Editorial: Optimizing Schools of Cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.

Optimizing schools of cytology: Discussions from the 2022 ASC/IAC Cytology Education Symposium, North American Strategies, and European Symbiosis.

This report highlights information and outcomes from the November 2022 ASC/IAC joint Cytology Education Symposium, an annual conference organized by the Cytology Programs Review Committee. The manuscript provides information on shared educational opportunities and practices for cytology students and other learners in anatomic pathology, discusses recruitment strategies for schools of cytology, conveys teaching resources, introduces perspectives on virtual microscopy and online learning, and transmits information about wellness of students in schools of cytology.

Oil Red O Staining of Pulmonary Macrophages in Bronchoalveolar Lavage Specimens Is Not Specific for Vaping-Associated Lung Injury.

OBJECTIVES: Oil Red O (ORO) positivity in bronchoalveolar lavage (BAL) fluid macrophages in the setting of e-cigarette, or vaping, product use-associated acute lung injury (EVALI) has been frequently requested by clinicians based on rare reports and subsequent US Centers for Disease Control and Prevention guidelines. The aim of this study was to determine the specificity of ORO staining in BAL specimens with disease states other than EVALI. METHODS: Consecutive BAL specimens (October-December 2019) were stained with ORO. The lipid-laden macrophage index (LLMI) was calculated for each case. RESULTS: We studied BAL samples from 50 patients. Indications for BAL were surveillance bronchoscopy for lung transplantation (27/50), suspected infection (12/50), sarcoidosis/suspected sarcoidosis (3/50), nodules or ground-glass opacities (3/50), hemoptysis (2/50), asthma or eosinophilic pneumonia (2/50), and idiopathic pulmonary fibrosis (1/50). ORO staining was seen in BAL fluid macrophages in 45 of 50 cases (focal in 18, moderate in 23, diffuse in 4); LLMI ranged from 0 to 218. Using a threshold of LLMI of 85 or higher as positive, ORO was positive in 7 of 50 (14%) cases (range, 85-218). CONCLUSIONS: ORO staining in BAL fluid macrophages is not specific for EVALI. Even when an LLMI of 85 or higher is used as a threshold for positivity, ORO positivity occurs in a significant subset of non-vaping-related cases.

Impact of education on institutional and faculty rates of atypical squamous cells.

INTRODUCTION: Papanicolaou test quality metrics include the ASC rate, ASC:SIL ratio, and ASC HPV+ rate. What a laboratory should do when metrics show a worrisome trend is not well defined. In 2015, our laboratory noted a worrisome trend in our quality metrics and decided to implement a systemic education program in 2016; we monitored the effectiveness of our program. METHODS: An educational intervention was designed for March/April 2016. Cytotechnologist education consisted of: group meeting on March 10 to discuss metrics, lecture, and written materials on ASC-US criteria, a quiz on challenging ASC-US cases, encouragement to seek consultation, and each cytotechnologist received quarterly individual metrics. The cytopathologist education consisted of: group meeting on April 16 to discuss metrics, encouragement to bring borderline cases to consensus conference, and each faculty received quarterly individual metrics. The ASC rate, ASC:SIL ratio, and ASC HPV+ rate was collected for the institution and each individual faculty in 2016 for January to March (pre-interventions, Q1), April to June (post-interventions, Q2), and July to September (post-interventions, Q3). ASC-H was included in the calculation of ASC %, ASC:SIL, and ASC HPV+ rates. RESULTS: There was a substantial decline in the lab ASC rate and ASC:SIL ratio, and the ASC HPV+ rate increased. Individual faculty changes in ASC:SIL ratio and ASC HPV+ rate also improved. CONCLUSIONS: In our institution, an educational program has been very effective in improving Papanicolaou test metrics. It is helpful to perform re-education at all levels within the department.

Mammary mesenchymal and fibroepithelial lesions: An illustrated cytomorphologic update with differential diagnoses.

