Value of endoscopic retrograde cholangiopancreatography-guided brushings in preoperative assessment of pancreaticobiliary strictures: what's new?

Brush cytology plays a prominent role in confirming the presence of extrahepatic biliary tract malignancy. However, its value is limited by its relatively low and widely variable sensitivity values. Various factors seem to influence the accuracy of cytologic diagnosis and are attributed to sampling, technical and interpretation errors. Ancillary methods, such as immunocytochemistry, flow cytometry, image analysis, fluorescence in situ hybridization (FISH) and the newly discovered method of global analysis of gene expression are helpful in resolving cases with inconclusive cytology and are vigorously investigated for their value in assessing the expression of novel tumor markers for the diagnosis and prognosis of pancreatic and bile duct carcinomas. However, their routine use in clinical practice remains in doubt. To increase the sensitivity of brush cytology and strengthen its role in the preoperative assessment of patients with pancreaticobiliary malignancies, the following are of the utmost importance: improvement of current sampling and cytopreparation techniques, introduction of a uniform system for reporting epithelial abnormalities based on strict and clearly distinct morphologic criteria for each pathologic entity and incorporation of experience and knowledge derived from standard cytologic methods and novel diagnostic technologies in clinical practice without compromising the high specificity associated with brush cytology.     

Bile duct brushings cytology – improving sensitivity of diagnosis using the ThinPrep® technique: a review of 113 cases

OBJECTIVE: Common bile duct (CBD) brushings have been recognized as a technique of moderate sensitivity and high specificity in identifying carcinoma of the ampulla and pancreatico-biliary regions. This study evaluated the increase in sensitivity of this technique using the ThinPrep technique of specimen preparation when compared with conventional cytology smears. METHODS: A total of 113 bile duct brushings were included in the study (38 conventional smears and 75 slides prepared using the ThinPrep technique). All slides were reviewed by one cytologist. Five categories of reporting were used: inadequate, negative, atypia, suspicious and malignant. RESULTS: The inadequate category of reporting disappeared in the ThinPrep group with improved specimen fixation and preparation and hence reduced artefact. Sensitivity of diagnosis of malignancy increased from 39% in conventional smears to 53% in the ThinPrep group. Specificity, positive and negative predictive values and accuracy were 100%, 100%, 60% and 68% for conventional smears and were 100%, 100%, 60% and 72%, respectively, for ThinPrep specimens. CONCLUSIONS: ThinPrep technique was associated with increased sensitivity of diagnosis, in part due to improved specimen fixation and reduced artefact. Cytology of bile duct brushings is an important diagnostic tool for sites from which it can be difficult to obtain a histology biopsy. It may therefore provide the only opportunity for tissue diagnosis of carcinoma from these sites, hence the importance of optimizing sensitivity.     

Outcomes of endoscopic ultrasound‐guided pancreatic FNAC diagnosis for solid and cystic lesions at Manchester Royal Infirmary based upon the Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme

Objective

To compare endoscopic ultrasound (EUS)‐FNAC diagnosis of pancreatic lesions with patient outcome based upon the Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme diagnostic categories: Panc 1 (non‐diagnostic); Panc 2 (negative for malignancy/neoplasia); Panc 3 (atypical); Panc 4B (neoplastic, benign); Panc 4O (neoplastic, other); Panc 5 (suspicious of malignancy); and Panc 6 (positive/malignant).

Methods

All EUS‐FNA pancreas specimens taken at Manchester Royal Infirmary in 2015 were prospectively classified according to the above scheme at the time of cytology reporting and data recorded prospectively. Subsequently, outcomes based on clinical follow‐up or histopathology diagnosis were compared with the cytology diagnosis.

Results

120 EUS‐FNA pancreas specimens from 111 patients were received, of which 112 (93.3%) specimens had follow‐up data. There were 79 and 41 EUS‐FNA pancreas specimens from solid and cystic lesions, respectively. Based on the cytology diagnosis the specimens were classified as Panc 1 (7.5%), Panc 2 (33.3%), Panc 3 (2.5%), Panc 4B (2.5%), Panc 4O (15.0%), Panc 5 (3.3%) and Panc 6 (35.9%). The performance indicators for diagnosis of malignancy or neoplasia with malignant potential, included sensitivity (95.4%), specificity (100%), positive predictive value (100%), negative predictive value (92.3%), false positive rate (0%) and false negative rate (4.6%).

