Current state of whole slide imaging use in cytopathology: Pros and pitfalls

Whole slide imaging (WSI) allows generation of large whole slide images and their navigation with zoom in and out like a true virtual microscope. It has become widely used in surgical pathology for many purposes, such as education and training, research activity, teleconsultation, and primary diagnosis. However, in cytopathology, the use of WSI has been lagging behind histology, mainly due to the cytological specimen's characteristics, as groups of cells of different thickness are distributed throughout the slide. To allow the same focusing capability of light microscope, slides have to be scanned at multiple focal planes, at the cost of longer scan times and larger file size. These are the main technical pitfalls of WSI for cytopathology, partly overcome by solutions like liquid‐based preparations. Validation studies for the use in primary diagnosis are less numerous and more heterogeneous than in surgical pathology. WSI has been proved effective for training students and successfully used in proficiency testing, allowing the creation of digital cytology atlases. Longer scan times are also a barrier for use in rapid on‐site evaluation, but WSI retains its advantages of easy sharing of images for consultation, multiple simultaneous viewing in different locations, the possibility of unlimited annotations and easy integration with medical records. Moreover, digital slides set the laboratory free from reliance on a physical glass slide, with no more concern of fading of stain or slide breakage. Costs are still a problem for small institutions, but WSI can also represent the beginning of a more efficient way of working.     

The BSCC Code of Practice – exfoliative cytopathology (excluding gynaecological cytopathology)

Exfoliative cytopathology (often referred to as non‐gynaecological cytology) is an important part of the workload of all diagnostic pathology departments. It clearly has a role in the diagnosis of neoplastic disease but its role in establishing non‐neoplastic diagnoses should also be recognised. Ancillary tests may be required to establish a definitive diagnosis. Clinical and scientific teamwork is essential to establish an effective cytology service and staffing levels should be sufficient to support preparation, prescreening, on‐site adequacy assessment and reporting of samples as appropriate. Routine clinical audit and histology/cytology correlation should be in place as quality control of a cytology service. Cytology staff should be involved in multidisciplinary meetings and appropriate professional networks. Laboratories should have an effective quality management system conforming to the requirements of a recognised accreditation scheme such as Clinical Pathology Accreditation (UK) Ltd. Consultant pathologists should sign out the majority of exfoliative cytology cases. Where specimens are reported by experienced biomedical scientists (BMS), referred to as cytotechnologists outside the UK, this must only be when adequate training has been given and be defined in agreed written local protocols. An educational basis for formalising the role of the BMS in exfoliative cytopathology is provided by the Diploma of Expert Practice in Non‐gynaecological Cytology offered by the Institute of Biomedical Science (IBMS). The reliability of cytological diagnoses is dependent on the quality of the specimen provided and the quality of the preparations produced. The laboratory should provide feedback and written guidance on specimen procurement. Specimen processing should be by appropriately trained, competent staff with appropriate quality control. Microscopic examination of preparations by BMS should be encouraged wherever possible. Specific guidance is provided on the clinical role, specimen procurement, preparation and suitable staining techniques for urine, sputum, semen, serous cavity effusion, cerebrospinal fluid, synovial fluid, cyst aspirates, endoscopic specimens, and skin and mucosal scrapes.     

Role of fine needle aspiration cytology in diagnosis of pleomorphic adenomas

Role of fine needle aspiration cytology in diagnosis of pleomorphic adenomas This retrospective study was carried out to review the cases diagnosed as pleomorphic adenoma in major or minor salivary glands and determine the difficulties encountered on typing this tumour on fine needle aspiration cytology (FNAC). Over a 19‐year period (1982–2000) 488 pleomorphic adenomas were diagnosed on FNAC from different sites (parotid – 372 cases, submandibular – 95 cases; oral cavity – 21 cases). Histology was available in 232 cases. Twenty‐nine cases where a histological diagnosis of pleomorphic adenoma was made but the cytological diagnosis was variable were also reviewed. In 216 of the 232 cases a good cytohistological correlation was available. On review only 4 of the 16 cases initially diagnosed as pleomorphic adenoma on FNAC where the histology revealed a different tumour were categorized as pleomorphic adenoma, while 3 each were classified as adenoid cystic carcinoma and benign tumour ?type, and 2 each were diagnosed to be muco‐epidermoid carcinoma, monomorphic adenoma and acinic cell carcinoma. On review of the FNAC smears from 29 cases where a histological diagnosis of pleomorphic adenoma was available while the cytological diagnosis was variable, only 11 (38%) were categorized as pleomorphic adenoma. In the majority of the remaining cases the cytological diagnosis did not alter markedly, 7 of 10 cases where the tumour could not be typed on cytology initially could not be typed even on review. In conclusion, FNAC is an ideal, fairly accurate preoperative procedure for the diagnosis of pleomorphic adenomas. Certain diagnostic problems occur in differentiating pleomorphic adenomas from adenoid cystic carcinoma, monomorphic adenoma and mucoepidermoid carcinoma. Carcinoma ex‐pleomorphic adenoma is difficult to identify on FNAC and in our series all 4 such cases on histology were considered benign on cytology.     