The Uniform Approach to Breast Fine Needle Aspiration Biopsy was put forward by a learned group of breast physicians in 1997. This landmark manuscript focused predominantly on diagnosis and reporting of mammary epithelial lesions. Today, most American practitioners turn initially to core biopsy rather than aspiration biopsy for the first line diagnosis of solid breast lesions; however, recent efforts from the International Academy of Cytology have produced a system called the Standardized Reporting of Breast Fine Needle Aspiration Biopsy Cytology (colloquially labeled in 2017 as the "Yokohama System"), suggesting a new interest in breast fine needle aspiration (FNA), especially in resource limited settings or clinical practice settings with experienced breast cytopathologists. Fibroepithelial lesions of the breast comprise a heterogeneous group of biphasic tumors with epithelial and stromal elements. Mesenchymal lesions of the breast include a variety of neoplasms of fibroblastic, myofibroblastic, endothelial, neural, adipocytic, muscular, and osteo-cartilaginous derivations. The cytology of mesenchymal breast lesions is infrequently described in the literature and is mainly limited to case reports and small series. This illustrated review highlights the cytologic features of fibroepithelial and mesenchymal mammary proliferations and discusses differential diagnoses and histomorphologic correlates.

Pleomorphic and atypical multinucleated giant cells in solid pseudopapillary neoplasm of pancreas: A diagnostic pitfall in cytology and a review of the literature.

Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare low-grade malignancy typically occurring in young women. Occasionally, these neoplasms present with pleomorphic to atypical multinucleated giant tumor cells which may mimic high-grade malignancy. Our patient is a 25-year-old male who presented with one year of intermittent epigastric pain. Magnetic resonance imaging showed a 3.1 × 2.5 cm mass in the pancreas body. Endoscopic ultrasound-guided fine needle aspiration of the mass showed large pleomorphic cells and atypical multinucleated giant cells in a background of singly scattered polygonal cells. Focally, these cells surrounded delicate hyalinized to fibrovascular cores forming pseudopapillae. Immunohistochemical stains show tumor cells are positive for beta-catenin, CD10, vimentin, and CD56. Although rare surgical pathology publications have described the presence of pleomorphic to atypical multinucleated giant cells occurring in SPN, to our knowledge, this is the first case reported example focused on cytomorphologic illustration and description.

Unsatisfactory exfoliative anal cytology samples, 15-year experience with histologic, cytologic, and molecular follow-up.

BACKGROUND: The incidence of anal carcinoma has risen in recent decades. Exfoliative cytology screening of selected high risk patients is performed in many centers. Unsatisfactory cytology results are frustrating to patients, clinicians, and laboratorians. The aim of this study is to ascertain outcomes of patients with non-diagnostic anal cytology. METHODS: A retrospective review of anal cytology testing performed at the Cleveland Clinic between 01/01/2001 and 12/31/2015 was performed. All cases were received as liquid-based samples and processed as ThinPreps (Hologic, Marlborough, MA). Co-testing for HR-HPV DNA was performed using Hybrid Capture 2® (Qiagen, Germantown, MD) in the majority of patients. RESULTS: Of 1,276 ThinPrep anal cytology samples, 130 (10%) were deemed unsatisfactory. 77% of patients were HIV positive. 85% were males. Of the unsatisfactory cases, 116 (89%) were co-tested for HR-HPV DNA. Of those, 40 patients (34%) had a simultaneous positive HR-HPV DNA. Adequate follow up cytology within a one year and a two year period revealed that 18/130 (14%) and 26/130 (20%) of patients had ASC or SIL respectively. Histologic follow-up within one and two years showed 3 patients (2%) and 8 patients (6%) with HSIL or worse. CONCLUSIONS: High risk patients with unsatisfactory anal cytology are not "negative". At least one-third proved to be concomitantly HR-HPV DNA positive with one-fifth showing subsequent cytologic squamous abnormalities and with more than 5% being diagnosed with a high grade intraepithelial lesion within two years. Prompt repeat cytology and/or HR-HPV DNA is recommended for high risk patients with non-diagnostic cytology.

Next-generation sequencing of liquid-based cytology non-small cell lung cancer samples.

