Henry, Michael R

BACKGROUNDThe objective of the current study was to establish a process for validating immunohistochemistry (IHC) protocols for use on the Cellient cell block (CCB) system.METHODSThirty antibodies were initially tested on CCBs using IHC protocols previously validated on formalin‐fixed, paraffin‐embedded tissue (FFPE). Cytology samples were split to generate thrombin cell blocks (TCB) and CCBs. IHC was performed in parallel. Antibody immunoreactivity was scored, and concordance or discordance in immunoreactivity between the TCBs and CCBs for each sample was determined. Criteria for validation of an antibody were defined as concordant staining in expected positive and negative cells, in at least 5 samples each, and concordance in at least 90% of the samples total. Antibodies that failed initial validation were retested after alterations in IHC conditions.RESULTSThirteen of the 30 antibodies (43%) did not meet initial validation criteria. Of those, 8 antibodies (calretinin, clusters of differentiation [CD] 3, CD20, CDX2, cytokeratin 20, estrogen receptor, MOC‐31, and p16) were optimized for CCBs and subsequently validated. Despite several alterations in conditions, 3 antibodies (Ber‐EP4, D2‐40, and paired box gene 8 [PAX8]) were not successfully validated.CONCLUSIONSNearly one‐half of the antibodies tested in the current study failed initial validation using IHC conditions that were established in the study laboratory for FFPE material. Although some antibodies subsequently met validation criteria after optimization of conditions, a few continued to demonstrate inadequate immunoreactivity. These findings emphasize the importance of validating IHC protocols for methanol‐fixed tissue before clinical use and suggest that optimization for alcohol fixation may be needed to obtain adequate immunoreactivity on CCBs. Cancer (Cancer Cytopathol) 2016;124:89‐99. © 2016 American Cancer Society.

Background:Bronchial brush (BB) cytology carries low sensitivity for detecting neuroendocrine carcinomas (NECs), including typical carcinoid (TC) tumors of the lung. We aimed to investigate the detection of neuroendocrine tumors including TC through BB routine cytology cell block (CB), immunohistochemistry (IHC), and fluorescencein situhybridization (FISH).Materials and Methods:A SNOMED search showed 187 lung biopsy or resection specimens from 2008 through 2011 containing neuroendocrine or carcinoid in the diagnosis. Residual BB specimens retained in PreservCyt were used to prepare a ThinPrep slide for FISH analysis. CBs were stained with H and E and IHC for chromogranin and synaptophysin.Results:Of the 187 cases, 16 had residual BB material available within 1 year of diagnosis and were used in CB preparation for IHC and FISH slides. Cytologic evaluation determined 1 case positive for malignancy (small cell lung carcinoma [SCLC]), 1 suspicious for adenocarcinoma, and 14 negative for malignancy. On the basis of histologic diagnosis, FISH was performed. SCLC showed polysomy (86% abnormal cells); 2 TC tumors showed a gain of 7p12 (15% abnormal cells) and a gain of 5q15 (72% abnormal cells), respectively. Two cases had CBs with positive immunoreactivity for chromogranin and synaptophysin. The sensitivity for detection of NEC was 18.8%, 15.4%, and 25% for cytologic evaluation, CB, and FISH, respectively.Conclusion:Neuroendocrine tumors, including TC are difficult to detect with BB cytologic evaluation, most likely because tumor cells lack in the specimen. Assessment of further studies is needed to explore the role of cytology and ancillary methods for detection of these tumors.

Because of the complexity of cervical cancer prevention guidelines, clinicians often fail to follow best-practice recommendations. Moreover, existing clinical decision support (CDS) systems generally recommend a cervical cytology every three years for all female patients, which is inappropriate for patients with abnormal findings that require surveillance at shorter intervals. To address this problem, we developed a decision tree-based CDS system that integrates national guidelines to provide comprehensive guidance to clinicians. Validation was performed in several iterations by comparing recommendations generated by the system with those of clinicians for 333 patients. The CDS system extracted relevant patient information from the electronic health record and applied the guideline model with an overall accuracy of 87%. Providers without CDS assistance needed an average of 1 minute 39 seconds to decide on recommendations for management of abnormal findings. Overall, our work demonstrates the feasibility and potential utility of automated recommendation system for cervical cancer screening and surveillance.