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Joel S Bentz

Publications and source records attributed to Joel S Bentz.

14 recordsLinked to original sources

Utility of BRAF V600E mutation detection in cytologically indeterminate thyroid nodules.

BACKGROUND: Fine needle aspiration (FNA) is widely utilized for evaluation of patients with thyroid nodules. However, approximately 30% are indeterminate for malignancy. Recently, a mutation in the BRAF gene has been reported to be the most common genetic event in papillary thyroid carcinoma (PTC). In this retrospective study, we assessed the utility of BRAF V600E mutation detection for refining indeterminate preoperative cytologic diagnoses in patients with PTC. METHODS: Archival indeterminate thyroid FNAs and corresponding formalin-fixed, paraffin-embedded (FFPE) surgical samples with PTC were identified in our patient files. DNA extracted from slide scape lysates and 5 mum FFPE sections were evaluated for the BRAF V600E mutation using LightCycler PCR and fluorescent melting curve analysis (LCPCR). Amplification products that showed deviation from the wild-type genomic DNA melting peak, discordant FNA and FFPE matched pairs, and all benign control samples, underwent direct DNA sequencing. RESULTS: A total of 19 indeterminate thyroid FNAs demonstrating PTC on FFPE surgical samples were included in the study. Using BRAF mutation analysis, the preoperative diagnosis of PTC was confirmed in 3/19 (15.8%) FNA samples that could not be conclusively diagnosed on cytology alone. However, 9/19 (47.4%) FFPE tissue samples were positive for the V600E mutation. Of the discordant pairs, 5/6 FNAs contained less than 50% tumor cells. CONCLUSION: When used with indeterminate FNA samples, BRAF mutation analysis may be a useful adjunct technique for confirming the diagnosis of malignancy in an otherwise equivocal case. However, overall tumor cell content of some archival FNA smear slides is a limiting factor for mutation detection.

Journal Article↗

Tumor cell nuclei extraction from paraffin-embedded lymphoid tissue for fluorescence in situ hybridization.

In this study the authors evaluated a technique for isolating intact tumor nuclei from paraffin-embedded lymphoma samples before performing FISH testing to detect the lymphoma-specific trans-location t(11;14) that defines mantle cell lymphoma. Well-characterized surgical pathology cases of mantle cell lymphoma were identified from pathology archives. Thin sections were cut from the paraffin-embedded tissue blocks. One section was stained using hematoxylin and eosin and an area composed exclusively of malignant cells was identified and marked on the slide. The corresponding area of the tissue block corresponding to this region underwent needle core biopsy, and the tissue was processed to isolate tumor cell nuclei and deposited onto a glass slide. The paired sample preparations underwent routine FISH testing for detection of the t(11;14)(q13;q32) chromosomal trans-location. DNA probe hybridization quality was compared between the tissue and isolated nuclei. Individual tumor cell nuclei were successfully extracted from each of the tissue blocks. The t(11;14) trans-location was detected by FISH in all of the samples diagnosed as mantle cell lymphoma. The hybridization signals found in the nuclei of extracted tumor cells were bright, planar, and easily identified. Detection of signal was superior to that on whole tissue samples, where signals often overlapped or were truncated. This technique produces intact nuclei for analysis, preserves the tissue block for additional studies, and allows sampling of a specific area of the tissue block. This approach may be particularly useful when the amount of diagnostic tissue is limited.

Cell Nucleus↗

The significance of certification in liquid-based cytology and performance in the college of american pathologists interlaboratory comparison program in cervicovaginal cytopathology.

CONTEXT: Morphology training and certification provided by the manufacturer is required before laboratories are allowed to prepare and interpret liquid-based cytology (LBC) gynecologic slides. Whether this certification is associated with improved LBC interpretation performance is not known. OBJECTIVE: To determine whether LBC certification correlates with performance. DESIGN: The results of the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytopathology for the year 2004 were reviewed. During this year a question on the answer form asked participants whether they were certified in LBC preparations. Participant responses were analyzed at 2 levels of agreement with the reference diagnosis of unknown glass slides mailed quarterly. RESULTS: For cytotechnologists and pathologists, participants who were LBC certified had a significantly lower total discordant rate to series than participants who were not certified for validated LBC ThinPrep (Cytyc Corp, Marlborough, Mass) preparations (P < .001 for both groups). The results were similar for validated conventional preparations for pathologists but not for cytotechnologists. The differences were present across most individual diagnostic series. Differences were most striking for low-grade squamous intraepithelial lesions. In addition, cytotechnologists and pathologists who were certified had a significantly lower total discordant rate to the exact diagnosis for validated LBC ThinPrep slides than those who were not certified (discordant rates for cytotechnologists, 14.14% and 23.36%, respectively, P < .001; for pathologists, 15.99% and 24.07%, respectively, P < .001). CONCLUSION: Although not all confounding factors were excluded in this study, LBC certification is associated with a significantly lower discordant rate to both series and exact diagnosis for validated LBC ThinPrep preparations.

