Brush cytology of colorectal malignancies

OBJECTIVE: To evaluate the specificity and sensitivity of brush cytology and biopsy in colorectal malignancies. STUDY DESIGN: The study was performed over 3 years, 1998-2000. Seventy-six patients with any colorectal lesion on colonoscopy were selected, and in all of them brush cytology and biopsy were done at the same time. The cytologic smears and biopsies were reviewed separately. The cytologic smears were categorized as negative, suspicious, suggestive or positive for malignancy. The results of cytology and biopsy were compared based on sensitivity and specificity. The gold standard for positive cases was the tissue specimen after surgery; negative cases were followed for at least 1 year. Cases with 1 year of disease-free survival were considered negative. RESULTS: Among 76 cases, 4 were excluded because of unsatisfactory cytologic smears. Of the remaining 72 cases, 31 were male and 41 female. The age range was 19-80 years. Cytology showed 23 positive and 49 negative cases (1 false positive and 3 false negative). Biopsy showed 24 positive and 48 negative cases (no false positives and 1 false negative). There were 47 negative cases, followed for at least 1 year, and after that we considered them definitively negative for malignancy. Sensitivity of cytology and biopsy was 88% and 96%; specificity was 98% and 100%, respectively. Combined use of brush cytology and biopsy had the highest sensitivity, 100%. CONCLUSION: Brush cytology of the colon is a safe, fast and reliable method for the diagnosis of colorectal cancer. We recommend performing it in conjunction with biopsy. It is also reasonable to perform a repeat biopsy in patients with negative biopsy and positive cytology for a definitive diagnosis.     

Brushing cytology in biliary tract obstruction

During a period of eight years (1980 to 1987), cytologic samples were obtained by brushing and reverse screw devices from 54 patients undergoing transhepatic cholangiography for evaluation of obstructive jaundice. Eight patients were excluded from this study, seven for inadequate follow-up and one because of unsatisfactory cytologic material. Of the remaining cases, 32 were cytologically diagnosed as adenocarcinomas; all but one patient proved to have malignant disease by histologic examination and/or through clinical follow-up. These included 21 pancreatic carcinomas, 6 bile duct carcinomas, 1 ampullary carcinoma, 1 gallbladder carcinoma and 2 metastatic carcinomas. In one case, the diagnosis of malignancy was found to be in error upon review of the cytologic smears. Of 14 patients with negative cytologic diagnoses, 7 were found to have malignant neoplasms and 7 had benign diseases. These findings indicate that, while a positive cytologic diagnosis is a reliable indicator of a malignant biliary obstruction, a negative result does not exclude malignancy.     

Preoperative aspiration cytology of breast tumors

During a ten-year period, 1,942 aspirations of 1,906 mammary tumors in 1,874 patients were performed before excisional biopsy or mastectomy. The cytology findings were categorized as positive (1,107 cases), suspicious (152 cases), atypical (183 cases), benign (166 cases) and unsatisfactory (298 cases). All cytologically positive cases with follow-up were confirmed histologically or by clinical observation. Follow-up showed that 96% of the cases in the suspicious category, 86% of the cases in the atypical category, 51% of the cases in the benign category and 72% of the cases in the unsatisfactory category had malignant neoplasms. Aspiration cytology diagnosed 1,031 of 1,539 primary malignant mammary neoplasms (67%) and 19 of 28 neoplasms (68%) metastatic to the breast; if unsatisfactory cases are excluded, these figures become 1,031 of 1,365 cases (75%) and 19 of 25 (76%), respectively. If those cases reported as suspicious are included with the positive cases and those reported as atypical are included with the negative cases, aspiration cytology would have a sensitivity of 84% for the presence of carcinoma, a specificity of 97% for the absence of carcinoma, a predictive value of 99% for a positive diagnosis and a predictive value of 56% for a negative diagnosis; the diagnostic efficiency would be 86%. Our findings reaffirmed that the cytologic diagnosis of mammary carcinomas is reliable but that negative or inconclusive cytologic findings should not be regarded as a definitive diagnosis if there is clinical suspicion of a malignant neoplasm.     

