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PubMed2006

Cytologic differential diagnosis of follicular lymphoma grades 1 and 2 from reactive follicular hyperplasia: cytologic features of fine-needle aspiration smears with Pap stain and fluorescence in situ hybridization analysis to detect t(14;18)(q32;q21) chromosomal translocation.

Fine-needle aspiration cytology (FNAC) is a well-established technique for diagnosis of malignant lymphoma (ML). Generally, Giemsa but not Pap stain is used in FNAC. However, cytologic features obtained from Pap stain are also valuable. Very few studies on the cytologic characteristics of ML, as determined by Pap stain, are available. It is easier to observe nuclear irregularity and to identify nucleoli in ML cells by Pap stain than by Giemsa stain. Here, we applied Pap stain for cytomorphologic differential diagnosis of follicular lymphoma (FL) from reactive follicular hyperplasia (RFH). Eighteen biopsy-confirmed cases of FL grades 1 and 2, with available FNAC smears, and six cases of RFH were selected for this study. Low-power magnification showed well-known features, and tingible body macrophages and lymphoid cell aggregates were observed frequently in RFH and FL, respectively. In addition, the so-called two-nuclei-like cleaved cells were observed frequently in FL. These cells showed notably cleaved nuclei, and therefore, appeared to possess two nuclei. Under high-power magnification, the occurrence of cells with nucleoli >1 microm and of cleaved cells was high in FL compared to RFH. It is believed that FL derives from centrocytes and that FL cells are slightly larger than non-neoplastic small lymphocytes. However, analysis of cell diameter in this study indicated that small lymphoma cells were predominant in half the cases of FL grades 1 and 2, and the percentage of these cells was similar to that in RFH, showing why false-negative diagnosis of FL grades 1 and 2 occasionally occurs. There are limitations of FNAC in the diagnosis of FL. However, we believe that the appearance of two-nuclei-like cleaved cells and the high percentage of nucleoli-possessing cells, which we describe here, provide significant and valuable clues for the differential diagnosis of FL from RFH. Of 18 cases of FL grades 1 and 2, t(14;18)(q32;q21) was found in 13 cases with the use of destained FNAC smears. Our study suggests that, together with the cytomorphologic findings described earlier, FISH analysis for the chromosomal translocation, t(14;18)(q32;q21), is crucial for final cytologic diagnosis of FL grades 1 and 2.

Biopsy, Fine-Needle↗
PubMed2001

Manual method for liquid-based cytology: a demonstration using 1,000 gynecological cytologies collected directly to vial and prepared by a smear-slide technique.

We report on the formulation and use of an alcoholic-agar additive solution generally useful for rapid, inexpensive liquid-based cytology slide preparation. Gynecological cytology specimens were collected from 1,000 women. Two hundred fifty aliquots each of CytoRich, CytoRich Red (Tripath Imaging, Inc., Burlington, NC), Preservcyt (Cytyc Corp., Boxborough, MA), and DINA*TRANS (DINA*CYT Corp., Portland, OR) fixatives were used for this study. Fixed cell suspensions from 1,000 women, seen consecutively by a general obstetrics and gynecology practice, were vortex-mixed and transferred into a premeasured amount of alcoholic-agar in test tubes. Test tubes were conventionally centrifuged, cells were trapped in a spontaneously formed agar-gel, and the supernatant solutions were decanted. Vortex-mixing cell buttons caused a rapid gel-to-sol transition, affording viscous cell suspensions that were applied to slides, smeared, and stained using Papanicolaou stains. Slides showed unclumped, monolayered, uniform, random cell-spreads. All of the fixatives afforded crisp presentation of normal and abnormal cells. There was an about 3-fold increase in HSIL+ (0.7-1.8%) and LSIL diagnoses (1.3-4.4%), and a 45% reduction in ASCUS diagnoses (3.3-1.8%), as compared to our cytology laboratory's previous year's patients' statistics with a concurrent 0.2% unsatisfactory rate, due solely to inadequate sampling. This manual method makes liquid-based cytology inexpensive and does not require specialized preparative devices.

