Evaluating of HPV-DNA ISH as an adjunct to p16 testing in oropharyngeal cancer.

AIM: Current guidelines recommend p16 immunohistochemistry (IHC) for testing human papillomavirus (HPV) in oropharyngeal carcinoma (OPSCC). We evaluated the value of adding DNA in situ hybridization (ISH) to p16 IHC. METHODS: Fifty patients with OPSCC were analyzed. Concordance between HPV-DNA ISH and p16 IHC was measured by Gwet's agreement coefficient. RESULTS: p16 IHC was positive in 35/48 (72.9%), negative in 8/48 (16.7%) patients. Wide spectrum DNA-ISH was positive in 9/23 (39%) and negative in 14/23 (60.9%) patients. High-risk 16/18 (HR) HPV DNA-ISH was positive in 11/23 (47.8%) and negative in 12 (52.2%) patients. The agreement between HPV DNA-ISH and p16 IHC is fair (Gwet's AC1 = 0.318). CONCLUSION: The agreement between p16 IHC and HPV-DNA ISH was fair. However, ISH sensitivity was low. Our findings add to the current data that p16 IHC testing is reliable and may be enough as a stand-alone test for HPV detection in OPSCC.

Diagnosis of Schistosoma haematobium on voided urine cytology: a case report with radiologic correlation.

BACKGROUND: Infection with schistosomal species is becoming a more frequent finding in hospitals throughout the United States. Some causes that can be attributed to the rise include increased immigration from and travel to endemic areas. CASE: We report a case of urinary schistosomiasis diagnosed on urine cytology in a 7-year-old Nigerian boy. Infection was suspected after review of the clinical history and correlation with radiologic images. CONCLUSION: The rise in incidence has made it necessary for cytopathologists to be increasingly aware of these infections, in particular, Schistosoma haematobium, because it is the most frequent agent to be encountered on a cytology specimen, particularly urine. Similar cases have been published, one with specimen concentration and one without. However, no cases of cytology diagnosis with radiologic correlation are seen in the English literature.

Risk stratification of salivary gland cytology utilizing the Milan system of classification.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is based on risk stratification. Our study is a retrospective review of salivary gland fine needle aspiration cytology (FNAC) with the goal of determining the risk of malignancy (ROM) in each of the categories proposed by the MSRSGC. METHODS: FNAC of salivary gland lesions with corresponding surgical resection specimens were retrieved over a 5-year period. Metastatic tumors were excluded. BothFNAC and corresponding surgical resections were reviewed blindly and classified as per criteria published by the MSRSGC. The ROM for each of the diagnostic categories was determined and compared with the ROM published by the MSRSGC. RESULTS: The total number of entities and ROM in 199 reviewed cases were as follows: Nondiagnostic 18 (9.2%) (ROM 0%), non-neoplastic 4(2%) (ROM 0%), atypia of undetermined significance (AUS) 12(6%) (ROM 33%), benign neoplasm 118(59.2%) (ROM 0.8%), salivary gland neoplasm of uncertain malignant potential (SUMP) 22(11%) (ROM 40.9%), suspicious for malignancy 3(1.5%) (ROM 100%), malignant 22(11%) (ROM 100%). CONCLUSION: The ROM reported in our study was mostly concordant with ROM published by the MSRSGC. This classification is helpful for the management of categories; nondiagnostic, non-neoplastic, benign neoplasm, suspicious for malignancy and malignant. The management is not standardized for the category, salivary gland neoplasm of uncertain malignant potential, as clinical information plays an important role in planning surgical procedures at an individual basis. Further studies will need to be performed using this new classification to help define appropriate management and predict ROM more accurately.

Lack of transformation zone in cervical Pap tests, should it be a concern? A quality assurance initiative.