Value of the cytologic analysis of fine needle aspiration biopsy specimens in the diagnosis of pancreatic carcinomas

Between 1982 and 1986, 410 preoperative percutaneous fine needle aspiration (FNA) biopsies of the pancreas were performed on 316 patients clinically suspected of having a malignant pancreatic tumor. Of 58 patients with pancreatic carcinomas subsequently confirmed by histologic investigation, the FNA biopsy yielded a cytologically positive diagnosis of carcinoma in 39 cases (67.2%) and suspicious findings in another 5 cases (8.6%). In 14 cases of malignancy (24.1%), the FNA puncture failed to sample material from the tumor; hence, the cytologic evaluation yielded false-negative results. Of 21 patients with inflammatory disorders of the pancreas, cytologically suspicious cells were observed in 5 cases (23.8%); in none of those 5 cases did the histologic examination show any evidence of carcinoma. This indicates that caution should be taken not to cytologically over-diagnose cases of pancreatitis. On the whole, cytology proved to be a valuable method for the diagnosis of pancreatic carcinoma; it provided the highest rate of positive results in comparison with other modern clinical diagnostic methods. Furthermore, cytology may improve the diagnostic results even in those cases with clinically negative or merely suspicious findings. FNA punctures of the pancreas produced no serious complications in this series.     

Sediment cytology in bone biopsies

The cytologic examination of smears prepared from the sediment of biopsy specimen fixatives ("sediment cytology") was used to study 70 bone lesions biopsied with a suspicion of malignancy. The smears were adequately cellular in most cases and showed good morphologic preservation; some contained fragments of tissue. Cytology was able to identify the smears from the 47 malignant lesions as malignant, but was not always able to identify the histologic type. While the osteoclastomas, Ewing's sarcomas and metastatic carcinomas were accurately diagnosed, the osteogenic sarcomas could only be identified as sarcomas and the scanty smears from chondrosarcomas only permitted a diagnosis of malignancy. The latter was also true for soft tissue lesions and lymphoma involving the bones. The 12 benign lesions yielded less cellular specimens and were more difficult to cytologically diagnose. The 11 inflammatory lesions were identified as nonmalignant. While this simple technique of sediment cytology can provide an early diagnosis for bone lesions, the final diagnosis requires the histopathologic study of the actual biopsy specimen.     

The cytopathology of bone marrow transplantation

Bone marrow transplantation (BMT) is an increasingly effective treatment for patients with hematologic disorders and malignant neoplasms. From 1975 to 1986, 1,457 specimens were obtained for cytologic evaluation from 328 of the 635 patients who received BMTs at Memorial Sloan-Kettering Cancer Center. These specimens consisted of 1,049 cerebrospinal fluids (CSFs) from 265 patients, 292 bronchoscopy specimens from 92 symptomatic patients and 116 other specimens (including brushings from the liver and gastrointestinal tract, sputa, urines and cervico-vaginal smears). CSF specimens examined before and after BMT from 80 (30%) patients showed an increased number of benign, nonepithelial cells, which were mainly lymphocytic or histiocytic in origin. Malignant cells were detected in CSF specimens from 44 (17%) patients. Bronchoscopy specimens from 3 patients had suspicious cells present; those from 27 patients contained opportunistic organisms. Atypical epithelial or lymphoreticular cells were seen in bronchial specimens from 49 patients. All cytologic findings were correlated with the pertinent clinical information as well as biopsy and autopsy material, including histopathologic evidence of graft-versus-host disease. Cytologic evaluation, especially of bronchial and CSF specimens, was useful in diagnosing the presence of malignant neoplasms, infectious organisms, inflammatory responses, reactive lesions and cellular atypia due to treatment.     

