Acute Myelomonocytic Leukemia With Tetrasomy 8: Histologic and Immunophenotypic Features Mimicking Acute Promyelocytic Leukemia

Rare cases of acute myeloid leukemia (AML) with tetrasomy 8 have been reported. Tetrasomy 8, a poor prognostic factor, has been predominantly associated with AML with monocytic differentiation. We report an unusual case of acute myelomonocytic leukemia (AMML) with tetrasomy 8 showing histologic and immunophenotypic features mimicking acute promyelocytic leukemia (APL). The patient is a 63-year-old African American man with molar pain, gum swelling and bleeding, generalized fatigue, leukocytosis, anemia, and thrombocytopenia. A peripheral blood smear showed increased white cells with many immature granulocytic forms. Approximately 40% of the cells exhibited classical blast morphology, 40% were slightly enlarged and exhibited a small to moderate amount of cytoplasm with a variable number of cytoplasmic granules resembling atypical promyelocytes, and 10% exhibited morphology typical of promyelocytes. The presence of promyelocytes and atypical promyelocytes was highly suggestive of APL. Flow cytometry performed on the peripheral blood showed the leukemic cells to express CD11b (subset), CD33, CD56, and CD64 (subset), with no expression of HLA-DR or CD34, suggestive of APL; however, the blasts were negative for CD117. Subsequent bone marrow aspirate/biopsy evaluation was consistent with AMML. FISH analysis showed tetrasomy 8 and absence of PML/RARA gene rearrangement. In this case, AMML with tetrasomy 8 morphologically and immunophenotypically mimicked APL. The treatment and prognosis of these subtypes of AML are significantly different. This case illustrates the importance of cytogenetic analysis and thorough bone marrow evaluation in determining accurate diagnosis of AML

The Pathology Workforce and Clinical Licensure

There has been a recent recognition of the need to prepare PhD-trained scientists for increasingly diverse careers in academia, industry, and health care. The PhD Data Task Force was formed to better understand the current state of PhD scientists in the clinical laboratory workforce and collect up-to-date information on the training and certification of these laboratorians. In this report, we summarize the findings of the PhD Data Task Force and discuss the relevance of the data collected to the future supply of and demand for PhD clinical laboratory scientists. It is clear that there are multiple career opportunities for PhD scientists in academic medical centers, commercial clinical laboratories, biotechnology and pharmaceutical companies, and the federal government. Certified PhD scientists have and will continue to form an important resource for our technologically advancing field, bringing training in scientific methods, and technologies needed for modern laboratory medicine. The data gathered by the PhD Data Task Force will be of great interest to current and future PhD candidates and graduate PhD scientists as they make decisions regarding future career directions

Medical Students in Microscopic Anatomy and Pathology Laboratories: Design of an E-Learning Histology and Histopathology Atlas as an Evolving Response to Interdisciplinary Pre-Clinical Curricular Needs

E-learning, also known as computer-assisted learning, successfully bridges anatomical knowledge and transferrable skills, such as critical analysis, teamwork, leadership and communication. Several institutions have already integrated histology and physiology in team based laboratory approaches, but integration of histology and pathology instruction has been done to a lesser extent. Our aim was to develop an e-learning atlas that integrates microanatomy and pathology laboratory for an interdisciplinary pre-clinical medical curriculum. A multidisciplinary team of teaching faculty and students developed an online atlas (microanatomyatlas.com) that includes a library of histology and histopathology images. Traditional laboratory manual instructions and study objectives were added onto the digital interface and made interactive by linking it to specific labeled images to allow for self-testing. Online clinical case studies involving a disease entity in a specific organ system were incorporated, which allows students to toggle between the normal as well as the pathological slides involving this disease as they apply their clinical reasoning skills to arrive at the correct diagnosis. Data is being collected on the number and frequency of students using the atlas. Also, a detailed survey to assess student satisfaction and learning will be administered. To assess the impact of this new teaching tool, a comparative study of two years of student performance and course evaluations between students who used the online atlas and students who did not use the online atlas in the pre-clinical medical curriculum will be conducted. Our preliminary data so far shows that student feedback has been positive and an e-learning atlas integrating microanatomy and pathology laboratory may be an essential tool that guides the studies and enhances the performance of students in an interdisciplinary pre-clinical medical curriculum. Disclosures/Acknowledgements: American Educational Institute, University and Campus Management (AEIUCM) developed, designed, and maintains the online portal

Medical Students in Microscopic Anatomy and Pathology Laboratories: Design of an E-Learning Histology and Histopathology Atlas

