MSK PATHOLOGY Initiatives Innovations REVIEW Accomplishments 4th Quarter 2019

A Journey of Technological Evolution in Research and Diagnostics Commentary from the Department Chair Case of the Quarter

CASE HISTORY 59 year old woman with palpable and tender 3.5 cm right lateral breast With this issue of the MSK Pathology Review, mass and weight loss and no axillary we resume the publication of our departmental lymphadenopathy. Of note, she quarterly newsletter after a 6 month hiatus. The lack presented with a 1.6 cm right upper of intervening issues has a simple explanation. Our lobe lung mass. Both biopsies are talented science writer, Hope Cristol, decided to move shown here. The patient ultimately on to new opportunities, and it took us quite some underwent mastectomy due to rapid Breast, biopsy time to find a replacement. Finally, we were fortunate growth of the breast mass. to find Onward Publishing, Inc., a professional writing group that has assigned several different The correct diagnosis will be writers to assist us with our production. Meanwhile, provided in the next issue of the MSK Sarah Virgo has continued to collect material and Pathology Review and on Twitter at ideas for stories. The current issue is among our @MSKPathology most comprehensive to date, including updates on Scan the QR code to view digital slides events over the past 6 months along with continuing available on mskcc.pathpresenter.com our series on diagnostic teams, individual faculty investigators, and fellows’milestones. We introduce a “Case of the Quarter” feature and highlight the quality Lung, biopsy improvement efforts throughout the department. Clearly, the MSK Pathology Review is back on track, and the continuing accomplishments and innovations from our department ensure we will have plentiful material for many issues to come! I would like to take this opportunity to acknowledge those who have contributed so much to this project – Hope Cristol, Allix Mazzella, Jordana Shapiro, and of course Sarah Breast, excision (10x) Virgo, whose investment in this effort is absolutely key to its success. I hope you will all enjoy this new edition!

- David Klimstra, MD

Breast, excision (100x)

MSK PATHOLOGY MSK PATHOLOGY 2 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 3 Research Profile

WENBIN XIAO, MD

The current World Health Organization “(WHO) classification is ‘mostly based on morphology and history, and integrates some genetic data. For nearly half of the AML, the genetic information is still not utilized to classify disease.’”

subclasses of AML. Among the subclasses, pathogenesis of ALMED. Xiao and colleagues mutations including PHF6 and RUNX1. “The core-binding factor AML tends to have were the first to explore the disease’s mutations of these two molecules probably a good prognosis. However, it can turn mechanisms of pathogenesis in humans and comprise about 60% of secondary AML into aggressive disease if it gains genomic concluded that the mechanism of pathogenesis cases,” he says. mutations over time. Xiao was the lead in humans is similar to that in animals. Xiao’s studies have relied on clinical author of a 2017 study, published in Blood His recent work also identified PHF6 and data. However, he has recently moved back Advances, in which a patient with inv(16) DNMT3A mutations in mixed phenotype to the bench, joining the lab of Ross Levine, For a relatively new Some MSK pathologists prefer the clinical strong research interest kept tugging at him AML achieved five complete remissions acute leukemia, a rare type of leukemia MD, the Laurence Joseph Dineen Chair in hematopathologist, Dr. Xiao side of their responsibilities; others are and soon he was back at the bench. with various chemotherapies but ultimately often challenging to diagnose. The findings, Leukemia Research and Chief of Molecular already has remarkable primarily researchers. Hematopathologist died from this aggressive and highly invasive published in Blood Advances in 2019, showed Cancer Medicine with the Human Oncology Wenbin Xiao prefers both. Instead of splitting STUDIES ON AML disease. Bone marrow biopsies performed a phenotype-genotype correlation between and Pathogenesis Program (HOPP). “I will research experience. his time evenly between them, his career has For the past three years, Xiao has been at each relapse revealed a consistent gain in mutations and mixed phenotype, which can apply my findings from the clinical side and focused primarily on either one or the other working to better classify hematological cytogenetic abnormalities and a KRASG12D use this knowledge to make mouse models to By Hope Cristol potentially facilitate the diagnosis. at different times. malignancies at the genetic level – especially mutation. Although unusual, this unique More recently, Xiao reported at the ASH learn about the mechanisms of the disease,” After completing his MD/PhD training, secondary acute myeloid leukemia (AML). case highlights how acquired genomic meeting a subset of AML patients showing Xiao says. Xiao spent six years doing bench work, first He cowrote a seminal review of the genetic alterations can quickly alter prognosis, even RUNX1 mutations and plasmacytoid Treatments for secondary AML are not as a postdoc and then as a research scientist. basis of hematologic malignancies, published for a chemosensitive patient. dendritic cell differentiation, a rare cell type adequate and disease prognosis is poor. This “At that time, my research was mostly focused in Blood. The current World Health Another study, published in Leukemia normally responsible for host immunity is partly because molecular targets have not on signal transduction in leukemic cells,” Xiao Organization (WHO) classification is “mostly in 2018, focused on an extremely rare and against viral infection. Accurate diagnosis yet been identified. Also, the disease usually says. “But I was trained as a physician, so I based on morphology, history, and integrates aggressive subclass: acute leukemia with of this AML variant may benefit the patients strikes people later in life who “cannot wanted to get involved in patient care as well.” some genetic data. For nearly half of the AML, megakaryocytic and erythroid differentiation from appropriate targeted therapies. tolerate regular cytotoxic chemotherapy. He returned to medicine, completing his the genetic information is still not utilized to (ALMED). The patient could die from complications,” residency and fellowship and then joined the classify disease”, Xiao says. Previous research in mice suggested a EVOLVING RESEARCH ROLE Xiao says. “So we need to find better targeted staff at MSK. For a while, much of his work Several of his recently published studies cooperative role of JAK/MAP kinase pathway Xiao continues to focus on secondary therapy, which means we need to find those was on the clinical side of pathology. But his explored the genetic underpinnings of rare activation and TP53 mutations in the AML and is adding to the evidence on targets.”

MSK PATHOLOGY MSK PATHOLOGY 4 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 5 genomic pathology, and mass spectrometry-driven proteomics. He THE FOURTH ANNUAL gave a lecture entitled “Mass Spectrometry as a Driver for Discovery in Lymphoma Pathogenesis.” SYMPOSIUM Dr. Elenitoba-Johnson is also the founding director of Penn Medicine’s Center for Personalized Diagnostics and chief of the IN TRANSLATIONAL Division of Molecular and Genomic Pathology at Penn Medicine. Attendees were welcomed to the symposium by Dr. David Klimstra, RESEARCH IN PATHOLOGY Chair of the Department of Pathology. Several other pathologists from Honors William L. Gerard Award the department gave presentations on a range of topics, including Winner and Highlights Cutting-Edge sample preparation, the role of fusion genes, and assessing minimal residual disease (see page 9 for a full lecture schedule). Pathology Research The Gerald Award was created to recognize the contributions and values brought to MSK’s Department of Pathology by William L. By Julie Grisham Gerald, who died in 2008. Dr. Gerald was a pioneer in the molecular characterization of cancer at a time when now-commonplace molecular techniques were still cutting-edge technology. Throughout On March 28, Memorial Sloan Kettering’s Department of his career, he provided mentorship and collaboration to numerous Pathology hosted its Fourth Annual Symposium in Translational trainees and colleagues. The award is a tribute to his scientific Research in Pathology. The event, which included the presentation contributions and personal attributes and to the legacy of his work of the William L. Gerald Award, was held in the Zuckerman Research in the department. Laboratory Auditorium. Past recipients of the Gerald Award include Drs. Arul Chinnaiyan The winner of this year’s Gerald Award was Kojo Elenitoba- of the University of Michigan Medical School, David Huntsman of the Johnson, the Peter C. Nowell MD Professor at the Perelman School University of British Columbia, Adrienne Flanagan of the University of Medicine at University of Pennsylvania. Dr. Elenitoba-Johnson is an College London Cancer Institute, and A. John Iafrate of Massachusetts international leader in the fields of hematopathology, molecular and General Hospital and Harvard Medical School.

