Assessment of a Diagnostic Classification System for Management of Lesions to Exclude Melanoma.

Importance: The proposed MOLEM (Management of Lesion to Exclude Melanoma) schema is more clinically relevant than Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MATH-Dx) for the management classification of melanocytic and nonmelanocytic lesions excised to exclude melanoma. A more standardized way of establishing diagnostic criteria will be crucial in the training of artificial intelligence (AI) algorithms. Objective: To examine pathologists' variability, reliability, and confidence in reporting melanocytic and nonmelanocytic lesions excised to exclude melanoma using the MOLEM schema in a population of higher-risk patients. Design, Setting, and Participants: This cohort study enrolled higher-risk patients referred to a primary care skin clinic in New South Wales, Australia, between April 2019 and December 2019. Baseline demographic characteristics including age, sex, and related clinical details (eg, history of melanoma) were collected. Patients with lesions suspicious for melanoma assessed by a primary care physician underwent clinical evaluation, dermoscopy imaging, and subsequent excision biopsy of the suspected lesion(s). A total of 217 lesions removed and prepared by conventional histologic method and stained with hematoxylin-eosin were reviewed by up to 9 independent pathologists for diagnosis using the MOLEM reporting schema. Pathologists evaluating for MOLEM schema were masked to the original histopathologic diagnosis. Main Outcomes and Measures: Characteristics of the lesions were described and the concordance of cases per MOLEM class was assessed. Interrater agreement and the agreement between pathologists' ratings and the majority MOLEM diagnosis were calculated by Gwet AC1 with quadratic weighting applied. The diagnostic confidence of pathologists was then assessed. Results: A total of 197 patients were included in the study (102 [51.8%] male; 95 [48.2%] female); mean (SD) age was 64.2 (15.8) years (range, 24-93 years). Overall, 217 index lesions were assessed with a total of 1516 histological diagnoses. Of 1516 diagnoses, 677 (44.7%) were classified as MOLEM class I; 120 (7.9%) as MOLEM class II; 564 (37.2%) as MOLEM class III; 114 (7.5%) as MOLEM class IV; and 55 (3.6%) as MOLEM class V. Concordance rates per MOLEM class were 88.6% (class I), 50.8% (class II), 76.2% (class III), 77.2% (class IV), and 74.2% (class V). The quadratic weighted interrater agreement was 91.3%, with a Gwet AC1 coefficient of 0.76 (95% CI, 0.72-0.81). The quadratic weighted agreement between pathologists' ratings and majority MOLEM was 94.7%, with a Gwet AC1 coefficient of 0.86 (95% CI, 0.84-0.88). The confidence in diagnosis data showed a relatively high level of confidence (between 1.0 and 1.5) when diagnosing classes I (mean [SD], 1.3 [0.3]), IV (1.3 [0.3]) and V (1.1 [0.1]); while classes II (1.8 [0.2]) and III (1.5 [0.4]) were diagnosed with a lower level of pathologist confidence (≥1.5). The quadratic weighted interrater confidence rating agreement was 95.2%, with a Gwet AC1 coefficient of 0.92 (95% CI, 0.90-0.94) for the 1314 confidence ratings collected. The confidence agreement for each MOLEM class was 95.0% (class I), 93.5% (class II), 95.3% (class III), 96.5% (class IV), and 97.5% (class V). Conclusions and Relevance: The proposed MOLEM schema better reflects clinical practice than the MPATH-Dx schema in lesions excised to exclude melanoma by combining diagnoses with similar prognostic outcomes for melanocytic and nonmelanocytic lesions into standardized classification categories. Pathologists' level of confidence appeared to follow the MOLEM schema diagnostic concordance trend, ie, atypical naevi and melanoma in situ diagnoses were the least agreed upon and the most challenging for pathologists to confidently diagnose.