Centrifugation↗
PubMed1988

The diagnosis of chlamydial infection in a cytology laboratory: ten months' experience using immunofluorescence with and without previous cytologic prediction.

A Chlamydia diagnostic service has been established as part of a cytology laboratory, combining prediction of possible infection by routine cytology with definitive testing by immunofluorescence. The first 10 mo of operation have had good clinician acceptance with 527 specimens submitted and 128 reported as positive (24.3%). Routine cytology was more accurate in predicting chlamydial infection than was clinical evaluation (32.8% of cytologically suspected cases were positive versus 20.2% of clinically suspected cases); however, both failed to identify many infected women. The patient selection for testing must be improved since only about 22% of infected women in our population were tested. Nevertheless, the service identified a large number of patients infected with an important sexually transmitted pathogen. Chlamydial diagnosis has become a major component of the laboratory's workload and has been cost-effective.

Chlamydia Infections↗
PubMed1993

Malacoplakia and Rosai-Dorfman disease: two entities of histiocytic origin infrequently localized in the female breast--the cytologic aspect in aspirates obtained via fine-needle aspiration cytology.

We describe one case of Rosai-Dorfman disease (RDD) localized in the breast and one case of breast malacoplakia (MPK) both diagnosed by fine-needle aspiration cytology (FNAC). In RDD the cytologic features were lymphocytophagocytosis, large histiocytes with slight nuclear atypia, and lymphohistiocytic aggregates in a polymorphous background which included frequent plasma cells. In MPK the key diagnostic feature was the presence of Michaelis-Gutmann bodies (M-G bodies), in various stages of evolution, intermingled with vacuolized medium-sized histiocytes, other inflammatory cells, and debris. Pap staining is the technique of choice to show lymphocytophagocytosis and M-G bodies and there is no need to resort to special staining methods. RDD and MPK share a common cytologic background: the presence of numerous benign reactive histiocytes, either engulfing apparently intact lymphocytes, or phagocytizing M-G bodies. The cytologic findings seen in both cases suggest that the presence of histiocytes in a breast aspirate is far from being nonspecific and can represent an important lead to disparate diseases such as RDD and MPK.

Adult↗
PubMed1994

Melanocytic schwannoma: the cytologic aspect in fine-needle aspiration cytology (FNAC): report of a case located in the spinal cord.

We describe a case of intramedullary melanocytic schwannoma (MS) studied by means of fine-needle aspiration cytology (FNAC). The main cytologic features were (1) large three-dimensional clusters overshadowed by heavy pigment deposits which tested positive for Fontana Masson (and bleached with potassium permanganate), HMB-45, Vimentin, and S-100 protein; (2) loose syncytial monolayered sheets with very little pigment deposit; and (3) isolated spindle cells with polarized nucleus and tapered, thin cytoplasmic ends. Both the cytologic features and the immunophenotypic profile were nonspecific and on their own were insufficient to allow the diagnosis of MS to be reached. Clinical data and the magnetic resonance image (MRI) in conjunction with the cytologic findings did suggest the diagnosis of intramedullary MS.

Biopsy, Needle↗
PubMed1995

Quality assurance in breast cancer screening cytology: a review of the literature and a report on the U.K. national cytology scheme.

The National Breast Screening Programme in the United Kingdom has had an external quality assessment (EQA) scheme for breast screening histopathology since 1990. Recently, it was decided, by the Cytology sub-group of the National Co-ordinating Committee for Breast Screening Pathology, to institute two forms of cytology quality assurance. An EQA scheme is planned with circulation of slides to pathologists, but this involves extra time and effort from the participants at a time when general pathology workloads are high. Because of this, a computer routine has been written to analyse the data already present within the National Breast Screening Computer Systems, to enable the calculation of sensitivity and specificity of fine needle aspiration, correlating the cytology results with subsequent histology or follow-up mammography for lesions where no biopsy is performed. This routine uses standardised terminology and calculations and, therefore, inter-unit comparisons can be made. Where problems are identified within a unit, the Quality Assurance team can investigate the cause and institute appropriate measures to correct the problem. This article details the procedures involved in this audit and reviews the literature, recalculating the parameters in a standard manner for a number of publications. The results of the cytology quality assurance routine from seven screening units in one health region in the U.K. are presented and the measures taken to improve the level of service are discussed.

