Distinctive microvillous brush border staining with HBME-1 distinguishes pleural mesotheliomas from pulmonary adenocarcinomas.

HBME-1 is an antimesothelial monoclonal antibody that recognises an unknown antigen on microvilli of mesothelioma cells. The aim of this study was to evaluate the staining pattern with respect to antibody dilution, cellular distribution and intensity of immunohistochemical staining with HBME-1 in pleural mesotheliomas compared with pulmonary adenocarcinomas. A total of 27 pulmonary adenocarcinomas and 26 mesotheliomas were stained with commercially available HBME-1 at various antibody dilutions and evaluated for the site (membranous, +/- microvillous brush border or cytoplasmic), intensity and percentage of cells staining. On light microscopy, 23 mesotheliomas showed distinctive microvillous brush border staining with HBME-1 (three mesotheliomas--two sarcomatoid and one poorly differentiated--were negative). Twenty-five adenocarcinomas showed membranous +/- cytoplasmic staining but lacked the distinctive microvillous brush border staining. In a subgroup of tumours studied by electron microscopy following immunogold labelling by HBME-1, all of 16 mesothelioma cases showed strong immunogold labelling in the membranes of the long microvilli. In contrast, the 12 cases of pulmonary adenocarcinomas showed minimal labelling in the membranes of the short microvilli, but staining was seen within vesicles, often near the surface of the cells. This study shows that the presence of a distinctive microvillous brush border by immunohistochemical staining with HBME-1 allows distinction between pleural mesotheliomas and pulmonary adenocarcinomas (sensitivity of 88%, specificity of 100%). The difference in the ultrastructural distribution of immunogold labelling with HBME-1 between mesotheliomas and adenocarcinomas underscores the light microscopy findings.

Synvisc perisynovitis.

Synvisc (hylan G-F 20) is a high molecular weight hyaluronan which is manufactured from chicken combs. It is currently one of the options used in the treatment of severe osteoarthritis of the knee joint. Synvisc is directly injected into the diseased joint, where it provides elasticity and viscosity. Published experience suggests than Synvisc is a safe and well-tolerated material with occasional mild local reactions but no long-term adverse sequelae. This article describes a case of Synvisc-related granulomatous inflammation in the perisynovial adipose tissue. To our knowledge, this is the first histological account of tissue reaction to Synvisc.

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.

Ultrasound-guided fine needle aspiration cytology of impalpable breast lesions in a rural setting. Comparison of cytology with imaging and final outcome.

OBJECTIVE: To analyze the effectiveness of fine needle aspiration (FNA) cytology in a multidisciplinary setting in rural Australia and to compare the imaging (mammographic and ultrasound) appearances and cytomorphologic findings with the final outcome. STUDY DESIGN: Prospective analysis of ultrasound-guided FNA cytology results from 426 women, aged 40-86 years, with screening-detected mammographic abnormalities. Cases of microcalcification, assessed mainly by stereotactatic core biopsy, were not included in the study. The FNAs were performed at a rural breast screening and assessment program in New South Wales, Australia, over a three-year period between May 1993 and May 1996. RESULTS: Imaging, FNA and combined imaging and FNA results from 426 women were as follows. The imaging diagnoses included 176 (41%) benign, 34 (8%) probably benign, 17 (4%) equivocal, 104 (24%) suspicious and 95 (23%) malignant cases. The FNA findings showed 59 (14%) no epithelial cells seen (nondiagnostic), 175 (41%) benign, 36 (8%) atypical, 41 (10%) suspicious and 115 (27%) malignant. Combined imaging and cytologic results comprised 224 (52.6%) benign, 10 (2.3%) atypical/equivocal, 59 (13.9%) suspicious and 133 (31.2%) malignant cases. All the malignant cases, by combined assessment, had malignant histology, and all the benign cases behaved in a benign fashion. In 80% of the suspicious lesions, the histologic diagnosis was malignant, but only 10% of the atypical/equivocal lesions had malignant histology. The positive predictive value of diagnosis of malignancy by combined imaging and FNA was 100%, and the false negative rate was 0%. CONCLUSION: Despite the recent surge in the popularity of core biopsy, FNA cytology of impalpable, mammographically detected lesions, when practiced in a multidisciplinary setting, is an extremely accurate test with high sensitivity, specificity, predictive values and efficacy. FNA cytology of the breast is a well-tolerated, relatively noninvasive test with a very low risk of complications. The sensitivity and positive predictive values for malignant and suspicious mammographic categories are also very high.