Conclusions

The Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme is a logical system that can easily be introduced in a diagnostic cytopathology service. This classification scheme acts as an aid to diagnostic reporting, clear communication of significant results including risk of neoplasia/malignancy to clinicians, clinical audit and comparison of results with other centres.     

Laminin-5 immunocytochemistry: a new tool for identifying dysplastic cells in oral brush biopsies

BACKGROUND: The brush biopsy technique is not only a seminal technique but also a critically discussed method for detection of oral pre-cancerous stages and manifest carcinomas. The gamma2 chain of laminin-5 and its proteolytic fragments comprise an invasion factor for many carcinomas. OBJECTIVES: The aim of this study was to determine whether the immunocytochemical presentation of the laminin gamma2 chain identifies pre-invasive or invasive squamous cells in brush biopsies. METHODS: The value-based identification of atypical epithelia was analysed in 93 consecutive brush biopsies with histopathological diagnoses: standardized haematoxylin and eosin staining; standardized immunocytochemistry: monoclonal antibodies against laminin gamma2 chain: D4B5, 4G1, detection using ChemMate and Autostainer. RESULTS: Conventional cytology did not result in any false-positive cases, i.e. atypical cells in normal, inflamed or benignly hyperproliferative mucosa (specificity, 100%), whereas immunocytochemistry revealed one false-positive case (specificity, 98%). In brush biopsies of oral squamous cell carcinomas, the following immunocytochemical patterns were possible: (1) staining of the cytoplasm, (2) banded markings between clumped carcinoma cells and (3) positive hazes surrounding atypical cells. Bacterial colonies appeared as false-positive results. Four of 27 carcinomas and one of three recurrences were not cytologically identified (sensitivity of conventional cytology, 79%). Three of the five carcinomas not identified by cytology were immunocytochemically stained with laminin gamma2 chain antibody (sensitivity of laminin gamma2 chain immunocytochemistry, 93%). The positive predictive value was 100% for conventional cytology and 97% for laminin gamma2 chain immunocytochemistry. The negative predictive value attained was 92% for conventional cytology and 97% for laminin gamma2 chain immunocytochemistry. CONCLUSIONS: The high sensitivity level observed for method-enhanced brush cytology suggests that this technique be used as an initial diagnostic step.     

Proffered papers 14.00–15.00 Tuesday 16 September 2003 8 Ampullary,pancreatic and biliary duct exfoliative brush cytology prepared by the thinprep method: performance and morphology

Background ERCP‐directed brush cytology is used to sample lesions of the pancreatic and biliary ducts and the ampulla of Vater. With conventional preparations, the sensitivity and specificity range from 44% to 63% and 80% to 98%, respectively, and increased N : C ratio, nuclear molding and loss of honeycombing are reliable features of malignancy. The performance and morphology of specimens prepared by ThinPrep, a liquid‐based cytology technique is mostly unknown. Methods The laboratory information system was searched for all cases prepared by ThinPrep. Patient disease classification of benign or malignant was determined by linkage with the provincial cancer registry and was the gold standard against which sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. True positives and negatives were reviewed to identify predictive cytomorphologic features. Results Between 1996 and 2001, there were 149 ThinPrep specimens; 55 (37%) were reported as positive for malignancy and 94 (63%) as negative. Disease was classified as malignant in 86 (58%) patients and benign in 63 (42%). There were 42 false negative, 11 false positive, 52 true negative, and 44 true positive cytology results. Sensitivity was 51.2% (CI; 40.2 : 62.0), specificity 82.5% (CI; 70.5 : 90.6), and PPV and NPV 80.0% (CI; 66.6 : 89) and 55.3% (CI; 44.7 : 65.5), respectively. Cell groups with crowded, enlarged, irregular nuclei and nuclear features of vesicular chromatin and large, multiple irregular nucleoli correlated with malignant disease, while monolayered sheets of uniform columnar cells, regular nuclei and a finely granular chromatin correlated with benign disease. Conclusions The performance of ThinPrep brushings from this anatomic site equals conventional preparations. Cytomorphologic features of malignancy are more frequent and pronounced with ThinPrep.     