A Computational Tumor-Infiltrating Lymphocyte Assessment Method Comparable with Visual Reporting Guidelines for Triple-Negative Breast Cancer.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are clinically significant in triple-negative breast cancer (TNBC). Although a standardized methodology for visual TILs assessment (VTA) exists, it has several inherent limitations. We established a deep learning-based computational TIL assessment (CTA) method broadly following VTA guideline and compared it with VTA for TNBC to determine the prognostic value of the CTA and a reasonable CTA workflow for clinical practice. METHODS: We trained three deep neural networks for nuclei segmentation, nuclei classification and necrosis classification to establish a CTA workflow. The automatic TIL (aTIL) score generated was compared with manual TIL (mTIL) scores provided by three pathologists in an Asian (n = 184) and a Caucasian (n = 117) TNBC cohort to evaluate scoring concordance and prognostic value. FINDINGS: The intraclass correlations (ICCs) between aTILs and mTILs varied from 0.40 to 0.70 in two cohorts. Multivariate Cox proportional hazards analysis revealed that the aTIL score was associated with disease free survival (DFS) in both cohorts, as either a continuous [hazard ratio (HR)=0.96, 95% CI 0.94-0.99] or dichotomous variable (HR=0.29, 95% CI 0.12-0.72). A higher C-index was observed in a composite mTIL/aTIL three-tier stratification model than in the dichotomous model, using either mTILs or aTILs alone. INTERPRETATION: The current study provides a useful tool for stromal TIL assessment and prognosis evaluation for patients with TNBC. A workflow integrating both VTA and CTA may aid pathologists in performing risk management and decision-making tasks. FUNDING: National Natural Science Foundation of China, Guangdong Medical Research Foundation, Guangdong Natural Science Foundation.

Assessing comfort level with pediatric skin specimens among dermatopathologists and pediatric pathologists: A national cross-sectional survey.

BACKGROUND: Cutaneous histopathologic diagnoses in children often differ from those in adults. Depending on practice setting, these specimens may be evaluated by dermatopathologists or pediatric pathologists. We sought to determine whether comfort level with pediatric dermatopathology is associated with prior training, pediatric dermatopathology exposure during fellowship, career duration, or specimen subtype. METHODS: We surveyed dermatopathologists and pediatric pathologists practicing in the United States. Training and practice variables were evaluated by multivariable regression for association with comfort level. RESULTS: Of the 156 respondents, 72% were dermatopathologists (response rate 11.6%) and 28% were pediatric pathologists (response rate 9.3%). Dermatopathologists reported higher comfort overall (P < .001); this was also true for inflammatory dermatoses and melanocytic neoplasms (P < .001). Thirty-four percent and 75% of dermatopathologists and pediatric pathologists, respectively, reported lower comfort with pediatric skin specimens than their usual cases. Pediatric pathologists were 28% more likely to refer these cases to colleagues. Among dermatopathologists, dermatology-trained were more comfortable than pathology-trained colleagues interpreting inflammatory dermatoses (P < .001). CONCLUSIONS: Pathologists' comfort with pediatric dermatopathology varied significantly based upon prior training, career duration, and specimen subtype. These results suggest opportunities for improving education in this domain.

Terminology for melanocytic skin lesions and the MPATH-Dx classification schema: A survey of dermatopathologists.

BACKGROUND: Diagnostic terms used in histopathology reports of cutaneous melanocytic lesions are not standardized. We describe dermatopathologists' views regarding diverse diagnostic terminology and the utility of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) for categorizing melanocytic lesions. METHODS: July 2018-2019 survey of board-certified and/or fellowship-trained dermatopathologists with experience interpreting melanocytic lesions. RESULTS: Among 160 participants, 99% reported witnessing different terminology being used for the same melanocytic lesion. Most viewed diverse terminology as confusing to primary care physicians (98%), frustrating to pathologists (83%), requiring more of their time as a consultant (64%), and providing necessary clinical information (52%). Most perceived that adoption of the MPATH-Dx would: improve communication with other pathologists and treating physicians (87%), generally be a change for the better (80%), improve patient care (79%), be acceptable to clinical colleagues (68%), save time in pathology report documentation (53%), and protect from malpractice (51%). CONCLUSIONS: Most dermatopathologists view diverse terminology as contributing to miscommunication with clinicians and patients, adversely impacting patient care. They view the MPATH-Dx as a promising tool to standardize terminology and improve communication. The MPATH-Dx may be a useful supplement to conventional pathology reports. Further revision and refinement are necessary for widespread clinical use.