Flow-cytometric algorithm on fine-needle aspirates for the clinical workup of patients with lymphadenopathy.

To analyze the value and limitations of flow cytometry (FCM) in the investigation of patients with lymphadenopathy, a retrospective study of 196 patients, referred for fine-needle aspiration (FNA) cytology, was carried out in Canberra, Australian Capital Territory, Australia, between 1992-1997. Complete cytological, flow-cytometric, and outcome (clinical and histological) data were available on all the cases. The FNA appearances were read in conjunction with FCM findings. The following cytological categories were recognized: benign, 78 cases (39.8%); indeterminate, 9 cases (4.6%); and malignant, 109 cases (55.6%). None of the 78 cytologically benign cases had malignant outcome. All 109 cytologically malignant cases had malignant histology, and 8/9 of the cytologically indeterminate FNAs had malignant histology. The cytologically malignant category contained 106 B-cell lymphomas and three T-cell lymphomas. All 65 B-cell lymphomas with K light chain predominance had K/L ratio greater than 3/1, and all 34 B-cell lymphomas with L light chain predominance had an L/K ratio greater than 2/1. Clonality was therefore established for K/L and L/K at 3/1 and 2/1, respectively. When K/L and L/K ratios were below these figures (7 cases), other parameters, including the proportion of CD20 and the dual expression of CD19/CD10 and CD20/CD5, were used to determine the nature of the aspirate. In the B-cell lymphomas without demonstrable light chain restriction, CD20 positivity in excess of 85%, CD19/CD10 positivity of more than 18%, or CD20/CD5 positivity greater than 35% were independently diagnostic of B-cell lymphoma. In the T-cell lymphomas, greater than 90% of the cells were T cells, and aberrant T-cell antigen expression with loss of at least one pan-T-cell antigen was detected. In conclusion, the sensitivity of diagnosis of malignancy, false-negative rate, and predictive value of malignant diagnosis with combined FNA cytology and FCM were 99%, 0%, and 100%, respectively.

The role of peer review in internal quality assurance in cytopathology.

In 1992 we set up a peer review system to address all the steps involved in the production of a cytopathology report. The aim of the study was to generate accurate, timely and clinically relevant cytopathology reports. During a four year period we monitored and recorded activities such as turnaround time and adequacy of sampling as well as errors including typographical, SNOMED, coding, technical, labelling of slides, clerical, macroscopic and microscopic errors. The findings were discussed at weekly laboratory meetings attended by technical, scientific, clerical and medical staff. Minor errors not needing immediate action were discussed and incorporated as future improvements into the workings of the laboratory. For major discrepancies with potential implications for patient management, supplementary reports were issued and the relevant clinician was informed of the outcome. Detailed peer review of 1.3% of the total workload, during the period of the study, led to comments on some aspects of the original report in 24.9% of the reviewed cases. The majority of comments (57%) were minor, concerning issues related to the pre-analytical (clinical history, demographics, clerical and technical) aspects of the cases. The post analytical (microscopic description, diagnosis, recommendation and coding) phase of cases attracted 43% of the comments. In 1.1% of cases, the reviewer made suggestions regarding the diagnosis, and in 0.4% of cases a different recommendation was made. Cost-benefit analysis revealed that our internal quality assurance (IQA) activities added $1.20 to the total cost of each cytopathology case received and processed in the laboratory. On the benefit side, analysis of the data showed a continuous fall in the number of errors in both the pre-analytical and post-analytical phases of report generation. Furthermore, the turnaround time fell from 3.0 days at the beginning of the study to 1.7 days at present. These IQA activities have highlighted the importance of such a review system in detecting errors in cytopathology reporting. Recognition of the fact that cytopathology suffers from observer variability has led to the adoption of a uniform approach to cytological reporting among cytotechnologists and pathologists.

Fine needle aspiration cytology vs. core biopsy in a rural setting.

