Education and diversity in cytopathology: Past, present, and future.

Diversity, equity, and inclusion is a powerful goal which many of us strive toward in medicine, both in patient care and administrative leadership. As the world evolves, the practice of medicine must evolve with it. We are cognizant of the importance of the history of our medical specialties. If we do not acknowledge all parts of our history, we are doomed to repeat it. This special issue is unique and unlike anything that has previously been published in Diagnostic Cytopathology. This issue looks at some of the history of cytopathology. This historical review is followed by some of the present state of cytopathology. There are insights into global cytopathology. The final portion of this issue examines the critical need for cytotechnology schools in the United States. All of these areas are critical to the past, present, and future of cytopathology.

High-risk human papillomavirus testing in cytology aspiration samples from the head and neck part 2: a survey of the American Society of Cytopathology community.

INTRODUCTION: High-risk human papillomavirus (HR-HPV) status is critical in the diagnosis of oropharyngeal squamous cell carcinoma, informing prognosis and choice of therapy. HR-HPV status additionally plays a key role in the evaluation of squamous cell carcinoma of unknown origin metastatic to cervical lymph nodes. Thus, HR-HPV testing of fine needle aspirate (FNA) specimens from the head and neck is invaluable for accurate diagnosis, prognostication, and treatment planning. MATERIALS AND METHODS: American Society of Cytopathology members were surveyed to understand the current state of HR-HPV testing on FNA samples from the head and neck. The survey focused on 3 main topic areas: practice setting of respondents, methods of collection and processing of aspirate specimens for HR-HPV testing, and validation of HR-HPV testing methodologies on aspirate samples. RESULTS: The survey reveals that laboratories employ various methods to detect HR-HPV in FNA samples, most commonly p16 immunohistochemical staining of cell block sections. Although some laboratories have independently validated their HR-HPV detection method, such validation is not universal. Finally, not all respondents currently have HR-HPV testing available, but approximately half of those without a testing method desire to make HR-HPV testing of FNA samples available. CONCLUSIONS: Survey responses highlight that various testing modalities are utilized for HR-HPV detection in aspirate samples. However, internal laboratory validation of HR-HPV testing for FNA specimens is not ubiquitous despite professional society recommendations.

Atypical Hyperplasia Found Incidentally during Routine Breast Reduction Mammoplasty: Incidence and Management.

Atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) of the breast are premalignant lesions. Although the literature on ADH and ALH as a whole is well-developed, research on ADH and ALH incidentally discovered during breast reduction is less robust. METHODS: In this study, 355 patients undergoing bilateral reduction mammoplasty at West Virginia University were retrospectively reviewed. A variety of demographic and clinicopathologic variables were collected for each patient, and the incidence of atypical hyperplasia was calculated. Four patients (1.13%) were found to have atypical hyperplasia, three ALH, and one ADH, which is within the range reported in the literature. For patients incidentally found to have atypical hyperplasia, an in-depth analysis of postoperative management was performed. RESULTS: Of the four patients with atypical hyperplasia, three were referred to a cancer center, and one patient followed only with plastic surgery. The three patients who were referred to a cancer center saw a breast surgeon, whereas the patient followed only by plastic surgery did not. None of the four patients received anti-estrogen therapy, but each patient who followed with a cancer center was offered treatment and declined. CONCLUSIONS: As a relatively uncommon finding with complex management guidelines, atypical hyperplasia discovered on breast reduction should be referred to a cancer center for long-term follow-up and management when possible. Further research is needed to assess if the management of atypical hyperplasia discovered incidentally after routine reduction should mimic treatment of atypical hyperplasia found after biopsy for suspicion of malignancy.

Neuroendocrine Neoplasm of the Breast Presenting as a Liver Metastasis: A Rare Diagnostic Challenge.

We present a case of a 58-year-old female who presented initially to an outside institution with abdominal pain and was diagnosed on liver biopsy with a well-differentiated neuroendocrine tumor of an unknown primary source. She was referred to our academic institution for a second opinion after disease progression on the initial chemotherapy regimen. Through additional evaluation, diagnostics, and multi-disciplinary tumor board discussion she was diagnosed with metastases from a well-differentiated neuroendocrine neoplasm of the breast (NENB). Consequently, her treatment plan was modified leading to significant clinical and radiological improvement.

Educational Case: Malignant Melanoma.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Electronic Cigarettes and Vaping-Associated Lung Injury (EVALI): A Rural Appalachian Experience.