William L. Gerald, MD PhD

MSK PATHOLOGY MSK PATHOLOGY 6 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 7 in 2006. He is an elected member of the KOJO ELENITOBA-JOHNSON, MD American Society for Clinical Investigation Professor, Perelman School of Medicine at the University of Pennsylvania, and is the recipient of the 2012 Outstanding Research Presentations GLI1-Amplified Soft Tissue Neoplasm: A Novel Investigator Award from the American Selected Fellows and Faculty Entity Showing Morphologic Overlap with Tumors Founding Director, Penn Medicine’s Center for Personalized Diagnostics, Moderators: Drs. Hameed, Reis-Filho and A. Dogan Chief, Division of Molecular and Genomic Pathology, University of Pennsylvania, Society for Investigative Pathology. with GLI1 Gene Fusions Dr. Narsi Agaram Penn Medicine’s Center for Personalized Diagnostics Dr. Elenitoba-Johnson is a member of Comprehensive Solid Tumor Microbiome Profiling the Board of Scientific Counselors for the Via Analysis of Unmapped Reads in Large Panel, Detailed Morphologic and Genetic Features of National Cancer Institute in the National By Ahmet Dogan, MD, PhD Hybridization Capture-Based NGS Assay Data Urothelial Carcinoma in Patients with Lynch Institutes of Health. He is an associate Dr. Chad Vanderbilt Syndrome editor for the Journal of Hematopathology Dr. Hikmat Al-Ahmadie Kojo Elenitoba-Johnson is the inaugural Dr. Elenitoba-Johnson earned his and a member of numerous professional Developing a Robust Sample Preparation Procedure Peter C. Nowell, MD Professor at the medical degree from the College of Medicine societies, including the American Society for Deep Fourier-Transform Mass Spectrometric Evolving Landscape of Minimal Residual Disease Perelman School of Medicine at University at the University of Lagos. He completed his of Hematology, American Society for Profiling of Formalin-Fixed Paraffin-Embedded Assessment in Hematological Malignancies of Pennsylvania. He is also the founding residency in anatomic and clinical pathology Investigative Pathology, United States Clinical Tissue Specimens Dr. Mikhail Roshal director of Penn Medicine’s Center for at the Brown University School of Medicine, and Canadian Academy of Pathologists, Dr. Michael Roehrl Modalities and Applications for Quantitative Personalized Diagnostics, as well as the where he served as Chief Resident. He then and Association for Molecular Pathology Recurrent but Not Pathognomonic Fusion Genes in Multiplexed Immunostaining in Immuno-Oncology chief of the division of molecular and moved on to the National Cancer Institute to (AMP). He served as the Chair of the Hematopathology Division of the AMP Mucinous Carcinomas of the Breast Dr. Travis Hollmann genomic pathology. Dr. Elenitoba-Johnson complete a fellowship in hematopathology, Dr. Fresia Pareja is an international leader in the fields of as well as to the Leadership Development from 2008 to 2009. He has authored or co- authored more than 170 peer-reviewed Introduction, Gerald Award Presentation & Special hematopathology, molecular and genomic for Physicians in Academic Health Genomic Profiling of Mucinous Adenocarcinoma Lecture Mass Spectrometry as a Driver for pathology, and mass spectrometry-driven Centers program at the Harvard School research publications and has contributed more than 40 chapters to professional Can Assist in Determination of Site of Origin Discovery in Lymphoma Pathogenesiss proteomics. of Public Health. Before arriving at Penn, Dr. Amir Boroujeni Dr. Kojo Elenitoba-Johnson Dr. Elenitoba-Johnson was the Henry textbooks on pathology. Clay Bryant Professor at the University of Michigan and served as director of the Molecular Diagnostics Laboratory there. His research focuses on the pathogenesis The Fifth Annual Symposium of human malignant lymphomas, biomarker in Translational Research in discovery by genomic and proteomic profiling, and cancer. Dr. Elenitoba-Johnson Pathology will take place on has been recognized with numerous Thursday, March 26, 2020. Dr. awards, including the American Society for Sunil Lakhani of the University Investigative Pathology Scholarship in 1993, the Outstanding Graduating Resident Award of Queensland will receive the from Brown University in 1995, the Society William L. Gerald Award. for Hematopathology Pathologist- in-Training Award in 1998, Outstanding Teaching Awards For additional information or in Anatomic Pathology from to register for the course, the University of Utah (1999 please visit: and 2003), and the Ramzi S. Cotran Young Investigator www.mskcc.org/trs2020 Award from the United States and Canadian Academy of Pathology

MSK PATHOLOGY MSK PATHOLOGY 8 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 9 Research Profile

a microscope,” says Dr. Berger. “But the genetic offerings. Since receiving New York State analysis that we perform can tell us about certain Department of Health approval to use MSK- The test reaffirms genomic alterations that are characteristic of IMPACT™ as a clinical test in 2014, Dr. Berger “ certain tumor types, as well as which mutations, has made continual improvements, adding the importance of MICHAEL amplifications, or rearrangements might be additional analyses and the ability to sequence targetable by available drugs. This provides new types of biological specimens in order to pathology not only complementary biological and clinical expand the test’s clinical utility and its suitability BERGER, PHD information that can give a pathologist a better for additional populations of patients. to correctly diagnose idea of what type of cancer is there and how a “Originally, the test was used on patients a patient’s cancer particular patient might respond to a particular with advanced cancer who are treated by medical therapy.” oncologists and are candidates for clinical trials,” but to provide as Dr. Berger and his team spent years he says. “But we want to expand our program to developing, refining, and clinically validating also test patients with earlier stage disease who much information MSK-IMPACT™, carefully selecting what genes are typically treated by surgeons. In doing so, we to include in the test panel, coming up with may be able to identify prognostic biomarkers as possible to effective strategies to deal with lower-quality that could affect how aggressively patients tumor specimens, and creating a bioinformatics should be treated or monitored for disease oncologists so they platform to provide doctors with meaningful, recurrence.” actionable results. “The test reaffirms the He and his team have also developed can improve the importance of pathology not only to correctly a complementary sequencing test called diagnose a patient’s cancer but to provide as MSK-ACCESS, or Analysis of Circulating quality of care they much information as possible to oncologists Cell Free DNA to Evaluate Somatic Status. so they can improve the quality of care they are Sometimes referred to as a “liquid biopsy,” this are giving each giving each patient,” says Dr. Berger. offers clinicians a way to screen for cancer or metastasis from a simple blood sample without patient.” EXPANDING IMPACT the need for an invasive tumor biopsy. It was One of the most valuable aspects of the MSK- approved for clinical use by the New York State IMPACT™ program is the size of the dataset the Department of Health in the summer of 2019. pathology department has now accumulated. At “The opportunity to sequence DNA from last count, more than 200 scientific papers have a blood sample to detect mutations is very been published incorporating MSK-IMPACT™ exciting,” says Dr. Berger. “It allows us the ability data. “We are sharing this dataset in real time to profile tumor DNA levels longitudinally with all of the investigators at MSK,” says Dr. throughout a patient’s treatment course, even Berger. “It opens up a whole new set of research in patients from whom we cannot obtain tumor opportunities, both within pathology and in tissue. It’s exciting and continues to show how other departments. It is remarkable how these genomics can help inform clinical treatment data continue to provide new insights into how decisions to provide better outcomes for our cancer can and will be treated in the future.” patients. At the end of the day, that’s what In addition, Dr. Berger’s laboratory is everyone here at MSK wants.” working to expand pathology’s genomic When Michael Berger, PhD, now guide treatment decisions by identifying the Michael Berger, PhD, Associate Director of the Marie-Josée genetic pathways that may be dysregulated and Henry R. Kravis Center for Molecular in individual patients’ tumors.” Makes an IMPACT Oncology at Memorial Sloan Kettering Cancer Center, joined MSK in 2010 he had HONING GENOME SEQUENCING By Kayt Sukel never worked directly with pathologists. In the years since, Dr. Berger has That said, he hoped to find new ways to apply worked closely with his colleagues in the his training in genomics and computational Department of Pathology’s Molecular biology to improve diagnosis and treatment Diagnostics Service to develop a selection at one of the nation’s foremost groundbreaking genome-sequencing test cancer centers. At the time, work in cancer called MSK-IMPACT™, which stands for genomics was still largely confined to the Integrated Mutation Profiling of Actionable research lab and it wasn’t fully clear how it Cancer Targets. This unique, comprehensive might move from the bench to the bedside. test can detect specific mutations in “In hindsight, it was fortunate timing,” hundreds of genes, as well as alterations in he says. “Leading cancer centers like genetic pathways in both rare and common MSK were trying to determine how best forms of solid cancer tumors. With the MSK- to incorporate genomic technologies and IMPACT™ results in hand, clinicians have analysis into clinical care, which was exactly targeted information to guide them as they what I was excited to do. I’ve come to realize match patients to a specific therapy or to a that pathology really is at the center of our clinical trial that may benefit them. clinical genomics efforts, offering new ways “Typically, pathologists render a to diagnose different cancers as well as help diagnosis based on looking at tissue under

MSK PATHOLOGY MSK PATHOLOGY 10 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 11 A Journey of Technological

His next reaction was anxiety at the prospect of delivering the Dr. Klimstra first became interested in pathology while studying meeting’s highly anticipated keynote lecture. “I had no inkling I had at Yale. Like most who pursue a career in medicine, he was driven Evolution even been nominated. And then to be asked to give what is supposed largely by a desire to help people. But when his pathology courses to be the key lecture of my career — well, it was a little nerve-racking. first placed him in front of a microscope, he was immediately hooked. This isn’t your standard talk where you report on specific research “I’ve always loved science,” he says. “But, in medical school, I in Research findings or give some type of didactic lecture,” says Dr. Klimstra. became really interested in understanding disease at the morphologic “In this lecture, you need to reflect on where pathology’s been and level. If I can see it under a microscope, it somehow just makes more and Diagnostics then offer more philosophical thoughts on where it is heading in the sense to me. I really appreciate the more mechanistic aspects of how a future — and you give it in front of thousands of your peers. I was very cancer develops and progresses and the ability to put all those pieces honored. But I also knew I had a lot of work to do to get that type of together in a logical pattern to understand a disease.” MSK Pathology Chairman David Klimstra, MD, shares his vision talk ready.” Over the course of his career, Dr. Klimstra has put his microscope for the future in his prestigious Maude Abbott Lecture at the 2019 to good use by working to better understand the pathology of tumors A LONG AND PRESTIGIOUS CAREER of the digestive system, pancreas, liver, and neuroendocrine system. USCAP annual meeting Of course, Dr. Klimstra is no stranger to hard work. Twenty-eight Today, he is an internationally recognized expert on the correlations years ago, after completing his anatomic pathology residency at Yale between the clinical, morphological, immunohistochemical, and University, he followed his mentor, Juan Rosai, MD, to MSKCC to molecular features of both common and rare tumors that develop By Kayt Sukel complete an oncologic surgical pathology fellowship. He’s been with in those areas. the department ever since. When asked why he gravitated toward these forms of cancers “At the time, there were about 18 pathologists on the faculty, and even as early as his residency, he recounts an interesting case he now we are one of the largest cancer pathology departments in the encountered as a resident. That case, a pancreatic acinar cell world,” he says. “Back then, almost all of those faculty were diagnostic carcinoma, led to his first major publication. He realized that very When David Klimstra, MD, Memorial Sloan Kettering Cancer of Medical Museums (later known as the International Academy of pathologists who practiced general cancer pathology. The same few American pathologists were studying pancreatic neoplasia at Center’s Pathology Chairman and James Ewing Alumni Chair, Pathology), has been one of the greatest honors that can be conferred pathologists were signing out the skin biopsies, the bone marrow that time, and upon moving to MSKCC in 1991, it was clear there was a received word that he had been selected to give the 2019 Maude by the USCAP. Each year, USCAP’s executive committee puts forth biopsies, the breast biopsies, the colon resections — you name it. tremendous opportunity in pancreatic pathology. It was a challenging Abbott Lecture at the annual United States and Canadian Academy for consideration three candidates, “revered authorities” who It was a broad general practice. But now we have become very sub- topic, given the aggressive behavior of most pancreas cancers, but of Pathology (USCAP) meeting, his first reaction was disbelief. have contributed and continue to contribute to the advancement specialized with most of our now 100 faculty members focused on a it was also one with the potential to make a major difference in Since 1980, the Maude Abbott Lecture, named for the pioneering of pathology. Dr. Klimstra says his selection came out of the “clear specific niche, which gives us world-renowned diagnostic expertise cancer care. Even now, he notes, few pathologists have established Canadian pathologist who co-founded the International Association blue sky.” in literally every different area of cancer pathology.” themselves in this discipline.