Computer-assisted learning, also known as e-learning, has been successfully implemented to educate students in anatomical knowledge as well as transferable skills, such as critical analysis, teamwork, leadership and communication. E-learning allows students to self-teach material at their own paces and provides a platform for team-based laboratory approaches. Several institutions have already integrated histology and physiology in team based laboratory approaches, but integration of histology and pathology instruction has been done to a lesser extent. Our aim was to develop an e-learning atlas that integrates microanatomy and pathology laboratory for an interdisciplinary pre-clinical medical curriculum. A multidisciplinary team of teaching faculty and students developed an online atlas (microanatomyatlas.com) that includes a library of histology and histopathology images. Traditional laboratory manual instructions and study objectives were added onto the digital interface and made interactive by linking it to specific labeled images to allow for self- testing. Online clinical case studies involving a disease entity in a specific organ system were incorporated, which allows students to toggle between the normal as well as the pathological slides involving the disease as they apply their clinical reasoning skills to arrive at the correct diagnosis. We are collecting data on the number and frequency of students using the atlas. We are also administering a detailed survey to assess student satisfaction and learning. To assess the impact of this new teaching tool, a comparative study of two years of student performance and course evaluations between students who used the online atlas and students who did not use the online atlas in the pre-clinical medical curriculum will be conducted. Our preliminary data so far shows that student feedback has been positive and an e-learning atlas integrating microanatomy and pathology laboratory may be an essential tool that guides the studies and enhances the performance of students in an interdisciplinary pre-clinical medical curriculum. DISCLOSURES/ACKNOWLEDGEMENTS: American Educational Institute, University and Campus Management (AEIUCM) developed, designed, and maintains the online portal

An Innovative Interactive Modeling Tool to Analyze Scenario-Based Physician Workforce Supply and Demand

Effective physician workforce management requires that the various organizations comprising the House of Medicine be able to assess their current and future workforce supply. This information has direct relevance to funding of graduate medical education. We describe a dynamic modeling tool that examines how individual factors and practice variables can be used to measure and forecast the supply and demand for existing and new physician services. The system we describe, while built to analyze the pathologist workforce, is sufficiently broad and robust for use in any medical specialty. Our design provides a computer-based software model populated with data from surveys and best estimates by specialty experts about current and new activities in the scope of practice. The model describes the steps needed and data required for analysis of supply and demand. Our modeling tool allows educators and policy makers, in addition to physician specialty organizations, to assess how various factors may affect demand (and supply) of current and emerging services. Examples of factors evaluated include types of professional services (3 categories with 16 subcategories), service locations, elements related to the Patient Protection and Affordable Care Act, new technologies, aging population, and changing roles in capitated, value-based, and team-based systems of care. The model also helps identify where physicians in a given specialty will likely need to assume new roles, develop new expertise, and become more efficient in practice to accommodate new value-based payment model

Cabozantinib versus everolimus, nivolumab, axitinib, sorafenib and best supportive care: A network meta-analysis of progression-free survival and overall survival in second line treatment of advanced renal cell carcinoma

Background Relative effect of therapies indicated for the treatment of advanced renal cell carcinoma (aRCC) after failure of first line treatment is currently not known. The objective of the present study is to evaluate progression-free survival (PFS) and overall survival (OS) of cabozantinib compared to everolimus, nivolumab, axitinib, sorafenib, and best supportive care (BSC) in aRCC patients who progressed after previous VEGFR tyrosine-kinase inhibitor (TKI) treatment. Methodology & findings Systematic literature search identified 5 studies for inclusion in this analysis. The assessment of the proportional hazard (PH) assumption between the survival curves for different treatment arms in the identified studies showed that survival curves in two of the studies did not fulfil the PH assumption, making comparisons of constant hazard ratios (HRs) inappropriate. Consequently, a parametric survival network meta-analysis model was implemented with five families of functions being jointly fitted in a Bayesian framework to PFS, then OS, data on all treatments. The comparison relied on data digitized from the Kaplan-Meier curves of published studies, except for cabozantinib and its comparator everolimus where patient level data were available. This analysis applied a Bayesian fixed-effects network meta-analysis model to compare PFS and OS of cabozantinib versus its comparators. The log-normal fixed-effects model displayed the best fit of data for both PFS and OS, and showed that patients on cabozantinib had a higher probability of longer PFS and OS than patients exposed to comparators. The survival advantage of cabozantinib increased over time for OS. For PFS the survival advantage reached its maximum at the end of the first year’s treatment and then decreased over time to zero. Conclusion With all five families of distributions, cabozantinib was superior to all its comparators with a higher probability of longer PFS and OS during the analyzed 3 years, except with the Gompertz model, where nivolumab was preferred after 24 months

