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Proficiency testing in cytology laboratories in Ontario, Canada: a decade of experience. III. A precision study of consistency and reproducibility in cytology reporting.

The Ontario Laboratory Proficiency Testing Program's testing model and the results of early surveys of cytology laboratories have been previously described. To test consistency and accuracy, the same slides from one survey were recirculated to the same laboratory in the next survey. There was no statistical difference in either the accuracy or consistency in reporting by the various categories of personnel. Analysis of the data by category of diagnosis showed the reporting of "no abnormal cells" and "benign atypia" to be slightly more accurate and "moderate dysplasia" and "severe dysplasia" to be slightly less accurate than the reporting in other categories. Consistency in reporting appeared to be slightly less accurate in severe dysplasia than in the other categories. The analysis, which includes the results from all licensed cytology laboratories in Ontario, provides evidence that, in the reporting of cervical cytologic material, it is feasible to differentiate among the various categories within the spectrum of squamous epithelial abnormalities with a general level of accuracy and consistency that, although satisfactory, is not yet ideal.

Cytological Techniques↗

Cytologic-histologic correlation of nongynecologic cytopathology cases: separation of determinate from indeterminate cytologic diagnoses for analysis and monitoring of laboratory performance.

Much of the literature on the quality-assurance aspect of cytologic-histologic correlation (CHC) has focused on gynecologic cytology. For nongynecologic cytopathology, the process is complicated by the use of determinate (positive for malignant cells, negative for malignant cells) and indeterminate (atypical, suspicious, or follicular lesion) diagnostic categories. Here, we illustrate our routine methodology for analyzing CHC data on nongynecologic cytopathology cases by separating determinate from indeterminate cases. A focused list of determinate and indeterminate cytopathology cases with surgical pathology correlation is generated each week. The determinate cases are ascertained as true positive (TP), true negative (TN), false positive (FP), or false negative (TN). The discrepant cases (FP and FN) are investigated to determine the cause (sampling, interpretation, or screening). For indeterminate cases, the surgical pathology outcome (benign, malignant) and suitability of the cytopathology category utilized are reviewed. For the focused period of 4 mo, sensitivity was 70% and specificity was 100%. The most common reason for false-negative diagnoses was a sampling problem in the cytologic specimen; there were no false-positive diagnoses. Malignant outcomes for follicular lesion, atypical, and suspicious diagnoses were 29%, 40%, and 76%, respectively. Data derived from regularly performed CHC are useful in reviewing the diagnostic performance of the laboratory.

Cell Biology↗

Pelvic washing cytology in serous borderline tumors of the ovary using ThinPrep: are there cytologic clues to detecting tumor cells?

The detection of tumor cells in pelvic washings of patients with serous borderline tumors of the ovary (SBT) remains a diagnostic challenge. Accurate diagnosis of pelvic washings is important in determining therapeutic regimens and assessing patient prognosis. No study has exclusively examined pelvic washing cytology of patients with SBT using only ThinPrep methodology. The purpose of this study is to examine whether cytologic clues exist in detecting tumor cells of SBT in pelvic washings processed with ThinPrep. Using previously established criteria, we reviewed the pelvic washes of 37 patients with SBT and correlated them with the histologic findings in the omentum. We also compared their cytoarchitectural features with pelvic washes in patients with benign ovarian disease and serous carcinoma. Cytoarchitectural features that achieved statistical significance in distinguishing cells of a SBT from reactive mesothelial cells include the following findings: presence of a two-cell population (P = 0.001), psammoma bodies (P = 0.001), cytoplasmic vacuolization (P = 0.001), smooth group contours (P = 0.004), nuclear size >2x neutrophils (P = 0.004), high nuclear-to-cytoplasmic (N/C) ratio (P = 0.004), absent intercellular windows (P = 0.007), and course nuclear chromatin (P = 0.032). Psammoma bodies were the only statistically significant feature distinguishing SBT from serous carcinoma, being more common in SBT than serous carcinoma (P = 0.035). The prominent number of associated psammoma bodies seen in the SBT group was a notable finding that may aid as a valuable cytologic clue in detecting tumor cells. Overall cellularity remains a source of false-negative diagnosis. Correlation with histologic findings remains crucial given our inability to reliably distinguish tumor cells of SBT from endosalpingiosis or serous adenocarcinoma.