Evaluation of aspiration cytology of ovarian masses with histopathological correlation

T. Sood, U. Handa, H. Mohan and P. Goel
Evaluation of aspiration cytology of ovarian masses with histopathological correlation Objectives: To evaluate the efficacy and diagnostic accuracy of fine needle aspiration cytology (FNAC) in distinguishing non‐neoplastic and neoplastic ovarian lesions and to determine reliable cytological criteria for typing neoplastic ovarian masses into benign and malignant tumours and their subtypes. Methods: FNAC was performed on 50 patients diagnosed as having an ovarian mass clinically and/or ultrasonographically. Detailed history, clinical examination and ultrasound findings in each case were recorded. The cytological diagnoses were categorized as neoplastic and non‐neoplastic and further into benign and malignant neoplasms. These cytological diagnoses were then compared subsequently with the histopathological diagnoses. Results: The study material consisted of 57 aspirates from 50 patients. A comparison of cytological findings with the histological diagnosis was possible in 53 aspirates; in the remaining four cases (7%) the smears were acellular. On cytology, 31 lesions were diagnosed as neoplastic and 22 as non‐neoplastic. The overall sensitivity of cytology in diagnosing neoplastic and non‐neoplastic ovarian lesions was 93.9% and the specificity was 100%. The positive predictive value was 100% and negative predictive value 90.9%. The overall diagnostic accuracy was 96.2 %. Conclusion: FNAC of ovarian masses is a minimally invasive procedure that can differentiate neoplastic from non‐neoplastic ovarian lesions. It may help avoid unnecessary operations and preserve the reproductive ability in young patients. Furthermore, it also enables a satisfactory sub‐categorization of ovarian tumours, which facilitates the choice of appropriate therapy.     

Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomas

S. Schmid, M. Tinguely, P. Cione, H. Moch and B. Bode
Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomas Objective: Diagnosis of low grade non‐Hodgkin B‐cell lymphomas on cytological material may be problematic and in the past frequently required lymph node excision. We analysed our experience of the value of flow cytometry (FC) as an additional tool for the diagnosis of lymphoproliferative processes in the setting of a university cytology division with a busy fine needle cytology service. Methods: Consecutive cytological specimens with FC over a period of 3 years were retrospectively analysed and correlated with histology and follow‐up if available. FC was performed with the following antibodies: CD3, CD4, CD8, CD2, CD7, CD19, CD5, CD10, CD23, lambda and kappa chains. Results: Of 299 probes (273 fine needle aspirations and 26 fluids from 285 patients), 179 cases (60%) were diagnosed as reactive, 91 cases (30%) as malignant or suspicious and 29 cases (10%) as inconclusive. The results of histological examination of the lymph nodes were available in 41 of 91 (45%) malignant or suspicious cases and in 13 of 179 (7%) reactive cytological diagnoses. Cytologically diagnosed malignancy was confirmed in all histologically examined cases. In 12 of 13 reactive cytological cases (92%), a benign process was diagnosed histologically. In 34 of 299 cases (11%) additional molecular investigations of B‐cell clonality or specific translocations were performed. The lymphomas most frequently diagnosed were follicular lymphoma and lymphocytic lymphoma, followed by mantle cell and marginal zone lymphomas. Correlation with histology showed a sensitivity of 98% and a specificity of 100% for cytology in our series. Conclusions: FC is an important additional tool in the cytological diagnosis of lymphoproliferative disorders. The combined approach has a high diagnostic value that allows a reliable subclassification of low grade B‐cell non‐Hodgkin lymphomas.     

