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Distinct cytologic features of spindle cell lipoma. A cytologic-histologic study with clinical, radiologic, electron microscopic, and cytogenetic correlations.

BACKGROUND: Spindle cell lipoma (SCL) is a relatively uncommon, benign tumor that usually presents in the subcutaneous fat of adult men. Although some studies have addressed the histologic findings of SCL, only a few descriptions of aspiration cytology findings have been published. The cytologic features are poorly defined, and aspirates from SCL may cause diagnostic problems, because SCL shares some features with other fatty/spindle cell or myxoid lesions, benign as well as malignant. METHODS: Twelve patients underwent fine-needle aspiration (FNA) cytology as the primary diagnostic modality before surgery. FNA findings were evaluated and correlated with histologic features. In addition, radiologic, electron microscopic, and cytogenetic findings were analyzed. The objective of this study was to determine cytologic criteria of SCL by reviewing cytologic specimens in 12 patients with SCL who underwent FNA cytology. RESULTS: All of the tumors arose in adults, and 10 tumors developed in the subcutaneous tissue of the neck, back, or shoulder girdle. Two patients presented with tumors in atypical locations; one in the tongue and one in the cheek. Cytologically, all 12 tumors were characterized by a mixture of mature adipocytes, uniform spindle cells, and collagen bundles and/or fibers in varying proportions. The presence of a myxoid matrix and of mast cells was less specific and occurred in six aspirates. CONCLUSIONS: SCL has a characteristic cytologic appearance that, together with clinical data, helps to exclude low-grade liposarcoma as well as other spindle cell and myxoid lesions.

Adult↗

High risk human papillomavirus in women with normal cervical cytology prior to the development of abnormal cytology and colposcopy.

OBJECTIVE: To study the significance of the presence of high risk human papillomavirus (HPV) in women with initially normal cervical cytology for the development of abnormal cytology and an abnormal colposcopic impression. DESIGN: Prospective, observational study PARTICIPANTS AND METHODS: Sixty-eight women with cytomorphologically normal smears and at least one positive HPV test result were evaluated every six months by cytology, colposcopy and HPV testing. The endpoint of the study was abnormal cervical cytology. RESULTS: The median time of follow up from the first positive HPV test was 34 months. A total of 17 women developed abnormal cytology, of whom 16 (94%) had persistence of a high risk HPV infection. Women with persistent high risk HPV were more likely to develop abnormal cervical cytology than women without high risk HPV (hazard ratio 28.2, 95% CI 3.72-215.2); they also had an increased risk of developing an abnormal colposcopic impression (hazard ratio 4.4, 95% CI 1.69-11.7). Among the 17 women with abnormal cytology, high grade dysplasia was histopathologically demonstrated in eight women. CONCLUSION: Persistent presence of high risk HPV in normal cervical smears is associated with a significantly increased risk of developing abnormal cytology and to a lesser degree with developing an abnormal colposcopic impression.

Adolescent↗

Fine needle aspiration cytology of mammary duct ectasia: report of a case with novel cytologic and immunocytochemical findings.

BACKGROUND: Mammary duct ectasia (MDE), or periductal mastitis, is a well-defined clinical entity with a characteristic histopathologic appearance on breast biopsy specimens. However, the cytologic features of MDE have been described only recently in the cytopathology literature, and fine needle aspiration (FNA) cytologic findings are based mainly on a small number of case reports in the English-language literature. Therefore, awareness of this entity and recognition of its cytomorphologic features could aid in a more accurate diagnosis. We report the novel cytologic and immunocytochemical findings on a case of MDE that was confirmed by histologic examination on a subsequent biopsy. CASE: We report the findings of breast FNA cytology in a 50-year-old female with a mammographically and clinically suspicious lesion. Cytology displayed a paucicellular aspirate, typified by a few scattered, cohesive clusters of ductal epithelial cells with mild nuclear atypia and distinct, peripherally located myoepithelial cells. Intermingled within the ductal elements were numerous polygonal cells with abundant, finely vacuolated cytoplasm that were immunoreactive for macrophage-specific antibody, CD68. The background consisted of a variable number of foam cells and negligible amount of blood. CONCLUSION: The current case of MDE demonstrates cytomorphologic features that may pose diagnostic problems, particularly as a consequence of variable cytologic atypia this entity may present on FNA cytology. This diagnostic difficulty is compounded because of the abnormal mammographic and suspicious clinical findings that may be associated with MDE. CD68 immunoreactivity is a useful ancillary tool to verify the histiocytic, rather than epithelial and potentially neoplastic, nature of multivacuolated cells. To the best of our knowledge, there has been no prior reported case of MDE in the English-language literature studied utilizing CD68 antibody. This case report emphasizes that MDE is a heterogeneous entity with diverse cytomorphologic features. FNA cytology in conjunction with immunocytochemistry might permit accurate classification in the proper clinical setting.