Adult↗

Fine-needle aspiration cytology of pancreatic somatostatinoma: the importance of immunohistochemistry for the cytologic diagnosis of pancreatic endocrine neoplasms.

Pancreatic somatostatinoma is a rare pancreatic endocrine neoplasm representing as little as 1% of pancreatic endocrine neoplasms (PENs). The histologic features of this tumor are like those of other PENs, except that it commonly forms acinar structures and often has cells with abundant, granular cytoplasm. We have recently encountered two of these neoplasms sampled by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). We discuss the cytologic and immunohistochemical findings of these two cases and the cytologic similarities these neoplasms share with pancreatic acinar-cell carcinoma (PACC). We review the cytologic features of PEN and PACC and discuss the importance of cell block immunohistochemistry in the diagnosis of pancreatic neoplasia sampled by EUS-guided FNA.

Aged↗

[Diagnostic value of cytological investigations in metastatic tumours of the liver: comparison of laparoscopy, histology, and cytology (author's transl)].

Fine needle aspiration biopsy is generally a harmless method if contraindications are considered and provides sufficient tissue for cytological evaluation. The diagnostic value is very high: in 27 cases of metastatic tumours of the liver diagnosed by laparoscopy the diagnosis was confirmed in 26 cases and revised in one case. In a control group of 200 patients with various diffuse liver diseases or morphologically normal findings no false positive results were found. In no case were post-biopsy haemorrhage or other complications observed. Needle biopsy and cytological evaluation should be used with an increased frequency when a malignant tumour of the liver is suspected clinically. After primary localization of suspicious areas by ultrasound or scanning the pick-up rate is high. Laparoscopy with precisely aimed fine needle biopsy is the method for verifying the diagnosis in cases with cytologically negative results which is up to 100% accurate.

Biopsy, Needle↗

Fine-needle aspiration cytology of peripheral T-cell lymphoma. A cytologic, immunologic, and cytometric study.

The diagnosis of peripheral T-cell lymphoma (PTCL) is difficult. This entity can be misdiagnosed as Hodgkin's disease or a reactive process such as nonnecrotizing granulomatous lymphadenitis or it can present a problem in lymphoma classification. Fine-needle aspirates from 13 patients with histologically proven PTCL were evaluated by cytology, immunochemistry, and flow cytometry. Of the 13 patients with PTCL, initial cytologic diagnoses were atypical lymphocytic infiltrate (2), mixed-cell lymphoma (6), mixed-cell lymphoma with associated histiocytes (2), large cell lymphoma (2), and small cell lymphoma (1). Surface marker studies were performed on cytospin preparations. Antibodies against cytotoxic-suppressor (Leu-2a) and helper-inducer (Leu-3a,b) antigens were used in 11 cases. Ten lymphomas demonstrated helper phenotype and one showed phenotypic heterogeneity in two different sites. The most prominent cytologic features of PTCL were a variable combination of small, intermediate, and large lymphoid cells with irregular nuclei, presence of epithelioid histiocytes, and atypical mononuclear cells. Flow cytometry studies showed a diploid stem line with intermediate proliferative activity (mean S-phase of 6.7%) in most cases, despite the clinical aggressiveness of this neoplasm.

Adult↗

Liquid-based cytology can improve efficiency of cervical smear readers: evidence from timing surveys in two NHS cytology laboratories.