Utility of liquid-based cytology in endometrial pathology: diagnosis of endometrial carcinoma

Objective: The purpose of this study was to examine the utility of SurePath‐liquid‐based cytology (LBC) compared to conventional cytological preparations (CCP) in the identification of endometrial carcinoma. Methods: During a 13‐month period, direct endometrial samples were collected from 120 patients using the Uterobrush. The material comprised 30 cases each of endometrial carcinoma, proliferative endometrium, secretory endometrium and atrophic endometrium. The following points were investigated:(i) the frequency of cell clumps in endometrial carcinoma; (ii) the area of cell nuclei; (iii) overlapping nuclei. Results: (i) Comparison of the frequency of cell clumps with irregular protrusion pattern and papillo‐tubular pattern showed no statistically significant difference in either type of cell clump between CCP and LBC. (ii) Comparison of the nuclear area of cells showed a sequential decrease from endometrial carcinoma to secretory endometrium, to proliferative endometrium and to atrophic endometrium, which was significant in CCP and LBC. (iii) Nuclear area was significantly lower with LBC compared with CCP in endometrial carcinoma, secretory endometrium and proliferative endometrium but not atrophic endometrium. (iv) Comparison of the degree of overlapping nuclei showed a sequential decrease from endometrial carcinoma to proliferative endometrium, to secretory endometrium and to atrophic endometrium, which was significant in both CCP and LBC. (v) Comparison of the degree of overlapping nuclei between CCP and LBC showed no significant difference for normal types of endometrium, but LBC had significantly higher values (P < 0.0001) in endometrial carcinoma than in CCP. Conclusions: The results of this study revealed that applying diagnostic criteria used in CCP to LBC was easy to achieve, because LBC had excellent cytoarchitectural preservation and cells were well presented. Although we have not examined all cytological features of malignancy and have not considered atypical hyperplasia, we believe that this method may be a useful tool in the diagnosis of endometrial cytology.     

Significance of collagenous and mucinous spherulosis in breast cytology specimens

S. Hata, N. Kanomata, Y. Kozuka, M. Fukuya, E. Ohno and T. Moriya
Significance of collagenous and mucinous spherulosis in breast cytology specimens Objective: Spherulosis of the breast is a rare but distinct benign morphological entity. As there are few cytological reports of breast spherulosis, the significance of spherulosis among cytological specimens is unclear. The objective was to document cytological aspects of spherulosis. Methods: A total of 3491 consecutive breast fine needle aspiration cytology (FNAC) samples and 69 nipple discharge cytology samples were reviewed. Papanicolaou‐stained slides with or without Romanowsky staining were analysed. The corresponding 1926 histological specimens were also reviewed. Results: We detected 17 cases of collagenous spherulosis (CS) and/or mucinous spherulosis (MS) among 3560 breast cytology specimens (0.48%). All samples were from women, who varied in age from 22 to 69 years. CS and/or MS were present in 15 of 3491 FNAC specimens (0.43%) and in two of 69 nipple discharge cytology specimens (2.9%). Corresponding histological specimens were available for 14 of the 17 specimens. Of the 14 specimens, 12 consisted of intraductal papilloma, one of fibroadenoma, and one of fibrocystic change. There was no spherulosis among the 1251 cytological specimens of malignant diseases. Conclusions: Cytological evidence of spherulosis is a good indicator of intraductal papilloma.     

Value of EUS‐FNA cytological preparations compared with cell block sections in the diagnosis of pancreatic solid tumours