MSK PATHOLOGY MSK PATHOLOGY 12 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 13 A WAY FORWARD FOR PANCREATIC CANCER Pancreatic ductal adenocarcinoma, the most Here at MSK, we common type of pancreatic cancer, is an insidious and “are sitting at the particularly lethal form of the disease, explains Dr. Klimstra. “Its five-year survival rates are in the single cutting edge of cancer digits for the average patient. So, anything we can do pathology. What we to detect it earlier, even before it is radiographically evident, creates a greater opportunity to cure it. One of are learning is not my interests has been in characterizing the precursors only shaping our own of pancreatic cancer so we can intervene before invasive cancer develops.” discipline but also And based on our current knowledge, pancreatic cancer care at a global cancer is proving to be more heterogeneous than we first believed, which is another reason Dr. Klimstra level. Working in this feels it’s so important that more people investigate how field has been and it develops and progresses. “There are probably fifteen continues to be an different kinds of pancreatic cancer and each has very specific attributes,” he said. “But if we can understand enormous privilege. I’m how the distinctive clinical, histological, and molecular really very lucky.” features fit together to result in disease, we have the best chance to define treatments to help our patients.” To date, Dr. Klimstra has published more than He adds that, with big data analytics on the horizon, it will be 400 peer-reviewed articles on tumors of the pancreas, more important for pathologists to become comfortable with and other organs, and co-authored four Armed computational methods as well as a wide variety of “-omic” data. Forces Institute of Pathology books, two editions “We have a major program here at MSKCC where we can use each of Tumors of the Pancreas and Tumors of the digital representations of a microscopic slide or three-dimensional Gallbladder, Extrahepatic Bile Ducts and Ampulla of images of tissue and then use machine learning to do mathematical Vater. He has also worked closely with the World Health calculations on the images,” he says. “These tools can help us more Organization (WHO) and American Joint Commission easily recognize features we currently use for diagnosis today. But on Cancer (AJCC) to develop appropriate classification the real excitement is that the data embedded in these morphologic and staging systems for tumors of the digestive system representations can be integrated with data from molecular and and endocrine organs to aid in detection and treatment protein-based assays so we can understand a lot more about cancers of these conditions. than we do today. These new technologies hold enormous promise In his Maude Abbott lecture, Dr. Klimstra for the impact pathology can have on the rest of cancer medicine.” discussed the breadth of his research, starting As Dr. Klimstra reflects on his long career and his ongoing in residency and continuing even now into his David S. Klimstra, MD and Wendy L. Frankel, MD From left to right: Drs. Marcia Edelweiss, Gloria Young, Laura Tang, research program, he hopes that more medical students will consider chairmanship, including his work to better understand David S. Klimstra, Olca Basturk and Hui Chen pathology, particularly oncologic pathology, as a specialty. All less common forms of pancreatic cancer, acinar cell successful cancer treatments, he says, spring from a foundation of carcinoma (ACC) and pancreatic neuroendocrine tumor (PanNET). progress rather slowly as compared to conventional pancreatic that was done using traditional morphologic techniques. But as genetic accurate pathologic diagnosis. ACC makes up only about two percent of tumors that develop in the cancer, sometimes evolving over years or even decades,” he says. sequencing technology has evolved and become more affordable, we are “As pathologists, we not only recognize what the disease is and organ, but Dr. Klimstra says that even work on a rare disease like ACC “It’s a different type of tumor system and has different types of genetic now generating enormous amounts of information about mutations predict how it’s likely to behave, but we also provide information highlights how pathology investigations have evolved over the last aberrations that require a different kind of medical management. So, and other genetic alterations that may provide additional insights into about what drugs are best to treat it,” he notes. “Unfortunately, the few decades and provides valuable insights that can be generalized we’ve been working hard to characterize what features will predict the how to best diagnose and treat these cancers.” pathology that medical students experience is not really related to the to more common cancer types. biology of these tumors. How can you tell whether they will be more or In addition to generating data on the alterations in tumor DNA, daily practice of pathology. They don’t see how truly multidisciplinary The theme of the lecture was the evolution of technology available less aggressive? How do we identify which patients need immediate we are now analyzing gene expression, epigenetic alterations such the field is, how closely you work with the rest of the clinical team, and to pathologists to study neoplastic disease. “We started by studying treatment as opposed to those who just need to be observed?” as methylation, and protein profiles using mass spectrometry. These the kind of impact you can actually have on an individual patient’s care.” the conventional pathology. How do you make the diagnosis? How do That work, he says, has led to a new way of thinking about not only studies are generating an unprecedented amount of data that can Despite his love for his microscope, Dr. Klimstra said that he the tumors stain using immunohistochemistry? What happens to the pancreatic neuroendocrine tumors, but neuroendocrine tumors that help us better understand cancer biology. But only if they can make hopes future practitioners understand that cancer pathologists patients over time?” he explains. “But, over the years, with the availability arise in other parts of the body. sense of all that data. That’s why, as Dr. Klimstra noted in his Maude don’t just sit in a laboratory all day: they work closely with the rest of of conventional and then next-generation genomic sequencing, we’ve “Ultimately, the goal of pathology isn’t just to understand the Abbott lecture, one of the greatest challenges facing pathology in the clinical care team and play a pivotal role in diagnosis, treatment discovered more and more molecular events that contribute to the disease process, but to use those insights to make sure our patients the future is how to integrate and interpret these vast amounts of selection, and overall patient outcomes. When he looks at both his development of ACC, including some potentially targetable molecular are getting the best possible treatments.” complex data. own work and that of his colleagues, he has found this line of work to alternations that may allow us to treat patients specifically for this “To a certain extent, we are starting to do this today,” he says. “But be incredibly rewarding. “The opportunity that I have being chairman disease. We can learn a lot from unraveling the biology of tumors like TOWARD THE FUTURE OF PATHOLOGY we aren’t integrating all this information as well as we could be. The of this department and working with such an extraordinary group of this.” Data from newer technologies have enabled us to paint a much Dr. Klimstra says that advances in genomic techniques and other future will require us to develop better methods for data integration, faculty, trainees, technologists, and others, has been remarkable,” more complete picture of this and other rare neoplasms. technologies are now providing pathologists with a remarkable including the possibility of using machine learning and artificial he says. “Here at MSKCC, we are sitting at the cutting edge of cancer Dr. Klimstra’s lecture also touched on his work investigating amount of new information. “Ten years ago, the primary role of the intelligence to augment our abilities. We also need to consider ways to pathology. What we are learning is not only shaping our own discipline PanNETs. Though not as rare as ACCs, PanNETs have a compelling pathologist was to make the diagnosis and then provide any additional potentially automate some of that integration as well so we can make but also cancer care at a global level. Working in this field has been biology of their own. “Pancreatic neuroendocrine tumors tend to information that might help with prognosis,” he explains. “By and large, our practice more efficient.” and continues to be an enormous privilege. I’m really very lucky.”

MSK PATHOLOGY MSK PATHOLOGY 14 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 15 The symposium was created to feature research that is ongoing Warren Alpert Center and to highlight the collaborations between pathologists and the for Digital and digital and computational laboratories that have the potential to positively and substantively impact clinical cancer care. Attendees Computational Pathology have the opportunity to ask questions, meet with research staff and Highlights Research Advances in Digital and learn about the latest digital and computational advances within Computational Pathology the department. Presentations focused on topics ranging from the use of artificial By Julie Grisham intelligence in histopathology to the latest methods in microscopy and other imaging techniques. These new enhancements to cancer diagnoses offer a more in-depth analysis than is currently available. In May 2019, Memorial Sloan Kettering’s Warren Alpert Center “Pathology is in the midst of a revolution, from a qualitative to a for Digital and Computational Pathology welcomed speakers and fundamentally quantitative discipline. This transformation will be attendees to the Zuckerman Research Center Auditorium for driven by the next generation of scientific leaders who will be able to its Second Annual Digital and Computational Pathology Spring combine a deep understanding of machine learning, histology and Symposium. The meeting featured talks from faculty, research oncology to impact patient care,” says Dr. Thomas Fuchs, Director fellows and staff on the latest research initiatives at MSK in digital of Computational Pathology. and computational pathology. The Warren Alpert Center for Digital and Computational “Over the last 5 years, MSK has embraced new technologies Pathology was established in 2017 as an innovation center to that enable a truly digital workflow. The benefits of this investment facilitate novel research and development in digital pathology have come to fruition in that we now have unparalleled resources and algorithmic computational pathology for clinical cancer care for the integration of machine learning technologies in the review, and research. It also serves as a hub for existing digital pathology diagnosis, and prognostic assessment of digital whole slide efforts to establish a fully digital workflow in MSK’s Department of and tissue images. The work highlighted in the symposium Pathology. Please see page 18-19 for a full list of lectures and posters showcases just that,” says Dr. Yukako Yagi, Director of Digital from the 2019 Second Annual Warren Alpert Center For Digital Pathology at MSK. And Computational Pathology Spring Symposium.

