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ABSTRACT: The detection of aneuploidy by fluorescence in situ hybridization (FISH) has revolutionized how laboratories diagnose cholangiocarcinoma and pancreatic adenocarcinoma using cytology specimens. Numerous clinical studies have demonstrated that FISH increases the diagnostic sensitivity of routine cytology for detecting pancreatobiliary tract malignancy with minimal decreases in clinical specificity. FISH also provides useful information in difficult clinical scenarios, including the assessment of patients with biliary strictures who have equivocal cytology results and the assessment of patients with primary sclerosing cholangitis who have clinical features suggestive of malignancy. The improved ability to detect pancreatobiliary tract cancers offers the possibility of earlier detection when patients are amenable to surgical intervention and can decrease health care costs by reducing the amount of clinical evaluation required to arrive at a cancer diagnosis. Cytopathology personnel should maintain familiarity with molecular cytology testing methodologies, because morphologic and aneuploidy assessment of tumors will continue to be an integral part of large-scale genome analyses of individual tumors. Cancer (Cancer Cytopathol) 2013;. © 2013 American Cancer Society.
Cancer Cytopathology 04/2013; · 3.33 Impact Factor
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ABSTRACT: Context.-Controversy exists about whether thyroid fine-needle aspirates (FNAs) should be processed with conventional smears or liquid-based preparations (LBPs). Objective.-To compare the performance of conventional smears to LBPs for thyroid FNA slides circulated in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology. Design.-Participant responses for thyroid FNA slides were compared with the reference diagnosis at the level of 3 general diagnostic categories: negative, suspicious (which included only follicular and Hürthle cell neoplasm), and malignant. For specific reference diagnoses of benign/goiter and papillary thyroid carcinoma, the participants' specific diagnoses were analyzed and poorly performing slides were rereviewed. Results.-The 47 076 thyroid FNA slide responses, between 2001 and 2009, included 44 478 responses (94%) for conventional smears and 2598 responses (6%) for LBPs. For the general reference category negative, participant responses were discrepant in 14.9% of conventional smears compared with 5.9% for LBPs (P < .001). The specific reference diagnosis of benign/goiter was misdiagnosed as a follicular neoplasm in 7.8% of conventional smears, compared with 1.3% of LBP. For the general reference category of malignant, participant responses were discrepant in 7.3% of conventional smears compared with 14.7% of LBPs (P < .001). The specific reference diagnosis of papillary thyroid carcinoma was misdiagnosed as benign/goiter in 7.2% of LBPs, compared with 4.8% of conventional smears (p <.001). Conclusions.-LBPs performed worse than conventional smears for cases with a reference diagnosis of papillary thyroid carcinoma. However, LBPs performed better than conventional smears for cases with a benign reference diagnosis. Specific features in thyroid FNAs that may improve the diagnostic accuracy of LBPs and conventional smears are described.
Archives of pathology & laboratory medicine 01/2013; 137(1):26-31. · 2.58 Impact Factor
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ABSTRACT: Endometrial cancer is associated with numeric and structural chromosomal abnormalities, microsatellite instability (MSI), and alterations that activate oncogenes and inactivate tumor suppressor genes. The aim of this study was to characterize a set of endometrial cancers using multiple molecular genetic and immunohistochemical techniques. Ninety-six cases were examined for genomic alterations by MSI, MLH1 promoter hypermethylation, p53 and mismatch repair protein expression (MLH1, MSH2, MSH6, PMS2), and PTEN, PIK3CA, KRAS, and BRAF mutation analysis. At least 1 alteration was identified in 48 of 87 (55%) specimens tested for PTEN, making it the most common abnormality in this study. A PIK3CA alteration was observed in 16 (17%) specimens. Twenty-nine of 94 (31%) MSI tested tumors exhibited an MSI-H phenotype. Of the 29 MSI-H cases, 24 (83%) were positive for methylation of the MLH1 promoter region. Twenty-three (82%) of the 28 MSI-H cases with immunohistochemistry results showed loss of expression of MLH1/PMS2 (n=19), MSH2/MSH6 (n=2), or MSH6 only (n=2). Of the 19 MSI-H cases with loss of MLH1/PMS2 on immunohistochemistry, 18 were positive, and 1 was equivocal for MLH1 promoter hypermethylation. Twelve of 94 cases (13%) analyzed for KRAS mutations were found to have a mutation. No BRAF V600E mutations were indentified. This study provides a comprehensive molecular genetic analysis of commonly analyzed targets in a large cohort of endometrial cancers.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 04/2012; 31(3):195-205. · 2.07 Impact Factor