Y. Kopelman, S. Marmor, I. Ashkenazi and Z. Fireman
Value of EUS‐FNA cytological preparations compared with cell block sections in the diagnosis of pancreatic solid tumours Objective: Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is performed in order to achieve a definite tissue diagnosis of pancreatic lesions. This in turn is a guide to the appropriate treatment for the patient. Tissue samples collected by the same needle for cytological preparations and cell block histological sections (often referred to as FNA‐cytology and FNA–biopsy, respectively) are handled differently. The specific contribution of each of these tests was evaluated. Methods: One hundred and two consecutive patients underwent EUS‐FNA while being investigated for pancreatic solid lesions. Diagnosis was made by cytology, cell block sections or both. The diagnosis was confirmed by clinical outcome. Results: Male/female ratio was 61/41. Mean age was 65 ± 12 years (range, 22–94). Mean lesion size was 3.1 ± 1.8 cm (range, 0.6–10 cm); 68% were >2 cm and 75% were located in the pancreatic head. The average number of needle passes was two (range, 1–4 passes). Final tissue diagnosis was malignant in 66 (65%) patients. Sensitivity, specificity and accuracy were 73%, 94% and 81%, respectively, for cytology alone, and 63%, 100% and 78%, for cell blocks alone. Eighty‐two patients (80%) had cytology and cell blocks, which matched in 64 (78%) patients. EUS‐FNA results that relied on both techniques had 84% sensitivity, 94% specificity and 88% accuracy. Cytology revealed 13 malignancies not diagnosed on cell blocks, while cell blocks revealed five malignancies not diagnosed by cytology. Malignant lesions were more common in men; they were larger in size and located in the pancreatic head. Conclusion: EUS‐FNA cytology was more sensitive than cell blocks but less specific for the diagnosis of solid pancreatic lesions. The two methods are complementary and implementing both improves the diagnostic value of EUS‐FNA.     

Cervical cytology/histology discrepancy: a 4‐year review of patient outcome

E. L. Moss, A. Moran, G. Douce, J. Parkes, R. W. Todd and C. E. W. Redman Cervical cytology/histology discrepancy: a 4‐year review of patient outcome Objective: To investigate the diagnosis, review and management of women identified as having a cytology/histology discrepancy. Methods: A review of all patients diagnosed with a discrepancy between referral smear and cervical histology was performed between January 2003 and December 2004. Cases were followed for a minimum of 4 years and patient management and outcome reviewed. Results: A significant discrepancy was identified in 79 cases, 0.1% of all smears (n = 80 926) analysed during the study period. A discrepancy between cytology and histology, obtained from large loop excision of the transformation zone (LLETZ), was confirmed by multidisciplinary review in 42 cases (53.2%). In 37 cases (46.8%) the cytological and/or histological diagnosis was revised; the cytology was significantly more likely than the histology to be amended (chi square P = 0.005), most often because cytology had been overcalled. Of the confirmed discrepancy cases, 33 (78.6%) were due to high‐grade squamous cell or glandular abnormalities on cytology with a negative, inflammatory or human papillomavirus (HPV) infection on histology (HGC/NH). HGC/NH cases were managed by cytological follow‐up in 29 (87.9%), of which 72.4% of the smears were negative when performed at least 6 months post‐excision. During the 4‐year follow‐up period six women with a confirmed HGC/NH underwent a repeat cervical excision (hysterectomy or LLETZ), and of these, HPV effect was seen in two cases but no cervical intraepithelial neoplasia was detected in any of the histological specimens. Conclusion: Cytology overcall was responsible for the majority of cytology/histology discrepancies. A confirmed discrepancy is not an indication for a further excisional biopsy but follow‐up is essential because a small percentage of patients may have disease that has been missed.     

Extraction of DNA from exfoliative cytology specimens and its suitability for analysis by the polymerase chain reaction

The extraction of DNA from archival exfoliative cytology samples would allow the molecular biological analysis of this readily available material using the polymerase chain reaction (PCR). We have quantitatively and qualitatively studied the extraction of DNA from a variety of cytological preparations. For both fresh and archival cervical smears, overnight incubation with proteinase K produces high yields of high molecular weight DNA, but simply boiling the samples produces DNA suitable for PCR amplification of a single copy gene. Increasing the proteinase K incubation to several days allows the extraction of DNA from fixed and stained archival cytology slides from a variety of sites. The extracted DNA was again suitable for PCR analysis. Fresh and archival cytological material can be utilized for molecular biological study of disease processes using PCR. Archival cytological material is probably the best source of DNA and RNA after stored frozen tissue.     