Research Presentations Automated Cancer Segmentation Selected Fellows, Students & Faculty of Histopathology Images Using Moderators: Drs. Yukako Yagi and Thomas J. Fuchs Convolutional Neural Networks Dr. David J. Ho Introduction to Digital Pathology Imaging Dr. Yukako Yagi Precise Detection of PDL1 and PDL2 Amplification in Classical Hodgkin’s Learning Histopathology Patterns Using Spatial Lymphoma Using a Confocal Microscope Point Process and the Simultaneous Visualization of Chao Feng, PhD Candidate Immunophenotypes and FISH Signals Dr. Yanming Zhang Correlating Micro-Computed Tomography (Micro-CT) of Endoscopic Resected Towards Unsupervised Cancer Gastrointestinal Specimens with Histopathology Subtyping: Predicting Prognosis Dr. Makoto Nishimura Using a Histopathology Visual Dictionary Lung Immuno-Oncology Hassan Muhammad, PhD Candidate Dr. Chad Vanderbilt Closing Remarks on the Future of Pathology Dr. Thomas J. Fuchs Assessment of HER2 Amplification Status in Director, Medical Machine Learning & Invasive Breast Cancer Using Bright-Field In Computational Pathology Situ Hybridization and Digital Pathology Dr. Dara S. Ross

MSK PATHOLOGY MSK PATHOLOGY 16 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 17 FELLOWSHIP GRADUATION Class of 2018-2019

DAVID KLIMSTRA, MD VICTOR REUTER, MD Chair, Department of Pathology; Vice Chair, Department of Pathology; Director, James Ewing Alumni Chair of Pathology Genitourinary Pathology; Director, Genitourinary Pathology Fellowship; Director, Pathology Core Facility It has been a privilege for us to work with all of you this past year. Teaching fellows is certainly part of the core mission of our department, and it is very Dear fellows, you worked hard on behalf of our patients, rewarding to work with bright pathologists who challenge our concepts and Department and Center. Without your efforts it would be keep us sharp every day. We also understand that training here as a fellow impossible to fulfill our mission. I am certain your hard work and involves a lot of hard work! You have shown outstanding dedication and dedication will serve you well as you continue in your journey. professionalism - it is no understatement that our jobs and your jobs have We are proud to have had you among us and wish you success. been so intertwined, it is hard to conceive of them separately - it has been a true You are now part of our family and we are here to help you in any partnership. I hope that the experience you have gained - both from the unusual way we can. Don’t forget to come back and visit. cases you encountered here and from the more routine case material - will help you transition from trainee to attending and develop the confidence you will need as you go out into the “real world” of independent practice. Wherever you go, you will carry this fellowship experience with you. Don’t be surprised if, in your first few weeks of practice, your new senior colleagues seek your opinion MEERA HAMEED, MD about challenging cases. You have trained at Memorial, and everyone knows that you now bring a higher level of expertise to the diagnosis of cancer. So, with Chief, Surgical Pathology Service thanks, I bid you best wishes for your future, and I hope we will see all of again at our alumni reunions and other professional events. Congratulations to all!

Where are they now?

ONCOLOGIC PATHOLOGY Alpa Shah DERMATOPATHOLOGY Priyadarshini Kumar Breast Pathologist–Aurora Diagnostics, Las Vegas, NV Attending Hematopathologist– Laurence Briski - Pulmonary Pathology Fellowship–Univ of Amin Hedayat St. Jude Children’s Research Hospital, TN Michigan, MI Wenjing Shi Dermatopathology–Private Practice Cytology Fellowship–Univ of Southern California, CA Ying Liu Su Roychoudhury - Women’s Health Pathology Jad Saab Molecular Genetic Pathology Fellowship–MSK Fellowship–NYU Langone, NY James Van Gurp Pathologist (SurgPath, Derm, Molecular)–Canada Hematopathology Fellowship–MSK Hammad Tashkandi Rami Alhassan - Cytology Fellowship–Univ of Utah, UT Molecular Genetic Pathology Fellowship– Hai Wang Univ of Pittsburgh, PA M. Rizwan Haroon Al-Rasheed - Renal/GU Fellowship– Cytology Fellowship–Baystate Health/Univ of Mass, MA GASTROINTESTINAL PATHOLOGY Mt. Sinai, NY Monika Vyas Lisi Yuan Attending Pathologist–Beth Israel Deaconess Med Ctr/ Nicholas Bercovici Cytology Fellowship–Cleveland Clinic, OH MOLECULAR PATHOLOGY Breast/GYN Fellowship–Univ of Mass, MA Harvard Med Sch, MA Amir Momeni Boroujeni Angel de Dios Quintero Gynecologic Pathology Fellowship–MSK Asst Pathologist - Morristown Pathology Associates, NJ BREAST PATHOLOGY GENITOURINARY PATHOLOGY Elena Salagean Edwin Gandia Mohsin Jamal United States Army–Walter Reed Med Ctr, MD Sabbatical Sounak Gupta Molecular Fellowship–Univ of Pittsburgh, PA Faculty Position–Mayo Clinic, MN Jennifer Zeng James Solomon Pallavi Khattar Asst. Director of the Clinical Genomics Laboratory– Asst Attending Pathologist–Montefiore Med Ctr, NY Liwei Jia Asst. Professor, Hematopathology–Icahn School of Med Asst Professor–Univ of Texas Southwestern Med Ctr, TX Weill Cornell Med Ctr, NY at Mount Sinai, NY Jin Xu Asst Professor–UW Madison Sch of Med and Public Health, WI Efsevia Vakiani Pavel Kopach GYNECOLOGIC PATHOLOGY Associate Attending Pathologist Genitourinary Fellowship–MSK (GI & Molecular Pathology)–MSK Sheila Segura Nicolas Lopez-Hisijos CYTOPATHOLOGY Surgical Pathologist–Indiana Univ, IN Menglei Zhu Hematopathology Fellowship–Loyola Univ Med Ctr, IL Brie Kezlarian Hematopathology Fellowship–MSK Christopher Metter Asst Attending Pathologist (Cytology)–MSK Renal/Solid Organ Transplant Fellowship–Univ of Texas HEMATOPATHOLOGY Southwestern Dallas, TX Stephanie Muller THORACIC PATHOLOGY Pathologist–Private Hospital, CA Alexander Chan Asst Attending Pathologist (Hematopathology)–MSK Andrew Golden Reza Setoodeh Pathologist–Kaiser Permanente, MD Instructor–Cedar Sinai, CA Daniel Lubin Pathologist (H/N & Cytopathology)–Emory University, GA Ramya Gadde Cytopathology Fellowship–Dartmouth-Hitchcock Med Ctr, NH

MSK PATHOLOGY MSK PATHOLOGY 18 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 19 the opportunities for them to learn about careers in New Mentoring Program laboratory science,” says Christina White. “The truth is that there is a lack of exposure to opportunities that HIGHLIGHTS CAREERS exist in the lab. By connecting students who may have IN LABORATORY an interest in science but haven’t officially decided SCIENCE on a career with our laboratory staff, we have a real opportunity to address the critical staff shortages By Julie Grisham that exist not only in our labs, but across the US.” adds Sarah Virgo. The Memorial Sloan Kettering Department of The program is designed to provide students Pathology has announced the launch of mScope with exposure to a full range of pathology (Mentoring Scientific Careers with Opportunities specialties including histology, surgical pathology, in Pathology Excellence) — a new program that pairs cytology, hematopathology, and molecular HOW TO APPLY students with laboratory specialists. Its goal is to pathology. Participants will gain a unique, real- educate high school and undergraduate students time introduction to the world of pathology and its Applicants need to about careers in the laboratory sciences. connection to patient care. The program offers one- submit a complete Under the direction of Sarah Virgo and Christina on-one, recurring mentoring from working experts application and White, the mScope program seeks to encourage and familiarity with laboratory science careers participate in an the next generation of laboratory professionals by through observation of the critical work done by bringing them into the lab environment and educating MSK’s scientists. on-site interview. them about educational and career opportunities. It The first group of mScope participants will start in To learn more was designed to enable participating students to share June 2020. High school and undergraduate students about the mScope connections with laboratory scientists while fostering who are interested in applying must have at least a program, tomorrow’s laboratory workforce. 3.0 GPA and an interest in laboratory sciences.They “We’ve had so much success with bringing must be willing to commit at least one hour a week for visit www.mskcc. students from STEM [science, technology, eight weeks. Participants will do two-week rotations org/departments/ engineering, and math]-focused high schools into through four different areas within the Department pathology/mscope- the lab for field trips that we decided to increase of Pathology. program