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Michael J Levy,
Trynda N Oberg,
Michael B Campion, Amy C Clayton,
Kevin C Halling,
Michael R Henry,
Benjamin R Kipp,
Thomas J Sebo,
Jun Zhang,
Felicity T Enders,
Jonathan E Clain,
Ferga C Gleeson,
Elizabeth Rajan,
Lewis R Roberts,
Mark D Topazian,
Kenneth K Wang,
Gregory J Gores
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ABSTRACT: Digital image analysis (DIA) and fluorescence in situ hybridization (FISH) can be used to evaluate biliary strictures with greater accuracy than conventional cytology (CC). We performed a prospective evaluation of the accuracy of CC, compared with that of DIA and FISH, in detection of malignancy in patients undergoing endoscopic ultrasonography (EUS) fine-needle aspiration (FNA).
We collected a minimum of 6 FNA samples from each of 250 patients during EUS. CC or DIA and FISH analyses were performed on every other specimen (from every other FNA pass); patients were randomly assigned to the first test performed. CC slides were reviewed by gastrointestinal cytopathologists who were blinded to all data. Findings from cytohistologic analysis, after a minimum 24-month follow-up period, were used as the standard (n = 202; median age, 65 years).
Aspirates were collected from lymph nodes (n = 111), pancreas (n = 61), gastrointestinal lumen wall (n = 9), periluminal mass (n = 4), liver (n = 8), and miscellaneous sites (n = 9). Matched samples provided a mean of 3.2 passes for CC and 1.6 passes for DIA and FISH. The data indicate a potential lack of utility for DIA. The combination of CC and FISH detected malignancy with 11% greater sensitivity than CC alone (P = .0002), but specificity was reduced from 100% to 96%.
FISH analysis identifies neoplastic lesions with significantly greater sensitivity than CC in patients with diverse pathologies who underwent EUS with FNA, despite limited tissue sampling for FISH analysis.
Gastroenterology 02/2012; 142(5):1112-1121.e2. · 11.68 Impact Factor
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ABSTRACT: The role of cytotechnologists has focused primarily on the microscopic examination of cytologic specimens for diagnosing disease. Cytotechnologists currently evaluate a wide assortment of both gynecological and nongynecological cytology specimens. However, the Pap test remains the primary test for most cytology laboratories. Recently, human papillomavirus testing and newer cervical cancer screening guidelines have reduced the number of Pap tests, resulting in some anxiety and concern among the cytology community. However, as Pap test volumes continue to decrease, molecular oncology and ancillary testing volumes continue to increase with the advent of new biomarkers and associated personalized therapies. This change in clinical practice has resulted in evolving roles for many cytotechnologists. Cytotechnologists have skills based not only in morphology but also in understanding concepts of disease including neoplasia. These skills allow cytotechnologists to excel in many other types of laboratory testing. This article discusses how the roles of the cytotechnologist have recently expanded at our institution to include involvement in DNA ploidy analysis, quantitative immunohistochemistry, fluorescence in situ hybridization, circulating tumor cells, and molecular oncology testing. Lastly, this article discusses how these newer roles benefit both the cytotechnologist and the clinical laboratory.
Acta cytologica 01/2012; 56(6):678-85. · 0.49 Impact Factor
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ABSTRACT: Mucinous breast carcinoma has characteristic cytologic features, but few studies exist that analyze the reproducibility of this diagnosis.
To analyze participants' diagnosis of mucinous carcinoma in breast fine-needle aspiration (FNA) slides distributed in an educational interlaboratory peer comparison program.
Participant responses for FNA slides with a reference diagnosis of mucinous carcinoma, distributed between 2001-2008 in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology, were evaluated for concordance with the general category and reference diagnosis of mucinous carcinoma.
