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PubMed2005

Fine-needle aspirates of adenocarcinoma/metastatic carcinoma that resemble hepatocellular carcinoma: correlating cytologic features and performance in the College of American Pathologists Nongynecologic Cytology Program.

CONTEXT: The cytologic features of adenocarcinoma/ metastatic carcinoma in liver fine-needle aspirates are well described. We review the cytologic findings from 16 aspirates of adenocarcinoma/metastatic carcinoma that were frequently misclassified as hepatocellular carcinomas and compare them with 17 cases that were rarely misclassified. OBJECTIVE: To compare the cytologic features of adenocarcinoma/metastatic carcinoma in fine-needle aspiration specimens of the liver that were frequently misclassified as hepatocellular carcinoma with those of aspirates that were rarely misclassified. DESIGN: We reviewed a total of 1712 interpretations from 33 different cases of adenocarcinoma/metastatic carcinoma tumor in liver fine-needle aspiration specimens in the College of American Pathologists Nongynecologic Cytology Program and correlated the cytologic features with performance in the program. RESULTS: Overall, cases that were frequently misclassified as hepatocellular carcinoma were misclassified on average 26% of the time (range, 13%-54%), while infrequently misclassified cases were interpreted as hepatocellular carcinoma on average 0.7% of the time (range, 0%-3%). The difference was statistically significant (P < .001). On review, cases that were frequently misclassified most often had moderate amounts of granular cytoplasm (16/16 cases) and round nuclei with even chromatin (13/16 cases). Trabeculae (3/16 cases), bare nuclei (2/16 cases), and endothelial wrapping (1/16 cases) were also occasionally present. In contrast, cases that were rarely misclassified were more likely to have areas with cells showing scant cytoplasm that were crowded and overlapped or molded (13/17 cases) and contained dark hyperchromatic chromatin (13/17 cases) compared to cases that were frequently misclassified (P < .001 and P = .002, respectively). Trabeculae (2/17) and bare nuclei (2/17 cases) were also rarely present. CONCLUSION: Cases of adenocarcinoma/metastatic carcinoma with moderate amounts of granular cytoplasm and round nuclei with even chromatin are frequently misclassified as hepatocellular carcinoma. Recognition of this problem, attention to cytologic criteria, and frequent use of immunohistochemical studies and core biopsy may help avoid this pitfall.

Adenocarcinoma↗
PubMed1999

Diagnostic p53 immunostaining of endobiliary brush cytology: preoperative cytology compared with the surgical specimen.

BACKGROUND: Endobiliary brush cytology is important in the distinction of malignant and benign causes of extrahepatic bile duct obstruction. The additional diagnostic value of p53 immunostaining on these cytology specimens was assessed. METHODS: All patients with extrahepatic bile duct obstruction who underwent endoscopic retrograde cholangiopancreatography (ERCP) with endobiliary brush cytology and subsequent surgery at the Academic Medical Center in Amsterdam during a 3-year period were studied. p53 Immunocytology was compared with the corresponding conventional light microscopic cytology and p53 immunostaining of the subsequent surgical specimen. RESULTS: Fifty-three patients with the following diagnoses were included: pancreatic carcinoma (23), bile duct carcinoma (15), ampullary carcinoma (5), lymph node metastases (2), carcinoma of unknown origin (4), chronic pancreatitis (3), and primary sclerosing cholangitis (1). Fifty-one percent of the carcinomas showed positive p53 immunostaining; all four surgical specimens without carcinoma were negative. The sensitivities of conventional light microscopic cytology, p53 immunocytology, and both tests combined were 29%, 24%, and 43%, respectively. These sensitivities were higher in cases of bile duct carcinoma (46%, 40%, and 66%) compared with cases of pancreatic carcinoma (13%, 9%, and 22%). Specificities of both tests were 100%. CONCLUSIONS: p53 Immunostaining on endobiliary brush cytology may be helpful in the diagnosis of malignant extrahepatic bile duct stenosis, especially in patients with bile duct carcinoma. Cancer (Cancer Cytopathol)

Bile Duct Neoplasms↗
PubMed2004

Anorectal cytology as a screening tool for anal squamous lesions: cytologic, anoscopic, and histologic correlation.