Breast Neoplasms↗
PubMed2007

Basics of cytology and fluid cytology.

Cytology as a diagnostic tool has played a major role in the management of diseases affecting domestic mammals for over 20 years. It has also become a valuable diagnostic tool in the evaluation of nondomestic or the so-called "exotic" animal patients, such as small mammals and the lower vertebrates. Common cytologic specimens used to evaluate the exotic animal patient include aspirates of masses and organs, imprints of biopsy material, tracheal wash samples, aspiration of abdominal or coelomic fluid, and fecal smears. In general, the same cytologic sample collection and preparation techniques used for domestic mammals also apply to exotic animal patients. The interpretation of the cytology specimen is generally the same as that of domestic mammals.

Animal Diseases↗
PubMed1998

Guidelines for anal cytology--to make cytological diagnosis and follow up much more reliable.

Anal intraepithelial neoplasia is a difficult diagnostic and management problem, particularly when it occurs in women with synchronous or metachronous genital intraepithelial neoplasia. Diagnosis and follow up by colposcopy is too specialized for widespread use, and although anal cytology has been used before it has been thought of as too inconsistent for practical application. This study standardized collection of specimens and investigated interobserver variation. The aim of the study was to determine whether observers could reliably distinguish high grade anal intraepithelial neoplasia from other conditions. Standardized collection of anal preparations was achieved in the host centre. A meeting of experienced cytopathologists was convened to agree guidelines for anal cytology. These guidelines were sent to the panel of six observers who were subsequently circulated with 30 cytopathological preparations in random order and asked to report them all. The results were collected and processed centrally. Four individuals were in complete agreement about those preparations which were inadequate for reporting, but two others had a lower threshold for rejecting preparations as inadequate. There was agreement between the observers in over 95% of cases in distinguishing high grade intraepithelial neoplasia from other cytological conditions. Kappa values range from 0.66 to 1.00. This study demonstrates that the provision of guidelines for the interpretation of anal cytopathological preparations can result in a high degree of interobserver agreement about the clinically important distinction between high grade anal intraepithelial neoplasia and other conditions. Anal cytology is a more useful technique for diagnosis and follow up of 'at risk' individuals than has previously been suggested, and should be utilized more widely in this group of patients.

Anal Canal↗
PubMed2001

Liquid-based cervical cytologic smear study and conventional Papanicolaou smears: a metaanalysis of prospective studies comparing cytologic diagnosis and sample adequacy.

OBJECTIVE: We sought to evaluate the cytologic diagnosis and sample adequacy of the liquid-based cervical cytologic smear (ThinPrep) compared with that of the conventional Papanicolaou smear. STUDY DESIGN: Prospective studies of ThinPrep and conventional Papanicolaou smears were analyzed for cytologic diagnosis and sample adequacy. Computerized databases, references in published studies, and index reviews published in English were used to identify direct-to-vial and split-sample clinical trials of cervical smears performed by conventional and liquid-based techniques. Only published studies that used the Bethesda system nomenclature with clearly documented outcome data were included. Each trial was assessed for the quality of its method, inclusion and exclusion criteria, adequacy of randomization, sampling protocols, definition of outcome, and statistical analyses. RESULTS: Twenty-five studies met inclusion criteria for this review. Odds ratios with 95% confidence intervals were calculated for each outcome. Estimates of odds ratios and risk differences for dichotomous outcomes were calculated by use of random and fixed-effects models. Homogeneity was tested across the studies. Results indicate that the ThinPrep test is as good as or superior to the conventional Papanicolaou smear in diagnosing uterine cervical premalignant abnormalities. Also the ThinPrep test provides improved sample adequacy when compared with the conventional Papanicolaou test. CONCLUSION: The ThinPrep test improved sample adequacy and led to improved diagnosis of low-grade and high-grade squamous intraepithelial lesions. However, there is no difference in the rate of atypical cells of undetermined significance diagnosis between ThinPrep and conventional smear groups. The added cost of ThinPrep cytologic screening and, hence, its cost-effectiveness are not evaluated in this study.