Antigens, CD↗

[Cytologic atypical grade of exfoliative cytology versus histologic differentiation degree in prostatic carcinoma].

Our method of exfoliative cytology using a prostatic fluid collecting catheter is effective in detecting prostatic carcinoma. To presume histological diagnosis by means of the cytology we analyzed cytological findings of 62 cases of prostatic carcinoma in relation with their biopsy findings, clinical stages and clinical courses. In cases in which cellular atypism was low in the cytology the carcinoma was mostly well or moderately differentiated. Conversely, in cases in which the carcinoma was well differentiated atypism was mostly low in the cytology. In cases in which the cellular atypism was high the carcinoma was poorly differentiated, and vice versa. The poorer histological differentiation and the higher cytological atypism, the more advanced carcinoma and the higher death rate from the carcinoma. The tendency seemed to be more related with the cellular atypism than with the histological differentiation. Thus the cytological findings reflect the histology well and the degree of the histological differentiation can be presumed by the cytological atypism. The cellular atypism is not a less important factor than the histologic differentiation degree for determining the clinical stage and the prognosis.

Adenocarcinoma↗

Peritoneal cytology in patients with gastric cancer exposed to the serosa--a proposed new classification based on the local and distant cytology.

BACKGROUND/AIMS: The clinical impact of the cytology of intraperitoneal samples taken from the local and distant sites was examined in patients with gastric carcinoma. METHODOLOGY: Intraoperative peritoneal cytology was evaluated in 149 patients with gastric cancer invading the serosa but no metastasis to the peritoneum (macroscopic P0), the liver (H0), or distant organs (M0). Lavage samples were collected from the Douglas pouch and the left subphrenium (distant sites). Both lavage and smear samples were taken from the serosal surface invaded by the tumor (local). RESULTS: Positive peritoneal cytology was found in 33 of 149 patients (22.1%). All patients were categorized into three groups: Group I had negative cytology (n = 116, 77.9%), Group II had positive local cytology (n = 14, 9.4%), and Group III had positive distant cytology irrespective local status (n = 19, 12.8%). By multivariate analysis, peritoneal cytology was the only significant independent factor affecting survival. Median survival was significantly shorter in Group III (400 +/- 177 days) than in Group I (2228 +/- 599 days). The peritoneal recurrence-free interval was significantly shorter in Group II than in Group I. CONCLUSIONS: The extent of peritoneal seeding was variable and appeared to have a significant impact on prognosis. Peritoneal cytology should be evaluated not only at a distant site, but also locally to identify the subset of patients with limited peritoneal dissemination.

Female↗

Can viral load, semi-quantitatively evaluated, of human papillomavirus predict cytological or histological outcome in women with atypical squamous or glandular cells of undetermined significance cytology?

OBJECTIVE: 1) To assess the regression to normal cytology in women with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance (ASCUS/AGUS) and absence or clearance of human papillomavirus (HPV) infection; 2) To evaluate the association between viral load, semi-quantitatively evaluated, and cytological or histological outcome. MATERIAL AND METHODS: In this cohort study HPV test and biopsy was taken in 148 women with ASCUS/AGUS cytology. After 12-18 months a HPV test and cervical smear were repeated in 121 women. RESULTS: Absence or clearance of HPV showed significantly more regression to normal cytology than persistent or newly acquired infected women, odds ratio 27 (95% confidence interval; 7-103). The viral load of the HPV test at enrollment was not correlated with the follow-up cytological outcome (Spearman correlation coefficient 0.2, p = 0.2). A marked association between viral load and histological outcome at enrollment was shown (Spearman correlation coefficient 0.43, p < 0.0001). CONCLUSION: Absence or clearance of HPV can predict regression to normal cytology. Viral load at enrollment cannot predict cytological regression. There was a marked association between viral load and the underlying CIN at enrollment. However, there was large overlapping of viral loads among the grades of CIN. Therefore, viral load is not a useful parameter to predict high-grade lesions in women with ASCUS/AGUS cytology.

