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.

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 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.

Liquid-based rapid onsite evaluation of endobronchial ultrasound cytologies.

INTRODUCTION: Rapid onsite evaluation (ROSE) generally uses smears made at the site of the procedure ("smear-based ROSE"). It requires considerable time, generally 2 individuals, technical expertise, and it can be difficult to estimate material available for ancillary studies. We developed an alternative ROSE using liquid-based cytology ThinPrep with hematoxylin and eosin (H&E) stain ("liquid-based ROSE") and assessed its advantages. MATERIALS AND METHODS: Clinicians rinse the sample(s) into CytoRich Red and send to Pathology. A defined proportion of the needle rinse is removed for a ThinPrep stained with a rapid H&E. Adequacy and diagnosis were compared to final outcome. Total time was recorded. RESULTS: Among 52 liquid-based ROSE readings, 28 (53.8%) were interpreted as "adequate" with final as adequate; 17 (32.7%) were interpreted as "inadequate" with final as inadequate; 7 (13.5%) were interpreted as "inadequate" with final as adequate. Of 23 readings provided with onsite diagnosis, 15 (65.2%) were interpreted as definitive positive or negative diagnoses; 6 (26%) were interpreted as nondiagnostic; and 2 (8.7%) were interpreted as atypical. All definitive diagnoses were concordant with final diagnoses. The time for liquid ROSE performance ranges from 6 to 22 minutes (mean: 13 minutes) and required only 1 individual. CONCLUSIONS: Liquid-based ROSE allows accurate adequacy determination and diagnosis, takes about 15 minutes of cytologist time, and can be performed by just 1 person. The technique produces well-preserved and stained slides, it may allow a better estimation of the total amount of material in the specimen vial and may provide a better platform for telecytology.

Clinical history of HIV infection may be misleading in cytopathology.

Human immunodeficiency virus (HIV)-infected patients are at an increased risk for developing opportunistic infections, reactive conditions and neoplasms. As a result, a broad range of conditions are frequently included in the differential diagnosis of HIV-related lesions. The clinical history of HIV infection may, however, be misleading in some cases. Illustrative cases are presented in which knowledge of a patient's HIV status proved to be misleading and increased the degree of complexity of the cytologic evaluation. Case 1 involved the fine needle aspiration (FNA) of a painful 3 cm unilateral neck mass in a 38-year-old female with generalized lymphadenopathy. Her aspirate revealed a spindle cell proliferation devoid of mycobacteria that was immunoreactive for S-100 and macrophage markers (KP-1, PGM1). Multiple noncontributory repeat procedures were performed until a final excision revealed a schwannoma. Case 2 was a CT-guided FNA of a positron emission tomography positive lung mass in a 53-year-old man. The acellular aspirate in this case contained structures resembling fungal spore forms that were negative for mucicarmine and GMS stains, as well as cryptococcal antigen immunocytochemistry. A Von Kossa stain confirmed that these pseudo-fungal structures were calcified debris. Follow up revealed multiple calcified lung and hilar node based granulomata. Case 3 involved the cytologic evaluation of pleural fluid from a 47-year-old man with Kaposi sarcoma and recurrent chylous pleural effusions. Large atypical cells identified in his effusion were concerning for primary effusion lymphoma. Subsequent pleural biopsy revealed extramedullary hematopoiesis, documenting these atypical cells as megakaryocytes. These cases demonstrate that knowledge of a patient's HIV status can be misleading in the evaluation of cytology specimens, with potential for misdiagnosis and/or multiple procedures. To avoid this pitfall in the setting of HIV infection, common entities unrelated to HIV infection and artifacts should always be included in the differential diagnosis.

Cytomorphology of cervicovaginal melanoma: ThinPrep versus conventional Papanicolaou tests.

BACKGROUND: Primary cervicovaginal melanoma is a rare malignancy associated with a high risk of recurrence. Prior studies discussing the cytomorphology of cervicovaginal melanoma have been based primarily on review of conventional Papanicolaou (Pap) smears. The aim of this study was to evaluate cervicovaginal melanomas identified in liquid-based Pap tests, in comparison with features seen on conventional Pap smear preparation. MATERIALS AND METHODS: Cases of cervicovaginal melanoma identified on Pap tests with concurrent or subsequent histopathologic confirmation were collected from the Baystate Medical Center cytopathology files and personal archives of the authors over a total period of 34 years. All cytopathology (n = 6) and the available histology slides (n = 5) were reviewed. Cases were analyzed regarding clinical, histopathologic and cytomorphological findings. RESULTS: A total of six cases with invasive cervicovaginal melanoma diagnosed on Pap tests were identified. Most patients were postmenopausal with contact bleeding, correlating with surface ulceration (identified in biopsy/excision material in 5/5 cases). Most cases had deeply invasive tumors (5/5: modified Breslow's thickness > 5 mm and Chung's level of invasion IV/V). Pap tests included four ThinPrep and two conventional smears. Overall, ThinPrep Pap tests exhibited a higher ratio of tumor cells to background squamous cells. While all Pap tests were bloodstained, tumor diathesis was prominent only within conventional smears. Melanoma cells were present both as clusters and scattered single cells in each Pap test type. Both the preparations contained epithelioid tumor cells, whereas spindled tumor cells were seen in only two ThinPrep cases. Prominent nucleoli and binucleation of tumor cells were seen in both the preparations. Melanin pigment was identified in only ThinPrep (3/4) cases and nuclear pseudo-inclusions in one conventional Pap smear. Cell blocks were made in three ThinPrep cases and immunocytochemistry (S-100, HMB45, Melan-A) performed on additional vial material (one ThinPrep slide and one cell block) was immunoreactive in melanoma cells. CONCLUSION: Primary cervicovaginal melanoma, a rare malignancy seen predominantly in postmenopausal women, may be successfully diagnosed in either ThinPrep Pap tests or conventional Pap smears. While ThinPrep Pap tests did not demonstrate morphological advantage over conventional smears, liquid-based cytology specimens did provide additional material for cellblock preparation and immunocytochemical evaluation in a subset of cases.

