Smear cytology in the intra-operative assessment of periodontoid pseudotumour of the craniocervical junction

OBJECTIVE: Periodontoid pseudotumours are lesions of presumed degenerative aetiology which typically occur in elderly patients with cervical myelopathy. The clinical and radiological differential diagnosis includes neoplastic and inflammatory lesions, and the exclusion of such lesions may be of value in the intra-operative management of the patient. This audit aimed to examine the value of intra-operative smear cytology in the management of this condition. METHODS: The intra-operative smear cytological features of four cases of periodontoid pseudotumour were reviewed. RESULTS: In each case the intra-operative cytological interpretation was in keeping with a non-neoplastic and non-inflammatory process. CONCLUSION: These results suggest that intra-operative smear cytology can provide information on the value in the intra-operative management of patients with this lesion.     

Significance of endoscopic biopsy and cytology in the diagnosis of esophageal squamous cell carcinoma

We have tested the role and significance of histology combined with cytology in the diagnosis of esophageal squamous cell carcinomas. Biopsy specimens and samples for cytological smear were taken by a fiberoptic flexible endoscope. In order to minimise the loss of biological sample, the residue from the brush was removed with rinsing fluid. From 1973 to 2005 we examined 820 patients with squamous cell carcinoma of the esophagus. Endoscopic biopsy yielded positive result in 97.2%. Cytology performed in 724 patients turned out to be positive in 90.3%. Both examinations were conducted in 648 patients (79%), and yielded positive result in 572 patients (88.3%). Negative biopsy result was obtained in 22 patients, however, 14 of them had positive cytological diagnosis. Both biopsy and cytology were negative in 8 cancer patients (1%). No complication was observed with either diagnostic technique. In our material cancer was diagnosed in 776 patients by histology. However, in a further 14 of 22 patients with negative histology, cancer was detected by cytology. This means that the presence of cancer was also confirmed on the basis of morphological features in 790 cases, i.e. in 96.3% of the patients. Our results show that the combined use of biopsy and cytology in malignant tumours yields high diagnostic accuracy. Since abrasion exfoliate cytology is a quick and useful diagnostic measure it should be a routine examination in the evaluation of abnormal changes in the esophageal mucosa. The examination of the rinsing fluid of the sampling brush, introduced by us, yielded additional diagnostic information.     

The number of dyskaryotic cells on an initial ThinPrep® cervical sample showing mild dyskaryosis has predictive value

OBJECTIVES: Recent National Health Service Cervical Screening Programme (NHSCSP) guidelines suggest referral for colposcopy following an initial result of mild dyskaryosis. The aim of this study was to investigate if the number of dyskaryotic cells counted on an initial ThinPrep cervical sample showing mild dyskaryosis has predictive value. METHODS: Cases of mild dyskaryosis on ThinPrep cervical samples from 2002 were retrieved from the cytology department records of St Luke's Hospital. A total of 123 sequential cases with a first-time result of mild dyskaryosis on ThinPrep slides with follow-up cytology available in the same institution were identified. While blinded to outcome, the number of dyskaryotic cells was counted in each case. Follow-up colposcopy/histology information was retrieved where indicated. The number of dyskaryotic cells counted on each slide was collated with outcome data. RESULTS: Of the 123 cases, six women were lost to follow-up. Seventy-three had a negative outcome, 27 had a low-grade outcome and 17 had a high-grade outcome. Only one of 17 high-grade outcome cases had < or = 15 dyskaryotic cells on the initial slide. The distribution of women with a negative/low-grade outcome and those with a high-grade outcome with >15 and < or = 15 dyskaryotic cells on the initial slide was tested using a chi-square test (P = 0.008). The negative predictive value for a high-grade outcome when < or = 15 dyskaryotic cells were present on the initial slide was 97.7%. CONCLUSION: The number of dyskaryotic cells on ThinPrep slides showing mild cervical dyskaryosis has predictive value. The number of dyskaryotic cells may be used to select women suitable for cytological rather than colposcopic follow-up.     

