Robert A. Goulart

Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology and cotesting (cytology in combination with hrHPV testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for healthcare providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

Glypican-3 Immunocytochemistry in Liver Fine-needle Aspirates A Novel Stain to Assist in the Differentiation of Benign and Malignant Liver Lesions

Glypican‐3 (GPC3) is a heparan sulfate proteoglycan which is elevated in the serum of patients with hepatocellular carcinoma (HCC), but not in healthy blood donors, or patients with benign liver disease. GPC3 immunohistochemistry (IHC) is a promising marker of HCC in surgical pathology. This study explores the value of GPC3 expression in liver fine‐needle aspirates (FNAs) by immunocytochemistry (ICC), and compares its sensitivity and staining intensity with that of IHC.

The impact of digital imaging in the field of cytopathology.

With the introduction of digital imaging, pathology is undergoing a digital transformation. In the field of cytology, digital images are being used for telecytology, automated screening of Pap test slides, training and education (e.g. online digital atlases), and proficiency testing. To date, there has been no systematic review on the impact of digital imaging on the practice of cytopathology. This article critically addresses the emerging role of computer-assisted screening and the application of digital imaging to the field of cytology, including telecytology, virtual microscopy, and the impact of online cytology resources. The role of novel diagnostic techniques like image cytometry is also reviewed.

Expression of c-Kit in adenoid cystic carcinoma of the breast

Breast adenoid cystic carcinoma (BACC) is a biologically distinct tumor with morphologic mimickers, which might make accurate classification problematic. Because c-kit expression has been reported in adenoid cystic carcinoma of various anatomic sites, we evaluated BACC for c-kit by immunohistochemical analysis, comparing the findings to similarly stained mimickers. Tested cases included 6 BACCs, 15 low-grade infiltrating ductal carcinomas (LGIDCs) chosen as potential mimickers, and 15 head-neck adenoid cystic carcinomas (HNACCs). All BACCs showed plasma membranous and cytoplasmic staining equal to or greater than that of adjacent benign epithelium. Five BACCs (83%) expressed c-kit in more than 50% of tumor cells. Only 2 of 15 LGIDCs expressed low-intensity, focal c-kit staining. Of the 15 HNACCs, 10 (67%) expressed c-kit. Hormone receptors were consistently negative in BACCs. All BACCs expressed c-kit, whereas LGIDCs infrequently expressed low-intensity c-kit. Immunohistochemical evaluation for c-kit might aid in accurately classifying carcinomas with histologic features overlapping adenoid cystic carcinoma and LGIDC.

Impact of Digital Image Manipulation in Cytology

CONTEXT Digital images have become an important component of cytology practice. They are used in telecytology, automated screening, educational material, and Web sites and have potential for use in proficiency testing. However, there has been no formal evaluation to date to determine if digital image manipulation (intentional or unintentional) can affect their interpretation. OBJECTIVE To investigate whether alteration of digital cytology images affects diagnosis. DESIGN Acquired digital images of ThinPrep Papanicolaou test slides were manipulated (rotated 90 degrees and brightness, contrast, red-green-blue color, and luminosity adjusted) using Photoshop. A test composed of these altered images, along with their original (unaltered) image and exact duplicates was given to 22 cytologists (13 cytotechnologists, 8 cytopathologists, and 1 fellow). All images were rated as negative, atypical (atypical squamous cells of undetermined significance), low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, or positive for cancer. Weighted kappa and heterogeneity chi(2) statistics were used to measure levels of agreement and assess concordance between groups. RESULTS The level of agreement for identical duplicate images was excellent (kappa = 0.81), compared with the poor agreement for manipulated image pairs (kappa = 0.21), a statistically significant difference (P < .001). For all altered image types agreement was poor. There was no significant difference between cytotechnologists and cytopathologists in level of agreement (P = .56). CONCLUSIONS Manipulation of a Papanicolaou test digital image, irrespective of the specific category of cytologic material photographed, significantly affects its interpretation by both cytotechnologists and cytopathologists. This suggests that care needs to be taken when digital cytology images are used, to specifically ensure that their alteration does not affect diagnosis.

Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

Abstract In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk HPV (hrHPV) testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

Informatics applied to cytology

Automation and emerging information technologies are being adopted by cytology laboratories to augment Pap test screening and improve diagnostic accuracy. As a result, informatics, the application of computers and information systems to information management, has become essential for the successful operation of the cytopathology laboratory. This review describes how laboratory information management systems can be used to achieve an automated and seamless workflow process. The utilization of software, electronic databases and spreadsheets to perform necessary quality control measures are discussed, as well as a Lean production system and Six Sigma approach, to reduce errors in the cytopathology laboratory.

2013 Statement on Human Papillomavirus DNA Test Utilization

In 2009, the Cytopathology Education and Technology Consortium issued a statement on human papillomavirus (HPV) DNA test utilization that was published in multiple journals.1 This statement was a concise summary of the clinical indications for high-risk or oncogenic HPV testing based on guidelines from the American Society for Colposcopy and Cervical Pathology (ASCCP) and the American Cancer Society (ACS) published from 2002 through 2007.2,3 These organizations have since published newer consensus guidelines addressing HPV testing,4,5 and the previous summary no longer reflects current screening and management guidelines. High-risk HPV testing has proven utility in both cervical cancer screening and management. The 2012 screening guidelines endorsed by the ACS, ASCCP, and the American Society for Clinical Pathology state that combined cervical cytology and HPV testing is now the preferred strategy for women 30 years and older. The 2012 ASCCP guidelines for the management of abnormal cervical cancer screening tests and cancer precursors utilize cotesting extensively as both a sensitive and efficient way to manage and follow these women. Inappropriate or too-frequent screening, including HPV testing, can lead to increased costs without proven benefit and may also cause patient harm by overtreatment. The educational statement below is intended to improve adherence to current guidelines, thereby improving the health care of women. The American College of Obstetricians and Gynecologists affirms these recommendations and …

Diagnostic utility of p16 immunocytochemistry for Trichomonas in urine cytology

We present a case in which p16 immunocytochemistry helped establish the diagnosis of Trichomonas in urine from a male patient. Based on this finding, we recommend p16 immunocytochemistry as a diagnostic tool for unexpected patients or specimen types in which potential trichomonads are identified following routine cytologic evaluation.

Primary human papillomavirus screening for cervical cancer in the United States—US Food and Drug Administration approval, clinical trials, and where we are today

Once oneof the mostcommon cancers affecting USwomen, cervical cancer now ranks 14th in frequency. Althoug h the effectiveness of cytologic screening for cervicalcancer has never been demonstrated in a randomized trial, the impact of the Papanicolaou (Pap) test has been welldocumentedinnumerousobservationalstudies,anditssuccessasoneofthemostcost-effectivescreeningtestsservesaparadigmforsuccessfulpreventivemedicine.Particularlyin theUnitedStates,wherecervicalcancer screening wasandstillisopportunistic,thepositiveimpactofthePaptestonwomen’shealthisindeedremarkable.ThePaptestiscloselytiedtokeydevelopmentsrelatedtocervicalcancer.Itwasduringitsearlydaysthatthefield of gynecologic cytomorphology was defined; and, since its inception, there has been a gradual increase inunderstanding of cervical carcinogenesis. Although the Pap test has high specificity, its lower sensitivity requiresmultiplescreeningstodetectmostprecancersandcancers.Inanefforttoimprovesensitivity, thePaptestevolvedfrom conventional smears to liquid-based technologies, along with improved sampling devices, automated proc-essing,andcomputer-imagingscreeningdevices.TheintroductionoftheBethesdareportingterminologyforPaptestsin1988