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.

Anthracotic pigment in pleural fluid: a case report.

BACKGROUND: The presence of anthracotic pigment (carbon) in pleural fluid cytologic samples is unusual and to date has only been reported in individuals who are crack (freebase cocaine) smokers. We report the cytologic finding of carbon-laden macrophages in pleural fluid unrelated to crack abuse. CASES: Two patients were identified with anthracotic pigment within their pleural fluid on cytologic review; an 88-year-old human immunodeficiency virus (HIV)-negative man with a transudative effusion and a 46-year-old HIV-positive man with a history of crack abuse who presented with an exudative effusion. Dense black pigment within macrophages was identified in both the ThinPrep slide and cell block material. This pigment failed to stain for iron and was present within the cytoplasm of KP-1 immunoreactive and TFF-1 negative macrophages. CONCLUSION: Carbon-laden macrophages can be found in exudative and transudative pleural effusions and may be seen without any relationship to crack abuse. Because this finding may be secondary to a subclinical pneumothorax, its identification and reporting may be of clinical significance.

Cytologic findings of psammocarcinoma in peritoneal washings.

OBJECTIVE: To describe the cytomorphology of psammocarcinomas in peritoneal washings, including ThinPrep (Cytyc Corporation/Hologic, Marlborough, Massachusetts, U.S.A.)-processed material, in a series of patients. STUDY DESIGN: A retrospective, 19-year search was performed for cases of peritoneal washings in which psammomatous calcifications were reported. All clinical findings as well as cytospin, ThinPrep and cell block slides from peritoneal washings in patients with psammocarcinoma were reviewed. RESULTS: A total of 37 cases were identified with peritoneal washings containing psammomatous calcifications, 4 (11%) of which were associated with psammocarcinoma. Psammocarcinomas occurred in patients of average age 52 years (range, 39-68) and were of either peritoneal (n = 3) or ovarian (n = 1) origin. In these psammocarcinomas, peritoneal washings were bloody, were of moderate to high cellularity and contained many papillary serous cell groups. Tumor cells had high nuclear:cytoplasmic ratios, irregular nuclei, prominent nucleoli and variable hyperchromasia. Laminated psammomatous calcifications were abundant in 3 cases (> 80 bodies per cytologic slide and cell block) and of variable size (up to 150 microm), occurring both alone and in clusters associated with atypical epithelial cell groups. CONCLUSION: The characteristic cytologic finding of low grade epithelial atypia in papillary cell groups accompanied by numerous psammoma bodies is very distinctive of psammocarcinoma and closely resembles the striking histopathologic findings seen in this rare subset of serous carcinomas.

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.

Primary HPV cervical cancer screening in the United States: Are we ready?

In September 2017, the United States Preventive Services Task Force put forth updated draft guidelines for cervical cancer screening in the United States, which were then open to public comment. The recommendations allowed for every-3-year cervical cytology screening in women aged 21 to 65 years with an option for every-5-year high-risk human papillomavirus testing in women aged 30 to 65 years. There was no option for cotesting. Other recommendations were similar to those published by other professional organizations. The Cytopathology Education and Technology Consortium provided an official response during the open comment period, which is summarized here along with additional commentary by the authors.

An advocacy victory: final USPSTF cervical cancer screening recommendations revised to include cotesting option.

The recent reversal of the US Preventive Services Task Force decision to drop cotesting (Papicolaou test + high-risk human papillomavirus test) as an option for cervical cancer screening in women aged 30 to 65 years from their recommendations for cervical cancer screening was directly attributed to advocacy efforts by professional organizations and individuals. This communication summarizes the pathology and laboratory medicine community's role in this advocacy effort by collaboration of all major US Pathology organizations, via the Cytopathology Education and Technology consortium.

Cytologic features of müllerian papilloma of the cervix: mimic of malignancy.