Background: Electronic cigarette use has increased dramatically since their introduction in 2007. Respiratory complications, particularly lipoid pneumonia, have been reported as early as 2012. An outbreak of pulmonary injury in 2019 has been reported in patients using vaping products.Research Question: To describe a rural Appalachian tertiary center's experience of EVALI and to identify novel mechanisms of pulmonary injury patterns.Study Design and Methods: We present a consecutive case series of 17 patients admitted to our rural, academic, tertiary care institution with EVALI from August 2019 to March 2020. Demographics, baseline characteristics, co-morbidities, vaping behavior, and hospital course were recorded. Broncho-alveolar lavage specimens were assessed for lipid-laden macrophages and hemosiderin-laden macrophages with stains for Oil-Red-O (n = 15) and Prussian Blue (n = 14) respectively.The patient volunteered e-liquid materials (n = 6), and vapors were analyzed using a proton transfer reaction time-of-flight mass spectrometer (PTR-TOF-MS) to describe the chemical profile. Post-discharge interviews were conducted.Results: The most common CT finding was bilateral ground-glass opacities with a predilection for lower lung zones. The most frequent pulmonary injury pattern was lipoid pneumonia. The majority of EVALI patients were critically ill requiring ventilation or ECMO. The most severely ill patients were noted to be positive for iron stains in macrophages and showed higher volatile organic compound (VOC) levels in chemical analysis.Interpretation: Based on our experience, EVALI in rural Appalachia presented with relatively severe respiratory failure. Worse outcomes appear to be correlated to high levels of VOCs, iron deposition in lungs, and concomitant infection.

Results from the 2019 American Society of Cytopathology survey on rapid onsite evaluation (ROSE)-part 2: subjective views among the cytopathology community.

INTRODUCTION: This study aims to improve understanding of the cytopathology community's perspective regarding the value of rapid onsite evaluation (ROSE) in clinical practice. MATERIALS AND METHODS: The American Society of Cytopathology membership was surveyed in 2019 to obtain subjective data on the cytopathology community's perceptions regarding ROSE. Comments were categorized by major themes and attitudes and analyzed by respondent's role in laboratory, practice size, and practice setting (Fisher's exact and χ2 tests). RESULTS: A total of 541 responses were received from 255 cytopathologists/pathologists, 261 cytotechnologists, 19 trainees, and 6 others (as previously reported). Reasons for which cytopathology personnel provide this service aligned with their perceptions of why clinicians request ROSE. A minority of respondents, disproportionally from high volume centers, felt ROSE is unnecessary. Overall attitude regarding ROSE was generally positive. There were no significant differences in attitude regarding ROSE according to role in laboratory or practice size, but respondents from academic centers provided a significantly higher percentage of positive comments than those in private or community practice. Although survey respondents generally felt that ROSE is valuable to patient care, they also highlighted several challenges, including staffing, time commitment, and inadequate reimbursement. Implementation of telecytology was felt to potentially alleviate some of these challenges. CONCLUSIONS: Survey results show that the cytology community views ROSE favorably, practices vary considerably, and there is a perceived need for improved reimbursement. Data from this study may be used to identify areas that warrant additional research to clarify the clinical value of ROSE.

Educational Case: Febrile Nonhemolytic Transfusion Reaction.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Educational Case: Invasive Ductal Carcinoma of the Breast.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Tumor Board Shadowing: A Unique Approach for Integrating Radiation Oncologists Into General Medical Student Education.

PURPOSE: Radiation oncology is often overlooked in US medical school curricula, with few opportunities for most students to learn about the specialty or the value of radiation therapy in cancer care. Tumor boards represent a potential avenue not only to increase students' exposure to radiation oncologists but also to provide a fundamental understanding of the multidisciplinary nature of cancer care and effective collaboration in clinical practice. METHODS AND MATERIALS: In this study, we evaluated a novel radiation oncologist-driven tumor board shadowing experience at 3 medical schools in the United States and Canada. A total of 323 first- and second-year medical students participated, of whom 77.4% completed a follow-up survey assessing the effectiveness of the program as a learning tool. RESULTS: Compared with traditional clinical shadowing, students were more likely to believe that tumor board shadowing provided a similar or better experience in terms of educational content (85%), exposure to a new field (96%), and overall experience (89%). Forty-eight percent of students perceived a greater amount of multidisciplinary collaboration in oncologic care than they thought existed prior to attending. Forty-eight percent of students also felt more competent interacting with oncologists after participating, whereas 21% felt more competent interacting with patients with cancer. Students' perception of increased competence was correlated with the amount of time their assigned physician mentor spent answering their questions after the tumor board (P < .01). Second-year medical students also had a more favorable overall experience than first-year medical students did (P = .04). CONCLUSIONS: Multidisciplinary tumor boards can be used effectively as a unique immersive learning opportunity that can be feasibly implemented to improve knowledge of clinical oncology and multidisciplinary care in medical schools and expose students to physicians in smaller fields such as radiation oncology.