Proffered papers 14.00–15.00 Tuesday 16 September 2003

Background  ERCP-directed brush cytology is used to sample lesions of the pancreatic and biliary ducts and the ampulla of Vater. With conventional preparations, the sensitivity and specificity range from 44% to 63% and 80% to 98%, respectively, and increased N : C ratio, nuclear molding and loss of honeycombing are reliable features of malignancy. The performance and morphology of specimens prepared by ThinPrep, a liquid-based cytology technique is mostly unknown.
Methods  The laboratory information system was searched for all cases prepared by ThinPrep. Patient disease classification of benign or malignant was determined by linkage with the provincial cancer registry and was the gold standard against which sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. True positives and negatives were reviewed to identify predictive cytomorphologic features.
Results  Between 1996 and 2001, there were 149 ThinPrep specimens; 55 (37%) were reported as positive for malignancy and 94 (63%) as negative. Disease was classified as malignant in 86 (58%) patients and benign in 63 (42%). There were 42 false negative, 11 false positive, 52 true negative, and 44 true positive cytology results. Sensitivity was 51.2% (CI; 40.2 : 62.0), specificity 82.5% (CI; 70.5 : 90.6), and PPV and NPV 80.0% (CI; 66.6 : 89) and 55.3% (CI; 44.7 : 65.5), respectively. Cell groups with crowded, enlarged, irregular nuclei and nuclear features of vesicular chromatin and large, multiple irregular nucleoli correlated with malignant disease, while monolayered sheets of uniform columnar cells, regular nuclei and a finely granular chromatin correlated with benign disease.
Conclusions  The performance of ThinPrep brushings from this anatomic site equals conventional preparations. Cytomorphologic features of malignancy are more frequent and pronounced with ThinPrep.     

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.     

Detection of IGF2BP3, HOXB7, and NEK2 mRNA Expression in Brush Cytology Specimens as a New Diagnostic Tool in Patients with Biliary Strictures

Introduction

It is a challenging task to distinguish between benign and malignant lesions in patients with biliary strictures. Here we analyze whether determination of target gene mRNA levels in intraductal brush cytology specimens may be used to improve the diagnosis of bile duct carcinoma.

Materials and Methods

Brush cytology specimens from 119 patients with biliary strictures (malignant: n = 72; benign: n = 47) were analyzed in a retrospective cohort study. mRNA of IGF-II mRNA-binding protein 3 (IGF2BP3), homeobox B7 (HOXB7), Forkhead box M1 (FOXM1), kinesin family member 2C (KIF2C) and serine/threonine kinase NEK2 was determined by semi-quantitative RT-PCR using the ΔCt method.

Results

IGF2BP3 (p<0.0001), HOXB7 (p<0.0001), and NEK2 (p<0.0001) mRNA expression levels were significantly increased in patients with cholangiocarcinoma or pancreatic cancer. Median ΔCt values differed by 3.5 cycles (IGF2BP3), 2.8 cycles (HOXB7) and 1.3 cycles (NEK2) corresponding to 11-fold, 7-fold and 2.5-fold increased mRNA levels in malignant versus benign samples. Sensitivity to detect biliary cancer was 76.4% for IGF2BP3 (80.9% specificity); 72.2% for HOXB7 (78.7% specificity) and 65.3% for NEK2 (72.3% specificity), whereas routine cytology reached only 43.1% sensitivity (85.4% specificity). Diagnostic precision was further improved, when all three molecular markers were assessed in combination (77.8% sensitivity, 87.2% specificity) and achieved 87.5% sensitivity and 87.2% specificity when molecular markers were combined with routine cytology.

Conclusions

Our data suggest that measuring IGF2BP3, HOXB7 and NEK2 mRNA levels by RT-PCR in addition to cytology has the potential to improve detection of malignant biliary disorders from brush cytology specimens.     

Postoperative bladder washing cytology after transurethral resection. Can it predict the recurrence of urothelial carcinoma?