Müllerian papilloma is a rare benign tumor of the cervix and/or vagina that occurs predominantly in young children. The cytologic features of benign müllerian papilloma have never been described. We report for the first time, to our knowledge, the cytologic findings of a benign müllerian papilloma from the vaginal fluid specimen of a 15-mo-old girl using touch prep, ThinPrep, and cell block preparations. The deceptive cytologic features of a cellular specimen with complex papillary fronds composed of overlapping and crowded small hyperchromatic cells, with a high nuclear:cytoplasmic ratio, and feathering in this case resembled a malignant neoplasm. The clinical findings and cytomorphology of a benign müllerian papilloma can mimic those of malignant lesions of the female lower genital tract such as sarcoma botryoides and adenocarcinoma. An awareness of this entity and its potential to mimic these more aggressive neoplasms is essential for accurate diagnosis and to avoid over-treatment.

Diagnostic cytologic features of an epididymal melanotic neuroectodermal tumor of infancy present in scrotal fluid: a case report.

BACKGROUND: The cytologic features of melanotic neuroectodermal tumor of infancy (MNTI) have been described in rare cases only, and these reports have been based solely on direct smears obtained from aspirated tumor material or from touch preparations of resected tumors. CASE: We report, to our knowledge, the first documented case of an epididymal MNTI diagnosed from aspirated hydrocele fluid processed using the ThinPrep system (Cytyc Corp., Boxborough, Massachusetts, U.S.A.). CONCLUSION: Based on a 15 year retrospective review of scrotal fluids submitted for cytologic evaluation to our laboratory, MNTI represented the sole neoplasm that was represented in the fluid and could be specifically diagnosed. Compared to the direct smear evaluation in our case and other published reports, the ThinPrep method enables the recognition of both neuroblast-like cells and larger melanin-containing epithelial cells in scrotal fluid, thereby aiding in the specific diagnosis of MNTI and minimizing the risk of misdiagnosing this tumor as a more aggressive neoplasm.

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.

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.

Trichomonas vaginalis P16 Immunoreactivity in cervicovaginal Pap tests: a diagnostic pitfall.

Detection of p16 is emerging as a useful biomarker for Human Papillomavirus (HPV)-related dysplastic and malignant lesions of the cervix, and as such has potential application to cervicovaginal Papanicolaou (Pap) specimens. While evaluating p16 immunocytochemistry in our laboratory we observed one Pap test in which Trichomonas vaginalis stained positively for p16. We therefore proceeded to determine the frequency of T. vaginalis immunoreactivity for p16 in 10 consecutive, satisfactory, liquid-based Pap tests diagnosed as negative for intraepithelial lesion or malignancy in which T. vaginalis was present. For each case, a ThinPrep slide prepared from residual vial material was immunostained with p16. In an additional case, a prepared cell block was stained with p16. T. vaginalis were consistently p16 positive. We document, for the first time, p16 immunoreactivity of T. vaginalis that, on a Pap slide and cell block, may be morphologically misinterpreted as small dysplastic or malignant epithelial cells. The presence of this parasite in Pap tests may also potentially hinder the use of p16 as an adjunct to liquid-based cervical screening cytology.

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 or cotesting (cytology in combination with high-risk human papillomavirus [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 U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the 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 U.S. Food and Drug Administration (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.

Diagnostic agreement in the evaluation of image-guided breast core needle biopsies: results from a randomized clinical trial.

BACKGROUND: Image-guided core needle biopsies (CNBs) are commonly used as the initial sampling method for nonpalpable, mammographically detected breast lesions. Although prior studies have shown that this procedure is a highly sensitive and accurate method for the detection of breast cancer, the level of diagnostic agreement between pathologists in the analysis of CNB has not been previously studied in detail. METHODS: To address this, we reviewed the pathologic findings in 2004 CNB from patients enrolled in the Radiologic Diagnostic Oncology Group 5 study, a randomized, multicenter trial designed to determine the role of CNB and fine needle aspiration biopsy in the evaluation of nonpalpable breast lesions. Slides of CNB specimens were initially diagnosed by pathologists at the 22 participating institutions (local diagnosis) and were then sent to the study pathologists for central review (central diagnosis). Local and central diagnoses were compared. RESULTS: Overall, the central diagnosis and local diagnosis were concordant in 1925 cases (96%), indicating an excellent level of agreement by kappa statistic analysis (kappa = 0.90; 95% confidence interval 0.88-0.92). The level of agreement between local and central pathologists did not vary with the image guidance system (stereotactic mammography vs. ultrasound) or with the mammographic findings (soft tissue density vs. microcalcifications). The level of diagnostic agreement observed for CNB was comparable to that observed among 596 open surgical biopsies obtained from patients in this study and subjected to central pathology review (93% agreement; kappa = 0.89, 95% confidence interval 0.86-0.92). CONCLUSIONS: The level of diagnostic agreement in interpretation of breast CNB is extremely high among pathologists and is comparable to that seen for open surgical biopsy.