Allied Health Personnel↗

Cytologic features of nipple aspirate fluid using an automated non-invasive collection device: a prospective observational study.

BACKGROUND: Detection of cytologic atypia in nipple aspirate fluid (NAF) has been shown to be a predictor of risk for development of breast carcinoma. Manual collection of NAF for cytologic evaluation varies widely in terms of efficacy, ease of use, and patient acceptance. We investigated a new automated device for the non-invasive collection of NAF in the office setting. METHODS: A multi-center prospective observational clinical trial involving asymptomatic women designed to assess fluid production, adequacy, safety and patient acceptance of the HALO NAF Collection System (NeoMatrix, Irvine, CA). Cytologic evaluation of all NAF samples was performed using previously described classification categories. RESULTS: 500 healthy women were successfully enrolled. Thirty-eight percent (190/500) produced fluid and 187 were available for cytologic analysis. Cytologic classification of fluid producers showed 50% (93/187) Category 0 (insufficient cellular material), 38% (71/187) Category I (benign non-hyperplastic ductal epithelial cells), 10% (18/187) Category II (benign hyperplastic ductal epithelial cells), 3% (5/187) Category III (atypical ductal epithelial cells) and none were Category IV (unequivocal malignancy). Overall, 19% of the subjects produced NAF with adequate cellularity and 1% were found to have cytologic atypia. CONCLUSION: The HALO system is a simple, safe, rapid, automated method for standardized collection of NAF which is acceptable to patients. Cytologic assessment of HALO-collected NAF showed the ability to detect benign and pre-neoplastic ductal epithelial cells from asymptomatic volunteers.

Journal Article↗

Liquid-based cytology for cervical cancer screening.

In multiple studies during the last decade, liquid-based cytology for cervical cancer screening has been shown to increase the detection rate for preneoplastic squamous intraepithelial lesions equal to or greater than the conventional Papanicolaou (Pap) smear method. Liquid-based collection and processing provide more representative cervical sampling than conventional smearing of the specimen on a glass slide. Currently, there are two test methodologies that are widely marketed and available to clinical laboratories, health systems and clinicians that undertake cervical cytology. The purpose of this article is to provide an overview of the methodology and performance of SurePath Liquid-Based Pap Test in cervical cytology screening. The SurePath liquid-based Pap test significantly reduces the unsatisfactory rate of Pap test slides, and detects a significantly higher number of low- and high-grade squamous lesions when compared with the conventional Pap smear technique. Biopsy confirmation shows that this increased detection does not come at a cost of decreasing specificity, and sensitivity for histologic dysplasia is equal to or greater than the best available data for the conventional Pap method. The SurePath collection vial provides residual cellular material for adjunctive out-of-the-vial molecular testing, including sexually transmitted diseases and oncologic biomarkers associated with cervical carcinoma. Finally, SurePath slides can be placed on an automated cervical cytology screening device (FocalPoint), thus providing improved disease detection and enhanced laboratory productivity.

Biopsy↗

Rapid detection of the t(11;14) translocation in mantle cell lymphoma by interphase fluorescence in situ hybridization on archival cytopathologic material.

BACKGROUND: The cytomorphologic diagnosis of mantle cell lymphoma (MCL) can be difficult and requires ancillary studies for accurate subclassification. More than 95% of MCLs are known to carry the t(11;14) chromosomal translocation. However, traditional cytogenetic studies on cytologic material can be both difficult technically and time consuming. Interphase fluorescence in situ hybridization (FISH) can be a powerful tool for detecting chromosomal changes in individual tumor cells. The authors evaluated the utility of interphase FISH for the rapid detection of t(11;14) in archival cytologic material. METHODS: The cytopathology data bases at two institutions were searched for patients with well characterized MCL (biopsy, immunophenotyping). Ten patients with MCL (8 fine-needle aspiration samples and 2 body cavity fluid samples) were identified. The area of interest on the cytology slides was marked and hybridized with two-color, locus-specific identifier DNA probes. A dual-fusion probe signal was used to detect the juxtaposition of the immunoglobulin heavy-chain (IgH) (14q32) locus with cyclin D1 (CCND1) gene sequences (11q13). Samples with tumor cell nuclei that showed at least one yellow fusion signal in addition one green signal (IgH) and one orange signal (CCND1) were interpreted as positive. Positive and negative controls were used. RESULTS: The t(11;14) translocation was detected by FISH in 10 of 10 patients (100%) with MCL. CONCLUSIONS: The cytomorphology of small-to-intermediate cell lymphomas, including MCL, follicular lymphoma, and marginal zone/mucosa-associated lymphoid tissue lymphoma, can show overlapping cytomorphologic features with one another as well as with reactive lymphoid proliferations. In selected samples in which specific classification is not possible or when confirmation is required on a small sample size, molecular analysis and cytogenetics may be helpful in arriving at an unambiguous cytodiagnosis and subclassification. Distinction of MCL from other lymphomas is important, because the clinical course is aggressive, and response to conventional chemotherapy is poor. This study showed that the detection of t(11;14) by FISH can be performed rapidly and easily on archival cytologic material for the molecular diagnosis of MCL.

