Laboratory Workup of Lymphoma in Adults: Guideline From the American Society for Clinical Pathology and the College of American Pathologists.

CONTEXT.­: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery led to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings. OBJECTIVE.­: To develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma. DESIGN.­: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were derived based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework. RESULTS.­: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma. CONCLUSIONS.­: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions on specimen suitability, diagnostic capabilities, and correct use of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment.

Laboratory Workup of Lymphoma in Adults.

OBJECTIVES: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery lead to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings. THE AIM OF THIS REVIEW IS TO: develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma. METHODS: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of the literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were derived based on the available evidence, the strength of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework. RESULTS: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma. CONCLUSIONS: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions about specimen suitability, diagnostic capabilities, and correct utilization of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment.

CD20-Negative Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A 20-Year Consecutive Case Series From a Tertiary Cancer Center.

CONTEXT.­: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare, indolent Hodgkin lymphoma subtype with distinct clinicopathologic features and treatment paradigms. The neoplastic lymphocyte-predominant cells typically express bright CD20 and other B-cell antigens, which distinguishes them from Hodgkin/Reed-Sternberg cells of lymphocyte-rich classic Hodgkin lymphoma. OBJECTIVE.­: To characterize the clinicopathologic features of CD20-negative NLPHL at a single institution. DESIGN.­: A retrospective search for CD20-negative NLPHL in our pathology archives and medical records was conducted. RESULTS.­: Of 486 NLPHL patients identified with CD20 available for review, 14 (2.8%) had LP cells with absent CD20 expression. Patients with prior rituximab administration (n = 7) and insufficient clinical history (n = 1) were excluded, leaving 6 patients with rituximab-naïve, CD20-negative NLPHL. A broad immunohistochemical panel showed the LP cells in all cases expressed B-cell antigens, particularly Oct-2, although PAX5 and CD79a were frequently also dim. CD30, CD15, and Epstein-Barr virus-encoded small RNAs were negative in all evaluated cases. Two patients had high-risk variant immunoarchitectural pattern D. One patient had extranodal disease, involving the spleen and bone, and was suspected to have large cell transformation. Standard NLPHL therapy was given, including local radiation and/or chemotherapy. Of 5 patients with available follow-up, 4 are alive in complete remission after therapy, and 1 is alive with relapsed disease. CONCLUSIONS.­: NLPHL can lack CD20 de novo without prior rituximab therapy. In such cases, extensive immunophenotyping helps distinguish NLPHL from lymphocyte-rich classic Hodgkin lymphoma, which differ in clinical behavior and therapy. In our series, CD20-negative NLPHL showed both classic and variant histologic patterns and the expected range of clinical behavior seen in NLPHL, including 1 case with suspected large cell transformation.

Histology-Independent Signature Distinguishes Kikuchi-Fujimoto Disease/Systemic Lupus Erythematosus-Associated Lymphadenitis From Benign and Malignant Lymphadenopathies.

OBJECTIVES: Kikuchi-Fujimoto disease (KFD) and systemic lupus erythematosus (SLE) are benign entities with histologic features that raise concern about malignancy and infection. We searched for a histology-independent KFD/SLE signature relying on only immunophenotype and basic clinical characteristics. METHODS: A histology-independent KFD/SLE signature was generated using 975 excised lymph nodes with flow immunophenotyping, including 16 cases of KFD/SLE. This signature was then evaluated in 1,198 fine-needle aspiration (FNA) specimens. RESULTS: The top flow cytometry discriminant for KFD/SLE was uniform CD38+ expression on CD19+ events. Immunohistochemistry demonstrated nodules of IgD+, IgM- B cells surrounding necrotizing and activated T-cell areas. A signature combining 6 flow cytometry criteria with age and sample site had a positive predictive value of 88% for KFD/SLE, which had a prevalence of 1.6%. All 4 signature-positive FNA cases with follow-up excision were KFD/SLE. At a second institution, 4 of 5 KFD/SLE cases passed the top discriminant. CONCLUSIONS: A flow cytometry signature combined with age and biopsy site identifies KFD/SLE independent of histology, suggesting a shared immune composition and independently confirming that KFD/SLE represents a distinct entity. Unexpectedly, an IgD+CD38+ small B-cell population is a distinctive feature of KFD/SLE, suggesting a possible pathologic role for anergic/autoreactive B cells.

Will I Need to Move to Get My First Job?: Geographic Relocation and Other Trends in the Pathology Job Market.