Cytodiagnosis↗
PubMed1992

The British Society for Clinical Cytology Certificate of Competence in Cytology Screening: a report of the first 3 years' experience.

In 1988 the Department of Health (DOH) recognized the cytology screener grade of laboratory staff. Cytology screeners have a 2 year training period after which they must sit a 'competence examination'. The British Society for Clinical Cytology offers an examination to meet the DOH specification. It consists of a written paper, a practical screening test, a spot test and a short viva voce. The screening test is paramount and candidates who miss a dyskaryotic smear cannot be successful. In the first 3 years there have been 22 examinations, 294 candidates and a pass rate of 76%. The majority of candidates were Cytology Screeners of 2-3 years experience but significant numbers of Medical Laboratory Scientific Officers (MLSOs) and senior MLSOs also chose to sit the examination.

Cell Biology↗
PubMed1994

Cytologic changes induced by 131I in the thyroid glands of patients with hyperthyroidism; results of fine needle aspiration cytology.

Cytological changes in the thyroid glands of 120 patients who had received 131I treatment for hyperthyroidism were examined in detail. The cytological material was obtained by fine needle aspiration cytology. The patients were divided into four groups according to the amount of time elapsed after the 131I treatment. The control groups were selected from euthyroid patients with hypoactive or non-functional solitary nodules and patients with Graves' disease who had not received 131I therapy. The thyrocytes revealed degenerative changes in the immediate period after cessation of treatment. One year after the treatment some non-specific changes, such as oxyphilic metaplasia and regeneration, were seen. No malignant change has been observed clinically or cytologically during up to 20 years of follow up since receiving 131I.

Biopsy, Needle↗
PubMed2004

Interpretation of fine needle aspiration cytology of the breast: a comparison of cytological, frozen section, and final histological diagnoses.

This study examines the performance of the preliminary, on-site interpretation by the pathologist of fine needle aspiration (FNA) cytology smears compared to the final cytology report, the frozen section diagnosis and the final histopathological report. We found that both the preliminary and the final cytology reports gave satisfactory results over the minimum standards for quality assurance required by both the Norwegian breast screening programme and the NHS BSP in the UK with the exception of the 'suspicious' rate. We noted that the preliminary report had fewer false negatives (2.1%) than the final report (4.3%). We show that an unequivocal cytological diagnosis of malignancy is a reliable diagnosis, and in cases where mammography/ultrasonography and clinical examination are in agreement with FNA, frozen section examination is unnecessary. However, cases with a suspicious or equivocal FNA should be considered for frozen section analysis.

Adolescent↗
PubMed2004

Assessing HER-2 status in fresh frozen and archival cytological samples obtained by fine needle aspiration cytology.

Determination of HER-2 status is an essential prerequisite in considering a patient's eligibility for anti-HER-2 therapy; few studies have focused on its evaluation on cytological material. We present a new method of assessing HER-2 status on cytological samples, by fluorescence in situ hybridization (FISH) with an automated detection system, using fresh frozen (FF) and May-Grunwald-Giemsa (MGG) stained smears, and we evaluate the reliability of HER-2 determination on fine needle aspiration cytology (FNAC). The pre-treatment protocol for FF smears is easier and faster than for MGG stained slides. However, with the described procedure, FISH is also feasible on archival MGG stained slides. We conclude that with this method, cytological samples obtained by FNAC, either FF or MGG, are a reliable option for assessing HER-2 status.

Biopsy, Fine-Needle↗
PubMed2005

Proposed Sheffield quantitative criteria in cervical cytology to assist the grading of squamous cell dyskaryosis, as the British Society for Clinical Cytology definitions require amendment.