Incorporation of dermoscopy improves inter-observer agreement among dermatopathologists in histologic assessment of melanocytic neoplasms.

Histopathologic assessment of melanocytic neoplasms is the current gold standard of diagnosis. However, there are well recognized limitations including inter-observer diagnostic discordance. This study aimed to determine if integrating dermoscopy with histopathology of melanocytic neoplasms impacts diagnosis and improves inter-observer agreement. We conducted a prospective cohort study in a pigmented lesion clinic. Consecutive melanocytic lesions were identified for biopsy based on atypical gross or dermoscopic features. Standardized immunohistochemistry and levels were ordered on each specimen. The cases were randomized. Three dermatopathologists blinded to the clinical impression assessed each lesion. The cases were then re-randomized and re-assessed with addition of gross clinical and dermoscopic images. Inter-rater reliability (IRR) using Fleiss' kappa statistic revealed an increase from 0.447 without to 0.496 with dermoscopy amongst all dermatopathologists. The kappa increased from 0.495 before to 0.511 with dermoscopy in separating high-grade atypia or melanoma from moderate atypia or less. In 16 of 136 cases, at least 2 of 3 dermatopathologists favored a diagnosis of melanoma only after dermoscopy. In total, the consensus grade of atypia changed in 24.3% (33/ 136) of cases thereby representing changes to excisional margins and patient follow up. This study is limited by the cohort size. Dermoscopy significantly impacts diagnosis and improves identification of early melanomas in high risk populations and improves inter-observer agreement.

Medicare Trends in Pathologist Participation, Service Utilization, and Payments.

OBJECTIVES: Quantifying pathologist participation in Medicare services may be informative for the prediction of future workforce needs and reimbursement. METHODS: A retrospective examination was performed of pathologist professional (Part B) Medicare billings and payments from 2012 to 2017. The Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File was the primary data source. RESULTS: From 2012 to 2017, there was an increase (3.7%; 11,215 up to 11,627) in pathologists providing Medicare Part B services. Female pathologists increased from 36.10% to 40.8% of pathologists during this time period. Normalized per pathologist, there was an increase (7.8%; 1,382 up to 1,489) in beneficiaries served as well as an increase (4.1%; 2,442 up to 2,543) in services performed. The top 10 pathology Part B services performed in a facility were all surgical pathology. Although services increased, the overall payment of Part B pathology services decreased (3%; $996,519,358 down to $966,615,856) during the study period. CONCLUSIONS: Although there is increasing pathologist participation in Medicare, the workload per pathologist has increased.

Current and Historical Trends in Diversity by Race, Ethnicity, and Sex Within the US Pathology Physician Workforce.

OBJECTIVES: This study assessed historical and current gender, racial, and ethnic diversity trends within US pathology graduate medical education (GME) and the pathologist workforce. METHODS: Data from online, publicly available sources were assessed for significant differences in racial, ethnic, and sex distribution in pathology trainees, as well as pathologists in practice or on faculty, separately compared with the US population and then each other using binomial tests. RESULTS: Since 1995, female pathology resident representation has been increasing at a rate of 0.45% per year (95% confidence interval [CI], 0.29-0.61; P < .01), with pathology now having significantly more females (49.8%) compared to the total GME pool (45.4%; P < .0001). In contrast, there was no significant trend in the rate of change per year in black or American Indian, Alaskan Native, Native Hawaiian, and Pacific Islander (AI/AN/NH/PI) resident representation (P = .04 and .02). Since 1995, underrepresented minority (URM) faculty representation has increased by 0.03% per year (95% CI, 0.024-0.036; P < .01), with 7.6% URM faculty in 2018 (5.2% Hispanic, 2.2% black, 0.2% AI/AN/NH/PI). CONCLUSIONS: This assessment of pathology trainee and physician workforce diversity highlights significant improvements in achieving trainee gender parity. However, there are persistent disparities in URM representation, with significant underrepresentation of URM pathologists compared with residents.