Of 8061 responses, 6353 (78.8%) were categorized as malignant; 775 (9.6%) as suspicious; and 933 (11.6%) as negative. The most frequent incorrect responses for the benign category included fibroadenoma (51.7%), nonspecified benign lesion (12%), fibrocystic changes (7.8%), and fat necrosis/granulomatosis/foreign body reaction (6.9%). Conventional Papanicolaou-stained preparations were reviewed for 58.7% (4732) of responses; of these, 39.4% (3177) were from modified Giemsa-stained smears and 1.9% (152) from ThinPrep slides. Papanicolaou-stained conventional smears had the lowest concordance (86.5%) when compared to modified Giemsa-stained smears (91.2%) and ThinPrep challenges (92.1%) (P < .001). Participants specifically diagnosed mucinous carcinoma 37.3% of the time, and modified Giemsa-stained challenges performed best (43.1%, P < .001). There was no significant difference between cytotechnologists' and pathologists' responses (87.9% versus 88.2%; P = .69).
Mucinous carcinoma in FNA was not accurately identified in a glass slide interlaboratory comparison program. We observed better performance with modified Giemsa-stained and ThinPrep slides than with Papanicolaou-stained preparations. The most common response for the benign category of mucinous carcinoma was fibroadenoma. Increased awareness of the cytologic features of mucinous carcinoma may improve accuracy in breast FNA.
Archives of pathology & laboratory medicine 12/2011; 135(12):1533-8. · 2.58 Impact Factor
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ABSTRACT: Cytologic evaluation of pancreatobiliary brushings is specific but poorly sensitive for malignancy. Detection of polysomic cells by fluorescence in situ hybridization (FISH) is significantly more sensitive than routine cytology with similar specificity. The purpose of this study was to identify cytologic criteria most associated with malignancy in specimens unaffected by sample failure. Endoscopic brushings were split equally for routine cytologic and FISH analyses per clinical practice. We retrospectively evaluated 16 cytologic criteria on Papanicolaou-stained slides. We assumed that the presence of polysomic cells by FISH indicated successful tumor sampling in specimens from patients with pathologic evidence of malignancy on follow-up. We compared cytologic criteria of malignant brushings with corresponding positive FISH results (positive control, n = 39) with those without evidence of malignancy and corresponding negative FISH results (negative control, n = 30). The presence of single abnormal cells, irregular nuclear membranes, and enlarged nuclei were independent predictors of malignancy by logistic regression (P < .05).
American Journal of Clinical Pathology 09/2011; 136(3):442-9. · 2.60 Impact Factor
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ABSTRACT: A polysomy fluorescence in situ hybridization (FISH) result in a pancreatobiliary brushing from a patient with primary sclerosing cholangitis (PSC) is very worrisome for carcinoma. However, treatment is not recommended unless verified by corroborative evidence of malignancy because of less than perfect test specificity in this population. The aim of this study was to evaluate the clinical outcome of PSC patients with serial polysomy FISH results.
Patients with PSC underwent endoscopic retrograde cholangiopancreatography with brushings when clinically indicated per standard practice. Brushings were evaluated by routine cytology and FISH. Retrospective review identified patients with a polysomy FISH result without definitive imaging or pathological evidence of malignancy at the time of the first polysomy, who underwent follow-up examinations including subsequent FISH testing (n=30). Patient records were reviewed to determine clinical outcome.
In all, 9 of 13 patients (69%) with a subsequent polysomy result (i.e., serial polysomy) were diagnosed with cholangiocarcinoma (CCA) compared with 3 of 17 patients (18%) with subsequent non-polysomy results (P=0.008). There was a significant difference in time to a diagnosis of CCA between PSC patients with serial polysomy compared with those with subsequent non-polysomy (P=0.01). In four patients with serial polysomy results, imaging/pathological evidence of CCA was not found until 1-2.7 years after the initial polysomy FISH result.
FISH may detect polysomic cells in pancreatobiliary brushings before other pathological or imaging techniques identify CCA. Patients with serial polysomy FISH results are at higher risk for having CCA than those with subsequent non-polysomy FISH results.
