There is currently no gene expression assay that can assess if premalignant lesions will develop into invasive breast cancer. This study sought to identify biomarkers for selecting patients with a high potential for developing invasive carcinoma in the breast with normal histology, benign lesions, or premalignant lesions. A set of 26-gene mRNA expression profiles were used to identify invasive ductal carcinomas from histologically normal tissue and benign lesions and to select those with a higher potential for future cancer development (ADHC) in the breast associated with atypical ductal hyperplasia (ADH). The expression-defined model achieved an overall accuracy of 94.05% (AUC = 0.96) in classifying invasive ductal carcinomas from histologically normal tissue and benign lesions (n = 185). This gene signature classified cancer development in ADH tissues with an overall accuracy of 100% (n = 8). The mRNA expression patterns of these 26 genes were validated using RT-PCR analyses of independent tissue samples (n = 77) and blood samples (n = 48). The protein expression of PBX2 and RAD52 assessed with immunohistochemistry were prognostic of breast cancer survival outcomes. This signature provided significant prognostic stratification in The Cancer Genome Atlas breast cancer patients (n = 1100), as well as basal-like and luminal A subtypes, and was associated with distinct immune infiltration and activities. The mRNA and protein expression of the 26 genes was associated with sensitivity or resistance to 18 NCCN-recommended drugs for treating breast cancer. Eleven genes had significant proliferative potential in CRISPR-Cas9/RNAi screening. Based on this gene expression signature, the VEGFR inhibitor ZM-306416 was discovered as a new drug for treating breast cancer.

The transition to a value-based payment system offers pathologists the opportunity to play an increased role in population health by improving outcomes and safety as well as reducing costs. Although laboratory testing itself accounts for a small portion of health-care spending, laboratory data have significant downstream effects in patient management as well as diagnosis. Pathologists currently are heavily engaged in precision medicine, use of laboratory and pathology test results (including autopsy data) to reduce diagnostic errors, and play leading roles in diagnostic management teams. Additionally, pathologists can use aggregate laboratory data to monitor the health of populations and improve health-care outcomes for both individual patients and populations. For the profession to thrive, pathologists will need to focus on extending their roles outside the laboratory beyond the traditional role in the analytic phase of testing. This should include leadership in ensuring correct ordering and interpretation of laboratory testing and leadership in population health programs. Pathologists in training will need to learn key concepts in informatics and data analytics, health-care economics, public health, implementation science, and health systems science. While these changes may reduce reimbursement for the traditional activities of pathologists, new opportunities arise for value creation and new compensation models. This report reviews these opportunities for pathologist leadership in utilization management, precision medicine, reducing diagnostic errors, and improving health-care outcomes.

Assessment of physician workloads has become increasingly important in modern academic physician practice, where it is commonly used to allocate resources among departments, to determine staffing, and to set the compensation of individual physicians. The physician work relative value unit system is a frequently used metric in this regard. However, the application of this system to the practice of pathology has proven problematic. One area of uncertainty is the validity of using work relative value unit norms that were derived from general surgical pathology practice to assess the various subspecialties within anatomic pathology. Here, we used data from the 2017 Association of Pathology Chairs practice survey to assess salary and work relative value unit data for single-subspecialty practitioners in US academic pathology departments in the prior year (2016). Five subspecialties were evaluated: dermatopathology, gastrointestinal pathology, hematopathology/hematology, renal pathology, and neuropathology. Data for general surgical pathologists and cytopathologists were included for comparison. For this analysis, survey data were available for 168 practitioners in 43 US academic departments of pathology. Salary ranges varied little among subspecialties, with the exception of dermatopathology, where salaries were higher. In contrast, work relative value unit productivity varied widely among different subspecialties, with median values differing as much as 4- to 7-fold between subspecialties. These results suggest that the use of a single overall work relative value unit standard is not appropriate for specialty- or subspecialty-based anatomic pathology practice, and that either the benchmark norms should be tailored to individual practice patterns, or an alternative system of workload measurement should be developed.