OBJECTIVE: Cervical screening programmes in England and Wales were advised by the National Institute for Clinical Excellence in 2003 to adopt liquid-based cytology (LBC) in place of conventional Papanicolaou (Pap) cytology to facilitate laboratory efficiency. Pilot evaluations in England and Scotland monitored daily or weekly workloads of smear readers and concluded that LBC could increase hourly throughput rates. This study, instead, used timing surveys to determine screening rates. METHODS: Two National Health Service cytology laboratories in Manchester and Stockport were partially converted to the LBC ThinPrep process for a cervical screening trial. Three 1-week timing surveys were conducted over 7 months. The surveys covered all LBC-trained staff. The first survey in Manchester also covered staff undertaking conventional Pap screening. The smear readers used timers to record time taken for examining and reporting each slide. RESULTS: In Manchester, in the first survey, nearly 1 minute per slide was saved by the LBC method during primary microscopy. In both laboratories, the mean microscopy time for primary screening of LBC slides was reduced by almost 1 minute between the first and second surveys. There was no difference between the second and third surveys. Microscopy by cytopathologists was also 1 minute per slide quicker with LBC than conventional Pap. The LBC inadequate rates for both laboratories were <2.0%. Organizational factors impacted on the hourly LBC primary screening rates in the laboratories, the rate for Stockport being higher than the rates in the pilot evaluations. CONCLUSIONS: The timing surveys confirm that the LBC ThinPrep technology can improve laboratory efficiency. However, decision-makers should also consider the overall costs and benefits of introducing the technology in screening programmes, including the capital investment and workforce implications.

Efficiency↗

Parathyroid identification by ultrasonically guided aspiration cytology. Is correct cytological identification possible?

Reliable parathyroid identification is necessary before percutaneous inactivation of parathyroid tumours is carried out. Aspiration cytology is one of the methods used for this purpose. Some, but not all, investigators have found it difficult or impossible to make a cytological distinction between thyroid and parathyroid cells. In a blind morphological study of 16 parathyroid and 16 thyroid aspirations the specificity of a cytological diagnosis of parathyroid cells was 100%. The sensitivity of the same diagnosis was 9/16 = 56% if only certain diagnosis of parathyroid cells was considered, but 14/16 = 88% if also diagnoses of "probably parathyroid cells" were considered.

Biopsy, Needle↗

Cytological aspects of antimicrobial antibiosis. I. Cytological changes associated with the exposure of Escherichia coli to colistin sulfate.

Chapman, George B. (Cornell University Medical College, New York, N.Y.). Cytological aspects of antimicrobial antibiosis. I. Cytological changes associated with the exposure of Escherichia coli to colistin sulfate. J. Bacteriol. 84:169-179. 1962-Broth cultures of Escherichia coli were exposed to different concentrations of the antibiotic colistin sulfate for various lengths of time. Control (untreated) and treated cells were fixed, dehydrated, and embedded in methacrylate or Epon. Ultrathin sections were examined in an RCA EMU2-D electron microscope. Two conspicuous cytological changes were noted. First, the nuclear material disappeared from its normal sites and was no longer demonstrable. Second, the cytoplasm lost its granularity and became homogeneous. Cells which showed these changes were nonviable.

Anti-Bacterial Agents↗

Cytological aspects of antimicrobial antibiosis. II. Cytological changes associated with the exposure of Pseudomonas aeruginosa and Bacillus megaterium to colistin sulfate.

Chapman, George B. (Cornell University Medical College, New York, N.Y.). Cytological aspects of antimicrobial antibiosis. II. Cytological changes associated with the exposure of Pseudomonas aeruginosa and Bacillus megaterium to colistin sulfate. J. Bacteriol. 84:180-185. 1962-Broth cultures of Pseudomonas aeruginosa and Bacillus megaterium were exposed to the antibiotic colistin sulfate. Control (unexposed) and exposed cells were fixed, dehydrated, and embedded in methacrylate. Ultrathin sections were examined in an RCA EMU2-D electron microscope. Two conspicuous cytological changes were noted in P. aeruginosa. The nuclear material was no longer demonstrable in its normal sites, leaving an empty space, and the cytoplasm lost its granularity, becoming homogeneous. In B. megaterium, the latter change was also noted. The nuclear material, however, although no longer demonstrable, did not leave an empty space. Rather, it seemed that cytoplasmic material had engulfed and masked nuclear areas. Cells which showed these changes were nonviable.