The American Journal of Gastroenterology 08/2011; 106(11):2023-8. · 7.28 Impact Factor
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Shannon M Brankley,
Emily G Barr Fritcher,
Thomas C Smyrk,
Matthew E Keeney,
Michael B Campion,
Jesse S Voss, Amy C Clayton,
Kenneth K Wang,
Lori S Lutzke,
Benjamin R Kipp,
Kevin C Halling
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ABSTRACT: The progression of intestinal metaplasia to esophageal adenocarcinoma in patients with Barrett's esophagus is partly driven by chromosomal alterations that activate oncogenes and inactivate tumor suppressor genes. The goal of this study was to determine how alterations of 4 frequently affected genes correlate with the range of histopathologic lesions observed in resected esophagi of patients with Barrett's esophagus. Fluorescence in situ hybridization was used to assess 83 tissue sections from 10 Barrett's esophagus esophagogastrectomy specimens for chromosomal alterations of 8q24 (MYC), 9p21 (CDKN2A; alias P16), 17q12 (ERBB2), and 20q13.2 (ZNF217). Histologic lesions assessed included gastric metaplasia (n = 8), intestinal metaplasia (n = 43), low-grade dysplasia (n = 28), high-grade dysplasia (n = 25), and adenocarcinoma (n = 16). Histologic maps showing the correlation between fluorescence in situ hybridization abnormalities and corresponding histology were created for all patients. Chromosomal abnormalities included 9p21 loss, single locus gain, and polysomy. A greater number of chromosomal alterations were detected as the severity of histologic diagnosis increased from intestinal metaplasia to adenocarcinoma. All patients had alterations involving the CDKN2A gene. CDKN2A loss was the only abnormality detected in 20 (47%) of 43 areas of intestinal metaplasia. Polysomy, the most common abnormality in dysplastic epithelium and adenocarcinoma, was observed in 16 (57%) of 28 low-grade dysplasia, 22 (88%) of 25 high-grade dysplasia, and 16 (100%) of 16 adenocarcinoma. The findings of this study improve our understanding of the role that chromosomal instability and alterations of tumor suppressor genes such as CDKN2A and oncogenes such as ERBB2 play in the progression of intestinal metaplasia to adenocarcinoma in patients with Barrett's esophagus.
Human pathology 08/2011; 43(2):172-9. · 3.03 Impact Factor
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ABSTRACT: Human papillomavirus (HPV) infection is a major risk factor for cervical cancer. Imiquimod is a topical medication that enhances the immune response to HPV-induced genital warts. This study evaluated cervical application of imiquimod as an adjunct to standard treatment for cervical dysplasia.
Fifty-six patients were randomized to standard excisional/ablative treatment vs applications of imiquimod followed by standard treatment. The primary endpoint was dysplasia recurrence within 2 years.
There were no differences in dysplasia recurrence between the 2 groups. Treatment was well tolerated, with side effects being mild but significantly worse in women receiving imiquimod for, chills, fatigue, fever, headache, myalgias, and vaginal discharge.
This trial does not support the hypothesis that imiquimod, as used in this trial, has an impact on recurrence of cervical dysplasia, but the adequacy of findings are limited by sample size. The trial does support the feasibility and acceptability of the use of imiquimod on the cervix.
American journal of obstetrics and gynecology 07/2011; 206(1):42.e1-7. · 3.28 Impact Factor
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ABSTRACT: Cytologic features of low-grade neuroendocrine carcinoma are well described in primary sites. There are fewer reports of the cytologic features specific to metastatic liver lesions or the frequency of misdiagnosis.
To identify discriminating cytologic features and characterize the rate of misdiagnosis of low-grade neuroendocrine tumors metastatic to the liver in an educational interlaboratory slide comparison program.
Glass slides with the specific reference diagnosis of metastatic low-grade neuroendocrine tumor involving liver were circulated to 175 laboratories, with 575 participant responses in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology. Eight specific cytologic features were assessed to identify predictors of poor performance (>10% misdiagnosis).
