic biopsy and cytology versus biopsy alone in the diagnosis of gastric malignancies. STUDY DESIGN: This prospective study included 229 cases referred for endoscopy for visible gastric lesions during a four-year period (1996-2000). Both biopsy and brush cytology were performed, and all the slides were screened by a cytotechnologist and reviewed by a pathologist. RESULTS: Of the 229 cases, 97 (42.4%) were proven to be malignant and 132 (57.6%) definitely benign. Biopsy was positive in 90 patients (92.7%), while brush cytology was positive in 85 (87.1%). Combined use of biopsy and brush cytology yielded higher diagnostic sensitivity (100%). CONCLUSION: Brush cytology is a safe, easy and rapid method of diagnosing gastric malignancies. Brush cytology is a useful adjunct in the diagnosis of gastric malignancies and should be considered a routine method in combination with biopsy. Multiple repeated endoscopies are recommended in cases of positive cytology and negative biopsy to rule out or confirm malignancy.     

Methodologic aspects of evaluating brush samples from biliary strictures by cytology and DNA flow cytometry

OBJECTIVE: To present a method of increasing the cell yield from brush samples of the biliary tree for measurement of DNA content by flow cytometry (FCM). STUDY DESIGN: One hundred eight cell specimens from 86 patients were studied by FCM for DNA ploidy and cell cycle composition. All specimens were cytologically classified into benign, suspicious for malignancy and malignant. Two methods for preparation of the cell material were compared. RESULTS: Enzymatic treatment of formalin-fixed brushes for release of cell nuclei was superior to mechanical removal of the cells. The fraction of samples not possible to assess was reduced from 27% to 4%, and good quality histograms increased from 21% to 62%. Aneuploidy was detected in 7% of benign and 57% of suspicious malignant samples. Using DNA analysis in addition to cytology as a diagnostic marker for cancer, the sensitivity increased from 12% to 31%. CONCLUSION: FCM of cells from biliary strictures can be used routinely as an adjunct to cytology for DNA analysis.     

The clinical significance of class III (suspicious) urine cytology

I. Sternberg, R. Rona, S. Olsfanger, S. Lew and I. Leibovitch The clinical significance of class III (suspicious) urine cytology Background: Urine cytology, combined with cystoscopy, is the mainstay of the diagnosis and surveillance of urothelial carcinoma (UC). While classes I and II urine cytology are considered benign and classes IV and V are considered malignant the clinical significance of class III urine cytology is unclear. We evaluated the positive predictive value of class III urine cytology for concurrent and subsequent UC. Methods: The records of all class III urine cytology cases during a 3‐year period were retrospectively reviewed for the presence of concurrent and subsequent UC, determined by cystoscopy and histological confirmation. Results: Of 111 cases, 54 (48.7%) were associated with concurrent UC and 14 (12.6%) with subsequent UC after an initial evaluation negative for malignancy, with a mean time to diagnosis of 10.8 months. Of 27 cases of class III urine cytology with no prior history of UC, 13 (48.1%) had concomitant UC and none had subsequent UC. Of 84 cases of class III urine cytology with a prior history of UC, 41 (48.8%) had a concomitant diagnosis of UC and 14 (16.7%) developed UC during their follow‐up, leading to a total of 55 (65.5%) cases of UC. Conclusions: Patients with class III urine cytology and a prior history of UC should undergo a full initial evaluation of their urinary tract, and should be followed vigorously if this evaluation is negative for malignancy. Patients without a prior diagnosis of UC and class III urine cytology should also undergo a full initial evaluation, while further larger studies are needed to elucidate the need for further follow‐up in such patients.