OBJECTIVE: In 1986, the British Society for Clinical Cytology (BSCC) published quantitative criteria to assist diagnosis in a three-tier grading system of squamous cell dyskaryosis. In dyskaryotic cells, area nuclear to cytoplasmic (NC) ratios below 50%, between 50% and 66% and over 66% were defined as equating with mild, moderate and severe grades respectively. Following the Terminology Conference in 2002, however, the BSCC recommended on their website that the three-tier model should be replaced by a new two-tier system of low- and high-grade squamous abnormalities. The latter broadly equate with the two-grade Bethesda System (TBS) for reporting squamous intraepithelial lesions. The purpose of this study was to assess the accuracy and reproducibility of the BSCC three-tier quantitative definitions, to investigate if they were applicable to liquid-based cytology (LBC) and to see how they related to the proposed new two-tier BSCC system. METHODS: Quantitative image analysis was undertaken on illustrations from the 1986 BSCC terminology publication and on microscope slides from external quality assessment and Cytology Training Centre teaching sets. RESULTS: Analysis of mean NC ratios showed that mild, moderate and severe dyskaryosis exist as statistically different populations. Overlap of NC ratio ranges, however, limits their practical application in the three-tier model, although interestingly no overlap was noted between mild and severe dyskaryosis. No grade of dyskaryosis had a mean area NC ratio over 50%, indicating that the BSCC quantitative definitions are incorrect. The mean diameter NC ratios for mild, moderate and severe dyskaryosis were found to be 40%, 49% and 66% respectively. Accordingly it is possible that those reporting cervical cytology could be interpreting the BSCC NC ratios as meaning diameter rather than area. Amalgamation of the three-tier results into the proposed two-tier model shows that the resulting mean NC area and diameter ratios identify statistically different low- and high-grade populations. The reduced degree of overlap, however, of NC ratio ranges in the two-tier model implies that NC ratios could have a useful practical role in the separation of the low- and high-grade categories. The two categories were reasonably well separated by mean area and diameter NC ratios of 25% and 50% respectively. A two-tier model combining mild with moderate rather than severe dyskaryosis was found to be a statistically valid alternative but gave rise to NC ratios that would be difficult to use in practice. Except for moderate dyskaryosis, no significant differences were identified between the mean NC ratios of either conventional and LBC preparations or LBC preparations using two different commercial methodologies (SurePath and ThinPrep). Differences, however, were noted in area measurements between SurePath and ThinPrep and this has potential implications for classifications (such as TBS) using area comparisons as their basis. In addition, it was found that the increased NC ratio, associated with higher grades of dyskaryosis is more a consequence of progressive cytoplasmic area reduction rather than nuclear area increase. The similar NC ratios of borderline nuclear changes associated with human papilloma virus and mild dyskaryosis support the BSCC proposal that these can be combined to constitute a low-grade category. This study shows that the BSCC area NC ratio criteria of grading squamous cell dyskaryosis require amendment. In addition, this study supports the new BSCC recommendation of low- and high-grade squamous cell categories. CONCLUSIONS: The study proposes Sheffield quantitative criteria to assist the grading of squamous cell abnormalities. Quantitative diameter NC ratio measurements, however, must always be accompanied by detailed assessment of qualitative morphological features and in particular those relating to nuclear chromatin. This is equally relevant to both two- and three-tier models.

Carcinoma, Squamous Cell↗
PubMed2006

Fine needle aspiration cytology of the thyroid: a comparison of 5469 cytological and final histological diagnoses.

OBJECTIVE: We evaluated the efficacy of fine needle aspiration cytology (FNAC) of the thyroid in a series of 5469 lesions with histological control and studied the causes of, and the possibility of reducing the limitations of the method. METHODS: FNAC was always performed by a pathologist under the guidance of a clinician, using a 22-gauge needle. Generally two aspirations were carried out, and usually four slides were obtained for each nodule; they were then stained with May-Grünwald-Giemsa and with Papanicolaou. The cytological diagnoses were classified in four groups: inadequate, benign, suspicious and malignant. RESULTS: We obtained a complete sensitivity of 93.4%, a positive predictive value of malignancy of 98.6%, and a specificity of 74.9%. At histological control, the cytological diagnosis of Hurthle cell neoplasm corresponded to a significantly higher incidence of malignant neoplasms than the diagnosis of non-Hurthle cell follicular neoplasm (32.1% versus 15.5%). There were 66 false-negative findings, the main cause of diagnostic error (24 cases) being failure to recognize the follicular variant of papillary carcinoma. The number of inadequate FNACs was low (4.2%). CONCLUSION: Our study confirmed the great efficacy of thyroid FNAC. A cytological diagnosis of Hurthle cell neoplasm should be considered an indicator of high risk. Awareness that failure to recognize the follicular variant of papillary carcinoma was the main problem in the interpretation of thyroid FNAC should lead to a decrease of false-negative diagnoses. The inadequate rate was very low, as it was the pathologist personally who performed the needle aspiration.