There was an exact match diagnosis in 496 of 575 responses (86%); 555 of 575 responses (96.5%) were correctly identified as malignant. Incorrect responses included adenocarcinoma (27), hepatocellular neoplasm (21), small cell carcinoma (11), benign neoplasm not otherwise specified (6), benign liver (3) and inflammation (3). Three features were significantly associated with the misdiagnosis of adenocarcinoma: presence of large clusters (P = .02), lack of single-cell pattern (P = .02), and lack of stripped nuclei (P = .01).
Participants often recognize metastatic low-grade neuroendocrine carcinoma in an educational glass-slide program. Adenocarcinoma was the most common incorrect diagnosis, especially in the presence of large cellular clusters or absence of a single-cell pattern or stripped nuclei.
Archives of pathology & laboratory medicine 03/2011; 135(3):354-60. · 2.58 Impact Factor
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ABSTRACT: To examine the performance of our large pulmonary transthoracic fine needle aspiration/core biopsy (FNA/CB) practice over time, we performed a retrospective analysis of data from 333 consecutive procedures performed in 1996-1998 and 568 consecutive procedures performed in 2003-2005. Fluoroscopic guidance was performed more frequently in the earlier cohort, while a larger majority of procedures in the later cohort were by computed tomography (CT-guidance). A follow-up histologic diagnosis of cancer or clinical evidence of disease was considered the gold-standard. FNA/CB procedures during the later time period were performed on smaller lesions overall (3.60 cm versus 2.97 cm; P = 0.003) and malignant lesions also tended to be smaller (3.87 cm versus 3.14 cm; P = 0.006). Minimal improvements in sensitivity (94% versus 91%), specificity (99% versus 95%), diagnostic accuracy (95% versus 92%), negative predictive value (NPV) (80% versus 74%), and positive predictive value (PPV) (100% versus 99%) were noted during 2003-2005 when compared with 1996-1998 in all lesions. Larger improvements in sensitivity (94% versus 73%), diagnostic accuracy (95% versus 79%), and NPV (79% versus 50%) were identified in very small lesions (<1 cm) in the later patient cohort in comparison to the earlier patient cohort, as well as a significant decrease in total procedure complications. CT-guided transthoracic FNA/CB continues to be a very effective tool in our practice assessing lung lesions and performance has improved considerably at our institution for very small lesions. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
Diagnostic Cytopathology 03/2011; 40(10):876-81. · 1.16 Impact Factor
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ABSTRACT: Minichromosome maintenance protein 7 (MCM7) is involved in replicative licensing and synthesis of DNA. It was previously identified as an overexpressed gene in high-grade serous carcinomas compared with serous borderline tumors of the ovary in cDNA microarray studies. In this study, we sought to validate MCM7 expression in 342 ovarian tumors on tissue microarrays. MCM7 expression was quantified as the MCM7 labeling index, and it was independently generated by two methods: a score provided by manual review of each sample by a pathologist observer and by an automated cellular imaging system. Analyses of MCM7 scores indicated a high degree of concordance and distribution between the observer- and machine-generated MCM7 labeling indexes. MCM7 expression was significantly higher in high-grade serous carcinomas than in serous borderline tumors or other histological subtypes of ovarian cancer. For both observer- and machine-derived scores, univariate analyses indicated the significant association of a high MCM7 labeling index with better progression-free survival in high-grade serous carcinomas. These results suggest the clinical importance of MCM7 expression in high-grade serous carcinomas of the ovary and the need for further evaluation of MCM7 as a potential prognostic factor in ovarian cancer.