Adherence to the National Comprehensive Cancer Network Criteria of Complete Circumferential Peripheral and Deep Margin Assessment in Treatment of High-Risk Basal and Squamous Cell Carcinoma.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) has established guidelines for the treatment of keratinocyte carcinomas (KCs). Complete circumferential peripheral and deep margin assessment (CCPDMA) is recommended for "high-risk" tumors that cannot be closed primarily. If flap or grafts are needed and CCPDMA was not used, it is recommended that reconstruction be delayed until achieving clear margins. OBJECTIVE: To measure provider utilization rates of the NCCN guidelines for high-risk KCs and assess barriers that are limiting adherence. MATERIALS AND METHODS: A ten-item questionnaire was distributed to NCCN nonmelanoma skin cancer panel members and physicians participating in KC treatment at academic institutions. RESULTS: Response rate was 49% (57/116). Responses were categorized by practice area: Mohs surgery, pathology, and other specialties: General Dermatology, Otolaryngology, Plastic Surgery, Surgical Oncology, Radiation Oncology, and Oral and Maxillofacial Surgery. Mohs surgeons were most likely to use CCPDMA for tumors meeting NCCN criteria with 14/15 using this technique in a majority of their cases, versus 2/6 pathologists and 10/16 specialists from other fields. Reasons cited for not using CCPDMA included deference to pathologists to determine the appropriate method for margin assessment and logistical difficulty. CONCLUSION: Further efforts are needed to increase adherence to NCCN's guidelines regarding CCPDMA in KCs.

Assessment of Second-Opinion Strategies for Diagnoses of Cutaneous Melanocytic Lesions.

Importance: Histopathologic criteria have limited diagnostic reliability for a range of cutaneous melanocytic lesions. Objective: To evaluate the association of second-opinion strategies by general pathologists and dermatopathologists with the overall reliability of diagnosis of difficult melanocytic lesions. Design, Setting, and Participants: This diagnostic study used samples from the Melanoma Pathology Study, which comprises 240 melanocytic lesion samples selected from a dermatopathology laboratory in Bellevue, Washington, and represents the full spectrum of lesions from common nevi to invasive melanoma. Five sets of 48 samples were evaluated independently by 187 US pathologists from July 15, 2013, through May 23, 2016. Data analysis was performed from April 2016 through November 2017. Main Outcomes and Measures: Accuracy of diagnosis, defined as concordance with an expert consensus diagnosis of 3 experienced pathologists, was assessed after applying 10 different second-opinion strategies. Results: Among the 187 US pathologists examining the 24 lesion samples, 113 were general pathologists (65 men [57.5%]; mean age at survey, 53.7 years [range, 33.0-79.0 years]) and 74 were dermatopathologists (49 men [66.2%]; mean age at survey, 46.4 years [range, 33.0-77.0 years]). Among the 8976 initial case interpretations, physicians desired second opinions for 3899 (43.4%), most often for interpretation of severely dysplastic nevi. The overall misclassification rate was highest when interpretations did not include second opinions and initial reviewers were all general pathologists lacking subspecialty training (52.8%; 95% CI, 51.3%-54.3%). When considering different second opinion strategies, the misclassification of melanocytic lesions was lowest when the first, second, and third consulting reviewers were subspecialty-trained dermatopathologists and when all lesions were subject to second opinions (36.7%; 95% CI, 33.1%-40.7%). When the second opinion strategies were compared with single interpretations without second opinions, the reductions in misclassification rates for some of the strategies were statistically significant, but none of the strategies eliminated diagnostic misclassification. Melanocytic lesions in the middle of the diagnostic spectrum had the highest misclassification rates (eg, moderately or severely dysplastic nevus, Spitz nevus, melanoma in situ, and pathologic stage [p]T1a invasive melanoma). Variability of in situ and thin invasive melanoma was relatively intractable to all examined strategies. Conclusions and Relevance: The results of this study suggest that second opinions rendered by dermatopathologists improve reliability of melanocytic lesion diagnosis. However, discordance among pathologists remained high.