OBJECTIVE: To compare, contrast and analyze the value and limitations of fine needle aspiration (FNA) cytology and core biopsy (CB) in a rural setting. STUDY DESIGN: Retrospective analysis of 100 FNA cytology and 100 CB results of mass lesions from 193 patients matched for age, sex and body organs, and referred for FNA or CB in rural New South Wales, Australia, between September 1990 and May 1996. RESULTS: FNA cytology and CB results from 193 patients were analyzed, based on anatomic location and cytologic criteria. Sites included lung, retroperitoneum, liver, breast, kidney, pancreas and ovary. The FNA group contained 6 inadequate, 14 benign, 3 atypical, 6 suspicious and 71 malignant cases, whereas the CB group had 1 inadequate, 24 benign and 75 malignant conditions. The inadequate samples in both groups were due to technical difficulty in obtaining representative material. The indeterminate (atypical and suspicious) group, which was the main pitfall of FNA, contained 4 low grade carcinomas, 3 low grade non-Hodgkin's lymphomas and 2 fibrocystic breast changes. The benign FNA group comprised 8 cysts, 5 inflammatory/reactive conditions and 1 benign tumor/hamartoma, whereas the benign CB group contained 11 cysts, 9 inflammatory/reactive conditions and 4 benign tumors. CONCLUSION: FNA was comparable to CB at most anatomic sites. CB occasionally offered additional information. This slight advantage was due to the availability of tissue from the first and often the only pass for assessment of architecture and performance of ancillary tests, which obviated the need for further sampling. On-site assessment of the core imprints at the time of the procedure by the highly skilled and experienced interventional cytopathologist was responsible for limiting the number of attempts to one core in most of the instances, therefore minimizing complications. Pathologists are encouraged to become more familiar with the criteria of aspiration cytology, which has proven its validity in the new cost-conscious environment. Despite the recent surge in the popularity of core biopsy, FNA cytology, when practiced in a multidisciplinary setting, with involvement of pathologists, radiologists and clinicians, is an extremely accurate test with very high sensitivity, which approaches that of surgical pathology, and specificity very similar to that of frozen section. FNA has a positive predictive value for a malignant diagnosis of almost 100%. FNA is a well-tolerated, relatively noninvasive test with a very low risk of complications.

Fine needle aspiration cytology in a rural setting.

OBJECTIVE: To analyze the value and limitations of fine needle aspiration (FNA) cytology in a rural setting. STUDY DESIGN: Prospective analysis of 1,196 FNA cytology results of superficial and deep masses from 1,088 patients in rural New South Wales, Australia, between September 1990 and May 1996. The FNA procedures were performed by palpation and image guidance using various-gauge needles and core biopsies as appropriate. RESULTS: FNA cytology results were analyzed, based on body organs and cytomorphologic findings. Breast, 450 (41%); thyroid, 152 (14%); superficial lymph nodes, 150 (14%); lung, 98 (9%); and liver, 55 (5%), made up the majority of the cases. The following general cytologic categories were used: nonrepresentative (inadequate), 39 (3.58%); benign, 662 (60.85%); atypical, 45 (4.13%); suspicious, 30 (2.76%); and malignant, 312 (28.68%). Clinical and histologic follow-up (core biopsies in 100 patients and histology of the atypical, suspicious and malignant cytologic categories in 387 patients) showed over 96% sensitivity for a diagnosis of malignancy, with about a 4% false negative rate and 99.04% predictive value of a malignant FNA diagnosis. The false positive rate in the cytologically malignant group of 312 patients was 0.96%. The breast, thyroid and lymph node fine needle aspirations were mostly benign. The great majority of deep organ fine needle aspirations were malignant. Atypical and suspicious FNA cytology, seen in both superficial and deep sites, was due to either technical difficulty in obtaining material or problems of interpretation (genuine cytologic overlap or inexperience). The radiologically suspicious cases with negative cytology were either reaspirated or subjected to surgical biopsy. CONCLUSION: FNA cytology, when practiced in a multidisciplinary setting with direct involvement of pathologists, radiologists and clinicians, is an extremely accurate, well-tolerated, relatively noninvasive and low-risk test that obviates the need for surgical intervention in most benign conditions and disseminated malignancies. Therefore, by taking an active role with on-site assessment of the FNA material and discussion with radiologic colleagues, the cytopathologist could offer an FNA service comparable to surgical pathology in sensitivity and very similar to frozen section in specificity.