Pioneers of exfoliative cytology in the 19th century: the predecessors of George Papanicolaou

The purpose of our study was to summarize the knowledge on exfoliative cytology during the 19th century and to track down Papanicolaou's predecessors. A thorough study of texts, medical books and reports, together with a review of the available literature in PubMed, was undertaken. The study of cytological preparations as a diagnostic procedure can be traced back to the work of the famous French microscopist Alfred François Donné. However, the systematic study and the criteria for the diagnosis of malignant cells should be attributed to Johannes Müller. The increasing interest in the cytological examination of various fluids of the human body can be confirmed by a plethora of studies published during this period. By the end of the 19th century, the invention of new techniques in pathology, such as the introduction of cell block techniques, tissue sections and new staining methods which provided the opportunity to study surgical specimens in three dimensions, led to a decrease in the interest in exfoliative cytology, which was re‐discovered by George Papanicolaou almost three decades later.     

Image analysis of peripheral compression artefacts of ThinPrep® liquid‐based cytology preparations

J. Choi, H. S. Shim, J.‐W. Song, S. W. Chae, Y.‐N. Lee, J. E. Kim and S. H. Kim
Image analysis of peripheral compression artefacts of ThinPrep^® liquid‐based cytology preparations Objective: ThinPrep (TP), one of the Food and Drug Administration‐approved liquid‐based cytology (LBC) preparations, is widely used for gynaecological and non‐gynaecological cytology samples. A unique physical artefact caused by the compression at the periphery in TP slides has not been adequately evaluated to date. Methods: We processed four established tumour cell lines (MKN28, MKN45, KG‐1 and NB4) and mononuclear cells isolated from whole blood over Ficoll‐Plaque for TP preparations. For this part of the study, we included five normal cervical LBC preparations. We then auto‐counted and auto‐measured the area, mean grey value and Feret’s diameter in both the inner disc and peripheral rim of the preparations by image morphometry. In addition, we compared the distribution of atypical cell groups in the peripheral rim and inner disc of 132 lung aspirates, 80 thyroid aspirates, 212 cerebrospinal fluids (CSFs) and 50 gynaecological samples. Results: The areas and Feret’s diameters of the cytoplasm in the peripheral compressed rim area were statistically larger than those of cells in the inner disc. The mean grey values of cells (cytoplasm and nucleus) in the peripheral compression rim were also smaller than those in the inner disc cells, leading to decreases in nuclear and cytoplasmic chromatism. Except for the mean grey values, the differences were not significant in the cervical samples. Conclusions: Cellular morphology may be markedly distorted in the peripheral rim, regardless of cell malignancy, which may lead to the misinterpretation of cells during the screening. Accordingly, cytological diagnosis based on the findings within the peripheral rim should take this phenomenon into account. Compressed cells found in the peripheral rim should be interpreted with caution when TP slides are used for cytopathological diagnosis.     

Identification of components of fibroadenoma in cytology preparations using texture analysis: a morphometric study

S. Singh and R. Gupta Identification of components of fibroadenoma in cytology preparations using texture analysis: a morphometric study Objectives: To evaluate the utility of image analysis using textural parameters obtained from a co‐occurrence matrix in differentiating the three components of fibroadenoma of the breast, in fine needle aspirate smears. Methods: Sixty cases of histologically proven fibroadenoma were included in this study. Of these, 40 cases were used as a training set and 20 cases were taken as a test set for the discriminant analysis. Digital images were acquired from cytological preparations of all the cases and three components of fibroadenoma (namely, monolayered cell clusters, stromal fragments and background with bare nuclei) were selected for image analysis. A co‐occurrence matrix was generated and a texture parameter vector (sum mean, energy, entropy, contrast, cluster tendency and homogeneity) was calculated for each pixel. The percentage of pixels correctly classified to a component of fibroadenoma on discriminant analysis was noted. Results: The textural parameters, when considered in isolation, showed considerable overlap in their values of the three cytological components of fibroadenoma. However, the stepwise discriminant analysis revealed that all six textural parameters contributed significantly to the discriminant functions. Discriminant analysis using all the six parameters showed that the numbers of pixels correctly classified in training and tests sets were 96.7% and 93.0%, respectively. Conclusion: Textural analysis using a co‐occurrence matrix appears to be useful in differentiating the three cytological components of fibroadenoma. These results could further be utilized in developing algorithms for image segmentation and automated diagnosis, but need to be confirmed in further studies.     