BACKGROUND: The detection of mutated epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) with residual cell pellets derived from liquid-based cytology (LBC) samples (eg, endoscopic ultrasound-guided fine-needle aspiration) has been validated with allele-specific polymerase chain reaction. The aim of this study was to validate next-generation sequencing (NGS) technology for detecting gene mutations with residual cell pellets from LBC. METHODS: Archived DNA extracted from LBC samples of adenocarcinoma stored in PreservCyt with a known EGFR mutation status was retrieved. Genomic DNA was multiplex-amplified and enriched with Ion AmpliSeq Cancer Hotspot Panel v2 chemistry and the OneTouch 2 instrument; this was followed by semiconductor sequencing on the Ion Personal Genome Machine platform. The mutation hotspots of 6 NSCLC-related genes (BRAF, EGFR, ERBB2, KRAS, MET, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α [PIK3CA]) were analyzed with NextGENe and Torrent Suite bioinformatics tools. RESULTS: The commonly identified EGFR sequence changes, including 4 L858R mutations, 3 exon 19 deletions, and 1 exon 20 insertion, were in 100% concordance between the assay platforms. Less common NSCLC variants were also found in the mutation hotspots of ERBB2, KRAS, MET, and PIK3CA genes. CONCLUSIONS: NSCLC mutation analysis using NGS can be successfully performed on residual cell pellets derived from LBC samples. This approach allows the simultaneous examination of multiple mutation hotspots in a timely manner to improve patient care. Cancer Cytopathol 2017;125:178-187. © 2016 American Cancer Society.

Knowledge of the HPV status biases cytotechnologists' interpretation of Pap tests originally diagnosed as negative for intraepithelial lesion or malignancy.

BACKGROUND: Because of cervical cancer screening recommendations and forthcoming first-line human papillomavirus (HPV) screening, many Papanicolaou (Pap) tests will be performed in patients with known concurrent HPV results. This study was designed to evaluate whether knowledge of the HPV status affects cytotechnologists' interpretation of Pap tests. METHODS: A retrospective search of cervical screening Pap tests with known concurrent HPV results provided 250 ThinPrep Pap tests, which were chosen to reflect an atypical rate similar to the rate of the Cleveland Clinic's normal practice. Fifty percent of negative for intraepithelial lesion or malignancy (NILM) and atypical squamous cells of undetermined significance (ASCUS) cases were from patients with positive HPV results. Slides were re-evaluated twice by 8 cytotechnologists blinded to the diagnosis and study purpose. The HPV status was provided for 50% of the cases in the first phase; after a washout period, knowledge of the HPV status for each case was reversed in the second phase. Follow-up information was collected from the medical record. RESULTS: In both phases, there was a significant bias for HPV-positive NILM cases to be upgraded to ASCUS or worse when the HPV-positive status was provided (P < .001). When the HPV status was withheld, there was no difference in upgrading NILM cases (phase 1, P = .69; phase 2, P = .066). A combined analysis showed a significant bias in referral to the pathologist when the HPV-positive status was provided rather than withheld (P < .001). Follow-up data revealed no significant effect of bias when the HPV-positive status was provided between patient groups with benign, low-grade, or high-grade follow-up. CONCLUSIONS: A known HPV-positive status biases cytotechnologists' interpretation of Pap tests, and this results in a higher rate of upgrading to ASCUS or worse; however, it does not improve sensitivity for disease detection. Cancer Cytopathol 2017;125:60-69. © 2016 American Cancer Society.

Interobserver agreement in the cytologic grading of atypia in neoplastic pancreatic mucinous cysts with the 2-tiered approach.

BACKGROUND: The accurate cytologic grading of epithelial atypia in fine-needle aspirates of pancreatic mucinous cysts has important implications for clinical management. The Papanicolaou Society of Cytopathology has recommended a 2-tiered system of low-grade (LG) and high-grade (HG) for grading this atypia. Using this approach, this study examined the interobserver agreement within a group of cytopathologists at the Cleveland Clinic. METHODS: Twenty cases of fine-needle aspiration of pancreatic neoplastic mucinous cysts with documented histologic follow-up and representative lesional cells were selected. Blinded to the histologic outcome, 4 cytopathologists were independently asked to assign the highest grade of atypia with the 2-tiered system of LG and HG atypia for these cases. The interobserver agreement was calculated with the κ statistic. RESULTS: The overall raw agreement in the grading of atypia was 60%. The overall chance-adjusted agreement was fair (κ = 0.28). On the basis of the histologic outcomes, the cases were stratified into group A (HG dysplasia or worse) and group B (LG or intermediate-grade [IG] dysplasia on follow-up). Group A (n = 12) showed good chance-adjusted agreement (κ = 0.65). For group B, the chance-adjusted agreement among the observers was poor (κ = 0.03). CONCLUSIONS: This study shows that the cytologic recognition of HG dysplasia or worse as HG atypia in pancreatic mucinous cysts has a good degree of interobserver reproducibility among cytopathologists. In contrast, a problematic area with a lack of agreement appears to be the cytologic recognition of LG and IG dysplasia as LG atypia. Additional studies with the development of reproducible criteria and educational tools may help with this challenging distinction. Cancer Cytopathol 2016;124:909-916. © 2016 American Cancer Society.

