Role of urinary NMP-22 combined with urine cytology in follow-up surveillance of recurring superficial bladder urothelial carcinoma

OBJECTIVE: To determine efficacy and utility of NMP-22 in follow-up of bladder urothelial carcinoma (UC) and compare NMP-22 as a single evaluating test vs combination with cytology. STUDY DESIGN: Ninety-four consecutive urine cytology samples of bladder UC were identified. Patients received follow-up urine cytology, NMP-22 testing and cystoscopy with surgical biopsy. RESULTS: NMP-22 specificity was 100%, sensitivity 45%, positive predictive value (PPV) 100% and negative predictive value (NPV) 87%. NMP-22 showed lower sensitivity for high-grade lesions and higher for low-grade lesions. Cytologic diagnosis had a high inconclusive rate; when regarded as positive, it resulted in 75% sensitivity, 58% specificity, 33% PPV and 89% NPV. NMP-22 correctly classified 60% of false negative cases diagnosed by cytology with low-grade UC and clarified 27 inconclusive cytologic diagnoses. NMP-22 misclassified 9 cases as false negative, all with high-grade UC; all were correctly identified on cytology as true positive. Combined interpretation showed 90% sensitivity, 92% specificity, 75% PPV and 98% NPV. CONCLUSION: NMP-22 complements cytology by its higher sensitivity for low-grade lesions; its values are not affected by bacillus Calmette Guérin therapy changes, which are limiting in cytology. Combined interpretation of NMP-22 and cytology shows promise as an effective, noninvasive method for surveillance of UC.     

DNA ploidy in seminal vesicle cells. A potential diagnostic pitfall in urine cytology

OBJECTIVE: To verify that abnormal DNA ploidy in urine cytology can occasionally be attributed to contamination by seminal vesicle cells. STUDY DESIGN: In the first part of this study, we analyzed the DNA content of six urine cytology specimens containing seminal vesicle cells. In the second part, we evaluated 21 Feulgen-stained prostate core biopsies containing seminal vesicle-type epithelium using a CAS-200 system. DNA index, proliferative activity (S + G2M) and degree of hyperploidy (> 5C) were determined in each case. RESULTS: All six urine cytology specimens were diploid, with all but one containing hyperploid cells (range, 0-16%; mean, 6.3%). Seminal vesicle cells from prostate biopsies showed a broad range of ploidy abnormalities. Ten cases (48%) showed an aneuploid peak, two cases (9%) showed a tetraploid peak, and nine cases (43%) showed only a diploid peak. All but one case showed both an elevation in proliferative activity (mean S + G2M, 24.2%) and some hyperploid cells (mean, > 5C; 4.5%). CONCLUSION: Seminal vesicle cells, although rarely seen in urine cytology, can cause abnormal DNA ploidy measurements. Morphologic criteria remain vital to an accurate cytologic diagnosis.     

Detection of MicroRNAs in Archival Cytology Urine Smears

MicroRNAs’ dysregulation and profiling have been demonstrated to be clinically relevant in urothelial carcinoma (UC). Urine cytology is commonly used as the mainstay non-invasive test for secondary prevention and follow-up of UC patients. Ancillary tools are needed to support cytopathologists in the diagnosis of low-grade UC. The feasibility and reliability of microRNAs profiling by qRT-PCR analysis (miR-145 and miR-205) in archival routine urine cytology smears (affected by fixation/staining [Papanicolau] and room temperature storage) was tested in a series of 15 non-neoplastic and 10 UC urine specimens. Only samples with >5,000 urothelial cells and with <50% of inflammatory cells/red blood cells clusters were considered. Overall, a satisfactory amount of total RNA was obtained from all the considered samples (mean 1.27±1.43 µg, range 0.06–4.60 µg). Twenty nanograms of total RNA have been calculated to be the minimal total RNA concentration for reliable and reproducible miRNAs expression profiling analysis of archival cytological smears (slope = -3.4084; R-squared = 0.99; efficiency = 1.94). miR-145 and miR-205 were significantly downregulated in UC samples in comparison to non-tumor controls. These findings demonstrate that urine archival cytology smears are suitable for obtaining high-quality RNA to be used in microRNAs expression profiling. Further studies should investigate if miRNAs profiling can be successfully translated into clinical practice as diagnostic or prognostic markers.     