CONTEXT:- Human papillomavirus (HPV) is implicated in the development of oropharyngeal squamous cell carcinomas (OPC), particularly those cancers developing in tonsillar tissue.OBJECTIVES:- To review the prevalence, subtypes, and methods of detecting HPV in OPC and to review the epidemiology, histology, staging, management, and prevention of these cancers.DATA SOURCES:- The study comprised a review of the literature.CONCLUSIONS:- The incidence of HPV-OPC is rising globally and in the United States, but rates of HPV-positivity vary with the anatomic site(s) and the population studied, as well as the method of detecting HPV infection. These tumors are more common in men. In contrast to HPV- OPC, the rates of smoking and alcohol abuse are lower. The HPV 16 subtype is predominant, and immunohistochemistry staining for p16 and in situ hybridization are the most widely used methods clinically to detect transcriptionally active HPV. Moreover, HPV-OPC has a unique tumor phenotype with predominantly nonkeratinizing morphology and a variety of patterns. These cancers often present with cystic lymph node metastases. The prognosis for HPV-OPC is significantly better than HPV- OPC and has led to differences in grading, staging, and management. Although there are similarities to cervical cancer, there are challenges in preventing such cancers.

Respiratory exposure to multiwalled carbon nanotubes (MWCNT) or asbestos results in fibrosis; however, the mechanisms to reach this end point may be different. A previous study by our group identified pulmonary effects and significantly altered messenger RNA (mRNA) signaling pathways following exposure to 1, 10, 40, and 80 µg MWCNT and 120 µg crocidolite asbestos on mouse lungs over time at 1-month, 6-month, and 1-year postexposure following pulmonary aspiration. As a continuation to the above study, this current study took an in-depth look at the signaling pathways involved in fibrosis development at a single time point, 1 year, and exposure, 40 µg MWCNT, the lowest exposure at which fibrosis was pathologically evident. The 120 µg asbestos exposure was included to compare MWCNT-induced fibrosis with asbestos-induced fibrosis. A previously validated computational model was used to identify mRNAs with expression profiles matching the fibrosis pathology patterns from exposed mouse lungs. mRNAs that matched the pathology patterns were then input into ingenuity pathway analysis to determine potential signaling pathways and physiological disease functions inherent to MWCNT and asbestos exposure. Both MWCNT and asbestos exposure induced changes in mouse lungs regarding gene expression, cell proliferation, and survival, while MWCNT uniquely induced alterations in pathways involved in oxidative phosphorylation, mitochondrial dysfunction, and transcription. Asbestos exposure produced unique alterations in pathways involved in sustained inflammation. Although typically considered similar due to scale and fiber-like appearance, the different compositional properties inherent to either MWCNT or asbestos may play a role in their ability to induce fibrosis after pulmonary exposure.

CONTEXT:- Types 16 and 18 are the most widely studied high-risk types of human papillomavirus (HPV). However, other high-risk HPV types (HPV non-16/18) also play a significant role in cervical neoplasia. Currently, screening and management algorithms separate out HPV 16/18 from all other HPV non-16/18 types. In addition, most of the previously vaccinated population has only been vaccinated for these high-risk types, so many women are still vulnerable to HPV non-16/18 infections.OBJECTIVE:- To review the prevalence and role of HPV non-16/18 neoplasia and to review current surveillance, management, and vaccination strategies in view of these findings.DATA SOURCES:- The study comprised a review of the literature.CONCLUSIONS:- Although HPV non-16/18 types are less frequently associated with cervical intraepithelial neoplasia and cancer, they are nonetheless a significant cause of disease. Further stratification of higher-risk HPV non-16/18 may be necessary to improve prevention and management, however, regional prevalence differences may make a unified approach difficult. As HPV 16/18 infections decrease owing to vaccination of at-risk women, the relative frequency of HPV non-16/18 will increase, although the latest vaccine covers several more high-risk types.