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.     

Earliest detection of oral cancer using non-invasive brush biopsy including DNA-image-cytometry: report on four cases.

OBJECTIVE: We describe four patients presenting early oral cancers, detected cytologically on non-invasive brush biopsies including DNA-image cytometry as an adjunctive method before histology on scalpel biopsies confirmed the evidence of malignancy. METHODS: Brush biopsies were performed and smears thereof investigated cytologically. After Feulgen restaining, DNA-measurements were performed using a DNA-Image-Cytometer. CASE REPORTS: Oral squamous cell carcinomas were diagnosed cytologically in macroscopically suspicious lesions and malignancy confirmed by DNA-cytometry. The initially performed scalpel biopsies did neither supply evidence of oral cancer nor of severe dysplasia. After at least one to 15 months the occurrence of cancer was finally proven histologically on a second scalpel biopsy each (three microinvasive and one in situ carcinoma). CONCLUSION: Non-invasive brush biopsies are a suitable instrument for early cytologic detection of cancer of the mouth. DNA-image-cytometry, as an adjunctive method, can be used to confirm the cytologic diagnosis or suspicion of cancer in patients with doubtful lesions (dysplasias). DNA-aneuploidy is a marker for (prospective) malignancy in smears of the oral cavity, which may detect malignancy months prior to histology. In future this method could be used as a mass screening tool in dentists practice.     

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.     

Usefulness of light microscopy in lymph node fine needle aspiration biopsy

OBJECTIVE: To evaluate light microscopic examination of lymph node fine needle aspiration biopsy (FNAB) in order to determine the indications for ancillary procedures and biopsy. STUDY DESIGN: Reports and smears from 693 consecutive lymph node FNABs were reviewed. Fifty-five cases were excluded because of inadequacy of the material, and another 26 were excluded because follow-up information was not available. RESULTS: Cytologically, 220 cases were diagnosed as positive for malignancy and 392 as negative. Global sensitivity was 94.1% and specificity 96.9%. Sensitivity was higher for nonlymphoid neoplasms (98.2%) than for lymphoproliferative disorders (82.8%). CONCLUSION: Lymph node FNAB is a cost-effective procedure, and with adequate cytologic examination and follow-up, a large number of biopsies and time-consuming ancillary techniques can be avoided.     

Identification of Campylobacter pylori in gastric biopsy smears

The use of gastric biopsy imprint smears to diagnose Campylobacter pylori was compared with the use of tissue sections and cultures. Multiple gastric biopsies were taken from the mucosa of 42 patients during endoscopy. Imprint smears were prepared from the samples used to make tissue sections; other samples were used for microbiologic culture. There was a good concordance (93%) between the morphologic diagnosis of C pylori in the air-dried, Giemsa-stained smears and the tissue sections; the cytologic preparations were clearly positive in six cases (14%) whose sections contained low numbers of the organisms. There was a concordance of 83% between the combined morphologic techniques and the bacteriologic culture. Six positive cases were detected only by the morphologic techniques while one positive case was detected only by bacteriologic culture. C pylori was identified in one or more preparations of the antral biopsy specimens in 23 (55%) of the 42 cases, including 23 (74%) of the 31 cases with a final diagnosis of gastritis or ulcer. These results show the usefulness of the cytologic study of gastric biopsy smears in diagnosing C pylori infections.     