Modern Pathology 11/2010; 24(2):277-87. · 4.79 Impact Factor
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ABSTRACT: Pancreatobiliary tract strictures result either from malignancies of the biliary tract and pancreas or from nonmalignant etiopathogenesis. The goal of this study was to determine whether KRAS mutations could be identified in residual pancreatobiliary stricture brushings and to compare the performance characteristics of KRAS mutation analysis to cytology and fluorescence in situ hybridization (FISH) for the detection of carcinoma. Residual brushing cytology cell pellets were retrieved from 132 patients with subsequent clinicopathologic follow-up of cholangiocarcinoma (n = 41), pancreatic adenocarcinoma (n = 35), gallbladder cancer (n = 2), and nonmalignant strictures (n = 54). All specimens had a prior cytology and FISH UroVysion results as part of clinical practice. KRAS mutation analysis was performed using the quantitative PCR DxS KRAS Mutation Test Kit. KRAS mutation analysis was successful in 130 of 132 specimens. KRAS mutations and polysomic (ie, positive) FISH results were identified in 24 (69%) and 22 (63%) pancreatic adenocarcinoma specimens, respectively, with a combined sensitivity of 86% (30/35). KRAS mutations and polysomic FISH results were identified in 12 (29%) and 17 (41%) cholangiocarcinoma specimens, with a combined sensitivity of 54% (22/41). KRAS mutations were identified in two patients with primary sclerosing cholangitis, and benign follow-up. Residual cytology specimens can be used to detect KRAS mutations by quantitative PCR. Combined KRAS mutation and FISH analysis appear to increase the cancer detection rate in patients with pancreatobiliary strictures.
The Journal of molecular diagnostics: JMD 11/2010; 12(6):780-6. · 3.48 Impact Factor
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ABSTRACT: Differences in participant responses for ThinPrep (TP) and non-ThinPrep (NTP) preparations for gastrointestinal cytology challenges, which circulated in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology (CAP NGC), may help to identify performance variations between preparation types.
To compare the performance of TP-prepared slides of gastrointestinal exfoliative cytology specimens to that of NTP preparations in the CAP NGC program.
Participant responses between 2000 and 2007 were evaluated for esophageal wash/brush, gastric wash/brush, and biliary tract brush specimens with a reference diagnosis of adenocarcinoma, squamous cell carcinoma, carcinoid, or spindle cell neoplasm. ThinPrep challenges were compared with NTP preparations (conventional smears, cytospins) for discordant responses.
In all, 6023 pathologist responses and 3825 cytotechnologist responses were reviewed. Non-ThinPrep preparations comprised 93% (n = 11 588) of the challenges, while 7% (n = 912) were TP material. A match for a "positive/suspicious" diagnosis was seen in 88.5% of NTP and 95.9% of TP preparations (P < .001). These results were statistically significant when the specific reference diagnosis was adenocarcinoma (P < .001). Overall performance of cytotechnologists was not different from that of pathologists (89.2% versus 89.0%; P = .75). Cytotechnologists had better performance for detecting squamous cell carcinoma (96.3% versus 92.6%; P < .001), while pathologists had better performance for detecting spindle cell neoplasm (79.7% versus 42.9%; P < .001).
ThinPrep preparations performed significantly better than NTP preparations in gastrointestinal cytology specimens circulated in an interlaboratory comparison program. Performance varied by reference interpretation, with the best performance for the interpretation of adenocarcinoma. Cytotechnologists and pathologists performed at the same level overall, but with differences for the diagnosis of spindle cell neoplasm and squamous carcinoma.
Archives of pathology & laboratory medicine 08/2010; 134(8):1116-20. · 2.58 Impact Factor
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ABSTRACT: To assess Hybrid Capture 2 (HC2) and fluorescence in situ hybridization (FISH) for the detection of cervical intraepithelial neoplasia 2 or worse (CIN 2+) in patients with a cytologic diagnosis of low grade squamous intraepithelial lesion (LSIL).
Residual samples from 115 LSIL-diagnosed cervical cytology specimens were evaluated by high-risk human papillomavirus (HR-HPV) HC2 testing and FISH using biotin-labeled probes to HR-HPV and chromosomal probes to 3q26 (TERC) and 8q24 (CMYC). A cervical biopsy diagnosis of CIN 2+ was considered as evidence of high grade disease.
The positive and negative predictive values of HC2 and FISH for detecting patients with CIN 2+ were 32% vs. 37% and 100% vs. 93%, respectively. The sensitivities of HC2 and FISH for CIN 2+ were not significantly different (100% vs. 90%, p = 0.25), while the specificity of HC2 was significantly lower than that of FISH (28% vs. 48%, p=0.003). FISH diagnosed fewer specimens as positive as compared to HC2 (62% vs. 79%).