Adult↗

Prevalence and typing of HPV DNA by hybrid capture II in women with ASCUS, ASC-H, LSIL, and AGC on ThinPrep Pap tests.

Testing for human papillomavirus (HPV) DNA is now a viable option for the management of women with atypical squamous cells of undetermined significance (ASCUS). The utility of reflexive HPV DNA testing for women with a cytologic diagnosis of atypical glandular cells-not otherwise specified (AGC-NOS), ASCUS subtypes, and low-grade squamous intraepithelial lesion (LSIL) has not been well established. In the present investigation, reflex Hybrid Capture II HPV DNA testing results were evaluated for HPV prevalence and type in 371 women with abnormal cytologic diagnoses of ASCUS-not otherwise specified (ASCUS-NOS), ASCUS-suspicious for low-grade squamous intraepithelial lesion (ASCUS-L), atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H), AGC-NOS, and LSIL on ThinPrep Pap tests. Positive high-risk HPV DNA was identified in 53.6% of the study samples, including ASCUS-NOS 40.2% ASCUS-L 71.4%, ASC-H 37.5%, LSIL 88.6%, and AGC-NOS 0%. We conclude that reflex HPV DNA testing appears to not be useful for colposcopy triage for cytologic diagnoses of LSIL or AGC-NOS.

DNA Probes, HPV↗

A simple method to determine the need for glacial acetic acid treatment of bloody ThinPrep Pap tests before slide processing.

ThinPrep (TP) Papanicolaou (Pap) samples containing excessive blood often result in unsatisfactory preparations, possibly leading to undetected gynecologic disease, and added inconvenience to patients and clinicians. Reprocessing of these samples with a glacial acetic acid wash is effective at eliminating blood, providing satisfactory preparation and detection of lesions. However, it increases laboratory costs and decreases work flow efficiency. We report the use of a color standard for gauging the necessity of performing a glacial acetic acid wash before TP processing. This "preprocessing" was found to reduce the costs associated with reprocessing by 48%, while maintaining high preparation quality by improved sample adequacy.

Acetic Acid↗

One hundred percent thorough quality control rescreening of liquid-based monolayers in cervicovaginal cytopathology.

BACKGROUND: Quality control (QC) of Papanicolaou (Pap) smear testing focuses on the identification of screening errors by 10% random, rapid, or thorough manual rescreening of some portion of negative smears. One hundred percent thorough manual rescreening has been reported to be the most effective method of identifying screening errors in conventional Pap smears (CP), but to the authors' knowledge no experience with this QC method has been reported for the ThinPrep Pap test (TP). The current study reports the estimated screening error rate of TP as determined by a QC program using 100% thorough rescreening. METHODS: All TP samples received at the study institution between January 1, 1999 and December 31, 2000 and initially screened as negative underwent thorough manual QC rescreening. RESULTS: A total of 53,419 TP samples were received during the study period. Of these, 5,368 cases (10%) initially were interpreted as abnormal. A total of 47,247 cases (88.4%) were rescreened. Abnormalities were identified in 804 additional cases, for a screening error rate of 13.0%. Of the 804 cases, 678 (84.3%) were atypical squamous cells of undetermined significance, 116 (14.4%) were low-grade squamous intraepithelial lesions, and 10 (1.2%) were high-grade squamous intraepithelial lesions. No tumors were identified on rescreening. CONCLUSIONS: In the current study, 100% thorough rescreening of TP samples was found to result in the detection of a significant number of abnormalities that would have been missed by routine random 10% QC rescreening. The screening error rate determined by 100% thorough QC rescreening of TP is comparable to that reported for CP QC rescreening.

Carcinoma, Squamous Cell↗

PREPmate automated processor: comparison of automated and manual methods of liquid-based gynecologic sample preparation.