Diagnostic pitfalls in the evaluation of fine needle aspiration cytology of the thyroid: correlation with histopathology in 260 cases

Objectives:  Fine needle aspiration cytology (FNAC) of the thyroid is a non-invasive, cost-effective screening procedure that is valuable for distinguishing neoplastic lesions from non-neoplastic nodules. The aim of this study was to determine the diagnostic accuracy of FNACs performed at our institution by correlating FNAC results with histopathological diagnoses.
Methods:  Two hundred and seventy-one aspiration cytology specimens followed by thyroidectomy were included in the study, and the results of 260 adequate FNACs were compared with their histological diagnoses.
Results:  The sensitivity and specificity of thyroid FNAC for detecting neoplasia were 92.6% and 91.6%, respectively. There were 15 (5.7%) false positives and six (2.3%) false negatives.
Conclusions:  The results showed that follicular cells that exhibit some of the features of papillary carcinoma could be observed in a cytology slide of Hashimoto's thyroiditis, leading to a diagnostic pitfall. In addition, cellularity and overlapping cytological criteria in hyperplasia might lead to a false diagnosis.     

Factors contributing to false‐negative and potential false‐negative cytology reports in SurePath™ liquid‐based cervical cytology

N. Gupta, D. John, N. Dudding, J. Crossley and J. H. F. Smith
Factors contributing to false‐negative and potential false‐negative cytology reports in SurePath ? liquid‐based cervical cytology Objectives: The characteristics of false‐negative conventional cervical cytology smears have been well documented, but there is limited literature available for liquid‐based cytology (LBC), especially SurePath? samples. We aimed to assess the characteristics of false‐negative SurePath LBC samples. Methods: Over a period of 5 years, an audit of false‐negative reports in SurePath cervical cytology was undertaken. In a workload of 183, 112 samples, 481 (0.3%) false negatives were identified using two routes: those detected by routine laboratory internal quality control (rapid pre‐screening) (n = 463) and those reported as normal (true false negatives) with concurrent high‐grade cervical histology (n = 18). Ninety‐five false‐negative cases with a subsequent biopsy reported as at least cervical intraepithelial neoplasia grade 2 (CIN2+) were reviewed for a number of different cytomorphological features. Results: Of 95 samples with subsequent CIN2+, 30.5% predominately contained microbiopsies/hyperchromatic crowded cell groups (HCGs), 27.3% sparse dyskarytotic cells, 4.2% pale cell dyskaryosis, 6.3% small dyskaryotic cells; 3.2% were misinterpreted cells, 8.4% contained other distracting cells, 7.4% were low contrast, 5.3% were unexplained and 7.4% were true negatives. The mean number of microbiopsies/HCGs in that category was 4.6. The mean number of abnormal cells in the sparse dyskaryotic cell category was 13.8. Conclusions: Microbiopsies/HCGs were the commonest reason for false negatives. They were usually present in sufficient numbers to be detected but interpretation could be problematic. Dispersed single abnormal cells were usually not identified because of their scarcity or the presence of distracters.     

Posters. P17 Accuracy of fine needle aspiration cytology in diagnosis of thyroid swellings

Introduction Fine needle aspiration cytology is regarded as the gold standard investigation in diagnosis of thyroid swellings. Published data suggest an overall accuracy rate of 75% 1 in the detection of thyroid malignancy. The aim of this study was to determine the accuracy of FNA cytology in detection of thyroid malignancy in our surgical unit. Methods Between 1989–2002, 144 patients who underwent thyroid resection by single consultant surgeon and who had pre‐operative FNA were enrolled in this retrospective study. The pre‐operative FNA results were compared with definitive histological diagnosis following thyroid resection. Fine needle aspiration cytology was performed using aspirate and non‐aspirate techniques on each thyroid swelling. The cytological sample was assessed by a single cytopathologist and was classified as inadequate, non‐neoplastic, neoplastic, suspicious or indeterminate. The histology was classified as non‐neoplastic (benign) and neoplastic (malignant). Results Fine needle aspiration cytology analysis revealed 94 (13.88%) non‐neoplastic, six (65.27%) neoplastic and 20 (4.16%) suspicious aspirates. Twenty (13.88%) samples were inadequate and four (2.77%) samples were indeterminate. Histological analysis showed 118 (81.94%) benign, 26 (18.05%) malignant specimens. Fine needle aspiration cytology had a sensitivity, specificity and accuracy rate of 52.6%, 86.6% and 79.1%, respectively for diagnosing thyroid malignancy. Conclusion The results are comparable with the current published data and demonstrate that FNA cytology in our hands is accurate investigation for pre‐operative diagnosis for the detection of thyroid malignancy.     