OBJECTIVE: To assess the ability of postoperative bladder washing cytology, performed immediately after transurethral resection of mostly stage Ta or T1 papillary urothelial carcinoma, to predict early recurrence. STUDY DESIGN: In a 1-year period, preoperative and postoperative bladder washing cytology specimens were sampled from patients undergoing transurethral resections in which all visible tumor was removed. There were 38 resections in 32 patients. RESULTS: Postoperative cytology was satisfactory in 35 of 38 cases and positive in 17 (49%) after a mean of 6.9 months. Follow-up of these 35 transurethral resections disclosed a 15/17 (88%) recurrence rate after positive cytology and a 4/18 (22%) recurrence rate after negative cytology (P < .001). Postoperative cytology demonstrated a sensitivity for recurrence of 79%, specificity of 88%, positive predictive value of 88% and negative predictive value of 77%. In contrast, tumor in the transurethral resection specimen had a positive predictive value of 54% for recurrence, and its grade and stage were inferior to cytology in predicting recurrence. CONCLUSION: Postoperative bladder washing cytology is a useful adjunct to the management of papillary urothelial carcinoma. A positive result, signifying residual tumor, should encourage prompt follow-up and possibly repeat transurethral resection.     

Significance of anucleated squames in Papanicolaou-stained cervicovaginal smears

The significance of anucleated squames in Papanicolaou-stained cervicovaginal smears as a marker of hyperkeratosis with an underlying significant atypia was evaluated. Over a two-year period, 785 (0.47%) of 168,215 cervicovaginal smears were signed out as demonstrating anucleated squames without any other abnormality. Cytologic or histologic follow-up specimens were available for 304 of those smears (42%). Histology or cytology showed condyloma or a more significant lesion in 13 cases (4.3%); histology showed hyperkeratosis without atypia in 25 cases (8.2%) and chronic cervicitis in 23 (7.5%); follow-up cytology demonstrated persistent anucleated squames in 47 cases (15.4%) and was negative in 196 (64.6%). During this same period, the rate of condyloma or a more significant lesion in all Papanicolaou smears examined was 1.69%. Thus, reporting the presence of anucleated squames in the absence of any other abnormality appears to be of marginal value as a screening procedure for predicting the existence of a significant lesion. Noting their presence in patients with a prior diagnosis of condyloma or dysplasia remains an important tool for detecting a persistent lesion. Lack of standardization among pathologists in the recognition of anucleated squames may partially explain the low predictive value of this finding: an informally conducted survey revealed a mean accuracy of 46% in the identification of true anucleated squames.     

Accuracy of touch imprint cytology of image-directed breast core needle biopsies

OBJECTIVE: To evaluate the accuracy of touch imprint (TI) cytology of image-directed core needle biopsy (CNB) specimens of nonpalpable breast lesions. STUDY DESIGN: Fifty-two consecutive CNBs from 44 patients were performed under mammographic or ultrasound guidance. Air- dried TIs of CNBs were stained with Diff-Quik. TI cellularity was considered adequate if six or more ductal cell groups were identified. CNBs and TIs were interpreted in a blinded fashion. RESULTS: TI cellularity was adequate in 37/52 (71%) cases, including 17/20 carcinomas and 20/32 benign lesions. Among 17 carcinomas, TIs were positive in 12, suspicious in 4 and atypical in 1. One case of lactational change was suspicious on TI, and 5/8 fibroadenomas were atypical. No benign lesions were called "carcinoma" on cytology. When lesions categorized as "carcinoma" or "suspicious" were considered positive and those classified as "atypical" or "benign" were scored as negative, TI sensitivity and specificity were 94% and 95%, respectively. When the "atypical" cases were grouped with the positive cases, TI sensitivity was 100%, with 75% specificity. CONCLUSION: With satisfactory cellularity, TIs of CNBs are highly accurate. When immediate evaluation of CNB specimens is important, TIs can potentially decrease the number of biopsy passes required and provide preliminary diagnoses.     

Ultrasound guidance improves the adequacy of our preoperative thyroid cytology but not its accuracy