Overview of the instrumentation for the Dark Energy Spectroscopic Instrument

The Dark Energy Spectroscopic Instrument (DESI) embarked on an ambitious 5 yr survey in 2021 May to explore the nature of dark energy with spectroscopic measurements of 40 million galaxies and quasars. DESI will determine precise redshifts and employ the baryon acoustic oscillation method to measure distances from the nearby universe to beyond redshift z > 3.5, and employ redshift space distortions to measure the growth of structure and probe potential modifications to general relativity. We describe the significant instrumentation we developed to conduct the DESI survey. This includes: a wide-field, 3.°2 diameter prime-focus corrector; a focal plane system with 5020 fiber positioners on the 0.812 m diameter, aspheric focal surface; 10 continuous, high-efficiency fiber cable bundles that connect the focal plane to the spectrographs; and 10 identical spectrographs. Each spectrograph employs a pair of dichroics to split the light into three channels that together record the light from 360–980 nm with a spectral resolution that ranges from 2000–5000. We describe the science requirements, their connection to the technical requirements, the management of the project, and interfaces between subsystems. DESI was installed at the 4 m Mayall Telescope at Kitt Peak National Observatory and has achieved all of its performance goals. Some performance highlights include an rms positioner accuracy of better than 0.″1 and a median signal-to-noise ratio of 7 of the [O ii] doublet at 8 × 10−17 erg s−1 cm−2 in 1000 s for galaxies at z = 1.4–1.6. We conclude with additional highlights from the on-sky validation and commissioning, key successes, and lessons learned

Pathologists as Clinical Consultants

CONTEXT.—: Pathologists often provide extensive consultative services to other physicians beyond establishing a diagnosis or providing laboratory test results, but they are typically not financially compensated for these services. Another relatively new role for pathologists in the United States is as a consultant who works directly with patients. OBJECTIVE.—: To review how pathologists provide detailed consultation to other physicians, how pathologists can be financially compensated for this critical service, and how pathologists are increasingly serving as a consultant directly with patients and their families. DATA SOURCES.—: Sources were peer-reviewed medical literature and the author\u27s personal experience. CONCLUSIONS.—: In recognition of the extensive consultative services provided by both clinical and anatomic pathologists to other physicians, procedural codes recently approved and valued by the Centers for Medicare & Medicaid Services now provide a compensation mechanism for these services for government-insured and potentially privately insured patients. Pathologists are also increasingly providing consultative services directly to patients, resulting in significant patient satisfaction and providing important support for patients and their physicians

From HIV to Coronavirus Disease 2019 (COVID-19)

CONTEXT.—: From the onset of the human immunodeficiency virus (HIV) pandemic in the 1980s to the recent coronavirus disease 2019 (COVID-19) pandemic, multiple viral pandemics have occurred and all have been associated with hematologic complications of varying severity. OBJECTIVE.—: To review the hematologic complications associated with the HIV and other viral pandemics, the current theories regarding their causation, and the incidence and clinical impact of these complications on infected patients. DATA SOURCES.—: Peer-reviewed medical literature and the author\u27s personal experience. CONCLUSIONS.—: The HIV and other viral pandemics have been associated with a variety of hematologic complications that often cause significant morbidity and mortality in affected patients. HIV infection is associated with multiple hematologic disorders, many of which have a lower incidence in the era of highly active antiretroviral therapy but still represent a major clinical problem for HIV-infected patients. Our understanding of the pathogenesis of HIV-related hematologic complications, including HIV-associated lymphoproliferative disorders, has evolved in recent years. Other viral pandemics, including H1N1 influenza, severe acute respiratory syndrome (SARS) coronavirus, Middle East respiratory syndrome (MERS) coronavirus, and COVID-19, have also been associated with hematologic complications of varying severity. Our emerging understanding of the pathogenesis of the hematologic complications of HIV, COVID-19, and other viral pandemics may help in prevention, correct diagnosis, and treatment of these complications in current and future pandemics

Clinical consequences of specimen rejection: A College of American Pathologists q-probes analysis of 78 clinical laboratories

Context.—Clinical laboratory specimens may be rejected as unsuitable for analysis for a variety of reasons and specimen rejection may have significant clinical consequences.Objective.—To quantify the clinical consequences of specimen rejection and determine the impact of laboratories' policies and practices on these consequences.Design.—Participants prospectively reviewed consecutive blood and urine specimens submitted to the chemistry and/or hematology laboratories to identify rejected specimens. For each rejected specimen, the patient's age, specimen type, testing priority, rejection reason, time from specimen receipt to receipt of recollected/relabeled specimen, recollection method, and test result time were recorded. Specimen/test abandonment was determined by failure to recollect or relabel a rejected specimen. Each laboratory's policy regarding relabeling of incorrectly labeled specimens was recorded, along with how many relabeled specimens were subsequently discovered to be mislabeled.Results.—Specimen rejection led to a (1) high rate of specimen recollection, (2) delay in result availability (median of 65 minutes), and (3) high rate of specimen/test abandonment. Longer test result delay was associated with higher hospital bed size; and higher test abandonment rate, with failure of the laboratory to request specimen recollection. Relabeling of incorrectly labeled specimens was found to be of little benefit and was associated with a substantial percentage of subsequently mislabeled specimens.Conclusion.—Specimen rejection has significant clinical consequences, including patient discomfort, significant delay in result availability, and high rate of specimen/test abandonment. Allowing routine relabeling of incorrectly labeled specimens is a dangerous practice, with little measureable benefit and with an increased risk to patient safety.</jats:p