The evaluation of liquid-based ''Cyto-SEDTM'' cytology of bronchioalveolar lavage specimens in the diagnosis of pulmonary neoplasia against conventional direct smears

Historically, bronchioalveolar lavage (BAL) samples have been prepared by a direct smear (DS) technique. Recent advances in liquid-based cytology have led to a revolution in cytological specimen preparation. Cyto-SED system (CS) is a manual liquid-based cytology system, designed for small-scale use. A total of 137 samples from patients with radiographically detectable lesions underwent BAL procedures at Papworth Hospital NHS Trust over a 4-month period. After preparation for diagnostic purposes with the DS method, the remaining sample was prepared using the CS system. The slides produced were allocated a blind study number and screened by three independent screeners. The cellular morphology was well preserved and comparable between both techniques. Of the 137 patients, 38% were confirmed as malignant by cytology or histology; 71% of these malignant diagnosis were confirmed by the DS technique and 91% confirmed by the CS. The results demonstrate that the CS is a viable alternative to the DS technique. The cytological detail is clearly defined without a loss of three-dimensional information, thus aiding the differential diagnosis of malignancy. Cyto-SED cytology system yields a higher diagnostic accuracy than the conventional direct smear technique without compromising on cytological detail.     

Detection of bladder cancer by multitarget multicolour FISH: comparative analysis on archival cytology and paraffin-embedded tissue

Detection of bladder cancer by multitarget multicolour FISH: comparative analysis on archival cytology and paraffin-embedded tissue We have evaluated the possibility of using the same specimen for both cytological diagnosis and multitarget multicolour FISH (MtMcFISH) analysis in order to determine whether the routinely processed specimens used for diagnosis were also suitable for this ancillary procedure. For this purpose 18 positive samples (11 voided urine and seven bladder washings) were selected, together with a representative section of the corresponding immediately previous or subsequent histological specimens. Two negative cytology slides were added as negative controls. FISH analysis revealed a normal pattern for each probe in the two negative controls and an abnormal pattern in the 18 positive cases. In the latter the same FISH alterations were found in the cytology samples and in the corresponding histological sections, and superimposable cytological/histological features were observed in two cases where two different histology samples were analyzed. The results clearly show that MtMcFISH may be successfully applied to destained routinely processed cytology slides.     

Quality control in cervicovaginal cytology by cytohistological correlation

N. Izadi‐Mood, S. Sarmadi and S. Sanii
Quality control in cervicovaginal cytology by cytohistological correlation Objective: Frequent studies attest to the correlation of cytological interpretations with defined histopathological entities. Nevertheless, as part of quality control, cytology laboratories are required to compare Papanicolaou smear reports with those of cervical biopsies to search for discrepancies. We have attempted to determine and categorize the causes of existing discrepancies in our laboratory in order to clarify the source of errors. Methods: We reviewed 670 cervical smears that were paired with subsequent punch biopsy or endocervical curettage samples, obtained within 2 months of the cytology, and found out that 60 smear‐biopsy pairs were discrepant regarding the diagnosis. These cases were categorized into four error groups after careful re‐evaluation of the original smear and biopsy slides. Results: In 51 (85%) of 60 cervical smear‐biopsy pairs with reports that disagreed, the initial diagnoses of both cervical smear and biopsy were confirmed by the review opinion; in these cases, cytology and biopsy ‘sampling errors’ were responsible for 40 and 11 instances of discrepancy, respectively. Seven cases (11.1%) were discrepant due to ‘smear interpretation errors’ and consisted of five cases with initial under‐diagnosis and two cases with initial over‐diagnosis. One case (1.7%) was due to ‘screener error’. In another case, discordance was due to cervical ‘biopsy interpretation error’, with initial over‐diagnosis as squamous intraepithelial lesion. Conclusion: In this retrospective study, we determined the causes of cytohistological discrepancies in cervical samples. The main explanation for discrepancy was ‘sampling error’.     

An alternate model of thyroid cytology: practical not perfect

A sample of 384 thyroid cytology specimens prepared by cytospin over a 2.5-year period was classified by original report into inadequate, non-neoplastic and suspicious of neoplasia or worse. This was then compared with subsequent histology. The resulting data showed an inadequacy rate of 33%, a sensitivity of 55%, a specificity of 59%, a positive predictive value of 64% and a negative predictive value of 93%. On review of the cytology, in knowledge of the subsequent histology, the maximum achievable results were determined to have a positive predictive value of 79% and a negative predictive value of 97%. No clinically significant adverse event was detected.     

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.     