Cystoscopic biopsy supernate. A new cytologic approach for diagnosing urothelial carcinoma in situ

The examination of cystoscopic biopsy supernates is a new cytologic procedure that can aid the urologist in the differential diagnosis of urothelial carcinoma in situ (CIS) and cystitis. Within the past two years, the Cytodiagnostic Urinalysis Laboratory has received 79 cystoscopic biopsy supernate specimens from 29 patients; these were prepared using a membrane filtration technique and stained with a modified Papanicolaou method. Positive diagnoses were rendered on 17 (21.5%) specimens, including 7 (41%) CIS and 10 (59%) papillary neoplasms. An 87% cytohistologic correlation was seen. Of the 17 cases with biopsy specimens that were denuded and thus nondiagnostic, 11 had negative supernate cytologies and 6 had positive cytologic diagnoses. Half of these positive specimens were diagnosed as CIS. Because urothelial CIS is often a friable lesion that yields denuded bladder biopsies, the cytologic examination of cystoscopic biopsy supernates offers a valuable adjunctive method for diagnosing urothelial CIS on otherwise lost cellular material.     

Expression of vimentin and high‐molecular‐weight cytokeratin (clone 34ßE12) in differentiating reactive renal tubular cells from low‐grade urothelial carcinoma cells in voided urine

H. Ohsaki, E. Hirakawa, M. Nakamura, Y. Norimatsu, H. Kiyomoto and R. Haba Expression of vimentin and high‐molecular‐weight cytokeratin (clone 34ßE12) in differentiating reactive renal tubular cells from low‐grade urothelial carcinoma cells in voided urine Objective: Reactive renal tubular cells show features of an atypical repair reaction. Differentiation between reactive renal tubular cells and low‐grade urothelial carcinoma (LG‐UC) cells can therefore be a diagnostic challenge based on morphology alone. In this study, we evaluated the diagnostic utility of vimentin and a high‐molecular‐weight cytokeratin antibody (clone 34ßE12) in differentiating reactive renal tubular cells from LG‐UC. Methods: We evaluated voided urine cytology and surgical specimens from 40 patients with renal disease, and 17 patients with LG‐UC. All slides were stained with vimentin and 34ßE12. Results: In the reactive renal tubular cells in voided urine cytology, vimentin showed strong cytoplasmic staining in 39/40 (97.5%) cases, but all were negative for 34ßE12. LG‐UC cells showed positive staining for 34ßE12 in 3/17 (17.6%) cases, whereas none were positivity for vimentin. The reactive renal tubular cells of histological specimens in the renal disease group demonstrated positive for vimentin in all 40 cases and all were negative for 34ßE12. The LG‐UC group showed abnormal staining for 34ßE12 in 4/17 (23.5%) cases, whereas none were positive for vimentin. Conclusions: Vimentin expression in urine cytology can help to distinguish reactive renal tubular cells from LG‐UC. However, 34ßE12 does not appear to be a useful adjunct to distinguish these two groups in voided urine cytology.     

Collection fluid helps preservation in voided urine cytology

Objectives:  Degenerative change caused by delay in processing contributes to false-negative and false-positive diagnosis of urothelial carcinoma in cytology. The aim of the study was to see if the use of a collection fluid for urine samples made a significant difference to urine cytology diagnosis, and if one was better suited for routine use in the hospital laboratory. Three cell collection fluids were evaluated by analysing the preservation and degeneration of cells in urine samples, as was the routine preparation which did not use a collection fluid.
Methods:  In the design study 50 voided urine specimens were taken at random from the hospital haematuria clinic. Three commercially available collection fluids cytolyt^TM, cytospin^® and cytoRich^®Blue and the hospital's routine conventional preparation of urine were compared. The degree of degeneration, and so preservation, was assessed by a table of chosen criteria; then ranked and analysed by Friedman's nonparametric test, at P  = 0.05. A second table showing the cell content of each slide was also made.
Results:  These showed no significant diagnostic difference between the collection fluids, but there was a significant difference between the collection fluids and the routine preparation. Minor differences that do not affect diagnosis, such as crystals and ghost red blood cells, were noted in cytospin^® and cytoRich^®Blue.
Conclusion:  It is recommended that a collection fluid is used. This choice should be made after health and safety issues and cost are considered.     

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.     