BACKGROUND: Anorectal cytology has been increasingly used as a screening method for anal squamous lesions, particularly in high-risk, homosexual, patients with human immunodeficiency virus infection. The diagnostic cytologic, anoscopic, and histologic criteria bear some resemblance to the criteria used in cervicovaginal samples with few differences. It is important to recognize these differences because they can lead to an erroneous diagnosis of dysplasia and unnecessary procedures. METHODS: Seventy-eight anorectal cytology specimens from 51 patients were reviewed blindly. Of the 51 patients, 33 were HIV positive. The cytology specimens consisted of 75 ThinPrep (Cytyc, Boxborough, MA) and 3 conventional Papanicolaou-stained smear specimens. The revised diagnosis was compared with the original diagnosis, corresponding histology specimens, and anoscopic results, when available. RESULTS: Six specimens were unsatisfactory for review. The revised diagnosis was negative in 15 patients, atypical squamous cells of undetermined significance in 3 patients, low-grade squamous intraepithelial lesions in 24 patients, high-grade squamous intraepithelial lesions in 28 patients, and squamous cell carcinoma (SQC) in 2 patients. Five patients with an original diagnosis of SQC had the diagnosis revised upon review of their specimens. It is noteworthy that these five specimens showed the presence of atypical parakeratotic cells. Thirty-two patients had anoscopic evaluation and 30 patients had histologic correlation. Twenty-seven patients with abnormal anoscopic findings had confirmed abnormal histologic findings. Twenty- five of the 32 (78%) patients had abnormal cytology that correlated with abnormal anoscopic findings. CONCLUSIONS: Anorectal cytology is an accurate method for screening patients for anal squamous lesions. Atypical parakeratotic cells represent a potential pitfall. Anoscopy is important in confirming the presence of a lesion, but only a biopsy can accurately determine the grade of a lesion.

Adult↗
PubMed2001

Atypical squamous epithelium in cytologic specimens from the pancreas: cytological differential diagnosis and clinical implications.

Atypical squamous epithelium is an uncommon finding in cytologic specimens obtained from pancreatic lesions. A variety of pathologic conditions can result in the presence of these cells, including primary or metastatic carcinomas, chronic pancreatitis, and squamous metaplasia related to pancreatic or biliary duct stent placement. Primary adenosquamous and squamous-cell carcinomas of the pancreas are rare, representing 3.4% and 1.4 % of pancreatic carcinomas, respectively. Cytologic separation of these malignancies from less ominous metaplasias has immense clinical importance. We reviewed Indiana University Hospital's and Duke University's experiences with atypical squamous epithelium occurring within pancreatic aspirates. Study cases were identified using a computer to search the cytology records of these two institutions. Nine cases with a diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or atypical squamous epithelium were retrieved from the two institutions' Department of Pathology files. One case of pure squamous-cell carcinoma occurred in a patient with a known pulmonary primary; a single case of adenosquamous carcinoma was diagnosed in a patient with a coexistent endometrial primary; a single sample of adenocarcinoma with squamous differentiation was diagnosed in a patient without other known disease; and four primary squamous-cell carcinomas of the pancreas were detected. In addition, a single case of atypical squamous metaplasia associated with a stent was identified, and one case of atypical squamous epithelium associated with chronic pancreatitis was diagnosed. Despite the reactive atypia present in the examples of metaplastic squamous epithelium, separation of these cases from true squamous-cell carcinoma and adenosquamous carcinoma was achievable by cytologic evaluation. No cytologic criteria aided in separating primary pancreatic carcinomas with squamous differentiation from metastatic lesions. In this study, we report our findings in a series of nine cases where cytology disclosed atypical squamous epithelium in the aspirates derived from pancreatic lesions.

Carcinoma, Adenosquamous↗
PubMed2002

Human papillomavirus DNA testing by PCR-ELISA and hybrid capture II from a single cytological specimen: concordance and correlation with cytological results.

BACKGROUND AND OBJECTIVES: A persistent infection by high-risk HPV is now considered as the major cause of cervical carcinoma. The use of a single cytological specimen for HPV DNA testing by two different molecular methods was analyzed and validated. STUDY DESIGN: HPV DNA testing by PCR-ELISA and hybrid capture II HPV test (HC-II), was investigated on 317 cytological samples obtained from Italian women. Two hundred twenty-seven women were referred to virological lab for HPV DNA testing during cytological routine screening and 90 during a cytological and virological follow-up after a conization or hysterectomy. RESULTS: Overall, the concordance between the two assays was high (K=0.87). Compared with PCR-ELISA, the HC-II showed a sensitivity of 91.7% and a specificity of 95.4%. Although the analytical sensitivity of the PCR-ELISA was higher, the performance of the two tests did not differ in recognizing HPV DNA positive patients with either low or high-grade squamous intraepithelial lesions (LSIL or HSIL). HPV DNA positivity was directly correlated with the severity of cytological diagnosis (P<0.005). CONCLUSIONS: In view of the comparable results obtained with the two assays and of the ease of use, and higher throughput of HC-II, it seems advisable, with a single cytological specimen, to employ the HC-II test as a first-line assay, either for screening or diagnosis, and to perform reflex PCR on positive samples, if typing of prevalent high risk HPVs is needed.