Histopathology of excised midurethral sling mesh.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to compare the histological characteristics of pathological specimens of excised midurethral sling mesh and surrounding vaginal tissue in patients who presented preoperatively with pain and/or exposure of mesh to patients who underwent mesh excision for voiding dysfunction without pain and/or erosion. METHODS: This is a retrospective case-control study of women who underwent excision of midurethral sling mesh between 2008 and 2013. Three groups were identified: (1) voiding dysfunction without pain or exposure (control group), (2) pain and/or mesh exposure, and (3) voiding dysfunction with pain and/or mesh exposure. All original pathological specimens were rereviewed by one pathologist blinded to indication for excision and the previous pathology report. Degree of inflammation and fibrosis were recorded based on a 4-point scale along with the presence of giant cell reaction. RESULTS: A total of 130 subjects met inclusion criteria: 60 (46.2 %) with voiding dysfunction only, 21 (16.2 %) with pain/erosion, and 49 (37.7 %) with both pain/exposure and voiding dysfunction. The voiding dysfunction only group was found to have significantly higher levels of inflammation, median grade 2 (1-3), compared to the other two groups with a p value of 0.007. There were no statistical differences in fibrosis and giant cell reaction between the three groups. CONCLUSIONS: Midurethral sling mesh excised for voiding dysfunction demonstrates elevated levels of inflammation compared to mesh that is excised for pain and/or exposure. The vaginal tissue fibrosis and giant cell reaction are similar in patients who undergo mesh excision for voiding dysfunction and pain, and/or mesh exposure.

Endobronchial ultrasonography-guided transbronchial needle aspiration, an effective modality for sampling targeted thoracic lesions in adult lung transplant recipients.

INTRODUCTION: Lung transplantation (LTx) is performed for end-stage lung diseases that would be otherwise fatal. Pulmonary allograft recipients are a unique patient population as they are at high risk for malignancy and infectious complications due to the need for immunosuppression. Endobronchial ultrasonography (EBUS)-guided fine-needle aspiration (FNA) is a minimally invasive technique for evaluating abnormalities of the mediastinum/lungs. To our knowledge, this report is the first in the literature addressing targeted EBUS-FNA biopsies in patients who have undergone LTx. MATERIAL AND METHODS: During 5 years from May 1, 2009 to May 1, 2014, 582 patients underwent LTx at the Cleveland Clinic. A review of records indicated that 14 of these patients later underwent EBUS-FNA. Demographic and diagnostic parameters were recorded. RESULTS: A total of 14 patients (mean age 64 years) underwent EBUS-FNA after LTx. The mean interval between LTx and EBUS-FNA was 15 months. EBUS-FNA yielded cytologic material diagnostic of malignancy in 10 patients (71%) with one-half of those cases being squamous carcinomas. CONCLUSIONS: EBUS-FNA is a useful diagnostic modality in lung allograft recipients and is of value in confirming and staging thoracic malignancies in this population. Carcinoma subtyping is feasible by EBUS-FNA, and performance of ancillary studies to confirm clonality in post-transplant lymphoproliferative disorders is possible.

Squamous intraepithelial lesions and squamous cell carcinomas detected by endometrial sampling: Pap test correlation and outcome data.