Eosinophilic Angiocentric Fibrosis: A Review and Update of Its Association With Immunoglobulin G4-Related Disease.

Eosinophilic angiocentric fibrosis is a rare indolent lesion of the head and neck region that has characteristic histologic findings of onionskin fibrosis and prominent eosinophils. Its pathogenesis has been poorly understood and has been most commonly attributed to hypersensitivity or previous trauma. Recently, the lesion has been included in the spectrum of immunoglobulin G4 (IgG4)-related disease. However, few of the existing cases of eosinophilic angiocentric fibrosis have been evaluated for IgG4+ and IgG+ plasma cells. Therefore, we provide an update on the clinical and histologic features of eosinophilic angiocentric fibrosis to increase awareness of the entity and encourage its further characterization as an IgG4-related disease.

Primary High-Risk Human Papillomavirus Testing for Cervical Cancer Screening in the United States: Is It Time?

CONTEXT: - The most recent update to cervical cancer screening guidelines offers interim guidance on the use of primary human papillomavirus (HPV) screening, with algorithms for management of results. After decades of screening with pure cytology and a shorter time with adjunctive HPV or cotesting with Papanicolaou (Pap) test and HPV, this is a significant change to our screening methods. OBJECTIVE: - To briefly review the history of cervical cancer screening, the evidence upon which these interim guidelines were based, the arguments for and against primary HPV testing, and the current state of the field. DATA SOURCES: - Primary studies, review articles, and commentaries were reviewed. CONCLUSIONS: - While there is evidence both for and against primary HPV testing, there are a growing number of countries adopting the practice. It would be worthwhile to be informed and prepared for such a change in the United States as well.

Alveolar rhabdomyosarcoma in the cerebrospinal fluid.

Alveolar rhabdomyosarcoma (RMS) is an aggressive soft tissue mass demonstrating rapid growth, dissemination, and leptomeningeal spread. Primary diagnosis is usually established by core biopsy. In rare cases, cytopathologic evaluation is indicated to identify recurrent or metastatic disease. We present a case of a 24-year-old man with a previously diagnosed alveolar RMS of the foot who presented to our institution with back pain. A lumbar puncture was performed and the cerebrospinal fluid (CSF) showed atypical cells demonstrating nuclear enlargement, eccentricity, binucleation, and frequent karyorrhexis. Laminectomy and cytogenetic studies were subsequently performed, confirming metastatic disease. There are few published reports on the CSF appearance of RMS. However, because leptomeningeal involvement by RMS is primarily evaluated by lumbar puncture, awareness of the cytologic features is important for patient management.

Use of Pathology Data to Improve High-Value Treatment of Cervical Neoplasia.

We investigated the influence of pathology data to improve patient outcomes in the treatment of high-grade cervical neoplasia in a joint pathology and gynecology collaboration. Two of us (B.S.D. and M.D.) reviewed all cytology, colposcopy and surgical pathology results, patient history, and pregnancy outcomes from all patients with loop electrosurgical excision procedure specimens for a 33-month period (January 2011-September 2013). We used this to determine compliance to 2006 consensus guidelines for the performance of loop electrosurgical excision procedure and shared this information in 2 interprofessional and interdisciplinary educational interventions with Obstetrics/Gynecology and Pathology faculty at the end of September 2013. We simultaneously emphasized the new 2013 guidelines. During the postintervention period, we continued to provide follow-up using the parameters previously collected. Our postintervention data include 90 cases from a 27-month period (October 2013-December 2015). Our preintervention data include 331 cases in 33 months (average 10.0 per month) with 76% adherence to guidelines. Postintervention, there were 90 cases in 27 months (average 3.4 per month) and 96% adherence to the 2013 (more conservative) guidelines (P < .0001, χ2 test). Preintervention, the rate of high-grade squamous intraepithelial lesion in loop electrosurgical excision procedures was 44%, whereas postintervention, there was a 60% high-grade squamous intraepithelial lesion rate on loop electrosurgical excision procedure (P < .0087 by 2-tailed Fisher exact test). The duration between diagnosis of low-grade squamous intraepithelial lesion and loop electrosurgical excision procedure also increased significantly from a median 25.5 months preintervention to 54 months postintervention (P < .0073; Wilcoxon Kruskal-Wallis test). Postintervention, there was a marked decrease of loop electrosurgical excision procedure cases as well as better patient outcomes. We infer improved patient safety, and higher value can be achieved by providing performance-based pathologic data.