The development of procedures for fully automated processing of liquid-based gynecologic samples has been the focus of considerable interest to the cytology laboratory. Liquid-based collection and processing technology has been shown to improve sample adequacy, resulting in an overall improvement in quality of sample preparations. PREPmate, an accessory to the PrepStain slide processor, automates the initial enrichment process of mixing and dispensing the specimen over a density gradient. This report describes a study evaluating cellularity and diagnostic reproducibility in SurePath samples processed using the PREPmate accessory compared to samples processed using a manual technique. Samples processed using the PREPmate accessory contained 8.3% more squamous cells. Exact diagnostic reproducibility between preparation types was 83.3%; when considering negative vs. abnormal (ASCUS+), in adequate samples, reproducibility was 100%.

Automation↗

A stiff bristled, spiral-shaped ectocervical brush: a device for transepithelial tissue biopsy.

OBJECTIVE: To compare a new spiral-shaped tissue-sampling brush with a standard cervical punch biopsy. METHODS: Before large loop excision of the transformation zone, women with cervical intraepithelial neoplasia underwent a transepithelial brush biopsy of a portion of a colposcopically identified lesion, followed by a punch biopsy of the remaining portion. Brush biopsy samples were processed using liquid-based cytology and cell block techniques. Diagnoses were made using a consensus of three pathologists. Brush biopsy samples without basal cells were considered inadequate. The histological diagnosis was compared with the brush biopsy and punch biopsy samples. Patient-reported pain and physician-reported bleeding for punch and brush biopsies were compared. RESULTS: Fifty-two women were enrolled in the study; 47 successfully completed the study protocol. Eight brush biopsy specimens were inadequate. Thirty-nine women showed abnormal pathology (human papillomavirus/cervical intraepithelial neoplasia I or worse) on large loop excision of the transformation zone, and 32 women had high-grade (or worse) lesions. The punch biopsy correlated with high-grade disease in 53.1% of these women. The brush biopsy result correlated with high-grade disease in 79.3% of these women using a cell block technique and 76.7% using liquid cytology. There was significantly less pain (P <.001) and significantly less bleeding (P <.001) with the brush biopsy. CONCLUSION: When an adequate sample is collected, spiral brush biopsy is as good as a standard punch biopsy for detecting cervical pathology, with substantially less pain and bleeding. User training and guidelines for sampling are needed to assure that an adequate sample is collected.

Adolescent↗

The unsatisfactory ThinPrep Pap Test: missed opportunity for disease detection?

Cervical cytology specimens classified as "unsatisfactory for interpretation" represent a potential source of undetected disease. This prospective study analyzed the potential benefits of a laboratory procedure to reprocess unsatisfactory ThinPrep Pap Tests (Cytyc, Boxborough, MA). All unsatisfactory ThinPrep samples were reprocessed using a glacial acetic acid wash. The study period unsatisfactory rate was compared with that for the previous 12 months. The initial unsatisfactory rate was 1.3% (197/15,154). Of the unsatisfactory ThinPrep samples, 55.8% (110/197) had residual material for reprocessing. After reprocessing, 67.3% (74/110) were reclassified as "satisfactory" or "satisfactory but limited by," and the final unsatisfactory rate was 0.8% (123/15,154), a 62% decrease. Compared with the previous 12-month rate of 0.9% (209/23,730), this was a 12% reduction. Seven (6.4%) of 110 initially classified as unsatisfactory contained an epithelial abnormality (atypical squamous cells of undetermined significance, 3; atypical glandular cells of undetermined significance, 2; low-grade squamous intraepithelial lesion, 1; squamous cell carcinoma, 1) on the reprocessed slide. Reprocessing of unsatisfactory ThinPrep slides yielded additional cellular abnormalities that otherwise would have been undetected. The present study confirms that reprocessing of unsatisfactory ThinPrep slides is a beneficial laboratory procedure.

Acetic Acid↗

Accuracy of a slide profiler for endocervical cell detection in no-further-review conventional Pap smears.

OBJECTIVE: To evaluate the reliability of the Focal-Point slide profiler (TriPath Care Technologies, Burlington, North Carolina, U.S.A.) in determing the absence of endocervical cells in conventional Pap smear slides. STUDY DESIGN: A consecutive series of conventional Pap smears, designated by FocalPoint as requiring no further review (NFR) and as lacking endocervical cells, was manually screened to determine the true presence or absence of endocervical cells. These results were compared to those obtained by FocalPoint. RESULTS: From January 1, 2000, to December 31, 2001, FocalPoint indicated that 797 NFR slides did not contain endocervical cells. In contrast, manual screening revealed that 504/797 (63.2%) did contain endocervical cells. CONCLUSION: The reliability of a negative FocalPoint determination for endocervical cells is limited. Manual screening of NFR slides designated by the instrument as lacking endocervical cells appears to be necessary.

Carcinoma↗