BACKGROUND: Bethesda guidelines do not require presence of transformation zone (TZ) for a cervical Pap test to be deemed adequate. However, clinicians are concerned with specimens that are reported to lack TZ. METHODS: We analyzed 566 ThinPrep cases reported as negative for intraepithelial lesion or malignancy (NILM) with no cervical abnormality detected in previous 4 years (2007-2011). These cases were divided into two cohorts; those with TZ (ETZ) and those without TZ (NTZ). Patients' age, HPV status, time of sample collection (>14 days after last menstrual period), subsequent management, interval of subsequent Pap test (<1, 1-3, and >3 years), and result of subsequent examination were compared over a 5-year period. RESULTS: The rate of abnormal Pap test on 5 year follow-up was not statistically significant (P < .9520) between cohorts. Our data demonstrates lack of statistical significance between the variables studied. Five year follow-up of all abnormal Pap smears were analyzed (93% ETZ and 7% NTZ). Of the ETZ group, 25% ASCUS remained as ASCUS and 75% were reported as NILM in subsequent Pap smears. Additionally, 75% of the LSIL were subsequently reported as NILM and 25% reported as ASCUS. One patient reported as HSIL underwent hysterectomy. Two Pap smears performed two years after surgery were negative. Within the NTZ group, one case of ASCUS was NILM upon follow-up. CONCLUSION: Pap smears with NTZ were not at a higher risk for subsequent detection of cervical abnormalities, making earlier repeat testing unnecessary. Rescreening cases without TZ is neither cost effective nor necessary.

Fine-needle aspiration biopsy of lytic bone lesions: An institution's experience.

OBJECTIVES: Fine needle aspiration (FNAB) is an effective, minimally-invasive, inexpensive, diagnostic technique. The objective of this study was to evaluate the accuracy of FNAB in the diagnosis of bone lesions. METHODS: FNABs of bone lesions diagnosed at our institution over a 2-year period were retrospectively analyzed. RESULTS: 241 samples were reviewed. Patients included 121 males and 120 females, with ages ranging from 4-95 years (mean = 66 years). Of these 241 cases, 43.2% had FNAB and 56.8% had FNAB with core needle biopsy (CNB). The cytologic diagnoses were categorized as nondiagnostic, benign, atypical, suspicious, and positive for malignant cells. Total of 84.3% of FNABs were diagnostic. Of the malignant cases, 78.5% were metastases from nonosseous primary sites, 17.1% were lymphoproliferative lesions, and 4.4% were primary bone tumors. The most common site of metastasis was the pelvic bones (43.5%) followed by the vertebral column (38.7%). Breast (21%), lung (12.7%), and prostate (11.3%) were the most common identifiable primary site in metastatic cases. FNA smears and cell blocks allowed identification of metastatic lesions in 94.3% cases with immunohistochemistry (IHC). Obtaining a concomitant CNB did not result in a statistically significant increase in overall diagnostic yields (P = .20), ascertaining presence of metastatic lesion (P = .96) or ability to identify site of primary tumor in cases of metastasis (P = .53) compared to FNAB alone. Diagnostic accuracy was improved by reviewing clinical history, performing cell block, and IHC. CONCLUSIONS: FNAB is a reliable tool for diagnosis of bone lesions with comparable diagnostic sensitivity to CNB.

How "suspicious" is that nodule? Review of "suspicious" Afirma gene expression classifier in high risk thyroid nodules.

BACKGROUND: The Afirma gene expression classifier (GEC) is being increasingly utilized to confirm the benign nature of indeterminate FNA cytology results thus avoiding unnecessary surgical procedures. However the "suspicious" result of the Afirma GEC does not classify these indeterminate nodules further in determining appropriate management. This study investigated the outcome of the thyroid nodules deemed to be "suspicious" by the Afirma GEC in a high risk population. METHODS: The pathology database was searched for all thyroid nodules with Afirma test results over a three year period, 2013-2015. All thyroid nodules with a "suspicious" Afirma GEC result were investigated. Patient medical records were retrospectively reviewed for clinical history, FNA results, radiologic findings, management and follow-up. RESULTS: Afirma result was suspicious in 69 cases. On cytologic evaluation 3.0% of the cases were non diagnostic (ND), 9% benign, 62% AUS, and 26% suspicious for neoplasm (SN). There was no follow up in 13% of cases and 87% were resected (50% lobectomies and 50% total thyroidectomies). On surgical resection 82% were benign, with 45% follicular adenoma (FA), and 37% nodular goiter (NG). The remaining 18% were malignant. CONCLUSION: The rate of malignancy in nodules suspicious by Afirma was 18.3% (11/60). The rate of malignancy in nodules suspicious for neoplasm (SN) on cytology interpretation was 31.2% (5/16). False positive rate of Afirma was 56% (32/57). We conclude that cytology interpretation has a higher rate of predicting malignancy, in nodules interpreted as SN, when compared with the Afirma test, by almost twofold Diagn. Cytopathol. 2017;45:308-311. © 2016 Wiley Periodicals, Inc.