DNA, Viral↗
PubMed2002

Primary screening for cervical cancer precursors by the combined use of liquid-based cytology, computer-assisted cytology and HPV DNA testing.

Primary screening for cervical cancer precursors has considerably evolved with the introduction of new technology to improve the early detection of disease. The objective of this study was to elaborate a diagnostic pathway integrating liquid-based and computer-assisted cytology and human papillomavirus DNA testing to focus screening on women at risk which may be more cost-effective for the healthcare system. A single laboratory analysis was conducted during a 5-month period using liquid-based cytology followed by human papillomavirus DNA testing for women with an abnormal result or with previous abnormal cytology. Human papillomavirus prevalence was estimated by testing 909 consecutive unselected samples. All slides were then rescreened using automated cytologic testing and triaged into a high- or low-score group according to computer results. Of the 8676 slides scanned, 352 had a test result of atypical squamous cells of undetermined significance or worse. Two hundred and ninety-seven (84.3%) samples with an atypical squamous cells of undetermined significance or worse result and 100% of those with detection of high-grade squamous intraepithelial lesions and carcinomas (HSIL+) were triaged into the high-score group. The combination of instrument scores and human papillomavirus results indicated that 51.0% of high score/human papillomavirus-positive cases should be considered as ASCUS+, while 99.6% of low-score/human papillomavirus negative cases remained negative in the final cytologic diagnosis, representing 49.0% of all cases. Of the screened women 89.5% should test negative for human papillomavirus and be reported as such in the final cytologic diagnosis. In conclusion, preliminary results suggest that this diagnostic pathway has the potential to improve primary cervical cancer screening and cost-effectiveness. By using a combination of testing methods to focus screening and clinical attention to cases at risk, it would be possible to lengthen screening intervals for 90% of women and to archive without further review all low-score/human papillomavirus-negative slides, representing 50% of the screening workload.

Cohort Studies↗
PubMedDate not supplied

Cytologic and histologic review of atypical glandular cells (AGC) detected during cervical cytology screening.

This article is to determine the clinical significance and underlying pathology among patients with atypical glandular cells (AGC) identified during cervical Papanicolau (Pap) smear screening. AGC slides were searched from 51,412 computerized files of the cytology laboratory of Mackay Memorial Hospital during a 29-month period. The results of clinical evaluations were reviewed and an experienced gynecologic cytopathologist who was not involved in the original cytologic diagnosis and was not aware of the clinical results of the follow-up examinations rechecked all AGC slides. We used the z score to determine whether different results were achieved after the gynecologic cytopathologist rechecked the slides. We further analyzed all slides with different cytologic diagnoses and compared results with the histologic diagnoses. Forty-nine cases were initially identified as AGC. Among these, 29 were reviewed and identified as AGC again, and the result of biopsies revealed that they were all chronic cervicitis, ie, negative for malignancy or premalignancy. The other 20 cases were reviewed and diagnosed as non-AGC. Among the results of cytologic examinations, seven had inflammation, two had atypical squamous cells of undetermined significance (ASC-US), ten had high-grade cervical intraepithelial neoplasia (CIN), and one had adenocarcinoma. The results of histologic diagnosis included eight cases with normal tissue, two with CIN grade 1, eight with high-grade CIN, one with microinvasive squamous cell carcinoma, and one with adenocarcinoma. Histologic results revealed 20.4%1 (10/49) and 50% 1(10/20) at initial cytologic diagnosis of AGC and expert-reviewed non-AGC, respectively, which were finally at least high-grade CIN. According to the gynecologic cytopathologist's diagnosis, 59.2%1 (29/49) of cases would have eliminated unnecessary histologically diagnostic procedures. In conclusion, clinicians should be careful about the significance of the cytologic diagnosis of AGC, because there may actually be an underlying pathology, which can be identified by a pathologist who is an expert in gynecologic cytopathology. The interobserver variation in diagnosing AGC favors specialized training in gynecologic cytopathology. In addition, prompt diagnostic interventions, including colposcopy, endocervical curettage, and/or endometrial biopsy, should be performed after confirmation of the diagnosis of non-AGC by an experienced gynecologic cytopathologist.

Adenocarcinoma↗
PubMed2006

Comparison of human papillomavirus DNA tests, liquid-based cytology and conventional cytology for the early detection of cervix uteri cancer.