Visiting students from East Orange STEM Academy

MSK PATHOLOGY MSK PATHOLOGY 20 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 21 Dr. Ferrell has devoted her academic career Her numerous book chapters and major to the study of liver pathology. As evidenced liver pathology textbooks (including the by her numerous publications (more than premier text, MacSween’s Pathology of the 200 original articles), she has made great Liver, fifth, sixth, and seventh editions) have Today, as we contributions to the understanding of the benefitted liver pathologists everywhere. celebrate the pathology of liver tumors, particularly of Her contribution as the lead editor of Liver “ well-differentiated liver tumors, including Pathology (part of the consultant pathology memory of Dr. hepatocellular adenoma variants, focal nodular series from Demos Publishers), which hyperplasia-like lesions, vascular lesions, emphasizes difficult diagnostic problems in Stewart, a man who The Department of and malformations in the liver. Through liver pathology, has similarly offered invaluable early on brought participation in major organizations, such as guidance. Dr. Ferrell has lectured extensively surgical pathology Pathology's Annual the Clinical Research Network in Nonalcoholic both nationally and internationally. Her Steatohepatitis (a National Cancer Institute– lectures are always very well received. to the front lines of Alumni Meeting and sponsored consortium) and the International It is no surprise that numerous awards have Liver Pathology Study Group (of which she been bestowed on Dr. Ferrell in recognition of oncology, it is most Fred W. Stewart Award was a founding member), Dr. Ferrell worked her achievements. These include the 2008 Gold fitting that the medal relentlessly to ensure the most effective Headed Cane Award, the 2015 F. K. Mostofi in his name be given LINDA FERRELL, MD integration of pathology into the various Distinguished Service Award from USCAP, the studies of liver diseases. Her seminal works 2016 Harvey Goldman Master Teacher Award to an individual who By Jinru Shia, MD on liver pathology in recurrent hepatitis C from USCAP, the 2017 President’s Award from after transplantation and on the diagnosis the Arthur Purdy Stout Society of Surgical has dedicated her of dysplastic nodules have gained worldwide Pathologists, and numerous UCSF teaching career to the practice attention, and a number of these studies have awards for resident and medical student teaching. been recognized internationally as leading Today, as we celebrate the memory of Dr. of surgical pathology Linda Ferrell is the 2019 recipient of the Fred W. papers in the field. Stewart, a man who early on brought surgical and contributed Stewart Award, given annually by Memorial Sloan Dr. Ferrell is also an ardent educator. pathology to the front lines of oncology, it is Kettering’s Department of Pathology to an individual She has nurtured generations of pathology most fitting that the medal in his name be monumentally who has made outstanding contributions to the residents and fellows. She chaired two major given to an individual who has dedicated her to the continued understanding of human neoplastic disease. annual courses for pathologists for multiple career to the practice of surgical pathology and Dr. Ferrell is a world-renowned liver pathologist. years: at UCSF for 33 years and for the contributed monumentally to the continued advancement of this Her stellar career achievements exemplify how California Society of Pathologists for eight advancement of this discipline in modern discipline in modern dedicated surgical pathologists can have a momentous years. Through the years, she has served a times. We congratulate Dr. Ferrell on this well- impact on the field of medicine. wide variety of teaching roles via USCAP. deserved award. times.” Dr. Ferrell obtained an MD degree from the University of Kansas, where she also completed pathology residency training. She did fellowship training at the University of California, San Francisco (UCSF), then joined the faculty there, remaining at the university until 2015, when she retired to emeritus status. Over the years, Dr. Ferrell has served in multiple important roles at UCSF, including the distinguished Professor in Anatomic Pathology (Endowed Chair), Vice Chair of Clinical Affairs in the Department of Anatomic Pathology, Director of Surgical Pathology, Director of Surgical Pathology Fellowship, and Director of the Liver and Gastrointestinal Pathology Fellowship and Gastrointestinal Pathology Fellowship (2005 to 2014). At the national and international level, Dr. Ferrell has also played important roles: She is a past President of the Hans Popper Hepatopathology Society (2008 to 2009) and the United States and Canadian Academy of Pathology (USCAP) (2012 to 2013).

MSK PATHOLOGY MSK PATHOLOGY 22 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 23 2019 MSK Pathology Alumni Dinner

MSK PATHOLOGY MSK PATHOLOGY 24 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 25 Research Profile

MEERA HAMEED, MD

A SEARCH FOR UNDERSTANDING and the genetic changes involved, we may be the combination Dr. Hameed and her colleagues have able to find better diagnostic and prognostic worked on a variety of musculoskeletal markers, as well as treatments that can provide of“ advanced cancer types, including some of the more a better outcome for our patients.” common of these rare cancers in bone such molecular genetic as chondrosarcoma, which starts in the THE ROLE OF COMPUTATIONAL cartilage cells; and osteosarcoma, a childhood PATHOLOGY AND ARTIFICIAL techniques, new ways cancer that develops from cells which make INTELLIGENCE bone (osteoblasts). While osteosarcoma is Dr. Hameed has been a stalwart champion of imaging tumors, sensitive to chemotherapy, she explains, of implementing digital pathology and and new ways to chondrosarcomas are not sensitive to promoting computational pathology in the chemotherapy or radiation treatments — department of pathology at MSK. While harness the power which is why it is imperative to get a better many pathologists may be wary of new grasp of their underlying biology. Genetic artificial intelligence (AI) or machine- of the computer studies are helping to do that. “We are learning learning algorithms coming to the field, Dr. that some of these cancers have specific genetic Hameed sees them as a way of augmenting to integrate and alterations,” says Dr. Hameed. “By studying the her and her colleagues’ abilities in ways that incidence of these alterations, as well as the will benefit patients. analyze the mass of outcomes in patients, we are learning about “Pathology is a field in which we look for data we collect from those that may have clinical relevance — there patterns, and recognize those patterns that are even some clinical trials now for specific are indicative of disease,” she explains. “But patient specimens inhibitors related to some of the alterations.”. there’s so much data on a particular slide, For example, through next generation more than what the pathologist sees. These will lead to significant sequencing, my colleagues and I have found computational tools may offer us information certain alterations in osteosarcoma which may that can be applied to further our diagnosis, improvements in be of benefit for patients who have relapsed prognosis, or in future how to treat an or refractory to conventional therapy. In individual patient.” patient care” chondrosarcoma, a driver mutation in the With osteosarcomas, pathologists rely on IDH gene has impact on recurrence free and their eyes to assess tumor necrosis following Musculoskeletal tumors, or cancers of technologies, including molecular metastases free survival.” pre-operative chemotherapy as an indicator out of an image that we have not been able to Embracing the Future the bone and soft tissues, are both rare and diagnostics and digital and computational Dr. Hameed is also interested in very rare of prognosis and survival after therapy. This by visual means. Then we, as pathologists, can complex. Which is exactly what sparked the pathology, to help her and her colleagues tumors, like chordomas, which are tumors is a subjective measurement and can have analyze that information and determine how it of Pathology professional interest of Meera R. Hameed, better serve patients with rare cancers. that develop from notochordal cells which interobserver disagreement as to the degree relates to a particular patient’s disease.” By Kayt Sukel MD, Chief of the Surgical Pathology Service “The bone is a very difficult organ to play an important role in spine development. or percentage of necrosis. Dr. Hameed and Dr. Hameed says that as pathology evolves at Memorial Sloan Kettering Cancer access and treat,” she says. “With many Chordomas remain difficult to treat with Dr. Agaram (Bone and Soft Tissue team) to incorporate new technologies and tools in Center, who was drawn to the challenge of of the bone and soft tissue cancers, if the complex surgeries and there are not many are working with computational pathology various cancers and rare tumors like the ones specializing in this type of cancer. tumor comes back after surgery, there are options for patients who have recurrent colleagues (Dr.Fuchs’ laboratory) to develop she studies, the specialty will benefit in a “Compared to other types of cancers, not many therapeutic options left. Being disease. In preliminary studies Dr. Hameed machine learning tools and algorithms that variety of ways. Put them together under the there are fewer numbers of cases of bone able to make the right diagnosis, which and colleagues have found that chordomas can be trained to recognize necrosis in tumors. seasoned eye of a trained pathologist and the and soft tissue,” explains Dr. Hameed. include working closely with our radiology, are tumors with predominantly copy number These algorithms will provide a more objective data will be more pertinent to the individual “Because of that rarity, there is a lot we still surgery and oncology colleagues, is of vital alterations and chromatin remodeling genes and quantitative measure than the unaided patient with the disease and will help inform have to learn about these tumors. There importance so that the right treatment is may play a role in their biology, and she human eye. This will give the treating clinicians clinical decisions for optimal treatment. She are a host of challenges from diagnosis given from the start. It is important that all is pursuing further studies to explore the a more accurate assessment of how patients are notes that “the combination of advanced to treatment, and pathologists who work the modern technology tools are available epigenetic mechanisms in collaboration with responding to therapy. molecular genetic techniques, new ways of in this area have a unique opportunity to and used appropriately to enhance other experts in the field. “I think that as we adopt more of these imaging tumors, and new ways to harness explore these cancers especially in this era diagnostic accuracy. For this, one has to “There are many challenges when we algorithms, the field of pathology will become the power of the computer to integrate and of advancing technology. start with even basic tissue preparation are talking about diagnosis, prognosis, and more objective,” she says. “We will be able to analyze the mass of data we collect from Since coming to MSK in 2009, Dr. such as EDTA which allows preservation treatment for rare cancers,” she says. “But if we better assess prognostic factors in tumors. The patient specimens will lead to significant Hameed has worked to embrace new of DNA and RNA. can understand the biology of how they develop computer algorithms will be able to pull data improvements in patient care”.