Adolescent↗

Diagnostic accuracy of urinary cytology, and deoxyribonucleic acid flow cytometry and cytology on bladder washings during followup for bladder tumors.

PURPOSE: We evaluated the diagnostic accuracy of cytology on urine and bladder washings, and deoxyribonucleic acid (DNA) flow cytometry on bladder washings compared to cystoscopy during followup for bladder tumors. MATERIALS AND METHODS: A cross-sectional analysis was performed on 166 patients with a history of bladder tumor for the initial visit when cytology and DNA flow cytometry results were available for urine and bladder washing samples. There were 114 bladder tumor events and 52 negative controls (normal cystoscopy). A prospective study was conducted among the 66 patients with no tumor detected by cystoscopy at the initial visit and for whom the 3 test results were available. The patients were followed from this visit until tumor recurrence or the end of the followup period. Cytological examination was considered positive only when interpreted as malignant. Suspicious examinations were considered negative for the purpose of our study. RESULTS: Sensitivity and specificity of urinary cytology were 59 and 85%, respectively. Sensitivity was increased to 66% using bladder washing cytology whereas specificity was moderately decreased to 83%. The sensitivity and specificity of DNA aneuploidy were 45 and 87%, respectively. Inclusion within the aneuploid category of hyperdiploid samples (defined as more than 7% of cells in the S + G2M phase) increased sensitivity to 77%, while specificity decreased to 42%. Kaplan-Meier analysis of tumor-free survival in patients initially free of bladder cancer at cystoscopy showed an inability of DNA flow cytometry to predict recurrence, whereas positive urine or bladder washing cytology predicted a shorter time to recurrence (log-rank test p <0.01). CONCLUSIONS: These results show that DNA flow cytometry and cytology on bladder washing samples add little information to that obtained from voided urine cytology.

Cross-Sectional Studies↗

Computerized training and proficiency testing. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Computerized technologies probably will revolutionize the field of gynecologic cytology in the next century. Such technologies will be useful in both training and evaluating proficiency. However, manual screening/review of gynecologic cytology preparations is the current "gold standard" for both training and assessment of proficiency. CONSENSUS POSITION: Training programs for cytotechnologists and pathologists should provide instruction and experience in new technologies, but their introduction may depend on the availability of equipment and staff. Advantages of digital images for training include standardization of teaching sets and interactive capabilities, allowing educational feedback. Computerized support/assistance devices aid in complete screening of the slide during training and provide feedback to cytologists on screening techniques. Liquid-based cytopreparatory instruments facilitate multiple glass slides for teaching or testing. Proficiency testing (PT) in cytology has similar quality assurance goals as in other areas of the laboratory, but the subjective nature of cytologic analysis poses many challenges for implementation. There is consensus that all cytology practitioners would like to know the proficiency of the laboratory. However, the majority question the value and validity of any large-scale formal testing programs. Locator and diagnostic skills are both critical in cytology, but assessment of each skill may occur in different ways using computerized technologies. Any type of assessment should provide educational feedback to participants. Psychometric issues in PT include the consideration of different types of validity, including face, content, construct and criterion related. The reliability or consistency of the testing event is also critical. A valid and reliable correlation between work performance and performance on a PT needs to be established. The goal is to ensure that PT will identify submarginal practitioners and that persons successful on PT are in fact competent. Any cytology PT program should also be considered in the context of other laboratory quality assurance tools and the entire cervical cancer screening program. Regulatory agencies should evaluate entire laboratory performance, while each laboratory director should assume primary responsibility for evaluating and documenting the competency and daily performance of each practicing cytologist. Professional scientific organizations should take the lead in recommending methods and standards of performance assessment. ONGOING ISSUES: A reliable method of correlating daily competency with results on PT is not yet established. Methods may evolve ever time using new technologies. The use of computerized techniques and images for assessment will require careful deliberation by experts as well as validation by practicing cytologists. Variables include diagnostic categories for testing, numbers of challenges per testing event, types of slide preparations and characteristics of the digital images. Availability of equipment and staff will affect the introduction of new technologies in different regions.