Reproducibility of atypia of undetermined significance/follicular lesion of undetermined significance category using the bethesda system for reporting thyroid cytology when reviewing slides from different institutions: A study of interobserver variability among cytopathologists.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) offers a six-tiered diagnostic scheme for thyroid Fine Needle Aspiration (FNA): Benign, Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS), suspicious for follicular neoplasm, suspicious for malignancy, malignant, and unsatisfactory with an aim to standardize diagnostic criteria. Reported rate of AUS/FLUS category in the literature has varied from 3% to 20.5%. METHODS: The aim of this study was to assess interobserver variability among cytopathologists to assess reproducibility of the AUS/FLUS category. Seven cytopathologists brought FNA cases (a mixture of atypical and non-atypical FNA diagnosis) diagnosed using TBSRTC from their respective institutions which were reviewed and diagnosed by the participants. The analysis assessed interobserver variability among 7 cytopathologists and determined characteristics on the slides which were associated with concordance to the institutional diagnosis. RESULTS: Seventy eight of 125 (62.4%) benign cases were classified as benign by the reviewers and 26 (21%) were called AUS/FLUS on review. A third of the AUS/FLUS cases were called benign on review and 28.2% were classified as suspicious for neoplasia/malignancy. Roughly a third each of the suspicious for follicular neoplasm/suspicious for malignancy cases were classified as AUS/FLUS. DISCUSSION: When pathologists from different institutions shared their slides, concordance was high for specimens with adequate cellularity and those that were clearly benign but thresholds varied for the other indeterminate categories. Most definite categorization of the AUS/FLUS category was seen on review. Diagn. Cytopathol. 2017;45:399-405. © 2017 Wiley Periodicals, Inc.

Update on the College of American Pathologists Experience With High-Risk Human Papillomavirus Proficiency Testing for Cytology.

CONTEXT: - Since 2008, the College of American Pathologists has provided the human papillomavirus for cytology laboratories (CHPV) proficiency testing program to help laboratories meet the requirements of the Clinical Laboratory Improvement Amendments of 1988. OBJECTIVES: - To provide an update on trends in proficiency testing performance in the College of American Pathologists CHPV program during the 4-year period from 2011 through 2014 and to compare those trends with the preceding first 3 years of the program. DESIGN: - Responses of laboratories participating in the CHPV program from 2011 through 2014 were analyzed using a nonlinear mixed model to compare different combinations of testing medium and platform. RESULTS: - In total, 818 laboratories participated in the CHPV program at least once during the 4 years, with participation increasing during the study period. Concordance of participant responses with the target result was more than 98% (38 280 of 38 892). Overall performance with all 3 testing media-ThinPrep (Hologic, Bedford, Massachusetts), SurePath (Becton, Dickinson and Company, Franklin Lakes, New Jersey), or Digene (Qiagen, Valencia, California)-was equivalent (P = .51), and all 4 US Food and Drug Administration (FDA)-approved platforms-Hybrid Capture 2 (Qiagen), Cervista (Hologic), Aptima (Hologic), and cobas (Roche Molecular Systems, Pleasanton, California)-outperformed laboratory-developed tests, unspecified commercial kits, and other (noncommercial) methods in ThinPrep medium (P < .001). However, certain off-label combinations of platform and medium, most notably Cervista with SurePath, demonstrated suboptimal performance (P < .001). CONCLUSIONS: - Laboratories demonstrated proficiency in using various combinations of testing media and platforms offered in the CHPV program, with statistically significant performance differences in certain combinations. These observations may be relevant in the current discussions about FDA oversight of laboratory-developed tests.