Standardization of fine needle aspiration cytology of the breast – comparison of Auto Cyto Fix and conventional smears

In Japan, there are some problems with fine needle aspiration (FNA) cytology of the breast, such as insufficient smeared cells, air-drying artefact and excessive erythrocytes. Liquid-based cytology has been found to solve these problems. Equipment for such preparations has been developed, but can be expensive to purchase and operate. We developed Auto Cyto Fix 1000 (ACF), which is inexpensive and automatically smears and fixes cells. The purpose of this study was to compare the various cytological features of conventional and ACF specimens. We evaluated whether the ACF method would be able to replace the conventional method. Forty-eight FNA specimens of breast were studied. All specimens were prepared by the direct smeared (DS) and ACF methods and evaluated for unsatisfactory cell collection, air-drying artefacts, background findings and epithelial cell findings. Although ACF specimens were prepared using the cells remaining in the needle and syringe after preparing DS specimens, the cellularity of two of the ACF specimens was better than that of the corresponding DS specimens. ACF specimens never showed air-drying artefact. Unlike DS specimens, which have many erythrocytes in the background, erythrocytes were filtered out and the background of ACF specimens was clean. We believe that many problems attributable to conventional FNA specimen preparation have been solved in this study. Preparation using the ACF apparatus can reduce running costs and can be used to prepare FNA specimens of the breast for cytological examination as an alternative to the conventional method.     

Management of thyroid cytological material,preanalytical procedures and bio‐banking

Thyroid nodules are common and are increasingly detected due to recent advances in imaging techniques. However, clinically relevant thyroid cancer is rare and the mortality from aggressive thyroid cancer remains constant. Fine needle aspiration cytology (FNAC) is a standard method for diagnosing thyroid malignancy and the discrimination of malignant nodules from goitre. As the examined nodules on thyroid FNAC are often small incidental findings, it is important to maintain a low rate of undetermined diagnoses requiring further clinical work up or surgery. The most important factors determining the accuracy of the cytological diagnosis and suitability for biobanking of thyroid FNACs are the quality of the sample and availability of adequate tissue for auxiliary studies. This article discusses technical aspects (preanalytics) of performing thyroid FNAC, including image guidance and rapid on‐site evaluation, sample collection methods (conventional slides, liquid‐based methods, cell blocks) and storage (bio‐banking). The spectrum of special studies (immunocytochemistry on direct slides or liquid‐based cytology, immunohistochemistry on cell blocks and molecular methods) required for improving the precision of the cytological diagnosis of the thyroid nodules is also discussed.     

Cytology of colorectal adenomas

A study of the cytological appearances of benign and malignant colorectal adenomatous polyps is reported. The aim of the study was to characterize the cytological features of adenomatous polyps and predict the likelihood of malignancy using cytology. A five grade classification of colorectal cytology has been developed and the characteristic appearances of cells from adenomatous polyps are described. The reproducibility of cytological diagnosis based on this classification has been tested in 120 smears from normal mucosa and adenomatous polyps (including polyp cancers). Correlation with histology was achieved in 88% and correlation of the cytological diagnosis between two observers was achieved in 84%. We conclude that cytology can be used reliably as an adjunct to histology in the assessment of malignancy of adenomatous polyps.     

Diagnostic accuracy of liquid‐based endometrial cytology in the evaluation of endometrial pathology in postmenopausal women