Diagnostic utility of galectin-3 in aspirates of thyroid follicular lesions

OBJECTIVE: To investigate the expression of galectin-3 in various thyroid follicular lesions, including diffuse hyperplasia, nodular hyperplasia, and benign and malignant follicular neoplasms, to clarify the diagnostic utility of galectin-3 in aspirates of follicular lesions. STUDY DESIGN: A total of 146 follicular lesions diagnosed cytologically, obtained from patients who had undergone thyroidectomy for either benign or malignant nodules, were evaluated using Papanicolaou-stained slides and cell blocks with galectin-3 immunostaining. We primarily categorized the aspirated specimens as benign, indeterminate or suspicious for a follicular neoplasm based on cellularity, architectural arrangement of the follicular cells and presence or absence of colloid. Galectin-3 immunostaining was evaluated according to the proportion and intensity of positively stained cells. Cytologic diagnoses were correlated with the results of galectin-3 and categorized into 3 groups (benign, indeterminate for malignancy, suspicious for malignancy) and compared with the corresponding histologic diagnoses. RESULTS: When the histologic diagnoses were compared with the cytologic diagnoses, the accuracy in the distinction between benign and malignant cases was 79.5% except for 8 cytologically and 3 histologically indeterminate cases. Except for 11 indeterminate cases, there were 18 (12.3%) discrepant cases. False positive cases included 8 of 62 (12.9%) nodular hyperplasias and 1 of 42 (2.4%) follicular adenomas. Of 9 false negative cases, 4 minimally invasive carcinomas and 2 widely invasive carcinomas were included. Three follicular tumors of uncertain malignant potential were cytologically categorized as malignant, and all cases showed positivity for galectin-3. CONCLUSION: Galectin-3 could be used as a useful supplementary marker for cytologic diagnosis, although it was not an absolute marker in determining whether a lesion was benign or malignant.     

Nonaspiration-needle smear preparations of pulmonary lesions. A comparison of cytology and histology

Material for cytologic smears was obtained from pulmonary lesions in 146 patients at the Ohio State University between 1979 and 1984 using Rotex or Lee screw needles. Corresponding histologic specimens were available for comparison in 77 of these cases. Diagnoses of malignant neoplasms made by cytologic evaluation (55 cases) were confirmed by the corresponding histologic specimens in 93% of those cases. Possible explanations for the cytologic false-positive diagnoses of malignancy are presented. Correlations between the cytologic and histologic diagnoses of the morphologic type of tumor were 100% for adenocarcinoma, 75% for squamous-cell carcinoma and 20% for large-cell undifferentiated carcinoma. The correlation was 100% for small-cell carcinoma when the histology specimen represented the tumor. Nonneoplastic benign lesions diagnosed cytologically had corresponding benign histologic diagnoses in 94% of the cases. These results compare favorably with those reported for other fine needle aspiration studies of pulmonary lesions. The advantages of using Rotex needles as compared to fine needle aspiration are discussed.     

Cytologic detection of hepatic metastases

Cytologic preparations and histologic specimens from 404 liver biopsies were reviewed. The cytologic specimens were prepared from the saline rinsings of the Klatskin biopsy needle. Malignant neoplasms were detected by both methods in 50 cases. In seven cases, neoplasms were diagnosed by cytologic techniques alone; in nine cases neoplasms were present in the biopsy only. No false-positive cytologic diagnoses of malignancy occurred. The results of this study show that cytologic examination of the rinsings of the biopsy needle is a sensitive and highly specific adjunct to biopsy in the detection of hepatic metastases.     

Comparison of cytologic and acridine-orange flow-cytometric detection of malignant cells in human body cavity fluids