AIMS: Our thyroid cytology audit results of 1990-1995 showed an unsatisfactory rate of 43.1% and prediction of neoplasia with a sensitivity of 86.8%. Increasingly, ultrasound scan (USS)-guided core sampling for cytology is proving a valuable tool instead of freehand fine needle aspiration (FNA) or following unsatisfactory freehand FNA. We present the results of freehand FNA and USS-guided core samples for cytology in two separate patient groups in our centre. METHODS: Patients who had a thyroid resection and preoperative thyroid cytology in our institution between 1996 and 2002 were included. The histological diagnoses were correlated with the preceding cytology results. RESULTS: A total of 450 FNAs were performed on 394 patients. Freehand FNAs were performed for 348 (77.3%) samples and USS-guided core for 102 (22.7%) samples; 121 (26.8%) were repeat aspirates performed on 45 patients. Using aspiration cytology (AC) grading, freehand FNA was cytologically inadequate (AC0 or AC1) in 34.8% cases whereas USS-guided core was inadequate in 17.6% cases (P = 0.001). Freehand FNA (AC3, AC4, AC5) predicted neoplasia with a sensitivity of 83.2%, specificity of 46.6%, accuracy of 63.0%, positive predictive value of 56.0% and negative predictive value of 77.1%. USS-guided core sample for cytology (AC3, AC4, AC5) predicted neoplasia with a sensitivity of 93.5%, specificity of 26.0%, accuracy of 51.9%, positive predictive value of 43.9% and negative predictive value of 86.7%. CONCLUSIONS: Although USS-guided core provides more satisfactory specimens than freehand FNA, in our centre it does not provide increased accuracy.     

Role of urinary NMP-22 combined with urine cytology in follow-up surveillance of recurring superficial bladder urothelial carcinoma

OBJECTIVE: To determine efficacy and utility of NMP-22 in follow-up of bladder urothelial carcinoma (UC) and compare NMP-22 as a single evaluating test vs combination with cytology. STUDY DESIGN: Ninety-four consecutive urine cytology samples of bladder UC were identified. Patients received follow-up urine cytology, NMP-22 testing and cystoscopy with surgical biopsy. RESULTS: NMP-22 specificity was 100%, sensitivity 45%, positive predictive value (PPV) 100% and negative predictive value (NPV) 87%. NMP-22 showed lower sensitivity for high-grade lesions and higher for low-grade lesions. Cytologic diagnosis had a high inconclusive rate; when regarded as positive, it resulted in 75% sensitivity, 58% specificity, 33% PPV and 89% NPV. NMP-22 correctly classified 60% of false negative cases diagnosed by cytology with low-grade UC and clarified 27 inconclusive cytologic diagnoses. NMP-22 misclassified 9 cases as false negative, all with high-grade UC; all were correctly identified on cytology as true positive. Combined interpretation showed 90% sensitivity, 92% specificity, 75% PPV and 98% NPV. CONCLUSION: NMP-22 complements cytology by its higher sensitivity for low-grade lesions; its values are not affected by bacillus Calmette Guérin therapy changes, which are limiting in cytology. Combined interpretation of NMP-22 and cytology shows promise as an effective, noninvasive method for surveillance of UC.     

The impact of liquid-based oral cytology on the diagnosis of oral squamous dysplasia and carcinoma

OBJECTIVE: Even though diagnostic oral exfoliative cytology is a useful, economical and practical tool in the diagnosis of oral dysplasia and carcinoma, it is not yet extensively used. The results of conventional exfoliative and liquid-based diagnostic cytology in oral potentially malignant lesions (PML) are herein reported and compared with the histological diagnosis. METHODS: Either conventional (89) or liquid-based (384) exfoliative cytology was used for the diagnosis of oral dysplasia/carcinoma in 473 subjects and the results were compared with scalpel biopsy histology. Cells were collected using a Cytobrush device for conventional smears and with a dermatological curette for the liquid-based cytology. The 'curette technique' also allowed for the collection of 'accidental' tissue fragments, utilized as microbiopsies. RESULTS: Histological diagnosis was squamous carcinoma in 96 of 473 cases, high-grade dysplasia (oral intraepithelial neoplasia two to three) in 24 and other lesions in 353 cases. The smears in the conventional cytology group were inadequate in 12.4%, with an 85.7% sensitivity and a 95.9% specificity. There were 8.8% of inadequate specimens in the liquid-based cytology group; sensitivity was 95.1% and specificity was 99.0%. CONCLUSIONS: Although conventional cytology is useful when diagnosing oral PML (better sensitivity and predictive positive value if compared with the cervical smear test with similar specificity) and can improve the accuracy of histological diagnosis, liquid-based cytology gives better results, as it not only enhances both sensitivity and specificity, but also provides material for further investigation (AgNORs, DNA, microbiopsies, etc.).     

Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast

X. Jing, E. Wey and C. W. Michael Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast Objective: To evaluate the utility of ThinPrep® as an optional specimen processing method for the detection of axillary lymph node metastasis of invasive breast carcinoma. Methods: A computer SNOMED search from the file at our institution between January 2003 and August 2011 retrieved a total of 209 fine needle aspiration (FNA) specimens of axillary lymph nodes prepared by ThinPrep and followed by axillary lymph node biopsy and/or dissection. Original cytological diagnoses and corresponding histological diagnoses were documented. Using the histological diagnoses as the gold standard, the diagnostic parameters including sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and diagnostic accuracy were calculated. Both cytology and histology slides from cyto‐histologically discrepant cases were reviewed. Results: Out of a total of 209 specimens, 193 (92%) had adequate diagnostic material while the remaining 16 specimens (8%) were inadequate for cytological assessment. The diagnostic specimens included 168 invasive ductal carcinomas (IDC), 15 invasive lobular carcinomas (ILC) and 10 mixed carcinomas (IDC and ILC). Excluding 19 cases with malignant cells on FNA in which no residual tumour was found in fibrotic lymph nodes after neoadjuvant therapy (cytology and histology confirmed on review) ThinPrep detected nodal metastasis with an overall sensitivity of 77.5%, specificity of 100%, PPV of 100% and NPV of 53.7%. Diagnostic accuracy was 82.2%. There was no difference in Bloom–Richardson grade or the number or size of metastases between tumours with true‐positive and false‐negative cytology. Sampling error was the sole factor contributing to cyto‐histological discrepancy. Conclusions: ThinPrep is a good alternative to the conventional smear for cytological assessment of axillary lymph node status in patients with invasive breast carcinoma, particularly when specimens are collected at remote sites or when cytologists are not available for assistance during FNA.     

Brush cytology of colorectal malignancies

OBJECTIVE: To evaluate the specificity and sensitivity of brush cytology and biopsy in colorectal malignancies. STUDY DESIGN: The study was performed over 3 years, 1998-2000. Seventy-six patients with any colorectal lesion on colonoscopy were selected, and in all of them brush cytology and biopsy were done at the same time. The cytologic smears and biopsies were reviewed separately. The cytologic smears were categorized as negative, suspicious, suggestive or positive for malignancy. The results of cytology and biopsy were compared based on sensitivity and specificity. The gold standard for positive cases was the tissue specimen after surgery; negative cases were followed for at least 1 year. Cases with 1 year of disease-free survival were considered negative. RESULTS: Among 76 cases, 4 were excluded because of unsatisfactory cytologic smears. Of the remaining 72 cases, 31 were male and 41 female. The age range was 19-80 years. Cytology showed 23 positive and 49 negative cases (1 false positive and 3 false negative). Biopsy showed 24 positive and 48 negative cases (no false positives and 1 false negative). There were 47 negative cases, followed for at least 1 year, and after that we considered them definitively negative for malignancy. Sensitivity of cytology and biopsy was 88% and 96%; specificity was 98% and 100%, respectively. Combined use of brush cytology and biopsy had the highest sensitivity, 100%. CONCLUSION: Brush cytology of the colon is a safe, fast and reliable method for the diagnosis of colorectal cancer. We recommend performing it in conjunction with biopsy. It is also reasonable to perform a repeat biopsy in patients with negative biopsy and positive cytology for a definitive diagnosis.     

Posters. P11 Positive predictive values for high and low‐grade cytological abnormalities as surrogates for specificity and sensitivity