MSK PATHOLOGY MSK PATHOLOGY 26 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 27 The Pathology of NEOPLASTIC DISEASES COURSE April 29 - May 3, 2019

2019 Course Directors

Lung Cancer Classification Molecular Diagnostics of GI Tumors Mimics of Urothelial Carcinoma William D. Travis, MD Jaclyn Hechtman, MD Victor Reuter, MD

Molecular Pathology of Lung Cancer Appendiceal Epithelial Neoplasms - Prognostic and Predictive Factors in Jason C. Chang, MD Bewildering Between Goblet and Bucket of Urothelial Carcinoma; Grading, Staging and Mucin Beyond Laura Tang, MD Emerging Issues in Lung Adenocarcinoma Hikmat Al-Ahmadie, MD William D. Travis, MD Gastroesophageal Adenocarcinoma and Their Urothelial Tumors of the Upper Urinary Tract Precursor Lesions - The Barrett’s Anxiety Immunohistochemistry for Lung Tumor Hikmat Al-Ahmadie, MD Meera Hameed, MD Laura Tang, MD Diagnosis and Biomarker Testing: An Update Natasha Rekhtman, MD, PhD A Practical Approach to the Morphological Gastric Polyps and Other Epithelial Evaluation of Tumors of the Testis and Its Neoplasms Diagnosis of Lung Cancer in Cytology and Adnexa Michael Roehrl, MD Small Biopsies Satish Tickoo, MD Darren J. Buonocore, MD Biomarker Testing in Upper GI Tumors Renal Neoplasia: Morphologic Spectrum and Michael Roehrl, MD Differential Diagnosis Neuroendocrine Tumors of the Lung Satish Tickoo, MD, Yingbei Chen, MD Natasha Rekhtman, MD, PhD Selected Issues in Colorectal Tumor Pathology Germline Mutations in Urogenital Tumors; Pleural Tumors Jinru Shia, MD Disease Spectrum and Clinical Implications Jennifer L. Sauter, MD Jinru Shia, MD Maria Carlo, MD GI Tumor Diagnosis: Lessons from Frozen Section Diagnosis of Thoracic Tumors Prior Mistakes New and Emerging Variants of Renal Darren J. Buonocore, MD Jinru Shia, MD Neoplasms Yingbei Chen, MD Mediastinal Tumors Biopsy Diagnosis of Hepatic Tumors Jason C. Chang, MD David Klimstra, MD Implementation of Whole Slide Imaging in Your Laboratory; Challenges and Pulmonary Lymphoproliferative Disorders Ductal, Intraductal and Cribriform, Oh My! Opportunities Ahmet Dogan, MD, PhD The Differential Diagnosis of Large Gland J. Sirintrapun, MD Lesions of the Prostate and its Clinical Import Ductal Adenocarcinoma of the Pancreas Samson Fine, MD The 2020 Pathology of Neoplastic Olca Basturk, MD Victor Reuter, MD Essential Data Elements for Prostate Cancer Diseases Course will take place from Monday, April 27- Friday, May Solid Nonductal Neoplasms of the Pancreas Reporting in 2019 Samson Fine, MD 1 and will feature Head and Neck David Klimstra, MD Pathology, Breast Pathology and Risk Stratification in Prostate Cancer; Gynecological Pathology under Cystic Neoplasms of the Pancreas the Role of Contemporary Tissue,Urine the direction of Drs. Hameed, Olca Basturk, MD and Serum-Based Assays Ghossein, Brogi, Wen and Ellenson. Anu Gopalan, MD Cytology of Pancreas Neoplasms For more information or to register Carlie Sigel, MD Two Cases to Remember: Presentation by for the course, please visit: the Genitourinary Pathology Subspecialty Neuroendocrine Neoplasms of the www.mskcc.org/ Fellows neoplasticdiseases2020 GI Tract – Conundrums and Caveats Liwei Jia, MD, Sounak Gupta, MD William Travis, MD Laura Tang, MD

MSK PATHOLOGY MSK PATHOLOGY 28 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 29 2019-2020 FELLOWS

Leonel Maldonado Oncologic Surgical Pathology Fellows Cameron Beech, MD Wissam Dahoud, MD Liz Edmund, MD Gonzalez, MD Yan Huang, MD, MS Yiang Hui, MD Rami Imam, MD Chief Fellow

Elizabeth Kertowidjojo, MD, PhD, MPH Anna Lee, MD Fanni Ratzon, MD Abeer Salama, MBBS Christopher Schwartz, DO Shenon Sethi, MBBS Brandon Umphress, MD Alan Xinyu Wu, MD, PhD Chen Yang, MBBS Lingxin Zhang, MBBS Chief Fellow

Specialty Fellows Raza Hoda, MD Marjorie Perron, MD, PhD Willard Wong, MBBS Jose Scarpa Carniello, MD Bogdan Isaila, MD Roshan Raza, MBBS Breast Pathology Breast Pathology Breast Pathology Cytopathology Cytopathology Cytopathology

Kevin Yen Chen Ko, Mahra Nourbaksh, Amir Momeni Akanksha Gupta, Laura Battle, MD John Kennedy, MD Pavel Kopach, MD James Van Gurp, DO Menglei Zhu, MD, PhD Donna Ferguson, MD MD, DMD MD, PhD Boroujeni, MD MBBS, MD Dermatopathology Genitourinary Pathology Genitourinary Pathology Hematopathology Hematopathology Molecular Pathology Dermatopathology Gastrointestinal Pathology Gynecologic Pathology Hematopathology

Stewart Soo Ying Liu, MD, PhD Douglas Mata, MD, PhD Rohit Sharma, MD Marina Baine, MD, PhD Ryum Yang, MD Molecular Pathology Molecular Pathology Molecular Pathology Thoracic Pathology Molecular Pathology

MSK PATHOLOGY MSK PATHOLOGY 30 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 31 ?

MSK CELEBRATES ?

LAB WEEK 2019 LAB WEEK LAB WEEK LAST PERSON LAB WEEK FAMILY By Julie Grisham TABOO COSTUME CONTEST STANDING FEUD CHALLENGE Rochelle Lopez Janet Guthrie TRIVIA Jean Allen Laura Coyoy Judy Zhu Viktor Moroz Madeline Cioffi Christina Lugo Luciana Kimmel Nora Plante Kimberly Lauderman Jessica Bautista Sylvie Wiener- Fedus Joann Rittersbach Nora Plante Ana Perez Camille Ramkaran Cathy Tan Lily Zhuo Tasfina Yousuf Matthew Brady Richmond Serofica David Puma

LAB WEEK B WINNERS

LAB WEEK LAB WEEK LAB WEEK PHOTO GREAT ESCAPE PERIODIC CONTEST David Puma TABLE BINGO Kerry Mullaney Melissa Fonseca David Puma Ana Perez Utsav Patel Rachel Oconnor Kelsy Merck Meiyi Wang Doris Wong Anita Yun Linda Moody Brow Roger Michael Sandino Gavin Guy Kerry Mullaney Medical Laboratory Professionals Week is a national Week Committee. “So much of what our two departments Laura Coyoy Debby Melgar celebration that takes place every year during the last full week do is behind the scenes, so it’s great to celebrate everyone Christina Logo of April. It was established to recognize the medical laboratory and highlight the important work that they do. Without Jonatan MontesDe Oca professionals who play a vital role in every aspect of health care. the essential work being done in the lab by our wonderfully Dondre Clarke At Memorial Sloan Kettering, Lab Week activities are jointly talented staff, our patients couldn’t receive the excellent care Rochelle Lopez sponsored by the Department of Pathology and the Department they receive here at MSK.” Bryan Lu of Laboratory Medicine. This event has incorporated events like In 2019, Lab Week featured scientific talks from researchers “Family Feud: Lab Week Challenge” and “The Great Escape” throughout MSK, career-building sessions, and activities ranging Julia Im provide an extra level of fun and bonding. from scavenger hunts to trivia to kickball. The week was rounded Judy Zhu MUSIC VIDEO EXTRA EFFORT LAB WEEK AMAZING “Lab Week is full of great team-building events,” says Sarah out on Friday with a luncheon held in the Rockefeller Research Yessica Saenz Cytogenetics AWARDS RACE SCAVENGER Virgo, Assistant Manager and Chair, Laboratory Professionals Laboratories building. Koch Center Bryan Lu HUNT Madeline Cioffi Dondre Clarke Kerry Mullaney Melissa Fonseca Gloria Flamenco David Puma Janet Guthrie

MSK PATHOLOGY MSK PATHOLOGY 32 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 33 ?

Towards Predictable Immune Reconstruction After Allo-Hematopoieric Cell Transplantation and Cellular Therapies Dr. Jaap J. Boelens

Modalities and Applications for Quantitative Multiplexed Immunostaining in Immuno-Oncology Dr. Travis Hollmann Lab Week Family Feud Challenge 2nd Place Winners ( from left to right): Cathy Tan, Tasfina Yousuf , Ana Perez, David Puma, Matthew Brady, Richmond Serofica Laboratory Professionals: Keynote Speaker Dr. Sergio Giralt

Mass Spectrometry Assays for Detecting Monoclonal Immunoglobulins Dr. Katie Thoren

Artificial Intelligence and the Clinical Lab Dr. Jamal Benhamida

Lab Week Family Feud Challenge 1st Place Winners (from left to right): Joann Rittersbach, Jean Allen , Madeline Cioffi, Nora Plante, Jessica Bautista

MSK PATHOLOGY MSK PATHOLOGY 34 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 35 Service Spotlight