Urinary cytology in renal transplant recipients with stable graft functions

The utility of routine urinary cytology in renal transplant recipients was investigated. Slides of 79 urine samples obtained from 59 renal transplant patients shortly after transplantation and of 275 urine sediments from 126 patients who had received a transplant before 1978 were screened for abnormal urothelial cells. None of the samples taken within one year of transplantation contained malignant cells. For five patients transplanted before 1978, repeated cytologic examinations showed malignant cells, but neither urologic examination nor clinical nor postmortem follow-up studies revealed a tumor. In all five cases, the abnormal cells disappeared from repeat samples within two to three months. None of the other 121 patients, with repeatedly normal urinary cytologies, exhibited a urinary tract carcinoma in the 24-month follow-up period. It would appear that the cytologic findings in the urine of renal transplant patients who have received long-term immunosuppressive medication may be transiently abnormal.     

Superficial urothelial (umbrella) cells. A potential cause of abnormal DNA ploidy results in urine specimens

OBJECTIVE: To determine the DNA ploidy distribution in urothelial superficial (umbrella) cells and to assess the value of the image analysis operator's experience. STUDY DESIGN: DNA ploidy was assessed in 12 cytologically negative bladder washes stained with Feulgen stain. All 12 cases were evaluated independently by three operators with different levels of cytopathology experience and different goals. Operator 1 (experienced) selected only nuclei of urothelial cells, avoiding nuclei of superficial cells; operator 2 (experienced) selected only nuclei of superficial cells; operator 3 (inexperienced) selected the largest and most-atypical-looking nuclei. Each operator measured a total of 100 nuclei per case. RESULTS: Operator 1 found all cases to be diploid (97% of nuclei on average). Operators 2 and 3 showed a wide range of results. Almost half the nuclei (47%) analyzed by operator 2 were in the diploid region, a third (35%) were in the tetraploid region, and the remaining (18%) ones had a DNA index (DI) in the range of 1.2-1.8 or > 2.5. Operator 3 obtained the most abnormal results. Only 9% of the nuclei were diploid, while 37% were in the tetraploid region, 18% were in the hyperploid region, and 35% had a DI in the range of 1.2-1.8. Differences among results obtained by each operator were statistically significant. CONCLUSION: The nuclei of superficial (umbrella) cells often have abnormal DNA content, which may cause abnormal DNA ploidy results in cytomorphologically normal bladder washes. Consequently, the nuclei of superficial cells should be avoided in the evaluation of urine samples. DNA analysis of urine specimens requires selection of nuclei only of deep urothelial cells by an experienced operator.     

Assessment of DNA flow cytometry as a surrogate end point biomarker in a bladder cancer chemoprevention trial

Although conventional cytology represents the most widely performed cytometric analysis of bladder cancer cells, DNA flow cytometry has, over the past decade, been increasingly used to evaluate cell proliferation and DNA ploidy in cells from bladder washings. We have investigated whether DNA flow cytometry and conventional cytology of epithelial cells obtained from bladder washings provide reliable surrogate endpoint biomarkers in clinical chemoprevention trials. We used cytometric and clinical data from a chemoprevention trial of the synthetic retinoid Fenretinide on 99 patients with superficial bladder cancer. A total of 642 bladder washing specimens obtained from the patients at 4 month intervals was analyzed. Intra-individual agreement and correlation of flow cytometric DNA ploidy (diploid vs. aneuploid), DNA Index, Hyper-Diploid-Fraction (proportion of cells with DNA content higher than 2C), and conventional cytologic examination, as assessed by kappa statistics and Spearman's correlation test, were poor from baseline through 24 months. Moreover, no correlation was found between DNA ploidy and cytology at each time point. The same results were obtained when the analyses were stratified by treatment group. In addition, the association between the results of bladder washing (by either DNA flow cytometry or cytology) and concomitant tumor recurrence was significant only for abnormal cytology, while neither biomarker was predictive of tumor recurrence at the subsequent visit. During the time of this study only four patients progressed to muscle-invasive bladder cancer, indicating the "low-risk" features of the patient population. We conclude that DNA flow cytometry and conventional cytology on epithelial cells obtained from bladder washings do not appear to provide suitable surrogate endpoint biomarkers during the early stages of bladder carcinogenesis.     