Introduction Positive predictive value (PPV), measuring the percentage of moderate dyskaryosis or worse confirmed as CIN2 or worse, is used as a measure of accuracy in cervical screening. However, it relates more to specificity than sensitivity because the denominator includes false positives rather than false negatives. Low values reflect over‐reporting of high‐grade dyskaryosis but high values may reflect under‐reporting. Sensitivity is impossible to measure from correlation of cytology with outcome because women with negative cytology are rarely referred for colposcopy. Rates of CIN3 resulting from referrals for low‐grade cytology may be used as a surrogate for sensitivity, as high values may reflect under‐reporting (ref). Study design Outcome of colposcopy referrals was monitored during a period of 4 years, using a fail‐safe database. Results PPV at Guy's & St Thomas rose from 54% in 1998/1999 to 69% in 2001/2002. The former was below the NHSCSP recommended range. During the same period of time CIN1 rates for moderate dyskaryosis fell from 37% to 24%, reflecting the main source of discrepancy. While specificity increased (as reflected by increasing PPV) sensitivity remained constant in that CIN3 rates for mild dyskaryosis and borderline remained below 6%: average rates in England have fallen over the last 3 years and were 7.4% in 2000/2001 (ref). CIN2 rates for mild dyskaryosis also remained constant at 11% to 12%. Conclusion Correlation of biopsy results with high‐ and low‐grade cytological abnormalities is a useful method of monitoring accuracy of cytology reporting, and can be used to measure over‐ and under‐reporting as surrogates for specificity and sensitivity.     

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.     

Intraoperative evaluation of sentinel lymph nodes in breast cancer: comparison of frozen sections,imprint cytology and immunocytochemistry

M. Francz, K. Egervari and Z. Szollosi
Intraoperative evaluation of sentinel lymph nodes in breast cancer: comparison of frozen sections, imprint cytology and immunocytochemistry Objective: We analysed the utility of imprint cytology with rapid immunocytochemistry and frozen section analysis for the evaluation of sentinel lymph nodes in breast cancer patients. Methods: The sensitivity, specificity, and positive and negative predictive values have been calculated for each method individually, each pair and all three together. We compared these results with those of routinely processed paraffin sections. Results: The sensitivity and specificity of each of the three methods for detection of metastatic carcinoma were as follows: 69.4% and 97.8% for touch imprint cytology; 58.3% and 100% for frozen sections; 68.5% and 98.9% for rapid immunocytochemistry. When the methods were combined, the highest accuracy was achieved by touch imprint cytology, frozen sections, touch imprint cytology plus rapid immunocytochemistry, or touch imprint cytology frozen section analysis and rapid immunocytochemistry, each of these having identical sensitivity and specificity of 72.2% and 97.8%, respectively. Conclusions: In our study the combined accuracy of the three methods was the same as combining touch imprint cytology and frozen sections or touch imprint cytology plus rapid immunocytochemistry. Rapid immunocytochemistry provides an additional parameter and preserves tissue for permanent sections.     

Cytologic and DNA-cytometric early diagnosis of oral cancer.

OBJECTIVE: The aim of this prospective study was to report on the diagnostic accuracy of conventional oral exfoliative cytology taken from white-spotted, ulcerated or other suspicious oral lesions in our clinic. In addition we checked DNA-image cytometry as an adjuvant diagnostic tool. Our hypothesis is that DNA-aneuploidy is a sensitive and specific marker for the early identification of tumor cells in oral brushings. STUDY DESIGN: 251 cytological diagnoses obtained from exfoliative smears of 181 patients from macroscopically suspicious lesions of the oral mucosa and from clinically seemingly benign oral lesions which were excised for establishing histological diagnoses were compared with histological and/or clinical follow-ups of the respective patients. Additionally nuclear DNA-contents were measured after Feulgen restaining using a TV image analysis system. RESULTS: Sensitivity of our cytological diagnosis on oral smears for the detection of cancer cells was 94.6%, specificity 99.5%, positive predictive value 98.1% and negative predictive value 98.5%. DNA-aneuploidy was assumed if abnormal DNA-stemlines or cells with DNA-content greater 9c were observed. On this basis the prevalence of DNA-aneuploidy in smears of oral squamous cell carcinomas in situ or invasive carcinomas was 96.4%. Sensitivity of DNA-aneuploidy in oral smears for the detection of cancer cells was 96.4%, specificity 100%, positive predictive value 100% and negative 99.0%. The combination of both techniques increased the sensitivity to 98.2%, specificity to 100%, positive predictive value to 100% and negative to 99.5%. CONCLUSIONS: Brush cytology of all visible oral lesions, if they are clinically considered as suspicious for cancer, are an easily practicable, cheap, non-invasive, painless, safe and accurate screening method for detection of oral precancerous lesions, carcinoma in situ or invasive squamous cell carcinoma in all stages. We conclude that DNA-image cytometry is a very sensitive, highly specific and objective adjuvant tool for the early identification of neoplastic epithelial cells in oral smears.