C. Remondi, F. Sesti, E. Bonanno, A. Pietropolli and E. Piccione
Diagnostic accuracy of liquid‐based endometrial cytology cytology in the evaluation of endometrial pathology in postmenopausal women Objective: The aim of this study was to compare liquid‐based endometrial cytology with hysteroscopy and endometrial biopsy regarding its diagnostic accuracy in a series of postmenopausal women with abnormal uterine bleeding (AUB) or asymptomatic women with thickened endometrium assessed by transvaginal ultrasound as a screening procedure. Methods: Inclusion criteria were: menopausal status; the presence of AUB and/or thickened endometrium assessed by ultrasound (cut‐off 4 mm); a normal Papanicolaou (Pap) smear; and no adnexal pathology at ultrasound. Exclusion criteria were: previous endometrial pathology; and previous operative hysteroscopy. Of 768 postmenopausal women referred to our general gynaecology clinics, 121 fulfilled the inclusion criteria and were recruited to the trial. Twenty‐one refused to participate. Cytological sampling was carried out by brushing the uterine cavity using the Endoflower device with no cervical dilation and the vial was processed using a ThinPrep® 2000 automated slide processor. The slides were stained using a Pap method. Results: In 98 cases with histological biopsies, endometrial cytology detected five cases of endometrial carcinoma, 10 of atypical hyperplasia and 47 of non‐atypical hyperplasia; 36 cases were negative. In two cases cytology was inadequate because of uterine cervical stenosis. Taking atypical hyperplasia or worse as a positive test and outcome, the diagnostic accuracy of the endometrial cytology was 93.5%, with a sensitivity of 92% and specificity of 95%, a positive predictive value of 73% and a negative predictive value of 99%. All the carcinomas were detected by cytology. Only 42% of women with a positive diagnosis were symptomatic. The cytological sampling was well tolerated by all patients. No complication was registered. Conclusions: Liquid‐based endometrial cytology can be considered an useful diagnostic method in the detection of endometrial pathology as a first‐line approach, particularly if associated with transvaginal ultrasound.     

Immunocytochemical detection of Ki‐67 in Diff‐Quik‐stained cytological smears of canine mammary gland tumours

U.S. Choi and D.Y. Kim Immunocytochemical detection of Ki‐67 in Diff‐Quik‐stained cytological smears of canine mammary gland tumours Objective: To investigate whether Diff‐Quik stained fine needle aspirate smears can be used to evaluate Ki‐67 expression by immunocytochemistry. Methods: Both cytological and histological samples were obtained from 24 dogs with spontaneously developed mammary gland tumours. The cytological and histological specimens were examined by Diff‐Quik and H&E stains, respectively. After examination, both samples were immunostained using the same Ki‐67 antibody. The % Ki‐67 values were calculated based on the percentage of positively stained tumour cells per 500 and 1000 tumour cells in cytology and histology specimens, respectively. Results: Ki‐67 staining was successful in 17/24 smears (71%) and 19/23 sections (83%). The correlation coefficient between the percentage of Ki‐67‐positive cells in cytological smears and in the histological sections was 0.677 (P < 0.01). These values were significantly different between histologically benign and malignant tumour groups both in cytology and histology samples (P < 0.001). The threshold value of the percentage of Ki‐67‐positive cells for distinguishing benign from malignant tumours was set at 4.85% with 90.9% sensitivity and 92.3% specificity by Receiver Operating Characteristic (ROC) curve using histopathology as the gold standard. Conclusion: Diff‐Quik‐stained cytology smears can be used to detect the presence of Ki‐67 antigen when histology sections are not available.     

Women’s preferences regarding options for management of atypical,borderline or low‐grade cervical cytological abnormalities: a review of the evidence

M. Z. Sadique and R. Legood Women’s preferences regarding options for management of atypical, borderline or low‐grade cervical cytological abnormalities: a review of the evidence Objectives: To review the evidence on women’s preferences for and valuation of alternative management pathways following identification of low‐grade cytological abnormalities as part of routine cervical cancer screening. The aim was to identify empirical studies evaluating women’s preferences regarding alternative management pathways and to compare the impact of alternative elicitation methods on results. Methods: A systematic review of the literature was conducted using the online bibliographic information service PubMed database. Empirical studies were identified that elicited general preferences, utilities or valuations based on willingness to pay (WTP) with respect to management of low‐grade cytology results. Data were extracted on the methodology used and the empirical results. Results: Where quality of life data were elicited directly from patients that were undergoing management of low‐grade abnormalities utilizing direct elicitation techniques such as WTP, general preference questionnaires and the Euroqol, the studies tended towards a preference in favour of HPV testing (and colposcopy referral if HPV positive) rather than repeat cytology. In contrast, where studies included the general population and presented hypothetical scenarios of treatment pathways, and explicitly tried to incorporate assessment of process utility, the evidence indicated a slight tendency to favour repeat cytology. Conclusion: Consideration of patient preferences in the management of low‐grade cytology is important for designing screening protocols. The reviewed studies indicate that potentially different conclusions may be drawn depending on the elicitation methodology and selection of participants in the research.