Methylation profiling of urothelial carcinoma in bladder biopsy and urine

OBJECTIVE: To test DNA methylation profiling in detection of urothelial carcinoma in urine. STUDY DESIGN: Thirty-three bladder specimens were analyzed for the DNA p16INK4a, RASSF1, APC, GSTP, E-Cad and CyclinD2 genes to determine if there is a difference in gene methylation between benign and malignant cases. Urine samples were analyzed in a feasibility study. Finally, methylation profiles of urine samples were obtained and compared with follow-up biopsy diagnoses. RESULTS: We found methylated genes in 18% benign, 37% urothelial carcinoma in situ and 93% infiltrating urothelial carcinoma cases (p = 0.001). Methylation profiles from the 18 urine samples revealed a significantly higher prevalence of methylated genes in carcinoma cases than benign cases (100% vs. 50%, p = 0.025). We analyzed methylation profiles in 37 cytologically atypical urine samples with malignant or benign diagnosis on surgical follow-up andfound that only APC (55% in malignant vs. 0% in benign, p=0.025) and CyclinD2 were differentially methylated (35% in malignant vs. 0% in benign, p=0.2) while p14ARF, p16INK4a, RASSF1, GSTP and E-Cad had similar methylation profiles. CONCLUSION: These results suggest that methylation of p14ARF, p16INK4a, RASSF1, GSTP and E-Cad genes may not accurately identify carcinoma, but methylated APC and CyclinD2 might be useful biomarkers for urothelial carcinoma in urine.     

Micropapillary variant of transitional cell carcinoma of the urinary bladder: a report of three cases with cytologic diagnosis in urine specimens

BACKGROUND: Micropapillary transitional cell carcinoma is a recently described, aggressive variant of bladder cancer. Its cytologic features in urine have not been previously characterized. CASES: Three cases illustrate the urinary cytologic features of this high grade urothelial carcinoma and its concurrent biopsy findings. This tumor is similar to low. grade urothelial lesions of the bladder, tends to present as micropapillary clusters in urine and yet has high grade nuclear features within these clusters that help with the differential diagnosis of a flat, high grade urothelial carcinoma. CONCLUSION: The micropapillary type of transitional cell carcinoma is a distinct morphologic entity with an aggressive clinical course. Recognizing its presence in urinary cytology, albeit a rare occurrence, is important in distinguishing this lesion from the more indolent, low grade papillary lesions and high grade urothelial carcinomas, which continuously shed single malignant urothelial cells.     

Cytopathology of extramedullary plasmacytoma of the bladder: a case report

BACKGROUND: Plasmacytoma of the bladder is an extremely rare tumor, with all information concerning this neoplasm derived from case reports. It can be a major diagnostic pitfall on both histology and urine cytology. CASE: A 95-year-old woman presented with gross hematuria and a large bladder mass detected by ultrasound. The case was initially misdiagnosed as a high grade urothelial carcinoma. Since the urine cytology did not show the classical cytologic features of urothelial carcinoma, the histologic sections were reviewed and immunohistochemical staining performed. The final diagnosis was plasmacytoma of the bladder. Subsequently the patient underwent a skeletal survey and bone scan, which did not reveal any lesion suspicious for multiple myeloma. The patient was scheduled for radiotherapy. CONCLUSION: In this case of bladder plasmacytoma, urine cytology provided a clue to the diagnosis. Urine cytology can be a diagnostic tool to help make this diagnosis in the case of poorly differentiated bladder neoplasm, especially in a patient with a known history of multiple myeloma.     

Fine needle aspiration biopsy versus sputum and bronchial material in the diagnosis of lung cancer. A comparative study of 168 patients