CONTEXT.­: There is an ongoing perception that the pathology job market is poor, which may be discouraging medical students from pursuing the specialty. Academic pathologists believe that jobs are available but relocation may be necessary. OBJECTIVE.­: To identify trends regarding the geographic relocation of pathologists taking their first job after training. DESIGN.­: The College of American Pathologists (CAP) Graduate Medical Education Committee has sent an annual job search survey from 2012-2016 to CAP junior members and fellows in practice for 3 years or less and seeking their first job. Data were analyzed across demographics and geographic domains consisting of the following: stayed at same institution/city, relocated within the same region, or relocated to a different region. Standard statistical methods were used. RESULTS.­: Of 501 respondents, 421 reported completing combined anatomic pathology (AP)/clinical pathology (CP) training, while 80 reported AP- or CP-only training. Of the 421 AP/CP respondents, 109 (26%) stayed at the same institution or city, while of the 80 AP- or CP-only respondents, 36 (45%) stayed at the same institution or city. One hundred ninety-nine respondents completed surgical pathology fellowships with 124 (62%) general/oncologic surgical pathology and 75 (38%) subspecialty surgical pathology trainees. Job seekers who completed general surgical pathology/surgical oncologic pathology fellowship accounted for 34 of 52 (65%) of those remaining at the same institution or city, while those with subspecialty training accounted for 40 of 77 (52%) of those relocating to a different region. Relocation did not demonstrate any significant trends in regard to other demographics studied. CONCLUSIONS.­: The pathology job market appears stable with no precedent for geographic hardship.

Flow immunophenotyping of benign lymph nodes sampled by FNA: Representative with diagnostic pitfalls.

BACKGROUND: Fine-needle aspiration with flow cytometry (FNA-FC) is routinely used in the evaluation of lymph nodes suspicious for lymphoma, yet data comparing immunophenotype distributions and outliers in benign lymph nodes sampled by fine-needle aspiration (FNA) versus excision are lacking. METHODS: Flow cytometry data from 289 benign lymph node FNA cases were assessed for the overall antigen distribution, with a focus on outliers relevant to the diagnosis of lymphoma. Distributions and outlier proportions were compared with those of a separate cohort of 298 excisional biopsies. RESULTS: Compared with excisional biopsies, FNA specimens overrepresented CD3+ events (72% vs 63%), underrepresented CD19+ events (22% vs 29%), and had 25% fewer large cell-gated events. Normalized antigen distributions in FNA were equivalent to those in excisional biopsy. Twenty-three percent of FNA-FC cases exhibited an outlier, including a skewed kappa:lambda light-chain ratio, increased CD5+ or CD10+ B-cell events, a skewed CD4:CD8 ratio, and increased CD7 loss on T cells, with no significant differences in frequency or type in comparison with excisional specimens. Outliers for the light-chain ratio and T-cell antigens were enriched among older patients and included patients with a variety of autoimmune/rheumatologic conditions. CONCLUSIONS: Benign lymph node FNA yields flow immunophenotypes remarkably similar to those from excisional biopsies. Outlier flow immunophenotypes are identified in benign lymph nodes sampled by FNA at a frequency similar to that with excisional biopsies. Older patients, who have a higher baseline risk of lymphoma, are more likely to exhibit lymphoma-mimicking outliers such as a light-chain predominance on B cells and skewed CD4:CD8 ratios or increased CD7 loss on T cells, and they warrant additional diagnostic caution.

Development of Professionalism in Graduate Medical Education: A Case-Based Educational Approach From the College of American Pathologists' Graduate Medical Education Committee.

Professionalism and physician well-being are important topics in academic medicine. Lapses in professional judgment may lead to disciplinary action and put patient's health at risk. Within medical education, students and trainees are exposed to professionalism in the institution's formal curriculum and hidden curriculum. Development of professionalism starts early in medical school. Trainees entering graduate medical education already have developed professional behavior. As a learned behavior, development of professional behavior is modifiable. In addition to role modeling by faculty, other modalities are needed. Use of case vignettes based on real-life issues encountered in trainee and faculty behavior can serve as a basis for continued development of professionalism in trainees. Based on the experience of program directors and pathology educators, case vignettes were developed in the domains of service, research, and education and subdivided into the areas of duty, integrity, and respect. General and specific questions pertaining to each case were generated to reinforce model behavior and overcome professionalism issues encountered in the hidden curriculum. To address physician burnout, cases were generated to provide trainees with the skills to deal with burnout and promote well-being.

Normative data for flow cytometry immunophenotyping of benign lymph nodes sampled by surgical biopsy.