Encapsulated classic and follicular variants of papillary thyroid carcinoma: comparative clinicopathologic study.

OBJECTIVE: To compare the clinicopathologic features of papillary thyroid carcinoma classic variant (PTC-CV) and papillary thyroid carcinoma follicular variant (PTCFV), with a focus on the encapsulated form. METHODS: In a retrospective search of computerized pathology files for 1996 to 1998, a cohort of 114 cases (58 cases of PTC-CV and 56 cases of PTC-FV) were selected for this study. Clinicopathologic data and long-term follow-up (serum thyroglobulin measurements, radiologic studies, and additional tissue sampling) through the date of compilation of study data were extracted from the medical records. RESULTS: The median patient age at initial diagnosis was 46 years for the PTC-CV group and 45.5 years for the PTC-FV group. Complete tumor encapsulation was seen in 40 PTC-CV cases (69%) and in all PTC-FV cases (100%). A higher rate of tumor capsule invasion (CI), lymphovascular invasion (LVI), extrathyroidal extension, and lymph node metastatic lesions was seen in PTC-CV than in PTC-FV: CI, 26% versus 18%; LVI, 17% versus 4%; extrathyroidal extension, 19% versus 7%; and lymph node metastatic lesions, 68% versus 29%. Clinical, radiologic, or pathologic follow-up data were available in 36 PTC-CV cases (62%) and 34 PTC-FV cases (61%). The median duration of follow-up for the PTC-CV group was 10 years and for the PTC-FV group was 9 years. Tumor recurrence was found in 10 patients with PTC-CV (28%) and 2 with PTC-FV (6%). Distant metastatic lesions occurred in 3 patients with PTC-CV (8%) and 1 patient with PTC-FV (3%) (P = .17); of these, 2 cases of PTC-CV were encapsulated and showed CI, LVI, and lymph node metastatic lesions. CONCLUSION: Our current study confirms previous reports that both encapsulated PTC-CV and encapsulated PTC-FV are indolent tumors and are associated with very low mortality.

Triple-negative breast cancer in West Virginia.

In 2007, the American Cancer Society ranked West Virginia 43rd in breast cancer incidence rates for individual states. Despite our improvements in medical care, the advanced pathological characteristics of breast cancer at diagnosis receive little attention. Consequently, we compared the changing pattern of early breast cancer in several cohort studies conducted at regional medical centers in West Virginia. The data used in this analysis was derived from 320 women presenting at West Virginia University Hospital (WVUH) in Morgantown between 1999 and 2004, with a diagnosis of invasive breast cancer. Details of age, tumor size and axillary lymph node status were compared with tumor registry information published from a cohort study of 191 patients from the Charleston Area Medical Center (CAMC) between 1990 and 1991. Only histologically documented adenocarcinomas of the breast were included. Tumor size was characterized using the TNM system and staged according to AJCC criteria. For comparative purposes, details from the two regional centers were compared with tumor characteristics from a large longitudinal cohort of 2,484 breast cancers from the Women's Health Initiative (WHI) study. Baseline median age at diagnosis of women screened at WVUH was younger than patients at CAMC (52 vs. 60). Women diagnosed with triple-negative breast cancer at WVUH and CAMC had similar age distributions. Within the triple-negative patients at WVUH, 44% of patients were less than 50 years of age and 20% were less than 40 years of age. At CAMC, 35% were less than 50 years of age and 7% were less than 40 years of age. For women at WVUH, 61.5% presented with T1 tumors compared to 65.5% at CAMC. These figures were lower than the WHI average of 80.3%. In contrast, more women presented with larger T2 tumors at our medical centers compared with the national study, 32.6% versus 17.4% respectively. At WVUH, 2.3% of women had T3 tumors (> or =5 cm) compared with 1% at CAMC. Similar to the WHI study, 35-42% of women at WVUH and CAMC were diagnosed at the T1c stage. Approximately, 30% were diagnosed with positive lymph nodes, compared to 23% in the national study. Combined breast cancer data from our medical centers show an increase in more advanced tumors and positive regional lymph node involvement at the time of diagnosis compared to national reports. Other factors such as obesity, diabetes, poverty and access to mammography screening could be influencing the poorer outcomes for women with breast cancer in West Virginia.