Grading of Total Mesorectal Excision Specimens: Assessment of Interrater Agreement.

BACKGROUND: Total mesorectal excision is the standard of care for patients with rectal cancer. Pathological evaluation of the quality of the total mesorectal excision specimen is an important prognostic factor that correlates with local recurrence, but is potentially subjective. OBJECTIVE: This study aimed to determine the degree of variation in grading, both between assessors and between fresh and formalin-fixed specimens. DESIGN: Raters included surgeons, pathologists, pathology residents, pathologists' assistants, and pathologists' assistant trainees. Specimens were assessed by up to 6 raters in the fresh state and by 2 raters postfixation. Four parameters were evaluated: mesorectal bulk, surface regularity, defects, and coning. Interrater agreement was measured using ordinal α-values. SETTING: The study was conducted at a single academic center. MAIN OUTCOME MEASURES: The primary outcome was agreement between individuals when grading total mesorectal excision specimens. RESULTS: A total of 37 total mesorectal excision specimens were assessed. Reliability between all raters for fresh specimens for mesorectal bulk, surface regularity, defects, coning, and overall grade were 0.85, 0.85, 0.92, 0.84, and 0.91. When compared with all raters, pathologists and residents had higher agreement and pathologists and surgeons had lower agreement. Ordinal α-values comparing pathologist and pathologist's assistant agreement for overall grade were similar pre- and postfixation (0.78 vs 0.80), but agreement for assessing defects decreased postfixation. Among pathologists' assistants, agreement was higher when grading specimens postfixation than when grading fresh specimens. LIMITATIONS: Assessment bias may have occurred because of the greater number of pathologists' assistants participating than the number of residents and pathologists. CONCLUSIONS: The results indicate good interrater agreement for the assessment of overall grade, with defects showing the best interrater agreement in fresh specimens. Although total mesorectal excision specimens may be consistently graded postfixation, the assessment of defects postfixation may be less reliable. This study highlights the need for additional knowledge-transfer activities to ensure consistency and accurate grading of total mesorectal excision specimens. See Video Abstract at http://links.lww.com/DCR/A497.

Training the Next Generation of African Pathologists.

Quality patient care requires correct and timely evidence-based diagnoses. Pathology and laboratory medicine training varies significantly across the continent, but is inadequate to serve the needs of the population. This article summarizes the current state of pathology workforce and training in sub-Saharan Africa; discusses challenges to recruitment and retention; and outlines the necessary elements for training and sustaining a robust workforce in pathology and laboratory medicine. The authors provide several case studies of institutions around the continent that include expansion of existing programs, a de novo program, South-South collaborations, and skill building for the existing workforce.

The Recent Pathology Residency Graduate Job Search Experience: A Synthesis of 5 Years of College of American Pathologists Job Market Surveys.