To compare the performance of human papillomavirus DNA tests (samples collected by a healthcare professional and self-collected) and liquid-based cytology with conventional cytology in the detection of cervix uteri cancer and its precursor lesions. A cross-sectional study was carried out in 1777 women living in poor communities in Rio de Janeiro State, Brazil. Eligibility criteria included ages 25-59 years and not having had a Papanicolau test within at least 3 years prior to the study. Cytology (conventional or liquid-based) and human papillomavirus DNA (collected by a healthcare professional or self-collected) tests were performed using samples collected in a single visit. Women with abnormalities in at least one test and a systematic sample of 70 women with negative test results were referred to a colposcopic examination. Test readings were double-masked, and the outcome of interest was high-grade squamous intraepithelial lesion or worse. The pathology report was used as the gold standard. The prevalence of high-grade squamous intraepithelial lesion or worse was 2.0%. Human papillomavirus DNA test collected by a health professional alone or combined with conventional cytology had the highest sensitivity (91.4 and 97.1%, respectively). The highest specificity was found for conventional cytology (91.6%) and for a human papillomavirus DNA test collected by a healthcare professional (90.2%). On the basis of only test performance, the use of human papillomavirus DNA tests, alone or combined with cytology, would seem to be recommended. Its population-wide implementation, however, is conditional on a cost-effectiveness analysis.

Adult↗
PubMed2007

Analysis of loss of heterozygosity in atypical and negative bile duct brushing cytology specimens with malignant outcome: are "false-negative" cytologic findings a representation of morphologically subtle molecular alterations?

CONTEXT: Conventional cytologic evaluation of bile duct brushings for neoplasia has high specificity but relatively low sensitivity. OBJECTIVE: The aim of this pilot study was to examine whether K-ras mutations and loss of heterozygosity for multiple microsatellite markers in bile duct brushings would contribute to the detection of malignancy in cases initially reported as "negative" or "atypical." DESIGN: Bile duct brushing specimens with a negative or an atypical cytologic result (9 cases) had a benign result on the surgical pathology specimen, and 9 additional negative or atypical cases demonstrated adenocarcinoma on the resected surgical specimen. Cells from representative cytopathology and histology slides were microdissected and analyzed for K-ras mutations and for loss of heterozygosity with a panel of 15 polymorphic markers on chromosomes 1p, 3p, 5q, 9p, 9q, 10q, 17p, and 22q. RESULTS: Among cytology cases with malignant outcome, loss of heterozygosity or K-ras mutation was detected in 8 (88.8%) of 9 cases. In the corresponding 9 surgical pathology specimens with adenocarcinoma, K-ras mutations and/or allelic losses were detected in all (100%). Loss of heterozygosity or K-ras mutation was not detected in cytology cases that had a benign surgical outcome. The fractional allelic loss of these 9 cytology specimens ranged from 0 to 0.25 (mean, 0.14). This compared with the fractional allelic loss ranging from 0.15 to 0.42 (mean, 0.27) for the corresponding surgical specimens. CONCLUSIONS: This pilot study suggests that low-level fractional allelic loss or K-ras mutation in the negative/atypical cytology samples with malignant outcome is a representation of morphologically subtle molecular alterations.

Adenocarcinoma↗
PubMed1990

[Clinical study of urinary cytology in bladder tumors--analysis of factors related with positivity of urinary cytology].

To clarify the clinical and pathological determinants affecting the sensitivity of urinary cytology, we reviewed cytological findings from 119 patients with bladder cancer who were initially treated between January 1982 and March 1988. Cytological specimens obtained from voided urine were stained by the Giemsa and Papanicolaou techniques, and were classified into three categories of malignant cells: positive, suspicious, and negative. Of 311 specimens examined, 114 (37%) were positive, 81 (26%) were suspicious, and the remaining 116 (37%) were negative. The overall positive rate, or sensitivity, was 50% (60 out of 119 patients). The sensitivities were 7% for patients with grade 1 tumors, 42% for grade 2 tumors, and 97% for grade 3 tumors. Univariate analysis by logistic regression analysis revealed that grade, stage, histological pattern of growth, size and number of tumors, and patient age were significantly related with the positivity of voided urinary cytology. The logistic regression model, as a multivariate analysis, demonstrated that grade was the most important determinant affecting the positive cytologic finding, followed by number of tumors with statistical significance. We conclude that the lower sensitivity in conventional urinary cytology for low-grade tumors necessitates new adjuncts, including immunocytochemistry and flow cytometry, to lower the false-negative rate.

Adult↗
PubMedDate not supplied

Conventional respiratory cytology versus fine needle aspiration cytology in the diagnosis of lung cancer.