Anti-Bacterial Agents↗

CYTOLOGICAL ASPECTS OF ANTIMICROBIAL ANTIBIOSIS. III. CYTOLOGICALLY DISTINGUISHABLE STAGES IN ANTIBIOTIC ACTION OF COLISTIN SULFATE ON ESCHERICHIA COLI.

Kaye, Jeremy J. (Cornell University Medical College, New York, N.Y.) and George B. Chapman. Cytological aspects of antimicrobial antibiosis. III. Cytologically distinguishable stages in antibiotic action of colistin sulfate on Escherichia coli. J. Bacteriol. 86:536-543. 1963.-Broth cultures of Escherichia coli were subjected to a constant concentration of colistin sulfate for varying periods of time. Controls and treated cells were fixed, dehydrated, and embedded in methacrylate, and ultrathin sections were examined in an electron microscope. Three stages in the antibiotic process were discerned. Stage 1 was characterized by a disruption of the axial orientation of the nuclear material and by an invasion of nuclear areas by tufts of material presumably of cytoplasmic origin; no loss of cellular contents could be detected cytologically. Stage 2 was characterized by the loss of nuclear material and by a loss of typical cytoplasmic granularity, an increase in cytoplasmic electron density, and an agglomeration of the cytoplasm into packed tufts of material; in contrast to the nuclear material, there was no loss of cytoplasmic material in this stage. Stage 3 was characterized by the loss of the altered cytoplasmic material but with the persistence of mesosomes, plasma membrane, and cell wall. Speculation that each and all of these changes might have resulted from an altered intracellular milieu secondary to a primary effect of the antibiotic on the plasma membrane is presented.

Anti-Bacterial Agents↗

Can sensitivity of voided urinary cytology or bladder wash cytology be improved by the use of different urinary portions?

OBJECTIVE: To improve sensitivity by using different portions of voided urine cytology (VUC) and bladder wash material cytology (BWC). MATERIALS AND METHODS: 52 patients with biopsy-proven superficial transitional cell carcinoma (TCC) of the bladder were studied. Voided urine specimens were divided into a first stream, mid-stream and terminal stream. Bladder wash material was also divided into a first portion, mid-portion and last portion. All portions were investigated for cytology abnormalities. RESULTS: Sensitivity for the detection of malignant cells was 34.6, 38.5 and 38.5% for the first, mid- and terminal stream of VUC and 34.6, 38.5 and 34.6% for the first, mid- and last portion of BWC, respectively. The sensitivity of VUC was 20-25% for grade I, 30-40% for grade II, and 50-75% for grade III tumors, respectively. The sensitivity of BWC was 25% for grade I, 35-45% for grade II, and 33-50% for grade III tumors, respectively. There was no statistical significant difference for sensitivities between either grades (p = 0.06) or portions or streams (p = 0.3) of VUC and BWC. CONCLUSIONS: In this small group of patients, we did not find any significant difference, but we found highest sensitivity in grade III tumors with the terminal portion of the voided urine when compared to other portions of VUC. Therefore, we believe that further study in a large series is necessary to investigate this approach of differentiated BWC and especially VUC.

Carcinoma, Transitional Cell↗

Scrape cytology of meningioangiomatosis: a report of two cases with diagnostic cytologic features.