These preliminary data suggest that FISH testing may be useful for determining which patients with LSIL are most likely to have CIN 2+ on clinical follow-up.
Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology 06/2010; 32(3):121-30. · 0.41 Impact Factor
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Ferga C Gleeson,
Benjamin R Kipp,
Jill L Caudill,
Jonathan E Clain, Amy C Clayton,
Kevin C Halling,
Michael R Henry,
Elizabeth Rajan,
Mark D Topazian,
Kenneth K Wang,
Maurits J Wiersema,
Jun Zhang,
Michael J Levy
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ABSTRACT: It is broadly accepted that the false positive (FP) rate for endoscopic ultrasound fine needle aspiration (EUS FNA) is 0-1%. It was hypothesised that the FP and false suspicious (FS) rates for EUS FNA are greater than reported. A study was undertaken to establish the rate and root cause of discordant interpretation.
Using a prospectively maintained endoscopic database, cytohistological discordant EUS FNA examinations from 30 July 1996 to 31 December 2008 were identified retrospectively.
Tertiary referral centre.
Discordant FNA was defined by positive or suspicious FNA cytology in the absence of malignancy or neoplasm in the subsequent surgical pathology specimen, specifically in the absence of neoadjuvant therapy. Three cytopathologists conducted a blinded review of randomised discordant and matched specimens.
FNA was performed in 5667/18 066 (31.4%) patients undergoing EUS, of whom 2547 had cytology results interpreted as 'positive' or 'suspicious' or 'atypical' for malignancy or neoplasm. Subsequent surgical resection without prior neoadjuvant therapy was performed in 377 patients with positive or suspicious cytology. The FP rate was 20/377 (5.3%) and increased to 27/377 (7.2%) when FS cases were included. The incidence of discordance was consistent over time (1996-2002: 10/118 (8.6%) vs 2003-2008: 17/259 (6.6%); p=0.5) and was higher in non-pancreatic FNA (15%) than pancreatic FNA (2.2%; p=0.0001). Two-thirds of the non-pancreatic FP cases involved sampling of perioesophageal or perirectal nodes in patients with luminal neoplasms or Barrett's oesophagus. Following pathological re-review, discordance was attributed to translocated cell contamination/sampling error (50%) or cytopathologist interpretive error (50%).
These findings refute the accepted paradigm that FP cytology rarely occurs with EUS FNA. Further investigation revealed that FP FNA developed secondary to endosonographer technique or initial cytological misinterpretation, and is particularly likely when perioesophageal or perirectal nodes are aspirated in the setting of a luminal neoplasm or Barrett's oesophagus. Further study is needed to determine the significance of these findings and potential impact on the performance of FNA and patient outcomes.
Gut 05/2010; 59(5):586-93. · 10.11 Impact Factor
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ABSTRACT: Liquid-based preparations (LBPs) and human papillomavirus testing have led to changes in cervical cytology practices. The College of American Pathologists attempts to track practice patterns using a supplemental questionnaire, which allows laboratories to report diagnostic practices.
To analyze the 2006 reporting practices and to compare the results with the 2003 survey data.
Questionnaire was mailed to 1621 laboratories. Participants included laboratories enrolled in the 2006 College of American Pathologists Gynecologic Proficiency Testing Program or the educational Interlaboratory Comparison Program in Gynecologic Cytology.
Of the 679 responding laboratories (response rate, 42%), most (97.8%; n = 664) had implemented the Bethesda 2001 terminology. The median rate for all preparations with low-grade squamous intraepithelial lesions was 2.5% (2.9% for LBPs) compared with a 2003 median rate of 2.1%; the increase was confined to LBPs. Rates for high-grade squamous intraepithelial lesions (median, 0.5%) and atypical squamous cells have changed little. High-grade squamous intraepithelial lesions and unsatisfactory rates varied at statistically significant levels between types of LBPs. Most atypical squamous cell cases were subclassified as undetermined significance (median, 4.3%). The median ratio of atypical squamous cells to squamous intraepithelial lesions and carcinomas for all specimen types combined was 1.5, similar to the 2003 median ratio of 1.4. The median rates for findings of squamous cell abnormalities for 2006 were significantly higher for LBPs than for conventional smears.