The results of 184 fine needle aspiration (FNA) cytologic examinations were compared with the findings of "conventional" respiratory cytology (on sputums, bronchial brushings and bronchial washings) and histology (on biopsy and autopsy samples) and with the medical records. Positive cytologic results were obtained in 6 (10%) of 60 sputums, 17 (21%) of 80 brushings, 16 (19%) of 84 washings and 82 (44%) of 184 aspirates. These positive results were confirmed by biopsy for 6 of 6 sputums, 16 of 17 brushings and 15 of 16 washings. Among the 82 patients with a positive FNA cytology, malignancy was confirmed by lung biopsy in 39 and by autopsy in 2; the cytologic diagnosis was supported by clinical and radiographic findings in all but 1 of the remaining 41 patients. Using transbronchial lung biopsy, autopsy and medical records as final standards, the positive predictive values were 100% for sputum, 94.1% for brushings, 93.0% for washings and 98.6% for FNA samples. The high positive predictive values of FNA and the other cytologic procedures indicate that these diagnostic modalities provide simple, rapid and reliable methods for the diagnosis of lung cancer.

Autopsy↗
PubMedDate not supplied

From "exfoliative" to "diagnostic" cytology. A statistical evaluation of pulmonary cytology.

During the year 1975, a total of 2,877 cytologic examinations in our laboratory included 2,277 examinations on 580 patients related to pulmonary cytology. Statistical evaluation of these studies indicates that the present trend of pulmonary cytology examination is moving from "exfoliative" cytology to "diagnostic" cytology. As long as one maintains the specificity of the examination high enough by the application of stringent criteria for cytodiagnosis, further radio and/or chemotherapy can be justifiably instituted on the basis of cytologic examination along with clinical evaluation of the patients when histopathologic diagnosis is not obtainable.

Bronchi↗
PubMed1979

[Bronchial cytology--value of various methods for the diagnosis of primary lung neoplasms. A computation of the materials sent in to the cytological laboratory of the Institute of Pathology, Kantonspital, St. Gallen].

During the period 1973-1977 some 6100 sputum cytologies from 3000 patients were performed. All patients had suspected primary bronchogenic carcinoma. Sputum cytology was diagnostic in 547 patients (18%). A synopsis of all patients with proven lung cancer and at least one primary sputum cytology shows that this method was diagnostic in 80%. Fiberoptic bronchoscopy with its associated procedures (biopsies, brushings, washings) was the most frequently performed endoscopic method at our Department of Medicine. Fiberbronchoscopy used in combination with cytologic brushings was diagnostic in 83% of the proven cancers. Formerly, bronchial washings and bronchial secretions were obtained by means of rigid bronchoscope. This material yielded the lowest percentage (51%) of all cytological methods used at the Cantonal Hospital. The indications for use of the different diagnostic methods mentioned above and important factors which yield a high percentage of positive cytologies are discussed.

Bronchoscopy↗
PubMedDate not supplied

Ultrasound-guided percutaneous fine needle aspiration biopsy of abdominal and retroperitoneal masses. Accuracy of cytology in the diagnosis of malignancy, cytologic tumor typing and use of antibodies to intermediate filaments in selected cases.

The reliability of ultrasound-guided fine needle aspiration biopsy (FNAB) in the detection of intraperitoneal and retroperitoneal malignancies was evaluated in 308 consecutive cases seen between 1979 and 1983. The prevalence of malignant neoplasms was 68.5%. The overall accuracy of FNAB diagnosis was 88.9%, with a sensitivity of 84.4% and a specificity of 98%. The predictive value of positive and negative results were 98.9% and 74.6%, respectively. Additionally, the cytologic results were statistically evaluated with respect to the different sites of the biopsied lesions (including pancreas, liver, kidneys and miscellaneous sites). The overall accuracy was highest for malignant lesions in the liver (96.4%) and in miscellaneous sites (89.5%). Reasons for false-negative results included incorrect areas sampled, limited material due to fibrosis or necrosis and cytologic misinterpretations. The accuracy of cytologic tumor typing with respect to histogenetic origin was 96.8%. Cytologic subclassification was performed with lower accuracy (82.5%), and exact determination of the site of the primary tumor from cytologic criteria alone was possible for 35.7% of carcinomas. In selected cases, routine cytologic examination was supplemented by intermediate filament typing using well-characterized antibodies against cytokeratin, vimentin, desmin and neurofilaments. Examples are shown in which use of this method clearly increased the accuracy of the diagnosis. Only two serious complications (bleeding) of fine-needle aspiration biopsy were encountered in this series.

Antibodies↗