Cell Biology↗

Distinguishing carcinoid tumor from small cell carcinoma of the lung: correlating cytologic features and performance in the College of American Pathologists Non-Gynecologic Cytology Program.

CONTEXT: The cytologic features of carcinoid tumor of the lung are well described. Nevertheless, some carcinoids may be difficult to distinguish from small cell carcinomas. OBJECTIVE: To correlate the cytologic features of individual cases of carcinoid tumor of the lung in fine-needle aspiration specimens in the College of American Pathologists Non-Gynecologic Cytology Program with the frequency of misclassification as small cell carcinoma. DESIGN: We reviewed 1100 interpretations from 26 different cases of carcinoid tumor in lung fine-needle aspiration specimens in the College of American Pathologists Non-Gynecologic Cytology Program and correlated the cytologic features with the performance in the program. RESULTS: Cases were divided into those that were frequently misclassified as small cell carcinoma (at least 20% of the responses, 19 cases) and those that were infrequently misclassified as small cell carcinoma (<10% of all responses, 7 cases). All cases had areas with classic features of carcinoid tumor. Cases were reviewed independently by 3 cytopathologists specifically looking for cytologic features that might be responsible for misclassification as small cell carcinoma. All 7 cases that were infrequently misclassified consisted of numerous monotonous well-preserved tumor cells that were either entirely round or were a mixture of round and spindle-shaped cells. Six of 7 cases showed a prominent streaming vascular pattern with tumor cells attached to the endothelial cell core. In contrast, cases that were frequently misclassified had 1 of 6 patterns that were not seen in cases that were rarely misclassified. These 6 patterns were: (1) poorly preserved and pale-staining cells with fine chromatin and a suggestion of molding (5 cases); (2) numerous large, well-preserved, spindle-shaped cells (2 cases); (3) numerous cells varying markedly in both size and shape (both round and spindle-shaped cells), with a common finding of degenerated, smudgy, small round and spindle-shaped cells (9 cases); (4) hypocellular specimens (8 cases); (5) obscuration of cells by blood (2 cases); and (6) tumor cells present predominantly in groups, with few isolated cells (8 cases). In none of these cases were mitoses or true necrosis identified. CONCLUSIONS: Frequent misclassification of carcinoid tumor as small cell carcinoma in lung fine-needle aspiration specimens in this program correlates strongly with specific cytologic features, some of which are common in small cell carcinoma (fine chromatin, molding, smudgy chromatin) and others that are not (spindle-shaped cells). In addition, hypocellular specimens or specimens with cellular obscuration performed poorly, along with specimens exhibiting absence of the commonly described carcinoid feature of streaming vascularity. Awareness of these patterns may aid in avoiding misdiagnosis.

Biopsy, Fine-Needle↗

Fine-needle aspirates of hepatocellular carcinoma that are misclassified as adenocarcinoma: correlating cytologic features and performance in the College of American Pathologists Nongynecologic Cytology Program.

CONTEXT: The cytologic features of hepatocellular carcinoma in fine-needle aspirates are well described. While some cases are easily distinguished from adenocarcinoma, poorly differentiated tumors can be difficult to differentiate. We reviewed the cytologic findings for 9 aspirates from cases of hepatocellular carcinoma that were frequently misclassified as adenocarcinoma and compared them with another 10 cases of hepatocellular carcinoma that were rarely misclassified. OBJECTIVE: To compare the cytologic features of cases of hepatocellular carcinoma in fine-needle aspirates that were both rarely and frequently misclassified as adenocarcinoma. DESIGN: We reviewed a total of 762 interpretations from 19 different cases of hepatocellular carcinoma in liver fine-needle aspiration specimens in the College of American Pathologists Nongynecologic Cytology Program and correlated the cytologic features with performance in the program. RESULTS: Overall, cases that were frequently misclassified as adenocarcinoma were misclassified 39% of the time (range, 18%-70%), while cases that were rarely misclassified were classified as adenocarcinoma 2% of the time (range, 0%-8%). The difference was statistically significant (P < .001). On review, 4 cytologic patterns were found. The most common pattern for cases that were rarely misclassified was prominent trabeculae of cells and endothelial cells wrapping the trabeculae (6/10 cases vs 2/9 cases that were frequently misclassified). The most common pattern among cases that were frequently misclassified was clusters of cells with granular cytoplasm and associated stripped nuclei (5/9 cases vs 2/10 cases that were rarely misclassified). However, the distribution of neither pattern was significantly different (P = .16 for both). One case with large atypical granular cells, as seen in the fibrolamellar variant, was rarely misclassified. The remaining 3 cases (2 frequently misclassified, 1 rarely misclassified) had a nonspecific a pattern of cells with granular cytoplasm without obvious trabeculae or stripped nuclei. CONCLUSION: Correctly classifying hepatocellular carcinoma by cytology alone remains a significant challenge. While some patterns are more common in cases that performed well and other patterns are more common in cases that performed poorly, there was no significant difference in the distribution of these patterns. These results suggest that people should support their interpretations of aspirations with either immunologic evidence, biopsy evidence, or review by an experienced cytopathologist. Continued educational efforts in this area may be of value.