Adolescent↗
PubMed1991

Quantitative tear meniscus cytology versus quantitative conjunctival fluid cytology.

A technique for quantitative cytology of tear fluid collected by a micropipette from the tear meniscus is presented. This technique has been compared with that using the standardized Norn-pipette collecting fluid from the lateral part of the inferior fornix. The two methods show the same magnitude of sensitivity and specificity, the same coefficient of variation, as regards neutrophilic leucocytes and erythrocytes (200 samples). The normal tear meniscus contains less than 40 leucocytes or erythrocytes per microliter. The tear cell concentration is about 200 times lower in the meniscus than in the fornix inferior in normal eyes. This observation supports the compartment-theory of a rapid flow in the tear meniscus and a slow flow with insignificant admixture in the conjunctival fluid in the fornices. The tear meniscus cytology is of use in association with testing of other parameters in the tears, for instance. The conjunctival fluid cytology is quicker and more convenient for the patient. In addition, it is necessary in connection with observation for pathological epithelial desquamation, because the tear meniscus cytology brings about an artificial increase of the epithelial cell concentration.

Conjunctiva↗
PubMed1981

The Cardiff Cervical Cytology Study: prevalence of cytological grades and initial histological findings.

Among 45 266 women in the Cardiff Cervical Cytology Survey the peak prevalence of suspicious or positive smears was 11.2/1000 at age 45-50 years and of dyskaryosis 10.2/1000 at age 25-29. A suspicious or positive cytological picture at prevalence testing was associated with occult or clinical invasion in 24% of cases, and only 4% of patients with suspicious or positive smears were normal histologically. When dyskaryosis was detected in the prevalence test 20% had carcinoma in situ or microinvasion and 3% had occult or clinically invasive carcinoma. One hundred and twenty-nine (51%) women with dyskaryotic smears did not have a biopsy initially (that is, within two years of the prevalence test), but they were followed up at regular intervals. Subsequently 15 of the 129 gave smears consistently dyskaryotic or worse cytologically and were subjected to biopsy. Of these, two showed dysplasia, 12 carcinoma in situ, and one clinically invasive carcinoma. These findings emphasise the need for repeat cytological or histological examination in any woman with evidence of dyskaryosis in a cervical smear.

Adult↗
PubMedDate not supplied

Imprint cytology of core needle biopsy specimens of breast lesions. A rapid approach to detecting malignancies, with comparison of cytologic and histopathologic analyses of 173 cases.

OBJECTIVE: To investigate whether imprint cytology of core needle biopsy (CNB) specimens from breast lesions is a useful method of rapidly obtaining additional diagnostic information and potentially can be used to reduce the number of biopsies needed. STUDY DESIGN: Cytologic analysis was performed on 173 breast lesions and compared with their histopathologic diagnoses (143 malignant and 30 benign). For imprint cytology, one CNB specimen was rolled between two slides and stained with Diff-Quik and Papanicolaou stain. RESULTS: The diagnostic overall accuracy of Diff-Quik stain (Papanicolaou stain) was 95.4% (95.9%), with a sensitivity of 96.5% (97.2%), specificity of 90% (90%), positive predictive value of 97.8% (97.8%) and negative predictive value of 84.3% (87.0%). There was no statistically significant difference between the stains. Histopathologic analysis had an overall accuracy of 97.7%, with a sensitivity of 97.2%, specificity and positive predictive value of 100% and a negative predictive value of 88.2%. CONCLUSION: Imprint cytology of CNBs is a sensitive method of detecting malignancies in breast tumors. Diff-Quik is a rapid and reliable approach that can reduce the number of biopsies. Inadequate and suspicious cases should be evaluated based on complementary diagnostic procedures for breast lesions.

Adolescent↗