Papillomavirus, a ubiquitous double-stranded deoxyribonucleic acid virus, has been identified in almost all mammalian species, and in birds, snakes, and turtles, although the virus is host (species) specific. More than 170 human papillomaviruses (HPVs) have been sequenced. The viral genome is approximately 80 kilobases in length and encodes 6 early proteins needed for viral replication as well as 2 late capsid proteins (L1 and L2). The virus infects the basal layer of mucosal surfaces and skin. HPV genotypes classified as high-risk are associated with cancer at a number of sites. The percentage of cancers associated with HPV infection and its worldwide disease burden is highest for cervical cancer followed by cancers of the anus, vagina, penis, vulva, and oropharynx. However, even those HPV types that are considered low-risk can be associated with other lesions, including but not limited to verruca vulgaris (warts), genital condylomas, and squamous papillomas of the respiratory tract.The development of a cervical cancer screening test by George Papanicolaou in 1927, named in his honor, and its widespread adoption in the 1940s decreased cervical cancer mortality rates throughout the developed world. Further investigations over the decades led to the identification and classification of precancerous cervical neoplasia with nomenclature changes from mild/moderate/severe dysplasia/carcinoma in situ to cervical intraepithelial neoplasia (I/II/III) and finally to low- and high-grade squamous intraepithelial lesions. At the same time, treatment for precancerous neoplasia has become less invasive (including the loop electrosurgical excision procedure). Increased understanding of the role of HPV in cervical neoplasia and the molecular underpinnings have led to the development of screening tests for high-risk HPV types and vaccinations targeted at the highest-risk types.Although cervical cancer mortality rates have fallen throughout the developed world, the lack of access to medical care, including screening for cervical cancer, has meant that cervical cancer remains an important cause of morbidity and mortality in developing countries. In the setting of immunosuppression, infection with HPV is associated with increased rates of neoplasia in the setting of human immunodeficiency virus (HIV) and with posttransplant neoplasia. In addition, cervical cancer rates remain high in pockets of the United States and are associated with socioeconomic and racial disparities. One such pocket includes Appalachia, including Kentucky and West Virginia. This association led to this special section in Archives of Pathology & Laboratory Medicine on the impact of HPV-associated disease, with contributions from medical students and pathology faculty, fellows and residents from West Virginia University. This special section includes articles on the role, pathogenesis, and diagnosis of HPV-related disease for all sites.The paradigm for cervical cancer screening is under review. Pure cytology is no longer an option and the current guidelines incorporate HPV genotyping into the algorithmic approaches. The current debate centers upon whether testing for DNA is by itself sufficient for initial screening in adult women or whether cotesting is a better screening paradigm. Flanagan summarizes the debate based not only on the traditional benefits and harms of screening tests, but also on other considerations such as the effect on the cytotechnology workforce. While primary HPV testing has not been widely adopted in the United States, several European countries are in the process of piloting or adopting this method.As an increasing number of girls and young women are vaccinated against the highest-risk HPV genotypes, the role of non-16/18 types will become relatively more important. Even though new vaccines contain more types, the initial vaccines contained only types HPV 16 and 18. The importance of non-16/18 HPV types and their association with cervical precancerous lesions and invasive carcinoma, particularly in the setting of coinfection with HIV neoplasia, is discussed by Robadi and colleagues.Nweke et al discuss the impact of HPV infection in the developing world, with emphasis on sub-Saharan Africa, where cervical cancer is still the most important cause of years of life lost due to cancer in women. This sobering finding demonstrates both the ongoing global burden of HPV-related cancer as well as the impact of screening upon cervical cancer rates. Major challenges to eradicating HPV-related disease in this population include lack of access to medical care, lack of a trained cytotechnologist workforce, and lack of access to vaccinations. In the developing world, primary HPV screening is likely to be adopted as cost and ease of use provide more access to this technology than traditional cytology.Bacaj and Burch discuss various manifestations of HPV infection in the skin. In this setting, HPV lesions can vary from common warts of the soles and palms to invasive cancers of the anogenital region, many with specific associations to HPV types. In addition, the body site and host factor may also play a role in the process. Similarly, Hanbazazh and Gyure discuss ocular disease associated with HPV infection. In this setting, HPV is implicated in the pathogenesis of squamous papillomas, pterygia, and ocular surface squamous neoplasia.The development of HPV-related neoplasms is especially important in the development of neoplasms associated with immunosuppression. Stiebing and colleagues discuss the pathogenesis of HPV-related neoplasms in the setting of solid organ transplants. Since transplant recipients are generally older, they are less likely to have been vaccinated against HPV. As the number and type of these transplants increase, the number of patients at risk will likewise increase.Ducatman describes the role of HPV in oropharyngeal squamous cell carcinomas. This association is recent, but the incidence of such tumors is increasing. It is important that pathologists recognize these tumors and that they be appropriately tested for HPV as this will change staging, management, and prognosis. In addition, implications for prevention strategies for HPV-positive oropharyngeal carcinoma are still under consideration with many challenges. In view of this association, Kunkle and Rosado describe a promising new frontier in HPV management and review the role and implications for therapy of the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) in this setting.Within the last century, the incidence and mortality of cervical carcinoma have dropped dramatically throughout the developed world owing to screening and treatment of precancerous lesions. Concomitantly, research has identified the role and pathogenesis of HPV infection in cervical cancer and other neoplasms, with the development of vaccines effective against the highest-risk types. Unfortunately, these advances are not uniform throughout the world or even the United States. Hopefully, better access to medical care and vaccination strategies to immunize both boys and girls throughout the world with more inclusive vaccines will eradicate the scourge of HPV-related neoplasia in the 21st century.