Most responding laboratories have implemented the Bethesda 2001 terminology. There is an increase in LBP low-grade squamous intraepithelial lesion rates when compared with 2003 data. Liquid-based preparations have higher median squamous intraepithelial lesion and atypical squamous cell rates.
Archives of pathology & laboratory medicine 03/2010; 134(3):331-5. · 2.58 Impact Factor
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Benjamin R Kipp,
Rhett P Ketterling,
Trynda N Oberg,
Margot A Cousin,
Amy M Plagge,
Anne E Wiktor,
Johnita M Ihrke,
Cecelia H Meyers,
William G Morice,
Kevin C Halling, Amy C Clayton
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ABSTRACT: Pathologic examination of products of conception (POC) is used to differentiate hydropic abortus (HA), partial hydatidiform mole (PM), and complete hydatidiform mole (CM). Histologic classification of POC specimens can be difficult, and ancillary testing is often required for a definitive diagnosis. This study evaluated 66 POC specimens by flow cytometry, digital image analysis, p57 immunohistochemical analysis, and fluorescence in situ hybridization (FISH). The final diagnosis, based on the combined analysis of all test results, included 33 HAs, 24 PMs, and 9 CMs. The p57 immunostain identified 9 CMs that were evaluated as nontriploid by all other techniques. FISH seems to have the best accuracy (100%) for determining whether a specimen contains a triploid chromosome complement. These data suggest that the combination of p57 and FISH seems to be the best ancillary testing strategy to aid pathologists in the appropriate identification of CM, PM, and HA in POC specimens.
American Journal of Clinical Pathology 02/2010; 133(2):196-204. · 2.60 Impact Factor
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Rodolfo Laucirica,
Joel S Bentz,
Rhona J Souers,
Patricia G Wasserman,
Barbara A Crothers, Amy C Clayton,
Michael R Henry,
Beth Anne Chmara,
Karen M Clary,
Mostafa M Fraig,
Ann T Moriarty
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ABSTRACT: The cytomorphology of liquid-based preparations in urine cytology is different than classic slide preparations.
To compare the performance of liquid-based preparation specimens to classically prepared urine specimens with a malignant diagnosis in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.
Participant responses between 2000 and 2007 for urine specimens with a reference diagnosis of high-grade urothelial carcinoma/carcinoma in situ/dysplasia (HGUCA), squamous cell carcinoma, or adenocarcinoma were evaluated. ThinPrep and SurePath challenges were compared with classic preparations (smears, cytospins) for discordant responses.
There were 18 288 pathologist, 11 957 cytotechnologist, and 8086 "laboratory" responses available. Classic preparations comprised 90% (n = 34 551) of urine challenges; 9% (n = 3295) were ThinPrep and 1% (n = 485) were SurePath. Concordance to the general category of "positive-malignant" was seen in 92% of classic preparations, 96.5% of ThinPrep, and 94.6% of SurePath challenges (P < .001). These results were statistically different for the exact reference interpretation of HGUCA (P < .001) but not for adenocarcinoma (P = .22). Cytotechnologists demonstrate statistically better performance for the general category of "positive-malignant" compared with pathologists for all urinary slide types and for the exact reference interpretation of HGUCA (94% versus 91.1%; P < .001) but not adenocarcinoma (96.3% versus 95.8%; P = .77) or squamous cell carcinoma (93.6% versus 87.7%; P = .07).
Liquid-based preparations performed significantly better in urinary cytology challenges when evaluating malignant categories in the College of American Pathologists interlaboratory comparison program. The liquid-based preparation challenges also performed better for the exact reference interpretation of HGUCA, but no difference was observed for adenocarcinoma challenges. Cytotechnologists perform better than pathologists for all slide types, as well as those demonstrating HGUCA. These results suggest that liquid-based preparations facilitate a more accurate diagnosis than conventional preparations.
Archives of pathology & laboratory medicine 01/2010; 134(1):19-22. · 2.58 Impact Factor