While most people think of pathologists working The service work may seem like hard behind the scenes, spending more time with their “regular, routine kind of work, but GASTROINTESTINAL microscope than with clinical colleagues, members of the GI pathology team play key roles within MSK’s signature we make sure each case is done in PATHOLOGY disease management teams (DMTs), helping zero in on the right way–the best way–so we treatment selections that best benefit individual patients. “Our approach ensures that we can have close can set the standards for the best communication with the clinical team early on and play pathology practice; our team is a major part in the process of determining care,” says Dr. Shia. “We meet regularly to discuss ongoing cases — and committed to that.” treatment decisions are made during that meeting. All the different disciplines at MSK contribute to these clinical- books as well including several AFIP fascicles. Dr. Shia based DMT meetings. By working together and sharing our was particularly proud to mention that one of the team expertise, we can help ensure the best possible outcome for members, Dr. Christine Iacobuzio-Donahue, also the our patients.” Director of MSK’s David M. Rubenstein Center for Pancreatic Cancer Research, was recently named a Christine Iacobuzio-Donahue MD, PhD Jinru Shia, MD David S. Klimstra, MD BIOMARKER REPORTING recipient of the Ruth Leff Siegel Award from Columbia Laura H. Tang, MD, PhD Director, David M. Rubenstein Chair Director, Gastrointestinal Pathology Chair, Department of Pathology When asked about specific examples of innovative University Irving Medical Center as the investigator with Attending Pathologist for Pancreatic Cancer Research Attending Pathology Attending Pathologist Attending Pathologist approaches the GI pathology team has brought on in the the most impactful contribution to the understanding of arena of clinical service, Dr. Shia mentions biomarker pancreatic cancer over the past year. reporting as an example. “In the current era of precision Dr. Shia is also anticipating the ways in which the oncology and targeted therapy, accurate reporting of team’s research will enhance the standard of care for GI biomarkers is of great importance,” Dr. Shia explains. And tumors worldwide, and seeing what sort of insights future she is particularly referring to what is known as predictive investigations may spark. “Many exciting research projects biomarkers, tumor tests that can predict whether the tumor are being carried out by our team members”, she says. is likely to respond to a given targeted therapy or not. Some examples she has provided are: the heterogeneity “Immunotherapy is particularly pertinent to GI of MSI cancers at both the molecular and phenotypical tumors,” says Dr. Shia. “One of the predictive markers for level and how that may translate to tumor response to Michael H. Roehrl, MD, PhD Jaclyn F. Hechtman, MD Olca Basturk, MD immunotherapy is the tumor’s microsatellite instability immunotherapy; the role of gut microbiome on tumor Director, Precision Pathology Carlie S. Sigel, MD Efsevia Vakiani, MD, PhD Assistant Attending Associate Attending Biobanking Center Associate Attending Pathologist Associate Attending Pathologist (MSI) status. So, today, every patient with a GI tract development and behavior; and the clinical and diagnostic Pathologist Pathologist Associate Attending Pathologist carcinoma gets tested for MSI markers (as well as some application of digital and computational pathology. “All other markers). To effectively report the results of the such efforts carry the promise of providing meaningful data various biomarkers, the GI team has worked closely with and ultimately helping advance the field of GI oncology”. Gastrointestinal (GI) cancers, which include “The service work may seem like regular, routine MSK’s medical oncologists, and together they implemented Setting the esophageal, gastric, colorectal, liver, gallbladder, kind of work, but we make sure each case is done standardized biomarker reporting systems for both upper THE NEXT GENERATION Standards and pancreatic cancers, are among the most in the right way — the best way — so we can set the and lower GI tract malignancies. Such systems not only Dr. Shia says she and the GI team greatly enjoy working commonly diagnosed cancers across the globe. standards for the best pathology practice; our team offer the data that is needed for the oncologists to make with their fellows. “The fellows’ unique perspective brings The Gastrointestinal Over the past decade, the incidence rates for many is committed to that.” treatment decision based on current guidelines, they also on views that we would otherwise have not seen; such views 14,000 Pathology team strives to of these cancers, including colorectal and liver capture additional information that can benefit future often help improve the way we work and teach,” Dr. Shia provide the most accurate cancer, have significantly grown. That is one of AN EVOLVING SERVICE retrospective studies, and can potentially help further says. For the fellows – both the first-year fellows and the improve our understanding of tumor behavior and how GI subspecialty fellows, the GI service provides a nurturing and relevant diagnostic the main reasons Jinru Shia, MD, Director of the When Dr. Shia came to MSK Pathology in 1998 GI Pathology team, and her team stay so busy at as a fellow, there were 2 attending pathologists best to achieve better treatment response. and supportive environment that allows them to freely “When we information clinicians Memorial Sloan Kettering Cancer Center. that had a special interest in GI. Today, there are 9 absorb knowledge and grow. looked at use to make treatment “The GI service here is one of the busiest in the dedicated GI pathologists, forming the GI pathology WORLD-CLASS RESEARCH Dr. Shia has served as Director of the Gastrointestinal our service decisions for patients, pathology department,” says Dr. Shia. “When we team and working nimbly together, integrating new While Dr. Shia is undeniably pleased to speak about the Pathology Fellowship Program at MSK for the past 10 years. load for the and researches promising looked at our service load for the year recently, we technologies that have enabled them to provide ever robust clinical services her team provides at MSK, she’s In 2020, her teammate Dr. Carlie Sigel will take over this year recently, avenues that inform the saw that our group had already signed out more more valuable and targeted information that, in also proud of her colleagues’ contributions on the research role. “Carlie has already been an integral part of our GI we saw that future of that care. than 14,000 cases for 2019. That accounted for more turn, helps inform treatment selection and disease front. Fellowship Program for many years. Carlie is a wonderful our group “Using the phrase ‘world-class’ to describe what they teacher and has mentored many fellows on various research than 16% of the total service volume.” management for the MSK patients. Everyone in the had already By Kayt Sukel Those cases include in-house biopsies and service, says Dr. Shia, shares the same dedication. do is not an exaggeration,” she says. “The World Health projects,” says Dr. Shia. signed out resections, and consultation cases from other “We all love what we do — and are passionate about Organization recently updated its GI tumor classifications. Whether she is discussing the past, present, or hospitals. It is a lot of work, Dr. Shia acknowledges doing really good work.” Many of our team members directly participated in this future, Dr. Shia exhibits great pride in the work that the more than — but in her view, such a heavy volume is a “welcome Within the subspecialty of GI pathology, the team new, fifth edition of these classifications. And if you open GI pathology team contributes to MSK. There is good 14,000 cases challenge” — one that she and her colleagues meet has further sub-subspecialized. Each team member the book and look at the different tumor subtypes, you’ll reason she’s remained in her post at MSK for more than for 2019. That head on. is focused on a particular part of the GI system: upper see that, quite often, the references that serve as evidence two decades: the kind of work the service does is simply accounted “Our main goal, always, is to stay at the forefront GI tract, lower GI tract, or hepato-pancreato-biliary for each came from members of our group. It feels good to unparalleled. “GI pathology at MSK has always performed for more than of clinical service, by both providing accurate system. “For each of those three major areas, we have see what a difference we are making.” at a very high level. Between our clinical service, research, 16% of the pathology information for all the cases we see and dedicated expert pathologists who can take our Similarly, her team members’ great work as evidenced and educational efforts, you can count on it always being total service ensuring effective integration of that information pathology diagnosis and help translate it to the best by the numerous publications has also earned them that way,” Dr. Shia concludes. volume.” into clinical treatment decision-making,” she says, clinical effect,” explains Dr. Shia. authorships and co-authorships of other major text

MSK PATHOLOGY MSK PATHOLOGY 36 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 37 The sudden passing of cytotechnologist Shadi Haddad “on May 31, 2019 shocked and saddened all of his extended SHADI 'work family', who he touched both professionally and HADDAD personally.” - David Klimstra, MD 1982-2019

By Carlie S. Sigel

The Cytology Service is nested within the Pathology present in the dictionary. He told me his wife Meghan called his Department and the services it provides require consistent trust language, “Shadanese” and the entry I will make in that lexicon is and interconnectedness among the cytology staff. We are tethered to “subsequental” which means the thing that happened after the one each other by Vocera, we cover those taking lunch, delayed by transit, we were talking about. And if Chloe, his daughter, ever finds herself or away on unexpected absences, and we suffer such intimacies having trouble pronouncing names, it is safe to say she inherited as having to recognize and decipher the worst of our colleagues’ that from her father. Shadi deeply cared about his family. They handwriting. Bonded in this way, we frequently choose to gather by understood his work family was an extension of theirs and gathered circling around the office, eating cake by the cubicles in the spirit of from near and far to attend the MSK memorial. My favorite memories celebration for life’s milestones such as new students, marriages, of him will be when he would poke his head into my office and ask me baby showers, holidays, promotions, and retirements. We are a close- if I was busy. “Of course, but c’mon in,” I’d say, and then he’d bound knit group, and when Shadi dropped out of our lives so tragically over to my desk with his phone out and show me the latest cute Chloe sudden, I felt unraveled and deeply sad. pic. The pureness of his excitement and joy in being a dad and loving I’ve been keeping his spirit alive in my mind and in my heart his baby girl was endlessly uplifting. Shadi had an awesome sense since June by remembering the qualities I admired most in him. of humor and an innate sense of when to be serious and when it was He was a model of positivity. Shadi was never simply present and okay to cut loose a little. working for the sake of completing a task. He aimed to be as helpful I count myself among the many who think of Shadi frequently. and available as possible and he always had a good attitude. Another I will honor his life by trying to embody in myself these traits that one of his admirable qualities was his accountability. Consistently, left such a deep impression on me and those of us who continue to he was free to admit uncertainty or his role in a mishap. Incapable grieve. If you want to add a little Shadanese to your life, just say “cool of lying, he would never obscure any details. I knew I could trust beans” when you agree with something and I guarantee it will help anything he said even if I couldn’t trust that the words he used were you smile through the sadness.

MSK PATHOLOGY MSK PATHOLOGY 38 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 39 “I will always remember Shadi’s “Shadi was always calm, humble, and laugh – it was like no other laugh I cordial towards other people. He have ever heard. He will always be brought positive attitude and effort in our hearts.” every day in our Cytology Service. Amazing colleague. " MARIA MAUGERI HANDY OEN

“A Bosnian and a Jordanian walk into “I had the privilege of working with a bar…... No, it’s not the beginning Shadi at MSK. He was a kind, smart, of a joke, but the beginning of friendly soul. My deepest a friendship! Shadi and I, with a condolences to Shadi's family. He couple of other members of the will be dearly missed.” cytology service, had a tradition LORRAINE CORSALE of going to a local bar before our yearly departmental Christmas party. Early on, our conversations focused on craft beers and cars. He loved Volvo’s. As the years progressed, our conversations turned to married life, our kids, “Dearest Shadi- One of the sayings family, and Bitcoin. Shadi enjoyed that has always struck a cord in my discussing the intricate details of heart is “Only the good die young”. the cryptocurrency process. Shadi Some things in life are not meant was genuine and caring. He loved to be explained, just accepted, his family. We will miss his laid- and your passing is certainly one back attitude, his laugh, and helpful of them. We miss you, today and nature.” always.”