AIMS: To create clinically relevant normative flow cytometry data for understudied benign lymph nodes and characterise outliers. METHODS: Clinical, histological and flow cytometry data were collected and distributions summarised for 380 benign lymph node excisional biopsies. Outliers for kappa:lambda light chain ratio, CD10:CD19 coexpression, CD5:CD19 coexpression, CD4:CD8 ratios and CD7 loss were summarised for histological pattern, concomitant diseases and follow-up course. RESULTS: We generated the largest data set of benign lymph node immunophenotypes by an order of magnitude. B and T cell antigen outliers often had background immunosuppression or inflammatory disease but did not subsequently develop lymphoma. CONCLUSIONS: Diagnostic immunophenotyping data from benign lymph nodes provide normative ranges for clinical use. Outliers raising suspicion for B or T cell lymphoma are not infrequent (26% of benign lymph nodes). Caution is indicated when interpreting outliers in the absence of excisional biopsy or clinical history, particularly in patients with concomitant immunosuppression or inflammatory disease.

Entrustable Professional Activities for Pathology: Recommendations From the College of American Pathologists Graduate Medical Education Committee.

Competency-based medical education has evolved over the past decades to include the Accreditation Council for Graduate Medical Education Accreditation System of resident evaluation based on the Milestones project. Entrustable professional activities represent another means to determine learner proficiency and evaluate educational outcomes in the workplace and training environment. The objective of this project was to develop entrustable professional activities for pathology graduate medical education encompassing primary anatomic and clinical pathology residency training. The Graduate Medical Education Committee of the College of American Pathologists met over the course of 2 years to identify and define entrustable professional activities for pathology graduate medical education. Nineteen entrustable professional activities were developed, including 7 for anatomic pathology, 4 for clinical pathology, and 8 that apply to both disciplines with 5 of these concerning laboratory management. The content defined for each entrustable professional activity includes the entrustable professional activity title, a description of the knowledge and skills required for competent performance, mapping to relevant Accreditation Council for Graduate Medical Education Milestone subcompetencies, and general assessment methods. Many critical activities that define the practice of pathology fit well within the entrustable professional activity model. The entrustable professional activities outlined by the Graduate Medical Education Committee are meant to provide an initial framework for the development of entrustable professional activity-related assessment and curricular tools for pathology residency training.

Perceptions of Unprofessional Attitudes and Behaviors: Implications for Faculty Role Modeling and Teaching Professionalism During Pathology Residency.

CONTEXT: - Changes occurring in medicine have raised issues about medical professionalism. Professionalism is included in the Core Competencies and Milestones for all pathology residents. Previous studies have looked at resident professionalism attitudes and behaviors in primary care but none have looked specifically at pathology. OBJECTIVE: - To examine behavior and attitudes toward professionalism within pathology and to determine how professionalism is taught in residency programs. DESIGN: - Surveys were sent to all College of American Pathologists junior members and all pathology residency program directors, and responses were compared. RESULTS: - Although no single behavior received the same professionalism rating among residents and program directors, both groups identified the same behaviors as being the most unprofessional: posting identifiable patient information or case images to social media, making a disparaging comment about a physician colleague or member of the support staff on social media or in a public hospital space, and missing work without reporting the time off. Faculty were observed displaying most of these behaviors as often or more often than residents by both groups. The most common means to teach professionalism in pathology residencies is providing feedback as situations arise and teaching by example. Age differences were found within each group and between groups for observed behaviors and attitudes. CONCLUSIONS: - As teaching by example was identified as a common educational method, faculty must be aware of the role their behavior and attitudes have in shaping resident behavior and attitudes. These results suggest a need for additional resources to teach professionalism during pathology residency.

Professionalism in Pathology: A Case-Based Approach as a Potential Educational Tool.

CONTEXT: -Professionalism issues in residency training can be difficult to assess and manage. Generational or role-based differences may also exist between faculty and residents as to what constitutes unprofessional behavior and how to manage it. OBJECTIVE: -To examine and compare how faculty and residents would approach the same 5 case scenarios detailing various aspects of unprofessional behavior. DESIGN: -Five case scenarios highlighting various unprofessional behaviors were presented in a workshop at an annual meeting of pathology department chairs, residency program directors, and undergraduate pathology medical educators (ie, pathologists involved in medical student pathology education). The same cases were presented to a cohort of pathology residents currently in training. A standard set of responses were offered to the participants, polling results were collected electronically, and results were compared. RESULTS: -Faculty and residents were fairly consistent within their respective groups. In a subset of cases, faculty were more likely to favor working with the individual in the scenario, whereas resident respondents were more likely to favor either no response or a severe response. Generational or role-based differences were also potentially evident. CONCLUSIONS: -Assessing expectations and differences around professionalism for both faculty and residents should be considered as part of any educational and management approach for professionalism. Although a level of generational differences appears to be evident in this study regarding the recognition and management of unprofessional behavior, there was also agreement in some cases. Further exploration into the discrepant responses between faculty and residents may prove useful in developing educational, assessment, and remediation resources.