BACKGROUND: Meningioangiomatosis is a rare, probably hamartomatous condition characterized by nonneoplastic intracortical proliferation of meningothelial cells, capillaries and fibroblasts. The lesion may mimic a tumor both clinically and radiologically. We present two cases of the entity, including its cytologic features. CASES: A 71-year-old man presented with an eight-month history of headache, change in vision, loss of depth perception and unsteady gait. Magnetic resonance imaging (MRI) revealed an infiltrative lesion of the left occipital lobe, diffuse in nature. Cytologic smears prepared at the time of intraoperative consultation showed numerous thin-walled capillaries together with bland spindle cells. Occasional large cells with prominent nucleoli were also present. Frozen section confirmed the presence of linear, small capillaries surrounded by fibroblasts and meningothelial cells, consistent with meningioangiomatosis. The second case was a 3-year-old girl who presented with a one-day history of seizure, vomiting, fever and perioral cyanosis. MRI revealed an enhancing lesion in a temporal lobe of the cerebrum. The patient underwent excision of the lesion. Intraoperative cytology showed numerous meningothelial whorls together with neurons and occasional capillaries. Both patients were well, one after three months and the other after six. CONCLUSION: Meningioangiomatosis is a lesion characterized by linear capillaries, meningothelial cells and neurons, some exhibiting nuclear atypia. The combination can lead to an erroneous diagnosis of more common conditions, such as meningioma (with intracortical extension) and anaplastic astrocytoma. Contrary to these more sinister diagnoses, meningioangiomatosis is a completely benign, presumably hamartomatous entity.

Aged↗

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

ISSUES: The conference participants addressed the following issues: (1) reporting of equivocal diagnoses, (2) strategies to minimize the use of such diagnoses, (3) morphologic criteria, and (4) management of women with equivocal diagnoses. CONSENSUS POSITION: Equivocal diagnoses should be minimized, to the extent possible, by emphasizing cytologist education and training, improved specimen collection and quality assurance monitoring of individual and laboratory diagnosis rates. Cases fulfilling criteria for other diagnostic entities should not be included in the equivocal category. Regardless of the term utilized, an equivocal diagnosis should be qualified in some manner to indicate that the diagnosis defines a patient at increased risk of a lesion, particularly for those cases which raise concern about a possible high grade lesion. Qualification of an equivocal diagnosis can also be accomplished by appending laboratory statistics of the likelihood of various clinical outcomes or recommendations for patient follow-up. In contrast to favoring a reactive process versus squamous intraepithelial lesion (SIL), a more rationale approach to qualification of atypical squamous cells of undetermined significance may be to separate cases equivocal for low grade SIL from those suspicious for high grade SIL. With regard to glandular lesions, the conference participants expressed unanimous support for the separation of adenocarcinoma in situ (AIS) from atypical endocervical cells of undetermined significance when sufficient criteria are present. However, the diagnosis of a precursor lesion to AIS, endocervical glandular dysplasia, was controversial. The majority of conference participants discourage the use of such terms as mild glandular dysplasia and low grade glandular dysplasia for cytologic diagnoses. ONGOING ISSUES: Conference participants agreed that a term reflecting diagnostic uncertainty is necessary to communicate findings that are equivocal. However, participants could not agree on the wording of such a term. Opinions differed as to: (1) use of atypical, abnormal or morphologic changes to describe cell changes, (2) whether the diagnosis should indicate a squamous or glandular origin of the cells in question when this determination can be made, and (3) the value of defining morphologic criteria for such a diagnosis. The debate over terminology, as well as morphologic criteria, is ongoing, and the readership is invited to communicate opinions to Acta Cytologica. Management of women with equivocal diagnoses varies widely from locale to locale and may differ based on how the equivocal diagnosis is qualified. Findings insufficient for the diagnosis of a high grade lesion may warrant more aggressive follow-up than cases equivocal for a low grade lesion. Where sensitivity of detection of lesions is of paramount importance, follow-up will generally consist of more frequent cytology screening or colposcopy and biopsy. However, in some countries it is considered unethical to have a high percentage of false positive diagnoses, which result in overtreatment and an unnecessary burden for women participating in cervical screening. Future studies may provide a morphologic, or perhaps molecular, basis for distinguishing true precursors of neoplasia from minor lesions of no significant clinical import; this would allow a more coherent and rational approach to diagnosis and management of women with equivocal cytologic findings.