Performance Characteristics of Adenoid Cystic Carcinoma of the Salivary Glands in Fine-Needle Aspirates: Results From the College of American Pathologists Nongynecologic Cytology Program.

CONTEXT: Although the cytomorphology of adenoid cystic carcinoma (ACC) has been well described, the accuracy of this diagnosis in fine-needle aspirates (FNAs) of the salivary glands has not been extensively evaluated. OBJECTIVE: To assess participants' responses in the College of American Pathologists (CAP) Nongynecologic Cytology (NGC) Program to determine the accuracy and false-negative rate of ACC cases in salivary gland FNAs. DESIGN: A retrospective review of the CAP NGC Program's cumulative data from 2000-2010 was performed for the general and the specific reference diagnosis categories for ACC in salivary gland FNAs according to preparation and participant types. RESULTS: Of 5156 responses, the overall concordance rates for both the general category of malignancy and the specific category of ACC were 63.6% (3279 of 5156) and 38.6% (1966 of 5088), respectively, with a false-negative rate of 36.4% (1877 of 5156). The most frequent false-negative responses were pleomorphic (1080) and monomorphic (526) adenoma (1614 of 5088, 31.5%), while lymphoma was the most frequent malignant misinterpretation. There was a significant statistical difference in concordance to the reference interpretation between the reader types: 39.9% (1006 of 2521) concordance rate for pathologists compared to 33.8% (503 of 1488) for cytotechnologists. However, there was no significant statistical difference for concordance to the general category or reference interpretation, based on preparation type (Papanicolaou versus modified Giemsa stained). CONCLUSIONS: In this interlaboratory comparison educational program, accurate identification of ACC has shown to be problematic, with ACC representing an important cause of false-negative responses. The most common diagnostic pitfall is distinguishing this entity from pleomorphic and monomorphic adenoma in the benign category and from lymphoma and adenocarcinoma in the malignant one.

Human papillomavirus testing and reporting rates in 2012: results of a College of American Pathologists national survey.

CONTEXT: College of American Pathologists (CAP) surveys are used to establish national benchmarks for laboratory parameters. OBJECTIVE: To evaluate changes in laboratory human papillomavirus (HPV) testing patterns in laboratories incorporating HPV testing with Papanicolaou tests in 2012. DESIGN: Data were analyzed from the CAP HPV Supplemental Questionnaire distributed to 1771 laboratories participating in either CAP HPV or CAP Papanicolaou proficiency testing in 2013. RESULTS: A total of 1022 laboratories (58%) responded. There were more high-risk (HR) HPV tests performed per institution as compared to previous surveys. There were more HPV tests performed within an institution as compared to previous surveys. Hybrid Capture 2 (HC2) remains the most common method (42.4%, 239 of 564); Cervista and cobas methods are used in 37.2% (210 of 564) and 14.9% (84 of 564) of laboratories, respectively. Human papillomavirus testing is offered as a reflex test after a Papanicolaou test result of atypical squamous cells of undetermined significance (ASC-US) in 89.6% of laboratories (476 of 531); as a cotest for women aged 30 years and older in 60.3% (404 of 531); as reflex testing after atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) in 42.7% (320 of 531); and as reflex testing after atypical glandular cells (AGC) in 27.3% (145 of 531). The HPV-positive rates for ASC-US and ASC-H were similar in 2012 and 2006. Cervista (49.2%, 88 of 179) and Roche cobas (27.4%, 49 of 179) are the most common methods used for genotyping. Most laboratories use the CAP Human Papillomavirus for Cytology Program for proficiency testing. CONCLUSIONS: There was an increase in annual volume of HR-HPV testing with a shift toward in-house HR-HPV testing. Genotyping volumes also increased. HC2 and Cervista are most commonly used, with an increasing volume of Roche cobas testing. The most common indication for HPV testing among all laboratories was ASC-US reflex testing, but an increase in HPV cotesting was observed. The data provide an update into persisting and newer trends in HPV testing practices.