INTRODUCTION: Squamous intraepithelial lesions (SIL) and squamous cell carcinomas (SCC) can rarely be detected in endometrial sampling. We reviewed all cases of SIL and SCC detected solely on endometrial biopsies and curettings to determine their significance and whether these findings were detected on prior or concurrent Papanicolaou (Pap) test. MATERIALS AND METHODS: Endometrial samples with detached fragments of SIL and SCC over a 13-year period were reviewed, along with prior and/or concurrent Pap tests, human papillomavirus status, and subsequent pathology results. Cases with concurrent cervical or endocervical sampling that showed SIL or SCC were excluded. RESULTS: Fifty patients had endometrial biopsies and/or curettings with SIL or SCC. Thirty-six patients (72%) had concurrent or previous Pap tests within 1 year prior to the endometrial sampling. The Pap test was negative for intraepithelial lesion or malignancy in 44% of patients (16/36) and atypical squamous cells of undetermined significance in 22% of patients (8/36). The source of the SIL and SCC in endometrial sampling was cervical SIL in 18 patients, cervical SCC in 14 patients, endometrioid carcinomas in 3 patients, metastatic carcinoma in 1 patient, and not definitively identified in 14 patients. CONCLUSIONS: The majority of SIL and SCC in endometrial samples are from the cervix. Prior and concurrent Pap tests were often negative for intraepithelial lesion or malignancy in patients with SIL and SCC detected by endometrial samples. This suggests that SIL and SCC detected on endometrial sampling may detect a subset of cervical SIL/SCC that are more proximal in the endocervical canal and are not sampled with conventional Pap tests.

Utility of GATA3, mammaglobin, GCDFP-15, and ER in the detection of intrathoracic metastatic breast carcinoma.

INTRODUCTION: Breast carcinoma (BC) metastatic to the intrathoracic cavity is difficult to diagnose due to low sensitivity of current immunohistochemical (IHC) stains. Mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15), and estrogen receptor (ER) immunomarkers show variable results. GATA3 is a recently described marker for detecting urothelial and breast cancers. Our goal is to test the utility of GATA3 in cell blocks from thoracic cytology specimens. MATERIALS AND METHODS: We retrieved cases of BC that metastasized to the thoracic cavity from January 1, 2005 to September 30, 2013. IHC was performed on the cell blocks for the presence of GATA3, ER, GCDFP-15, and mammaglobin. Stains were scored quantitatively and qualitatively. RESULTS: Fifty cases of metastatic BC found in pleural effusions and endobronchial ultrasound-guided fine-needle aspirates were identified in 48 patients. Thirty-four cases had sufficient material for IHC (19 pleural effusions, 15 endobronchial ultrasound-guided fine-needle aspirates). GATA3 showed strong nuclear positivity in 31 of 34 cases (91.2%). ER (25 of 34, 73.5%), mammaglobin (23 of 34, 67.6%) and GCDFP-15 (11 of 34, 32.6%) were positive in fewer cases. GATA3 and ER were concordant in 26 of 34 cases (76.5%) (24 ER/GATA3-positive, 2 ER/GATA3-negative). Discordant results were found in 8 of 34 cases (23.5%). Of these, GATA3 was positive and ER was negative in 7 cases. GATA3 was negative and ER was positive in 1 case. CONCLUSIONS: GATA3 is more sensitive than ER, mammaglobin, or GCDFP-15 in detecting metastatic BC in cytologic specimens. GATA3 may be positive when ER is negative. In cytologic specimens with limited diagnostic material, GATA3 may be used as a first-line marker in a limited IHC panel to support metastatic BC.

Atypical endometrial cells and atypical glandular cells favor endometrial origin in Papanicolaou cervicovaginal tests: Correlation with histologic follow-up and abnormal clinical presentations.