Adenocarcinoma↗

A prospective, randomized, blinded trial of cytological yield with disposable cytology brushes in upper gastrointestinal tract lesions.

Brush cytology is an important technique in the diagnosis of upper gastrointestinal tract lesions. Optimum cytological yields depend on cellularity (a measure of the amount of epithelial cellular material) and preservation (a measure of artifact induced by desiccation). We sought to determine the cytological yield of four disposable cytology brushes. Seventy-eight patients were studied, with a total of 80 disposable cytology brushes from four different manufacturers (Wilson-Cook, Microvasive, Mill-Rose, and Hobbs). Cellularity and preservation were assessed in a blinded fashion by experienced cytotechnologists. There was no significant difference in cellularity between the different non-disposable brushes. However, the Wilson Cook disposable cytology brush was significantly superior to the other disposable cytology brushes (P < 0.05) with regard to preservation. Its unique design features (longer head and more acutely angled bristles) may account for the better results.

Cytological Techniques↗

Randomized comparison of fine-needle aspiration cytology and Biopty-Cut needle biopsy after unsatisfactory initial cytology of discrete breast lesions.

In a minority of patients with a discrete breast lump the initial cytological assessment is either unsatisfactory or at variance with the results of other methods of diagnosis. A randomized comparison of repeat cytology and needle-core biopsy provided clinically useful information in 14 of 31 patients receiving repeat cytology and in 26 of 29 randomized to core biopsy. Nineteen patients had carcinoma: ten who received repeat cytology, which indicated malignancy in only three (diagnostic of malignancy in one, suspicious in two), while all nine patients who underwent core biopsy had a correct diagnosis (only suspicious of malignancy in one). The sensitivity for the definitive diagnosis of carcinoma on repeat cytology and core biopsy was 10 and 89 per cent respectively. Patients with a discrete breast lump and unclear cytology results require needle-core biopsy. This has more diagnostic value than repeat cytology.

Adult↗

Medicolegal affairs. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Increasing litigation over alleged false negative cervical cytologic (CC) smears threatens the viability of this test for cervical cancer detection. The problem appears to be largely American but is beginning to appear in some other countries. In the vast majority of cases there is either a settlement or jury verdict for the plaintiff based largely on the testimony of expert witnesses. Cases are judged on an individual basis without significant consideration of the general performance of the CC smear in laboratories operating in compliance with a wide array of laboratory regulations and with documented and comprehensive quality control practices in place. It is acknowledged that there are problem laboratories and cytology practitioners. There is an emerging issue of automated preparation and screening devices and issues of informed patient consent. CONSENSUS POSITION: Cytology professionals have done an extraordinary and commendable job of educating the public about the benefits of the CC smear. We have been less successful and conscientious about explaining and defining the limitations of the CC test. There is a need for public and professional education as to the benefits and limitations of the CC smear for cervical cancer detection. The process suggested is to work with women's groups, public health agencies, government agencies, and state and national legislatures and to coordinate professional committees working on liability issues. Contextual information could be included with the CC smear report to indicate that a negative report confers a low probability of developing cervical cancer. It is suggested that appropriate language and a menu of statements be developed. Increased efforts should be directed to physician education with respect to informed consent concerning the benefits and limitations of CC smear testing and the application of new technology to improve smear accuracy. The process should include development of appropriate statements on the use of alternative technology. The profession should develop "process guidelines" for review of CC smears in the context of possible litigation, including standardized methods for blind slide review of smears that reduce or eliminate context and outcome bias. It is suggested that review panels be anonymous, that the process be standardized and that there be limitations on liability for participating organizations. Professional cytopathology and pathology societies should formulate acceptable guidelines for expert witnesses. The standards should be applicable to both defendant and plaintiff experts. All materials to the extent practical, including consultant opinions, should be available for peer review. Professional cytopathology and pathology societies should monitor expert testimony for objectivity and scientific accuracy. ONGOING ISSUES: For the near future, litigation will continue to focus on false negative CC smears on a case-by-case basis. Laboratories and individuals can reduce the risk of malpractice liability by directing their attention to proactive quality control and quality assurance methods. In the final analysis, consumer education about the benefits and limitations of the test is key to limiting malpractice claims. To stem the tide of continued medicolegal challenges to the integrity of cytology practice, the cytology community has now focused its efforts on developing and utilizing standards that convey to patients, attorneys and cytologists the contemporary status of and reasonable expectations for the practice of cytology. Guidelines such as those for uniform reporting terminology and clinical management of cervical abnormalities form the basis of cytology practice standards on which legal standards of practice can be based. Consensus conference reports, clinical management trials and scientifically valid studies of false negative rates that analyze the type, frequency and cause of missed cases represent sounder methods of establishing defensible