A group of 168 consecutive lung cancer patients in whom a definitive diagnosis of primary lung cancer was established either in a conventional cytologic specimen of sputum or bronchial material or in a specimen obtained by fine needle aspiration (FNA) biopsy was reviewed to compare the relative accuracies between the modalities of sputum and bronchial material on one hand versus FNA cytology on the other in the diagnosis of lung cancer. The patients included in the study were selected from a total of 1,093 patients who had been diagnosed and treated for lung cancer at Duke University Medical Center over the five-year period of January 1, 1980, through December 31, 1984. In 325 (29.8%) of the 1,093 patients, a definitive cancer diagnosis was established from histopathologic study alone, without any cytologic diagnoses. In 420 patients (38.4%), both histologic and cytologic material had been interpreted as being conclusively diagnostic for lung cancer. In 348 patients (31.8%), a cytologic diagnosis of lung cancer was made without a histologic confirmation. Thus, in a total of 768 (70.3%) of the 1,093 cases, a definitive cytologic diagnosis of cancer had been made. Of these 768 patients, 168 had been evaluated by both conventional respiratory cytologic methods (examination of sputum and bronchial material) and with FNA biopsy cytology. In 9 patients (5.4%), only conventional respiratory cytologic specimens were conclusively diagnostic for cancer. In 122 patients (72.6%), only the FNA biopsy specimen was diagnostic. In 37 patients (22.0%), both conventional respiratory specimens and FNA specimens yielded a definitive lung cancer diagnosis. The FNA specimen was the only positive cytologic specimen in 90.2% of large cell undifferentiated carcinomas, 79.5% of adenocarcinomas, 66.7% of small cell undifferentiated carcinomas and 58.2% of squamous cell carcinomas. In 26.5% of the patients, a diagnosis of cancer could have been established on conventional cytologic specimens, without the necessity of proceeding to percutaneous FNA biopsy. From this study, it is concluded that the techniques of conventional respiratory cytology and FNA biopsy cytology are complementary in the diagnosis of lung cancer. While the percentage of lung cancers diagnosed by FNA biopsy cytology alone is much greater than that obtained by conventional respiratory cytology alone, more than one-fourth of these cancers could be detected by the less invasive techniques of sputum collection and bronchoscopy.     

DNA ploidy analysis and cytologic examination of sorted cell populations from human breast tumors

Two different flow cytometric procedures were applied on cell samples from human breast tumors. One procedure involved DNA ploidy analysis on suspensions of isolated nuclei. The mean ploidy ratios of 27 benign breast lesions to chicken erythrocytes and rainbow trout erythrocytes were found to be 2.66 +/- 0.03 and 1.25 +/- 0.02, respectively. From the 45 stemlines found in a series of 43 carcinomas, 12 were diploid, 13 hyperdiploid and 20 near-tetraploid. No association was found between the lymph node status and the DNA ploidy level. The second procedure involved sorting fixed cells from DNA "windows" for the preparation of permanent cytologic specimens. The sorted cells appeared to be shrunken, but the morphologic quality was similar to that of imprint specimens from the same tumors, permitting discrimination between various types of normal cells and tumor cells. The combined use of both flow cytometric procedures may lead to greater insight into the relationship between the cytologic and cytogenetic heterogeneity of breast carcinomas.     

DNA breaks as measured by the alkaline comet assay in exfoliated cells as compared to voided urine cytology in the diagnosis of bladder cancer: a study of 105 subjects

In this study we evaluated the clinical usefulness of identifying urothelial cells with increased DNA damage with the alkaline comet assay and compare it with voided urine cytology for the assessment of markers indicative of bladder cancer. The analysis was carried out on 105 subjects having clinical suspicion of bladder cancer, and who had undergone cytology for the first time. Urine cytology and alkaline comet assay were performed on the same fresh urine samples obtained from each patient. The subjects were divided according to negative or positive cytology. The Mann-Whitney U-test showed that the comet parameters (tail moment, tail length, and % of DNA in the tail) and the numbers of comets (cells with an arbitrary cut-off value of head intensity <90% of DNA content) in subjects positive in both tests were significantly higher than in the negative group. Sensitivity, specificity, and positive and negative predictive value of the comet assay were compared with those of cytology, which is regarded as the gold standard. Sensitivity was 71.4%, specificity was 91.8%, positive and negative predictive values were 38.5 and 97.8, respectively. Two subjects negative in the comet assay were positive in cytology. Eight patients were positive in the comet assay and negative for cytology. Interestingly, one of these eight patients was later found positive for cytology. Logistic regression analysis indicates that the tail moment is significantly associated with an increased risk for positive cytology.     

Relationship between the cellular composition of sputum and the cytologic diagnosis of lung cancer

In 410 patients with either a primary or a metastatic malignant lung process, the cellular composition of the sputum specimens was analyzed in relation to the diagnostic accuracy of sputum cytology and in relation to anamnestic and clinical patient characteristics. In patients with primary lung cancer, sputum samples with true-positive cytologic diagnoses contained significantly more cells from the deeper airways, such as alveolar macrophages and bronchial columnar cells, than did sputum specimens with a false-negative diagnosis, even though these cell types were present in both types of specimens. In sputum samples from patients with metastatic lung malignancies, differences in cellular composition of specimens with true-positive and false-negative diagnoses were not significant.     