The 2001 Bethesda system recommends further classifying atypical glandular cells (AGCs) as either endocervical or endometrial origin. Numerous studies have investigated the clinical significance of AGC. In this study, we investigated the incidence of clinically significant lesions among women with liquid-based Papanicolaou cervicovaginal (Pap) interpretations of atypical endometrial cells (AEMs) or AGC favor endometrial origin (AGC-EM). More importantly, we correlated patients of AEM or AGC-EM with their clinical presentations to determine if AEM/AGC-EM combined with abnormal vaginal bleeding is associated with a higher incidence of significant endometrial pathology. All liquid-based Pap tests with an interpretation of AEM and AGC-EM from July, 2004 through June, 2009 were retrieved from the database. Women with an interpretation of atypical endocervical cells, AGC, favor endocervical origin or AGC, favor neoplastic were not included in the study. The most severe subsequent histologic diagnoses were recorded for each patient. During this 5-year period, we accessioned 332,470 Pap tests of which 169 (0.05%) were interpreted as either AEM or AGC-EM. Of the 169 patients, 133 had histologic follow-up within the health care system. The patients ranged in age from 21 to 71 years old (mean 49.7). On follow-up histology, 27 (20.3%) had neoplastic/preneoplastic uterine lesions. Among them, 20 patients were diagnosed with adenocarcinoma (18 endometrial, 1 endocervical, and 1 metastatic colorectal), 3 with atypical endometrial hyperplasia, and 4 with endometrial hyperplasia without atypia. All patients with significant endometrial pathology, except one, were over 40 years old, and 22 of 25 patients reported abnormal vaginal bleeding at the time of endometrial biopsy or curettage. This study represents a large series of women with liquid-based Pap test interpretations of AEM and AGC-EM with clinical follow-up. Significant preneoplastic or neoplastic endometrial lesions were identified in 20.3% of patients. Patients with Pap test interpretations of AEM or AGC-EM and the clinical presentation of abnormal vaginal bleeding should be followed closely.

Hybrid Capture 2 human papilloma virus testing for head and neck cytology specimens.

INTRODUCTION: High-risk human papilloma virus (hrHPV)-associated head and neck (HN) squamous cell carcinomas (SCCs) have important differences from non-hrHPV-related HNSCCs. A highly sensitive and specific test for HPV in cytology fine-needle aspirations (FNAs) would be useful, as it has the potential to alter therapy. MATERIALS AND METHODS: Patients with an HN FNA diagnosed as SCC or suspicious for SCC were included. Hybrid Capture 2 (HC2) was performed on residual rinse material and chromogenic in situ hybridization (CISH) for hrHPV was performed on the cell block. HC2-positive samples were genotyped for HPV types 16, 18, and 45. "Gold standard" p16 and CISH testing was performed on histologic material from the primary tumor. Tumors concordantly positive for p16 and CISH were considered hrHPV-positive, concordantly negative were considered hrHPV-negative, and discordant results were considered hrHPV-equivocal. RESULTS: A total of 96 FNAs from 95 patients were included. Surgical material was available in 80 patients. Of those, 29 patients (36%) were positive for hrHPV by "gold standard" testing, and 3 patients (4%) had equivocal results. HC2 was 72% sensitive and 100% specific for hrHPV. Sixty percent of HC2-positive aspirate samples were positive for HPV16. CISH was 61% sensitive and 79% specific for hrHPV. HC2 had a significantly better sensitivity and specificity than did CISH on paired sample analysis (P < .05). CONCLUSIONS: HC2 is a highly sensitive and specific assay for the detection of hrHPV in HN FNA samples. This new application of a familiar, widely available testing method has the potential to be clinically useful in the management of patients with HNSCC.

Rapid on-site evaluation of endobronchial ultrasound-guided fine-needle aspirates: correlation of adequacy assessment and final diagnosis in patients with bronchogenic carcinoma.

INTRODUCTION: We review endobronchial ultrasound-guided fine-needle aspirate samples and investigate cases with discrepancies between rapid on-site evaluation (ROSE) and final diagnosis in patients with bronchogenic carcinoma. MATERIALS AND METHODS: Endobronchial ultrasound-guided fine-needle aspirates from 2009 to 2010 were studied. On-site adequacy assessments were compared with final diagnoses. Concordant diagnoses showed agreement between ROSE interpretation and final diagnosis. If the initial interpretation differed from the final diagnosis, the case was discordant. Slides from discordant aspirates were reviewed. Discordant results were categorized as sampling error or interpretive/screening error at ROSE. RESULTS: A total of 340 endobronchial ultrasound-guided procedures were performed in 335 patients (168 men, 167 women, median age 65 years). Diagnostic discrepancies between ROSE and final diagnoses occurred in 65 aspirates (11%) from 51 patients with carcinoma. Of the 65 discrepant cases, 52 (83%) were subsequently called positive for carcinoma. Rescreening of slides in 47 available cases with a final positive diagnosis showed insufficient tumor for diagnosis in 28 of 47 cases (60%). The remaining 19 of 47 cases (40%) were classified as interpretive/screening errors at ROSE. Most errors occurred in aspirates called atypical or atypical suspicious, which upon rescreening were considered diagnostic (16 aspirates, 84%). CONCLUSIONS: Initial and final diagnoses were concordant in 89% of aspirates from patients with carcinoma. All aspirates that were positive at ROSE were concordant. In discordant cases, all aspirates deemed "atypical suspicious for malignancy" and 86% of aspirates deemed "atypical cells" on ROSE had a final diagnosis of carcinoma. The majority of discordant cases with a positive final diagnosis were due to sampling (60%).