Flow cytometrically (FCM) derived DNA and RNA profiles were studied in acridine orange (AO)-stained body cavity fluid (BCF) specimens obtained from 78 patients with various solid tissue and hematologic malignancies. The ploidy (DNA index), RNA content (RNA index), proliferative activity (% S + G2M) and DNA and RNA scattergram patterns were tested "double-blind" against the cytologic scoring of specimens as malignant, benign or reactive. It was determined that expression of an "abnormal" RNA index (greater than or equal to 2.8) and an elevated proliferative activity (% S + G2M greater than or equal to 7.4) was dependent on the presence of malignancy; 21 of 22 specimens having those abnormal indices had DNA aneuploidy and were cytologically scored as positive. The AO FCM sensitivity and specificity for detecting malignant cells (when measured against cytology scoring) were 61% and 90%, respectively, using the "abnormal" RNA index and % S + G2M cut-offs together with the cellular DNA aneuploidy marker. By supplementing the cytologic scoring with AO FCM DNA and RNA features, the sensitivity for detecting malignant cells was 94%, as compared to 72% for cytology alone. Two specimens gave false-positive FCM results: a tuberculous effusion with a tetraploid subpopulation and a reactive mesothelial proliferation that was diploid and negative cytologically. Scoring for malignancy based on the visual pattern of the DNA and RNA FCM scattergrams, while showing good correlation for aneuploid specimens, in some cases failed to identify diploid disease. The results demonstrate the usefulness of FCM DNA and RNA analysis for supplementing cytologic examination of BCF specimens for the purpose of detecting malignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Accuracy of cytologic diagnosis of central nervous system neoplasms in sterotactic biopsies

The cytohistologic correlation is reported for 112 of the 128 consecutive sterotactic aspiration biopsies performed on patients with clinical and neuroradiologic evidence of brain tumors investigated at the Neurosurgery Department, Karolinska Hospital, from 1976 to 1979. The cytodiagnostic accuracy of benign and malignant tumors was 87% when adequate cell material was obtained. In 17 benign tumors of the sellar region, the diagnostic rate was 88%; cytologic examination independent of histologic biopsy is feasible in this area. The cytodiagnostic accuracy for 95 malignant central nervous system (CNS) tumors was 87% after adjusting for the appreciable sampling error inherent in the use of a stereotactic procedure during the early phase of the study. Two histopathologically proven infectious lesions were reported cytologically as benign. The main microscopic problems were the recognition of highly differentiated astroglial neoplasms and the differential diagnosis between poorly differentiated brain neoplasms and metastases to the CNS. Cytodiagnostic accuracy of CNS tumors can be increased by technical improvements in the stereotactic device, diagnostic experience and immunochemical staining.     

Renal fine needle aspiration cytology

OBJECTIVE: To audit and evaluate the pitfalls in renal fine needle aspiration (FNA) cytology. STUDY DESIGN: A retrospective analysis of 180 renal FNAs from 163 patients, encountered at Canberra Hospital, Australian Capital Territory, between June 1989 and July 1997 was undertaken. The FNA procedures had been performed by radiologists under computed tomography (CT) or ultrasound (US) guidance. The study correlated the FNA results with biopsy findings and clinical outcome. RESULTS: The initial cytologic diagnoses included 84 (47%) benign, 6 (3%) atypical, 7 (4%) suspicious, 70 (39%) malignant and 13 (7%) inadequate. Six of the 13 cytologically inadequate group, on further investigation, had malignant histology. The benign cytologic categories contained 79 benign conditions and 5 cases with a malignant outcome. The atypical cytologic group contained 5 benign and 1 malignant case. All nine cytologically suspicious cases had malignant histology. The cytologically malignant group contained 62 malignant, 7 benign and 1 patient lost to follow-up. The sensitivity was 92.5%, specificity was 91.9%, positive predictive value was 89.9%, negative predictive value was 94.0%, and efficacy of the test was 92.2%. CONCLUSION: Renal FNA can provide an accurate diagnosis in most instances; however, aspiration cytology of the kidney has limitations and pitfalls. Low grade renal cell carcinoma has to be differentiated from oncocytoma, angiomyolipoma, renal infarct and reactive conditions. Renal FNA has a high negative predictive value, which is useful in reassuring patients with radiologically and cytologically benign lesions. Negative FNA does not exclude malignancy in the presence of a radiologic suspicion.     