Adenocarcinoma↗

Cytology of grade 1 papillary transitional cell carcinoma. A comparison of cytologic, architectural and morphometric criteria in cystoscopically obtained urine.

OBJECTIVE: To assess the diagnostic criteria for grade 1 papillary transitional cell carcinoma (TCC) in cystoscopically obtained urine. STUDY DESIGN: We compared the sensitivity, specificity and positive predictive value of cytologic, architectural and morphometric (primarily architectural) criteria in 177 specimens with corresponding biopsy follow-up. RESULTS: Sensitivities ranged from 22% to 44%, specificities from 69% to 85% and positive predictive values from 59% to 66%. CONCLUSION: The currently described cytologic, architectural and morphometric criteria are inadequate for the identification of grade 1 papillary TCC, and the cytologic diagnosis of grade 1 papillary TCC in cystoscopically obtained urine remains unreliable.

Biopsy↗

[Cytologic and immunologic prognosis of infertility. I. Prognostic significance of cytologic study of peritoneal fluid of infertile patients].

Cytological investigation of the peritoneal fluid from 110 patients was performed. The fluid was taken during laparoscopical surgery. Cytological patterns of the peritoneal fluid from women with tube-peritoneal infertility, myoma utery, and ovarian cysts in combination with infertility were described. Cytological data on the peritoneal fluid can serve one of the criteria of the state of reproductive organs and future prognostication in infertal patients.

Adult↗

Fine needle aspiration cytology of neuroendocrine tumors of the pancreas. A cytologic, immunocytochemical and electron microscopic study.

We report the fine needle aspiration cytology findings in six cases of neuroendocrine tumor of the pancreas. Three cases were from the pancreas, two from hepatic metastases and one from a peripancreatic lymph node metastasis. The cytologic features that permitted a preoperative diagnosis of pancreatic neuroendocrine tumor were: a cellular aspirate; numerous isolated cells and irregular, loose, dyshesive cellular aggregates; minimal nuclear pleomorphism; infrequent mitoses; fine, evenly dispersed nuclear chromatin with occasional inconspicuous nucleoli; a scant-moderate amount of granular, amphophilic, well-defined cytoplasm; clustering of tumor cells around segments of capillaries; and rosette formation. The differential diagnosis includes cells derived from normal pancreatic acini, islet cell hyperplasia, acinic cell carcinoma, well-differentiated pancreatic adenocarcinoma, metastatic small cell undifferentiated carcinoma of the lung, pancreatic small cell anaplastic carcinoma and malignant lymphoma. The application of immunocytochemistry to cytologic smears can be easily and reliably performed to confirm the neuroendocrine nature of the tumor and identify the specific type of polypeptide hormone or hormones produced by these tumors. Four aspirates showed immunoreactivity for chromogranin, and one was positive for gastrin. Cells of a lipid-rich neuroendocrine tumor were negative for chromogranin; however, the tissue section contained neuron specific enolase, and neurosecretory granules were demonstrated by electron microscopy.

Aged↗

Diagnostic utility of fine needle non-aspiration cytology versus fine needle aspiration cytology in breast masses.

Fine needle aspiration cytology (FNAC) and fine needle non-aspiration cytology (FNNAC) techniques were studied in 145 cases of breast masses. All the needle-sampling procedures were done by single operator. The samples were assessed cytologically and evaluated using five parameters i.e. background blood or clot, amount of cellular material, degree of cellular degeneration, degree of cellular trauma and retention of appropriate architecture. Differences between all the individual parameters as observed in FNAC and FNNAC smears were insignificant. After evaluation of FNNAC and FNAC on the basis of these scores, greater number of diagnostically superior samples were obtained by FNNAC; however by FNAC more number of diagnostically adequate smears were observed. This difference was statistically significant. The number of unsuitable smears were also more by FNNAC technique.

Biopsy, Fine-Needle↗