Anaplastic thyroid cancer in young patients: a contemporary review.

PURPOSE: Little is known about prognostic factors and treatment outcomes in young patients with anaplastic thyroid cancer (ATC). The goal of this study is to define the clinical features of this subgroup. MATERIAL AND METHODS: Patients age 55 or younger with either ATC or well-differentiated thyroid cancer (WDTC) with anaplastic changes were identified using electronic medical record at the Cleveland Clinic. The same number of patients older than 55 was randomly selected to serve as control. Progression-free survival (PFS), overall survival time (OST) and cause-specific mortality (CSM) were measured against age, tumor histology, extent of disease, and treatment modalities. RESULTS: Twelve patients age 55 or younger were identified. The median age was 51 years. Four patients had WDTC with anaplastic components--mixed tumor group (MTG). Their median PFS, OST, and CSM at 24 months were 21.5 months, 51 months, and 25%, respectively. For the other 8 patients who had pure ATC, their median PFS, OST, and CSM were 3.5 months, 6 months, and 100%, respectively. Patients in the MTG had better survival compared to the pure ATC and control group in terms of PFS (p = 0.0047 and p = 0.0053), OST (p = 0.0028 and p = 0.0029) and the CSM at 24 months (p = 0.0339 and p = 0.0096). In the pure ATC group, patients with positive cervical lymph node and distant metastases had similar overall survival outcomes (6 vs. 8 months, p = 0.4995). CONCLUSION: Prognostic factors favoring survival in young patients with ATC include ATC arising within WDTC. Once full anaplastic transformation occurs, age was not a significant factor in survival.

Prospective and retrospective review of gynecologic cytopathology: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 2.

CONTEXT: Two quality metrics for gynecologic cytology are the subject of this review: "prospective rescreening" and "retrospective rescreening." OBJECTIVE: To offer consensus best practice approaches based on the College of American Pathologists' laboratory-based survey funded by the Centers for Disease Control and Prevention. DESIGN: The College of American Pathologists submitted a paper-based survey to 1245 laboratories. After review of initial results, follow-up Web-based survey results, and a literature review, consensus best practice statements were presented at a national consensus conference. These statements were discussed and voted upon by conference participants. Results.-A total of 541 laboratories responded to survey questions about prospective and retrospective rescreening. Most laboratories (>85%) prospectively rescreen more than 10% of Pap tests interpreted as negative for intraepithelial lesion or malignancy. Most (72%) report inclusion of less than 20% high-risk cases. Most laboratories use multiple measures to define "high risk." Most laboratories (96.2%) retrospectively rescreen Pap tests from the preceding 5 years only. In most laboratories (71.4%) only Pap test results with high-grade squamous intraepithelial lesion or worse prompt retrospective review. CONCLUSIONS: The number of Pap tests from high-risk patients should be maximized in prospective and retrospective rescreening. Unsatisfactory Pap tests should also be included. All readily identifiable high-risk human papillomavirus-positive cases with an interpretation of negative for intraepithelial lesion or malignancy should be prospectively rescreened. Cervical biopsy results with high-grade cervical intraepithelial neoplasia or worse (CIN 2+) should trigger retrospective rescreening. Regular feedback should be provided to cytotechnologists and cytopathologists. Upgraded diagnoses from negative for intraepithelial lesion or malignancy to atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, should be monitored.