Nipple discharge cytology in mass screening for breast cancer

Since 1977 mass screening for breast cancer has been conducted in Miyagi Prefecture, Japan; inspection, palpation and cytologic examination of any nipple discharge are part of the initial screening procedures. Among 149,681 subjects examined, 404 cancer cases and 63 papilloma cases were detected. The nipple discharges from 20,537 women were examined cytologically; of the 61 cancer cases, the smears were positive in 18 cases, suspicious in 7, negative with atypical findings in 12 and negative in 24. Ten of the cancer cases were detected exclusively by the cytologic examination of a nipple discharge. In eight of these ten cancer cases, there was no other initial evidence of the primary tumor. The cytologic diagnosis of discharges without blood from 28 cancer cases was positive or suspicious in 10 cases and negative in 18. Thirty-seven of the papilloma cases were initially detected only by the cytologic examination of a nipple discharge; neither physical examination nor mammography showed any abnormal findings.     

Membrane connectivity estimated by digital image analysis of HER2 immunohistochemistry is concordant with visual scoring and fluorescence in situ hybridization results: algorithm evaluation on breast cancer tissue microarrays

Because metaplastic carcinoma of the breast encompasses a great variety of histopathology, diagnostic challenges abound, especially within the realm of cytology. The authors compiled and studied an eight-case series comprised of metaplastic breast carcinomas and lesions initially suspicious cytologically for metaplastic carcinoma in order to assess the degree of cytologic-histologic correlation and to identify recurring problematic themes surrounding the cytology-based diagnosis of this neoplasm. The cytologic and histologic slides from eight cases suspicious for metaplastic breast carcinoma diagnosed by fine needle aspiration (FNA) were collected and analyzed through a seven-year retrospective search of case files at our institution. Based on cytologic characteristics, the cases were separated into three groups. Group 1 consisted of three cases presenting with poorly differentiated adenocarcinoma and squamoid components on FNA. Group 2 was composed of two cases that featured a monophasic, malignant ductal cell population on cytology, while the cytologic specimens for the third group of cases presented with a mesenchymal component with or without a malignant glandular constituent. Cytologic-histologic correlation was present in two of three cases demonstrating a mesenchymal component, and there was 100% sensitivity in the cytologic detection of those mesenchymal elements. However, in only one of three cases was there an accurate cytologic diagnosis of metaplastic carcinoma when squamoid changes were present on FNA. Both cases demonstrating only malignant glandular elements on cytologic specimens revealed an additional component of malignant squamous differentiation upon the examination of mastectomy-derived tissue. These results indicate that squamous-like changes identified on FNA should be interpreted with caution and that sampling error remains a problematic recurrence in cytology. Regardless, there appears to be promise concerning the accurate cytologic diagnosis of metaplastic carcinoma when the lesion is characterized by a mesenchymal component. A study implementing a larger case number is essential in determining the significance of these findings.     

Cytologic features of urothelial carcinoma in catheterized urine with cellular fragments

OBJECTIVE: To identify architectural and cytomorphologic differences that might help distinguish urothelial neoplasms from instrumentation artifact. STUDY DESIGN: We examined 73 cytologic smears of catheterized urine containing urothelial cell clusters between 1998 and 2004. All patients had at least 1 follow-up biopsy. Smears were reviewed for several morphologic features blindly, without knowledge of the follow-up diagnosis. RESULTS: Of the 73 smears, 39 had a benign diagnosis on follow-up biopsy, and 34 had urothelial carcinoma. Cytoplasmic collar, regular and rounded fragment borders, and fine nuclear chromatin were statistically more common in benign smears than those with urothelial carcinoma (p < 0.0001). No significant differences were identified with regard to the presence of background inflammation or nucleoli in the urine specimens. Of the 17 smears that had a cytoplasmic collar, regular fragment borders and fine nuclear chromatin, only 1 (6%) was found to have urothelial carcinoma on follow-up biopsy. All 20 smears in which all 3 features were absent were proven malignant on biopsy. CONCLUSION: Certain architectural and nuclear features can help differentiate urothelial neoplasms from instrumentation artifact in urine cytologic smears.