Internal quality assurance activities of a surgical pathology department in an Australian teaching hospital.

AIM: To assess the role of a quality assurance programme in improving the service provided by a surgical pathology department. METHODS: A continuous internal quality assurance study of the activities of an anatomical pathology department in an Australian teaching hospital was undertaken over a five year period. This addressed all steps involved in the production of a surgical pathology report. These were addressed in an open forum which included technical, scientific, clerical, and medical staff. Minor errors not needing immediate action were discussed and incorporated into laboratory practice. For major discrepancies with potential implications for patient management supplementary reports were issued and the relevant clinician informed of the outcome. RESULTS: Comprehensive peer review of 8.9% of the total workload of the department (3530 cases) and all the frozen sections (916 cases) over a period of five years, beginning in 1991, led to comments on some aspects of the original report by the reviewer in 19.6% of the cases. The great majority of the comments were minor, concerning issues related to the microscopic findings (4%), macroscopic description (3.1%), clerical aspects (3%), typographical errors (3%), coding errors (2.7%), technical errors including poor sections and incorrect labelling (1.7%), inadequate clinical history (1.2%), and incomplete or incomprehensible diagrams (0.9%). In two cases (0.05%) the original report did not state proximity of the tumour to surgical margins and in three of the frozen sections (0.3%) the original diagnosis was incorrect. However, in these cases the frozen section assessment did not alter the overall management of the cases. CONCLUSIONS: This study highlights the importance of a review system in detecting errors in surgical pathology reporting. Recognition of the fact that surgical pathology is not infallible has improved the end product. It has also minimised interobserver variability in the department, resulting in a uniform approach among the pathologists to macroscopic description, specimen sampling, special stains, and histological reporting.

Morphometric analysis of coronary artery stenosis: an accuracy and reliability study.

Luminal narrowing was assessed in 238 transverse segments obtained from coronary arteries removed at postmortem. In each segment, narrowing was assessed by gross visual estimation before and after fixation, and on histological sections by stereological point counting and computer-assisted planimetry. Computer-assisted planimetry was found to be accurate and reliable but the equipment needed is expensive, and requires specialized software and an experienced user. Morphometric measurement by stereologic point counting was accurate, rapid, simple, and inexpensive. In comparison with computer-assisted planimetry visual estimation was found to be neither accurate nor reliable. Our results indicate point counting as the method of choice for assessment of coronary artery luminal narrowing by atherosclerosis.

DNA ploidy in thin melanoma.

DNA ploidy in benign nevi (BN), thin non-metastasizing melanomas (TNM) and thin metastasizing melanomas (TMM) was investigated using an image analyser to determine whether characteristics such as nuclear area (NA) and nuclear integrated optical density (IOD) could be used to distinguish between these lesions. NA measurements showed significant differences between samples of nevus cells and melanoma cells and nuclear IOD differences were significant between TNM and TMM samples. Differences in NA and nuclear IOD were detected across the three groups (BN, TNM and TMM) but the large variability within samples and within groups indicate further studies would be necessary to determine the usefulness of these results in terms of the rate of correct group classification of a single sample for diagnostic purposes.

Stereological analysis of non-Hodgkins lymphomas.

A detailed stereological analysis was carried out on 30 lymph nodes at 2 ultrastructural levels. They were classified as follows: 10 were reactive lymph nodes, 10 were of low-grade non-Hodgkins lymphomas and 10 were of high-grade non-Hodgkins lymphomas. The mean and median values and interquartile ranges of nuclear profile diameter, nuclear volume, volume of cytoplasm, cell volume and absolute number of ribosomes were recorded for each case. The model proved very efficient in establishing several significant differences between the highgrade and lowgrade lymphomas and between the highgrade lymphomas and reactive lymph nodes but did not discriminate between lowgrade lymphomas and reactive nodes, nor did it distinguish neoplastic cells from reactive cells in the neoplastic group. The significance of these findings is discussed.