Modern cholangioscopy systems have been used for targeted evaluation and management of pancreaticobiliary diseases since 2007 (1). Its use has been limited to targeted evaluation and management of pancreaticobiliary diseases (2). We present a novel use of cholangioscopy system to assess and biopsy a high grade malignant duodenal stricture. A 42 year old male with past medical history of gastroesophageal reflux disease presented as a transfer from an outside hospital with gastric outlet obstruction secondary to an obstructing duodenal ulcer noted on upper endoscopy. Patient had initially presented with intractable nausea, vomiting, and a 20 pounds unintentional weight loss over a two week period. Biopsies from the gastric antrum resulted positive for Helicobacter pylori and biopsies from the duodenal ulcer only showed inflammatory cells. He was admitted to the outside hospital for antibiotics, nasogastric tube decompression and total parenteral nutrition. With minimal clinical improvement, patient was transferred to our facility where repeat upper endoscopy showed an obstructing duodenal ulcer (Figure 1). This was not traversable using scopes between 34 Fr to 16 Fr in size, despite dilating this stricture with a 12 mm TTS balloon over a 0.035 inch guidewire under fluoroscopy. Cholangioscopy system was then utilized which allowed visualization of a 6 cm, circumferential, malignant appearing stricture from the proximal second portion of duodenum to distal third portion of duodenum which was friable, ulcerated and edematous (Figure 2). Biopsies using cholangioscopy forceps returned positive for invasive adenocarcinoma (Figure 3). CT scan of the chest, abdomen and pelvis obtained for staging purposes demonstrated no convincing evidence of metastatic disease. Patient subsequently underwent an uncomplicated, standard pancreaticoduodenectomy with retroperitoneal lymphadenectomy. Modern cholangioscopy systems have been used for the evaluation and management of pancreaticobiliary diseases. We demonstrate an alternative application of cholangioscopy systems in assessing a high grade malignant duodenal stricture.Figure: Obstructing Duodenal Ulcer on Endoscopy.Figure: Duodenal Stricture on Cholangioscopy System.Figure: Pathology consistent with Duodenal Adenocarcinoma.

Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (−) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced. The main outcome was the percentage of cardiac marker studies performed within guidelines. Nonguideline orders dominated at baseline. Creatine kinase M and B isoenzyme testing in 7496 order sets failed to detect additional myocardial infarctions but was associated with 42 potentially preventable admissions/quarter. Interruptive computerized soft stops improved guideline compliance from 32.3% to 58% ( P < .001) in services not receiving peer leader intervention and to >80% ( P < .001) with peer leadership that featured dashboard feedback about test order performance. This successful experience was recapitulated in interrupted time series within 2 additional services within facility 1 and then in 2 external hospitals (including a critical access facility). Improvements have been sustained postintervention. Laboratory cost savings at the academic facility were estimated to be ≥US$635 000 per year. National collaborative data indicated that facility 1 improved its order patterns from fourth to first quartile compared to peer norms and imply that nonguideline orders persist elsewhere. This example illustrates how pathologists can provide leadership in assisting clinicians in changing laboratory ordering practices. We found that clinicians respond to local laboratory data about their own test performance and that evidence suggesting harm is more compelling to clinicians than evidence of cost savings. Our experience indicates that interventions done at an academic facility can be readily instituted by private practitioners at external facilities. The intervention data also supplement existing literature that electronic order interruptions are more successful when combined with modalities that rely on peer education combined with dashboard feedback about laboratory order performance. The findings may have implications for the role of the pathology laboratory in the ongoing pivot from quantity-based to value-based health care.

Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure to E-cig vapor on vascular function. The purpose of this study was to determine the cardiovascular consequences of chronic E-cig exposure. Female mice (C57BL/6 background strain) were randomly assigned to chronic daily exposure to E-cig vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group). Respective whole body exposures consisted of four 1-h-exposure time blocks, separated by 30-min intervals of fresh air breaks, resulting in intermittent daily exposure for a total of 4 h/day, 5 days/wk for 8 mo. Noninvasive ultrasonography was used to assess cardiac function and aortic arterial stiffness (AS), measured as pulse wave velocity, at three times points (before, during, and after chronic exposure). Upon completion of the 8-mo exposure, ex vivo wire tension myography and force transduction were used to measure changes in thoracic aortic tension in response to vasoactive-inducing compounds. AS increased 2.5- and 2.8-fold in E-cig- and 3R4F-exposed mice, respectively, compared with air-exposed control mice ( P < 0.05). The maximal aortic relaxation to methacholine was 24% and 33% lower in E-cig- and 3R4F-exposed mice, respectively, than in controls ( P < 0.05). No differences were noted in sodium nitroprusside dilation between the groups. 3R4F exposure altered cardiac function by reducing fractional shortening and ejection fraction after 8 mo ( P < 0.05). A similar, although not statistically significant, tendency was also observed with E-cig exposure ( P < 0.10). Histological and respiratory function data support emphysema-associated changes in 3R4F-exposed, but not E-cig-exposed, mice. Chronic exposure to E-cig vapor accelerates AS, significantly impairs aortic endothelial function, and may lead to impaired cardiac function. The clinical implication from this study is that chronic use of E-cigs, even at relatively low exposure levels, induces cardiovascular dysfunction. NEW & NOTEWORTHY Electronic cigarettes (E-cigs) are marketed as safe, but there has been insufficient long-term exposure to humans to justify these claims. This is the first study to report the long-term in vivo vascular consequences of 8 mo of exposure to E-cig vapor in mice (equivalent to ~25 yr of exposure in humans). We report that E-cig exposure increases arterial stiffness and impairs normal vascular reactivity responses, similar to other risk factors, including cigarette smoking, which contribute to the development of cardiovascular disease.

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.

Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 yr postexposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, up- and down-regulated gene expression was determined in lung tissue at 1 yr postexposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological alterations similar to those of crocidolite asbestos, but may reach these endpoints by different mechanisms.

The most common benchmarks for faculty productivity are derived from Medical Group Management Association (MGMA) or Vizient-AAMC Faculty Practice Solutions Center® (FPSC) databases. The Association of Pathology Chairs has also collected similar survey data for several years. We examined the Association of Pathology Chairs annual faculty productivity data and compared it with MGMA and FPSC data to understand the value, inherent flaws, and limitations of benchmarking data. We hypothesized that the variability in calculated faculty productivity is due to the type of practice model and clinical effort allocation. Data from the Association of Pathology Chairs survey on 629 surgical pathologists and/or anatomic pathologists from 51 programs were analyzed. From review of service assignments, we were able to assign each pathologist to a specific practice model: general anatomic pathologists/surgical pathologists, 1 or more subspecialties, or a hybrid of the 2 models. There were statistically significant differences among academic ranks and practice types. When we analyzed our data using each organization's methods, the median results for the anatomic pathologists/surgical pathologists general practice model compared to MGMA and FPSC results for anatomic and/or surgical pathology were quite close. Both MGMA and FPSC data exclude a significant proportion of academic pathologists with clinical duties. We used the more inclusive FPSC definition of clinical "full-time faculty" (0.60 clinical full-time equivalent and above). The correlation between clinical full-time equivalent effort allocation, annual days on service, and annual work relative value unit productivity was poor. This study demonstrates that effort allocations are variable across academic departments of pathology and do not correlate well with either work relative value unit effort or reported days on service. Although the Association of Pathology Chairs-reported median work relative value unit productivity approximated MGMA and FPSC benchmark data, we conclude that more rigorous standardization of academic faculty effort assignment will be needed to improve the value of work relative value unit measurements of faculty productivity.

Purpose:1) To determine SUVs and PET/CT characteristics of Warthin's tumors in patients presenting to a head and neck cancer clinic.2) To analyze the impact of PET/CT on the clinical course of these patients.Materials and methods: This is a single-institution retrospective analysis of patients with proven Warthin's tumors who underwent PET/CT done at or near the time of diagnosis and presented to a head and neck cancer practice. Data were obtained from the electronic medical records of these patients and the imaging and pathology databases.Results: Six patients with Warthin's tumor met the criteria for and form the study cohort. Three patients had bilateral tumors. The SUVs for Warthin's varied from 3.4 to 16.1 in these patients, with an average of 7.8 and these SUVs were higher for Warthin's than for the cancers. These findings on PET/CT in this group required additional workup of all patients and required FNA, surgery or SPECT-CT to confirm the diagnosis.Conclusion: Although it is known that Warthin's tumor may be hypermetabolic on PET, this finding in the parotid or neck on PET/CT alters the evaluation and treatment of head and neck cancer patients and patients with cancers outside the head and neck by raising the concern about metastatic disease or multiple primary cancers. In other patients, PET/CT obtained for other reasons may prompt concern about incidental malignancy. This series specifically characterizes clinical features, SPECT-CT and FNA findings that can help reinforce the diagnosis of Warthin's and facilitate management. (C) 2015 Elsevier Inc. All rights reserved.

Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns. For 687 patients, 13.8% developed metastases to bone (n = 42) or visceral sites (n = 53). Metastases to viscera occurred within five years, a latent period which was shorter than that for bone (P = 0.042). More women with visceral metastasis presented with grade 3 tumors compared with the bone and nonmetastatic groups (P = 0.0002). There were 135/574 women (23.5%) with triple-negative breast cancer, who presented with lymph node involvement and visceral metastases (68.2% versus 24.3%; P = 0.033). Triple-negative tumors that metastasized to visceral sites were larger (P = 0.007). Developing a visceral metastasis within 10 years was higher among women with triple-negative tumors. Across all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. The excess risk of metastatic spread to visceral organs in triple-negative breast cancers, even in the absence of positive nodes, was combined with the burden of larger and more advanced tumors.

285 OBJECTIVE: To develop a classification scheme for reporting the results of fine needle aspiration (FNA) cytology of a breast lesion according to its likelihood of being a carcinoma. STUDY DESIGN: To verify the validity of this scheme, we studied a total of 267 FNAs that were prospectively classified according to predefined criteria as positive (76), suspicious (41), proliferative with atypia (66), proliferative without atypia (48) and unremarkable (36), and compared these results with the final histology. RESULTS: The percentages of patients who had carcinoma on histology were 100% (76), 93% (38), 35% (23), 6% (3) and 31% (11) of cases diagnosed as positive, suspicious, atypical proliferative, proliferative without atypia and unremarkable on cytology, respectively. However, if only invasive carcinoma is considered, then the percentage of carcinoma was 99% (75), 93% (38), 23% (15), 2% (1) and 11% (4), respectively. The only invasive carcinoma in the proliferative-without-atypia category was a tubular carcinoma and represented a false negative diagnosis. All four invasive carcinomas with an unremarkable cytologic diagnosis were due to sampling errors. Definitive surgery after FNA was common in cases with positive (65%) and suspicious (42%) cytologic diagnosis, whereas all but one patient with atypical, proliferative and unremarkable diagnoses had a biopsy initially. CONCLUSION: This scheme of reporting breast FNA results with defined criteria according to the probability of identifying carcinoma provides a rational basis for guidelines for the management of breast lesions. (Acta Cytol 1998;42: 285–289)

Six patients with Warthin's tumor who met the criteria for the study had adequate PET/CT images. All six of these patients had a history of smoking tobacco. Four of the patients had bilateral tumors. Three of the patients had malignancy, which prompted the PET/CT, and three had other indications for PET/CT which were approved by third party payors. The SUV values for Warthin's varied from 3.4 to 16.1 in these patients, with an average of 7.8 and these SUV values were higher for Warthin's than for the cancers.

Context.—In 2006, the first gynecologic cytology proficiency tests were offered by the College of American Pathologists. Four years of data are now available using field-validated slides, including conventional and liquid-based Papanicolaou tests.Objective.—To characterize the pattern of error types that resulted in initial proficiency-test failure for cytotechnologists, primary screening pathologists, and secondary pathologists (those whose slides are prescreened by cytotechnologists).Design.—The results of 37 029 initial College of American Pathologists Papanicolaou proficiency tests were reviewed from 4 slide-set modules: conventional, ThinPrep, SurePath, or a module containing all 3 slide types.Results.—During this 4-year period, cytotechnologists were least likely to fail the initial test (3.4%; 614 of 18 264), followed by secondary pathologists (ie, those reviewing slides already screened by a cytotechnologist) with a failure rate of 4.2% (728 of 17 346), and primary pathologists (ie, those screening their own slides) having the highest level of failure (13.7%; 194 of 1419). Failure rates have fallen for all 3 groups over time. Pathologists are graded more stringently on proficiency tests, and more primary pathologists would have passed if they had been graded as cytotechnologists. There were no significant differences among performances using different types of slide sets. False-positive errors were common for both primary (63.9%; 124 of 194 errors) and secondary (55.6%; 405 of 728 errors) pathologists, whereas automatic failures were most common for cytotechnologists (75.7%; 465 of 614 errors).Conclusions.—The failure rate is decreasing for all participants. The failures for primary pathologist screeners are due to false-positive responses. Primary screening cytotechnologists and secondary pathologists have automatic failures more often than do primary screening pathologists.