Collection of tissue and culture samples from the canine reproductive tract

Definitive diagnosis of reproductive tract infection or other disease often requires sampling of tissue, either for culture or histopathology. Indications, sample collection technique, possible side-effects and interpretation of results are reviewed. Pertinent facts include: (1) collection of uterine biopsy specimens via laparotomy was associated with higher yield of diagnostic samples and fewer side-effects than other less invasive techniques; (2) vaginal culture samples should be collected from the anterior vagina to minimize number of contaminants in the sample; (3) collection of culture samples from the anterior vagina during proestrus or estrus, in the presence of discharge originating in the uterus, was a non-invasive technique for assessment for uterine infection; (4) samples for bacterial culture from mucosal surfaces, including the vagina and penis, must be quantitated to allow interpretation, with moderate to heavy growth of any single aerobic bacterial organism relevant; (5) mycoplasma and ureaplasma are part of the normal flora of the genitourinary tract in dogs and bitches and, because most laboratories cannot give reliable quantitative results, interpretation of positive results often is difficult; (6) collection of prostatic tissue samples for cytology or culture was more likely to yield a correct diagnosis than submission of ejaculated prostatic fluid.     

Stereotactic biopsy and cytological diagnosis of solid and cystic intracranial lesions

Cytological smears from 115 consecutive cases of stereotactic biopsies of intracranial lesions were reviewed. Ninety-five lesions were solid and 20 cystic. Material from 90 solid and 13 cystic lesions was sent both for cytological and histological examination. In 66 of the solid lesions, the cytological diagnosis was confirmed by histology (five were benign lesions and 61 malignant tumours: 56 primary brain tumours, three metastases and two lymphomas). In 24 cases with discrepant cytology and histology, the histology was inconclusive or insufficient in 14 cases, while cytology established the diagnosis of astrocytoma grade II (seven cases), metastases (two cases), gliosis (one case) and benign (four cases). Necrosis of tumour type was observed cytologically in six patients representing glioblastoma (two cases), anaplastic astrocytoma (one case), lymphoma (one case) and normal brain (two cases) histologically. Three cases reported cytologically as benign were primary brain tumour (two cases) and gliosis (one case). One smear of a glioblastoma was insufficient for cytological diagnosis. Cystic lesions were cytologically benign in 17 cases and malignant in three cases. Histology from the cyst wall confirmed the malignant diagnosis in three cases and showed tumour in six more cases, a benign process (two cases), changes induced by radiotherapy for arteriovenous malformation (one case) and insufficient material (one case). In conclusion, cytology from solid brain lesion allows an accurate diagnosis and subtyping of tumours in a majority of cases, and can thus be used to choose type of therapy. In cystic brain tumours, however, examination of the cystic fluid, is often inconclusive and a biopsy from the cyst wall should be performed if there is clinical or radiological suspicion of tumour.     

Accuracy of the analysis of multiple small fragments of glial tumors obtained by stereotactic biopsy.

To examine the reliability of the diagnoses reached on multiple small fragments of cerebral glial tumors obtained via stereotactic biopsy, samples obtained from 100 consecutive glial tumors (during real or simulated biopsy) were studied by cytology and histology. In comparison to the definitive diagnosis made on the whole tumor, a correct positive diagnosis on the biopsy sample was made by histology in 96% of cases and by cytology in 93% of the cases (with 96% correct results when combining both methods). A correct identification of the tumor type and grade was achieved by histology in 82% of cases and by cytology in 80% of the cases (with 85% correct results when combining both methods). The limits of stereotactic biopsy are related to the difficulty of identifying all of the typical tumor features on tiny tissue fragments of a pleomorphic neoplasm, such as a glioma. This study demonstrates that better results may be obtained by using both cytology and histology to study multiple stereotactic biopsy samples from glial tumors.     

Imprint cytology of vacuum-assisted breast biopsy specimens: a rapid diagnostic tool in non-palpable solid lesions

Objective:  Imprint cytology provides a rapid preliminary diagnosis shortly after the completion of breast biopsy. This study aims to assess the validity of imprint cytology for the pre-operative diagnosis of non-palpable mammographic solid lesions excised by vacuum-assisted breast biopsy (VABB).
Methods:  Seventy-two women with non-palpable Breast Imaging Reporting and Data System 3 and 4 mammographic solid lesions without microcalcifications underwent VABB on the stereotactic Fischer's table with 11-G Mammotome vacuum probes. Imprint samples were examined (Diff-Quick stain, modified Papanicolaou stain and May-Grünwald–Giemsa). The cores were dipped into a CytoRich Red Collection fluid for a few seconds in order to obtain samples with the use of the specimen wash. After the completion of cytological procedures, the core was prepared for routine pathological study. The pathologist was blind to the preliminary cytological results. The cytological and pathological diagnoses were comparatively evaluated.
Results:  The sensitivity of the cytological imprints for cancer was 90%. The specificity of the method for cancer diagnosis was 100%. Two precursor lesions were present in the material: one case of atypical ductal hyperplasia, which was successfully detected, and one case of lobular neoplasia, which escaped detection. The cytological imprints were inadequate in four out of 72 cases (5.6%), but none of them were included within the malignant subgroup.
Conclusions:  Imprint cytology seems to be an important adjunctive tool in the management of patients with non-palpable mammographic solid lesions. Its very satisfactory sensitivity and optimal specificity could establish its use in general clinical practice.     

