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Objectives Long-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA). Methods Histologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated. Results Follow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM). Conclusions Appropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.

Objectives: In an era of precision medicine, our aim was to determine the frequency and theranostic potential of mutations identified in malignant lymph nodes (LNs) sampled by endoscopic ultrasound fine-needle aspiration (EUS FNA) of patients with rectal cancer by targeted next-generation sequencing (NGS). Methods: The NGS Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, CA) and MiSeq (Illumina, San Diego, CA) sequencers were used to sequence and assess for 2,800 or more possible mutations in 50 established cancer-associated genes. Results: Among 102 patients, 89% had 194 pathogenic alterations identified in 19 genes. The identification of KRAS, NRAS , or BRAF mutations suggests that 42% are likely nonresponders to anti–epidermal growth factor receptor therapy. Among KRAS, NRAS , or BRAF wild-type patients, alterations in eight genes linked to alternative therapies were identified in 44%. Conclusions: Our data demonstrate the successful ability to apply a single multiplex test to allow multigene mutation detection from malignant LN cytology specimen DNA collected by EUS FNA.

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).

The goal of this study was to assess the performance characteristics of the Automated Cellular Imaging System (ACIS III) for HER2 immunohistochemical analysis. The study was performed on 187 biopsy slides from patients who underwent HER2 testing between January and February 2008. Three scoring methods by the ACIS III were compared with the manual score and fluorescence in situ hybridization (FISH) results for HER2 amplification. The equal distribution score (EQD) method, in which 2 areas each of high-, moderate-, and low-intensity staining were measured, most closely matched the FISH HER2 amplification result. The numbers of immunohistochemically negative (0 or 1+)/ FISH+ cases were equivalent for all methods. The EQD method had significantly fewer 2+ cases (n = 16) (P < .001) vs the manual method (n = 35) and yielded a higher positive predictive value (38%) for HER2 amplification compared with the manual method (20%). The EQD method may more accurately identify FISHamplified HER2 cases with fewer 2+ cases that would be “reflexed” to FISH compared with the manual method. The proto-oncogene HER2 is amplified in 20% to 30% of breast cancers, resulting in overexpression of the HER2 protein. HER2+ breast cancer is associated with rapid tumor growth, increased risk of recurrence after surgery, poor response to conventional chemotherapy, and significantly shorter disease-free survival and overall survival than HER2– breast cancer. 1-3 Trastuzumab (Herceptin, Genentech, San Francisco, CA), a humanized monoclonal antibody, has been shown to improve clinical outcomes in the setting of HER2+ metastatic disease or adjuvant treatment for HER2+ invasive breast cancer when used in combination with chemotherapy as a first line. 4 Currently, 2 laboratory methods used to assess HER2 status include immunohistochemical analysis and fluorescence in situ hybridization (FISH), which assess protein overexpression and gene amplification, respectively. Immunohistochemical analysis and FISH are commonly used assays for determining HER2 status because morphologic examination is used to ensure that HER2 analysis is localized within tumor cells. Unfortunately, recent studies have demonstrated less-than-optimal concordance rates between immunohistochemical analysis and FISH among laboratories performing HER2 testing, which has been attributed to lack of standardized testing protocols and test interpretation by inexperienced personnel. 4-6

The MonoPrep Pap Test (MPPT; MonoGen, Lincolnshire, IL) is a novel, liquid-based specimen collection and processing technology for cytologic and molecular testing. Its usefulness in the detection of cervical cancer and its precursors was evaluated in a multicenter, masked, adjudicated, split-sample study of 10,739 samples. After preparation of a conventional smear, the residuum on the collection device was rinsed into a collection vial from which an MPPT slide was prepared. Accuracy was assessed by masked reference interpretation by an independent pathologist. Slides prepared by MPPT, compared with smears, yielded statistically significant increases in relative sensitivity for atypical squamous cells of undetermined significance and worse, atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion/atypical glandular cells and worse, and low-grade squamous intraepithelial lesion and worse. There was no significant difference in relative specificity. MPPT provided a 58% reduction in unsatisfactory slides. There was no significant difference in the presentation of endocervical/transformation zone component or the detection of benign conditions. The MPPT is a promising new liquid-based technology for cervical cancer screening.

The goal of this study was to assess the performance characteristics of the Automated Cellular Imaging System (ACIS III) for HER2 immunohistochemical analysis. The study was performed on 187 biopsy slides from patients who underwent HER2 testing between January and February 2008. Three scoring methods by the ACIS III were compared with the manual score and fluorescence in situ hybridization (FISH) results for HER2 amplification. The equal distribution score (EQD) method, in which 2 areas each of high-, moderate-, and low-intensity staining were measured, most closely matched the FISH HER2 amplification result. The numbers of immunohistochemically negative (0 or 1+)/FISH+ cases were equivalent for all methods. The EQD method had significantly fewer 2+ cases (n = 16) (P.001) vs the manual method (n = 35) and yielded a higher positive predictive value (38%) for HER2 amplification compared with the manual method (20%). The EQD method may more accurately identify FISH-amplified HER2 cases with fewer 2+ cases that would be "reflexed" to FISH compared with the manual method.

This study was performed to identify differences in the frequency of specific cytologic diagnoses obtained between specimens prepared by the filtration and ThinPrep (Cytyc, Marlborough, MA) techniques and to assess how these cytologic diagnoses correlated with pathologic findings. Data were collected from 2,347 voided urine specimens analyzed 8 months before and after ThinPrep implementation. Urine cytologic and bladder biopsy specimens were obtained as part of clinical follow-up, and positive diagnoses were considered evidence of malignancy. After ThinPrep implementation, the proportion of specimens diagnosed as negative significantly decreased (85.5% vs 78.6%; P < .001), clusters (5.8% vs 5.6%; P = .597) and positive (2.8% vs 3.3%; P = .143) diagnoses remained similar, and atypical (3.1% vs 8.4%; P < .001) and “suspicious” diagnoses (2.7% vs 4.1%; P < .001) increased. After 1 year of follow-up, there was no significant difference in the percentage of patients diagnosed with bladder carcinoma between the 2 methods for all cytologic categories.