Cell Biology↗

Cytologic grading and DNA image cytometry of breast carcinoma on fine needle aspiration cytology smears.

OBJECTIVE: To correlate the cytologic grade of breast carcinoma with DNA image cytometry (ICM) and nuclear area on fine needle aspiration cytology (FNAC) smears. STUDY DESIGN: In this prospective study, FNAC material from 28 breast carcinomas were studied for cytologic grade and DNA ICM. Breast carcinomas were classified as grade 1-3 (low to high). DNA histograms were classified by the modified Auer method. Degree of hyperploidy (DH), ploidy balance (PB) and nuclear area (NA) were measured on Feulgen-stained smears by a CAS 200 image cytometer. Cytologic grade was correlated with DNA ICM findings and NA. RESULTS: There were 3 cytologic grade 1, 13 grade 2 and 12 grade 3 breast carcinomas. Seven of eight cases of hypertetraploid aneuploidy were grade 3 tumors. All cytologic grade 1 tumors were diploid. There were significant differences in DH, PB and NA in different grades of breast carcinoma (one-way ANOVA). CONCLUSION: DNA image cytometry in combination with cytologic grading might offer additional information for the characterization of breast carcinomas diagnosed by FNAC. These observations are of particular interest with the introduction of preoperative chemotherapy.

Adult↗

Improving the sensitivity of cervical cytologic screening. A comparison of duplicate smears and colposcopic examination of patients with cytologic inflammatory epithelial changes.

During a ten-month period, 264 cervical cytologic specimens were submitted in duplicate to two separate cytology laboratories. An attempt was made to perform colposcopy on all 45 patients reported as having an abnormality by either laboratory. All but one patient with a cytologic diagnosis of cervical intraepithelial neoplasia (CIN) underwent colposcopy, as did 68% of the patients with a diagnosis of nondysplastic atypia (inflammatory epithelial changes [IEC]). Five cases of histologically verified CIN were found by colposcopic study of patients with a cytologic diagnosis of CIN; two additional cases were found by colposcopic study of patients with a cytologic diagnosis of IEC. On the assumption that patients not colposcoped were not systematically different from the others with IEC, the screening sensitivities for both laboratories and for cytology followed by colposcopy of IEC cases were estimated. A statistically significant improvement in screening sensitivity was achieved by colposcopic examination of patients with IEC. This conclusion was tempered by a Bayesian analysis that suggested that some of the apparent improved sensitivity could be due to falsely positive biopsy reports. Despite potential benefits, it is premature to recommend universal colposcopic examination of patients with cytologic reports of inflammatory epithelial changes.

Cervix Uteri↗

[Diagnostic possibilities of the prostate cytology, particularly considering the influence of the cytological degree of differentiation with the prostate carcinoma upon the 5 year survival rate (author's transl)].