Cytogenetic abnormalities detected by fluorescence in situ hybridization on paraffin-embedded chronic lymphocytic leukemia/small lymphocytic lymphoma lymphoid tissue biopsy specimens.

Cytogenetic fluorescence in situ hybridization (FISH) panels are a major prognostic tool in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), but few data exist on using paraffin-embedded extramedullary tissue biopsy specimens for these purposes. Isolated whole nuclei were extracted from 20 paraffin-embedded tissue biopsy specimens with CLL/SLL and analyzed using a standard CLL FISH panel. FISH studies were successful in 18 (90%) of 20 cases, and chromosomal abnormalities were detected in 18 (100%) of the technically successful cases. Deletion 13q14.3 was most frequent (10 [56%]; isolated in 8 and with other abnormalities in 2), followed by trisomy 12 (5 [28%]), deletion 11q22.3 (4/16 [25%]), 14q32 (IGH@) translocation (3 [17%]), and deletion 17p13.1 (1/16 [6%]). One case with IGH@ translocation showed a BCL2 translocation partner. No cases showed 6q23 deletion. Results of this FISH panel performed on 42 additional peripheral blood (PB)/bone marrow (BM) CLL specimens were similar except for a significantly greater frequency of deletion 13q14.3 in combination with other aberrations. Cytogenetic FISH studies using paraffin-embedded tissue biopsy specimens in CLL/SLL had a high yield and, with 1 exception, demonstrated a profile similar to cases diagnosed in PB/BM.

Histopathologic variables predict Oncotype DX recurrence score.

Oncotype DX is a commercially available reverse transcriptase-polymerase chain reaction based assay that provides a Recurrence Score (RS) and has been shown to provide prognostic and predictive information in estrogen receptor-positive lymph node-negative breast cancers. Independent studies of its utility in routine practice are lacking. Slides and surgical pathology reports from 42 cases of breast carcinomas evaluated by Oncotype DX were retrospectively reviewed to determine patient age, tumor size, histologic grade, estrogen and progesterone receptor (ER and PR) and ERBB2 (HER-2/neu) data, with ER and PR reported as a semi-quantitative score reflecting both intensity of staining and proportion of positive cells. We show here that Recurrence Score is significantly correlated with tubule formation, nuclear grade, mitotic count, ER immunohistochemical score, PR immunohistochemical score, and HER-2/neu status, and that the equation RS=13.424+5.420 (nuclear grade) +5.538 (mitotic count) -0.045 (ER immunohistochemical score) -0.030 (PR immunohistochemical score) +9.486 (HER-2/neu) predicts the Recurrence Score with an R2 of 0.66, indicating that the full model accounts for 66% of the data variability. Although the Oncotype DX Recurrence Score holds potential, further validation of its independent value beyond that of histopathologic analysis is necessary before it can be implemented in clinical decision making.

Repeat thyroid nodule fine-needle aspiration in patients with initial benign cytologic results.

Fine-needle aspiration (FNA) is the standard of care for the initial workup of thyroid nodules, but there is no consensus algorithm to manage patients with benign results. We examined performance characteristics of initial and repeat satisfactory FNAs for all 402 patients who underwent thyroid surgery during a recent 22-month period. Of these patients, 267 had at least 1 satisfactory FNA and 70 had 2 or more. After an initial benign FNA, 1 repeat FNA correctly identified an unsuspected malignancy in 2 of 70 patients and was indeterminate in 17; of these, 7 of 17 were identified as malignant in the final pathologic diagnosis. Overall, the use of 1 repeat FNA increased the sensitivity for malignancy from 81.7% to 90.4% and decreased the false-negative rate from 17.1% to 11.4%. With more than 1 repeat FNA, there was no improvement in performance characteristics. These data make a strong argument for 1 repeat FNA following an initial benign FNA diagnosis.