CONTEXT: - Pathology residents and fellows tailor their training and job search strategies to an actively evolving specialty in the setting of scientific and technical advances and simultaneous changes in health care economics. OBJECTIVE: - To assess the experience and outcome of the job search process of pathologists searching for their first non-fellowship position. DESIGN: - The College of American Pathologists (CAP) Graduate Medical Education Committee has during the past 5 years sent an annual job search survey each June to CAP junior members and fellows in practice 3 years or less who have actively searched for a non-fellowship position. RESULTS: - Job market indicators including job interviews, job offers, positions accepted, and job satisfaction have remained stable during the 5 years of the survey. Most survey respondents who had applied for at least 1 position had accepted a position at the time of the survey, and most applicants who had accepted a position were satisfied or very satisfied. However, most attested that finding a non-fellowship position was difficult. Despite a perceived push toward subspecialization in surgical pathology, the reported number of fellowships completed was stable. Respondent demographics were not associated with job search success with 1 significant exception: international medical school graduate respondents reported greater perceived difficulty in finding a position, and indeed, fewer reported having accepted a position. CONCLUSIONS: - Pathology residents and fellows seeking their first position have faced a relatively stable job market during the last 5 years, with most accepting positions with which they were satisfied.

Clinical pathologists and physician in France: which partnership and which future?

Medical biology is a major area of medical specialization in French health care system. It is going through massive changes in public as in private sector since the 2010 Ballereau edict with the merging of laboratories and new quality standards based on accreditation. We have suggested that physicians had a negative feeling about the restructuring of medical biology in recent years. An electronic questionnaire has been sent to physicians so as to find out what they thought about the evolution of medical biology and to get suggestions to improve the taking care of the patient. Have answered 1364 residents and physicians from all specializations, all regions, practicing in public or private hospitals or in general practices. Doctors have on the whole a negative feeling about how medical biology has evolved in recent years thinking that it is moving towards industrialization with delay increasing. They are convinced that tests must be made on site. They remain satisfied with the quality of the tests and have a positive feeling about scientific evolutions and are in favor of a better clinical-biological cooperation. The study points out a lack of clarity concerning how private laboratories are organized and how they operate. A computer link between clinical pathologists and physicians to access results and a list of urgent medical examinations could be set up so as to have a more rapid access to results. Rapid diagnostic tests or delocalized biology could be used but doctors do not want these tests to replace the clinical pathologist.

Intra- and Interobserver Reproducibility Assessment of PD-L1 Biomarker in Non-Small Cell Lung Cancer.

Purpose: Reliable and reproducible methods for identifying PD-L1 expression on tumor cells are necessary to identify responders to anti-PD-1 therapy. We tested the reproducibility of the assessment of PD-L1 expression in non-small cell lung cancer (NSCLC) tissue samples by pathologists.Experimental Design: NSCLC samples were stained with PD-L1 22C3 pharmDx kit using the Dako Autostainer Link 48 Platform. Two sample sets of 60 samples each were designed to assess inter- and intraobserver reproducibility considering two cut points for positivity: 1% or 50% of PD-L1 stained tumor cells. A randomization process was used to obtain equal distribution of PD-L1 positive and negative samples within each sample set. Ten pathologists were randomly assigned to two subgroups. Subgroup 1 analyzed all samples on two consecutive days. Subgroup 2 performed the same assessments, except they received a 1-hour training session prior to the second assessment.Results: For intraobserver reproducibility, the overall percent agreement (OPA) was 89.7% [95% confidence interval (CI), 85.7-92.6] for the 1% cut point and 91.3% (95% CI, 87.6-94.0) for the 50% cut point. For interobserver reproducibility, OPA was 84.2% (95% CI, 82.8-85.5) for the 1% cut point and 81.9% (95% CI, 80.4-83.3) for the 50% cut point, and Cohen's κ coefficients were 0.68 (95% CI, 0.65-0.71) and 0.58 (95% CI, 0.55-0.62), respectively. The training was found to have no or very little impact on intra- or interobserver reproducibility.Conclusions: Pathologists reported good reproducibility at both 1% and 50% cut points. More adapted training could potentially increase reliability, in particular for samples with PD-L1 proportion, scores around 50%. Clin Cancer Res; 23(16); 4569-77. ©2017 AACR.