Today, the transrectal fine-needle biopsy is firmly integrated in the establishment of the diagnosis of prostate carcinoma within the prophylactic examinations and as a check-up examination during the treatment of prostate carcinoma. Cytologically, the prostate carcinoma may be divided into four different degrees of malignancy: high-grade, medium-grade, low-differentiated and anaplastic carcinoma. Differential-diagnostically, chronic prostatitis may raise certain problems both clinically and cytologically. Electronmicroscopic examinations of samples taken by fine-needle biopsy are possible. Certain changes under anti-androgen treatment are examined at present. Under the contra-sexual treatment of the prostate carcinoma carrier there occur changes of the normal and carcinoma cells the extent of which permits conclusions as to the therapeutic hormone effect. This, in turn, results in consequences for the respective treatment. In 496 prostate carcinomata cytologically diagnosed since March 1970 the author was able to demonstrate that the 5 years' survival rate is determined by the cytological degree of differentiation. Whereas highly and medium-differentiated prostate carcinomata show an average 5 years' survival rate of 62.5 per cent, this amounts only to 33.9 per cent with the low-differentiated and anaplastic prostate carcinomata. The total 5 years' survival rate of all cytologically diagnosed carcinomata came up to 46.8 per cent. The 1-, 2-, 3-, 4- and 5 years' survival rate of all cytologically diagnosed prostate carcinoma carriers is almost in conformity with the values found by Esposti. The degree cytological differentiation in connection with the clinical stage clearly determines the clinical course with our patients.

Biopsy, Needle↗

The sensitivity of bladder wash flow cytometry, bladder wash cytology, and voided cytology in the detection of bladder carcinoma.

The sensitivity of voided urinary cytology (VUC), bladder wash cytology (BWC), and bladder wash flow cytometry (BWFCM) in detecting cancer was studied in 70 patients with biopsy-proven bladder tumors. There were 11 Grade I papillomas, 14 Grade II TA, 18 Grade II-III TIS, 19 Grade II-III T1, and eight Grade II-III T2 carcinomas. One to five VUCs per patient (mean, 2.63) were obtained within the 24 hours preceding biopsy. At endoscopy a bladder wash specimen was obtained and divided for cytologic and flow cytometric examinations. For all tumor categories combined, the sensitivity for one, two, and three voided cytology examinations per patient was 41%, 41%, and 60%, respectively. The sensitivity of a single BWC was 61%, of a single BWFCM, 83%. Thus, one BWFCM is more sensitive than three VUC (binomial test; P = 0.006); one BWC is more sensitive than two VUC (P = 0.01); and one BWFCM is more sensitive than one BWC (P = 0.003). These findings remain significant when papillomas are excluded from the analysis (P less than or equal to 0.03) and when papillomas and T2 tumors are jointly excluded (P less than or equal to 0.02). Only four of 70 patients (6%) had their cancers detected by VUC and/or BWC rather than BWFCM. In summary, irrigation cytology specimens are more sensitive than voided urinary cytology, and bladder wash flow cytometry is more sensitive than either in diagnosing bladder cancer. Flow cytometry is more sensitive because of the better sampling of bladder irrigation compared with voided urine and because of the measurement technique itself.

Biopsy↗

The efficacy of urinary cytology in the detection of urothelial tumours. Sensitivity and specificity of urinary cytology.

The sensitivity and specificity of urinary cytology in the detection of urothelial tumours using voided urine and applying simple smear preparation and staining techniques have been assessed. Of the 2704 patients under investigation 207 had urothelial tumours. The first urine analysis was positive in 66% of the patients with urothelial carcinoma; an additional 23% of the patients showed positive cytology in repeat smears, resulting in a sensitivity of 89%. The efficacy of urinary cytology depends on the tumour type: for grade 2 tumours, 79% were cytologically positive, 92% of grade 3 and 98% of the grade 4 tumours. The diagnostic efficacy in cases of carcinoma-in-situ, squamous cell carcinoma and adenocarcinoma was comparable with that of grade 4 carcinomas. Grade 0-1 tumours did not result in positive cytology. In eleven cases of lithiasis and in two cases of cyclophosphamide therapy the cytological diagnosis was positive but no neoplasm could be established histologically; these represent true false positive diagnoses. Thus, the false positive rate, 13 out of 165, was 7.88% and the false negative rate, 61 out of 207, was 29.4% when grades 0-1 were included, but 8.75% (14 our of 160) when grades 0-1 were excluded.

Cytological Techniques↗