Diagnostic use of mean nuclear area and nuclear DNA content in preoperative breast cancer cytology

OBJECTIVE: Fine needle aspiration (FNA) cytology of breast lumps is a routine procedure, and the diagnostic accuracy can be 95%. Occasional discrepancies arise, and it would be valuable to have additional parameters for accurate diagnosis. We evaluated nuclear DNA content and mean nuclear area (MNA) using image cytometry in the diagnosis of preoperative breast cancers by FNA in those with a discrepancy between clinical, radiologic and cytologic diagnoses. STUDY DESIGN: One hundred eighteen consecutive preoperative FNA samples were evaluated for nuclear DNA and MNA and were compared to cytologic and postoperative histologic diagnoses. RESULTS: Sensitivity, accuracy and positive predictive value of routine cytology were 95%, 90%, 95% as compared to nuclear DNA (66%, 66%, 96%) and MNA (61%, 61%, 97%). Combining these 3 parameters gave a sensitivity of 97%, accuracy of 94% and positive predictive value of 99%. CONCLUSION: These results demonstrate that nuclear DNA and MNA combined with routine cytology may be useful adjuncts in preoperative breast cancer cytologic diagnosis when discrepancies arise. This may lead to better and more accurate planning of treatment regimens in preoperative breast cancer patients.     

Liquid-based cytology as a tool for the performance of uCyt+TM and Urovysion® Multicolour-FISH in the detection of urothelial carcinoma

The aim of the study was to assess the value of liquid-based urinary cytology as a tool to perform uCyt+ and Multicolour-FISH in patients under follow-up after urothelial cancer. Therefore, standard cytology was compared to liquid-based cytology with the addition of the uCyt+ test, which traces the three monoclonal antibodies M344, LDQ10 and 19A211 in exfoliated urothelial cells; and Multicolour-FISH (including centromere-specific probes for chromosomes 3, 7, 17 and a locus-specific probe for 9p21/p16) performed on thin-layer specimens. UCyt+ showed an overall sensitivity of 86.2% and cytology of 45.0%. Overall sensitivity of both the tests combined was 90%. Sensitivity of Multicolour-FISH was 96.4%. All conventional cytology diagnoses were confirmed by liquid-based cytology. Liquid-based cytology is a valid tool for the performance of adjunctive analyses, such as uCyt+ and Multicolour-FISH, on residual cellular material.     

Ten years of respiratory cytopathology at Duke University Medical Center. II. The cytopathologic diagnosis of lung cancer during the years 1970 to 1974, with a comparison between cytopathology and histopathology in the typing of lung cancer

In 1975 Duke University Medical Center, a retrospective and prospective survey of respiratory cytopathologic specimens was undertaken for the ten-year period 1970 to 1979. The purpose of this study was to document the role of cytopathology in the diagnosis of lung cancer at this institution. This paper presents the results of the cytopathologic and histopathologic typing of cases of lung cancer seen at Duke University Medical Center from 1970 to 1974. During this period, 9,892 cytologic specimens from the lower respiratory tract were processed. Cytopathologic diagnoses of cancer with tissue confirmation were made on 483 specimens from 232 patients. Because original cytologic diagnoses, but not histopathologic diagnoses, had been made in conformity with a modified WHO classification of lung neoplasms, all histopathologic material was reviewed and reclassified when necessary. This was carried out by one of the authors (E.H.B.) as a blind review without benefit of knowledge of either preexisting cytopathologic or histopathologic diagnoses. Twenty-six patients were excluded from the current study because of lack of satisfactory histologic material. In 94 patients classified by histopathology as having squamous cell carcinoma, 76.4% of the positive cytologic specimens were also called squamous cell carcinoma; 18.6% were interpreted as large cell undifferentiated carcinoma. In 39 patients classified by tissue as having large cell undifferentiated carcinoma, the cytology agreed in 42.4% of the positive specimens. For the 29 patients thought histologically to have small cell undifferentiated carcinoma, the same diagnosis was rendered in 95.5% of the cytologically positive specimens from these patients. For the adenocarcinoma group of 43 patients, a cytopathologic diagnosis of adenocarcinoma was made in 67.8% of the positive specimens.