Primary cervical lymphoma: the role of cervical cytology

Two cases of primary malignant lymphoma of the uterine cervix are reported. Both were confirmed by histology as high grade B cell lymphomas. In one case, the diagnosis was made on a second colposcopic biopsy after an initial cervical smear and colposcopic biopsy were negative. In the second case, dyskaryotic cells of uncertain type were identified in a cervical smear taken at colposcopy performed as part of follow up for previous cervical intraepithelial neoplasia (CIN)I. The cytologic features and differential diagnosis of this rare cervical neoplasm are discussed, with emphasis on the role of the Papanicolaou smear in the initial diagnosis of this tumour.     

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.     

Argyrophilic nucleolar organizer region (AgNOR) technique: a helpful tool for differential diagnosis in urinary cytology

The aim of this study was to investigate whether the AgNOR technique could be helpful for the cytologic diagnosis of neoplastic and non-neoplastic urinary tract lesions. We analysed the AgNOR pattern in urinary cytology in samples from 70 patients. In every case the average number of silver precipitations per nucleus was counted and the range between the minimum and maximum AgNOR value calculated. Furthermore we noted whether the AgNOR precipitations had a homogeneous or heterogeneous distribution. The diseases were classified in three groups: non-neoplastic lesions, low grade and high grade carcinoma. Linear discriminant analysis (with jack-knife procedure) was performed with the AgNOR parameters as independent variables. The final diagnosis of each patient had been established by histological analysis of bladder biopsies. We obtained a correct classification in 84.3% of the cases. All patients with normal or reactive lesions were correctly classified and only two cases of low grade malignancy were erroneously diagnosed as non-malignant. Five high grade neoplasms had been classified as low grade and four low grade carcinomas had been over-diagnosed as high grade neoplasms. We conclude that a combined qualitative and quantitative AgNOR analysis can be useful in the differential diagnosis of urinary cytology.     

Non-computer-assisted liquid-based cytology for diagnosis of oral squamous cell carcinoma

Abstract

The development of oral squamous cell carcinoma (OSCC) occasionally follows the neoplastic progression of other premalignant lesions. Although biopsy is the definitive diagnostic method, liquid-based cytology is an adequate method for screening suspicious lesions. We compared liquid-based cytology to histology for diagnosis of OSCC in patients with oral lesions that raised clinical suspicion of malignancy. Our sample consisted of 48 patients. Cytological samples were obtained by scraping the lesion superficially using Cytobrush^®. We conducted cytological and histopathological evaluation of all preparations. We estimated sensitivity and specificity levels as well as positive and negative predictive values. The degree of inter-observer agreement for both methods was assessed using the kappa index. Twenty-eight (58.3%) of the cases finally were diagnosed with OSCC and 20 (41.7%) were determined to be premalignant lesions. We observed eight false negatives and no false positives; OSCC prevalence was 56.5%. The values for diagnostic indices were: sensitivity, 69% (CI 95%, prevalence 51.87); specificity, 100%; positive predictive value, 100%; negative predictive value, 71% (CI 95% 54.82). A kappa index of 0.622 (CI 95% 0.93, 0.39) was observed.     

Application of the membrane filter technique to bromodeoxyuridine immunochemistry for exfoliative cytology

The membrane filter technique for smear specimens of tumors in bromodeoxyuridine (BrdU) immunochemistry is described. The staining results of Raji cells processed using the filter technique was compared with that obtained by the conventional cytospin method. Although the BrdU mean labeling index (LI) for in cytospin specimens was almost the same as the LI in membrane filter specimens, filter specimens showed excellent staining and less cell destruction compared with those processed by cytospin. Small amounts of tumor specimens such as squamous cell carcinoma and polymorphous low-grade adenocarcinoma also were processed using the membrane filter appliance. For squamous cell carcinoma, the LI for the filter specimens was 5.36 ± 0.38 and that of the paraffin sections was 5.56 ± 0.38. The membrane filter technique provided relatively undamaged specimens for exfoliative cytology and will be useful for immunohistochemical evaluation of tumor cells and for routine, noninvasive cytological screening.