RUSMIR FERATOVIC VERONICA KIM

MSK PATHOLOGY MSK PATHOLOGY 40 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 41 Pathology Project Recognized at MSK Quality Improvement Fair

By Julie Grisham

Every year, Memorial Sloan Kettering’s Quality Improvement (QI) The QI Fair was created to increase awareness of various projects Manager, Pathology Communications for the Fair showcases various improvement efforts and initiatives across and initiatives, improve collaboration, and emphasize patient safety Department of Pathology. the Center. The institution-wide event is hosted by the Division of and quality of care as top priorities, among other objectives. The project identified several areas for Quality and Safety. In April 2019, a project from the Department of Pathology won two improvement in the PC service, including common of the three awards at the QI Fair: the Judges’ Choice Award and the reasons that these cases are delayed and issues with Patients’/Caregivers’ Choice Award. communication, billing, and workflow. The leaders The project, called “Pathology Consultations 2.0: Empowering of the project focused on specific measures for Users, Improving Turn Around Time, and Embracing the Digital Age”, improvement. was aimed at improving workflow in the acquisition and analysis of The initiative included implementing a new pathology specimens obtained through MSK’s personal consultation digital portal for the electronic submission of PC (PC) service. These specimens are sent by non-MSK patients cases, streamlining workflows for easy submission of and physicians located anywhere in the world who are PC cases, and increasing marketing efforts to solicit seeking a second opinion from MSK’s expert team of sub- more PC submissions and recruit new patients to specialized pathologists. They make up about 10% of the MSK. The goals were to increase overall volume department’s volume. of PC cases, change the way billing information is “I’ve spent my entire career at MSK in the collected, and establish a revenue stream through Department of Pathology and received cancer the portal. care as a patient here; therefore I understand As presented at the QI Fair, the results of these the unique perspective of both needing an efforts were a reduction in overall turnaround expert opinion and being acutely aware of time for these samples as well as in the number of the knowledge my colleagues offer to the misdirected cases or cases with missing information world. Perfecting our personal consultation or material. In addition, the portal greatly exceeded service while increasing awareness of the anticipated number of PC portal submissions — by options available to patients, augmenting 433% —and increased overall annual volume by 12%. our revenue streams and making the The portal also increased web traffic and revenue overall cancer care process easier for our for the Pathology Department. As a result of the patients has been incredibly rewarding. project, 224 non-MSK patients chose to receive care I’m very proud of the team that allowed at MSK after using the portal and more than $20 these goals to come to fruition.” says million in revenue was generated as a result of these Sarah Virgo, Project Lead and Assistant new patients.

MSK PATHOLOGY 1st Quarter 2019 REVIEW

MSK PATHOLOGY 42 REVIEW 4th Quarter 2019 43 2019 Quality Improvement Fair

Pathology Consultations 2.0 Empowering Users, Improving Turn Around Time and Embracing the Digital Age Improving Preparedness for Emergencies in the Laboratory Setting

Sarah Cook Virgo • Christine England • Shadia Carlo • Thanayi Levy • Andrew Roth• Sarah Milana • Shirley Vargas • Allix Mazzella • Cytogenetics Laboratory, Department of Pathology Tracy Lynch • Maria Blanco • Izabella Rosado • Nina Gunhouse • Alba Rosario • Eric Sod • Johnny Leung• Jennifer Samboy• Michael Singer Christina Li • Dory Londoño-Sanchez • Tishome Persaud • Pedro Flores • Jordana Shapiro • Michael Hannon • Stacey Fox • Joy Macheda • Nicole Marino • Elizabeth Zannetti

Pathology’s Digital Consult Objective Emergency Response Workflow Laboratory Impact To expand emergency preparedness and training 1. Summarized a lab specific “Emergency Portal (TAT): Horizontal and Past incipient within the laboratory to deal with unforeseen Vertical Exits Response Workflow” for highest occurring BACKGROUND: PC case MRN PC case Submission PC case Case emergencies; such as fire, chemical spills, water emergencies submission generated in received via reviewed by delivered to the reported by received via Cadence staff Pathologist intrusion, power outages, and other events. In our FIRE R.A.C.E The Department of Pathology provides an mail Pathologist 2. Allows laboratory to have a faster and more portal project we: P.A.S.S – only if egress blocked, efficient response and recovery time. essential service to patients and physicians of Pre Project Incipient Evacuate using buddy 3. In conjunction with Emergency Management Memorial Sloan Kettering Cancer Center by Implementation 1. Reviewed possible emergencies system providing timely and vital diagnoses that guide 2. Consolidated current emergency plans to bring awareness to other labs of possible emergencies that can happen. Planning is key. treatment decisions. While the majority of specifically for the laboratory Evacuate area, close Place absorbent doors, wait for Safety Large Spill cases evaluated by MSK Pathology are fresh 3. Expanded on current policies, training and pads Advisor, get SDS specimens procured and processed directly at Potential DELAYS: Potential DELAYS: equipment for the laboratory HAZMAT Call Safety at information 1. Lack of required information 1. Receiving an MRN within SPILLS OneMSKCC.org - https://one.mskcc.org/sites/pub/ehs MSK, roughly 10% of the department’s volume 2. Error in information submitted 4. Raised awareness in conjunction with Ext: 2280 the business day Pre-Portal PC Case TAT Post-Portal PC Case TAT Use absorbent Laboratory Implementations is generated by our personal consultation (PC) 3. Billing discrepancies Emergency Management Small spill ≈2business days ≈.6875 business day pads service – cases sent by non-MSK patients and Emergency Implementations physicians located anywhere in the world Four Phases of Emergency Call Emergency • Additional Fire Code Charts by Exits seeking second opinion from our expert team of 2014 2015 2016 2017 2018 Vandalism hotline at Ext. Alert Manager Surgical Pathology Preparedness • Biannual Training 4,457 4,598 4,565 4,412 4,898 6000 sub-specialized pathologists. Service Fire • Fire Extinguisher Training HemePath Service 86 144 182 WORKPLACE • New Employee walkthrough Cytology Service 217 153 139 113 144 Mitigation Phase: Minimizing the likelihood of Call Security at AREAS FOR IMPROVEMENT: VIOLENCE & Aggression Alert Manager • Update Emergency Contact List 4674/12 = 4751/12 = 4790/12 = 4669/12 = 5224/12 = incidents Ext. 7866 Average 390 396 399 389 cases/ 435 VANDALISM 1. Errors in submitted material or missing • Absorbent Pads cases/month cases/month cases/month month cases/month Preparedness Phase: Developing plans on how to Hazmat/Spill information Call Emergency RUN • SDS/ChemTracker website training handle incidents when they arise Active Shooter hotline at Ext. HIDE 2. Billing discrepancies Personal Consultations Loss of 6000 Call • Critical vs. non-critical equipment log Web Page Views Response Phase: Manage emergencies as they occur FIGHT Equipment 3. Delays in receiving an MRN PHASE 1: PHASE 2: PHASE 3: PHASE 4: PHASE 5: PHASE 6: (Pre & Post Portal Implementation) SECTRA Portal Launch for 6000 Digital Portal Cadence Digital Portal Launch Data & Workflow Marketing & User Recovery Phase: Steps to restore affected area back WATER Call Safety Dept: Try to prevent • Tarps the submission of digital 5714 Identify Danger Water 4. Average TAT: 1-3 business days Creation Introduction on mskcc.org Revisions Feedback pathology slides worldwide 5000 to normal INTRUSION Ext: 2280 from spreading • Elevation of equipment and wiring off the Intrusion 5. Often ineffective workflows and 4000 Lab Risk Assessment: floor 3000 POWER Call Facilities Utilize communication • Glow in the dark tape 2000 Danger to Staff and Patient OUTAGE Ext: 7850 Emergency Kit 6. Potential for augmented revenue stream not • Ensure critical equipment connected to 8 Power Outage taken advantage of 1000 Care emergency outlets 0 Laboratory Safety Enhancements • Lanterns and flashlights purchased June 2016 through September 2017 (Pre October 2017 through January 2019 (Post 7. Lack of web visibility Portal) Portal) • Safe Room Violence • Emergency workflow reference sheet • Notification of staffing changes in the lab PROJECT GOALS: Impact to MSK: • Flashlights Post Project • Tarp • Priority Workflow list 1. Implement a new digital portal for the 238 new MSK patients Limited Implementation • First Aid Kit • Tech training chart electronic submission of personal consult Staffing $8,557,907 additional revenue • Chemical Treatment Kit • Cross-training cases • Enhanced laboratory floor plan 2. Streamline workflows for easy submission of PC cases "Transition Patient" Revenue: October 2017 to January 2019 $8,557,907 3. Reduce average TAT: less than 1 business day Surgery, $1,109,525 Lab Equipment Assessment Pathology, $233,473 Radiology, $2,735,488 4. Establish billing information prior to receiving Medicine, $797,930

cases Anes thesiology, 5. Introduce marketing efforts to solicit more $146,640 Facilities, $1,186,845 PC submissions and recruit new patients to Laboratory Medicine, MSK Ambulatory Care, $800,554 $1,308,758 Flood preparedness 6. Increase overall PC case volume Radiology Laboratory Medicine Ambulatory Care Facilities Anesthesiology Medicine Pathology Surgery Project Development Timeline 7. Establish a reliable MSK revenue stream from the Pathology portal Improve Review Lab Specific Laboratory Possible Training & Specific Emergencies Drills Plans

Special Acknowledgements: Cytogenetics Laboratory • Anirban Sikdar• Monika Kamalska • Edwin Rodriguez •

MSK PATHOLOGY MSK PATHOLOGY 44 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 45 The Life Changing Magic of Tidying Up HR Files: A Paperless Personnel File Management System MSK Pathology Scan Operations Monika Kamalska-Cyganik • Robert Cimera • Rose Khoobyar • Brian Murphy • Justyna Sadowska • Paulo Salazar • Angela Scalise • Joshua Somar • Nicole DeGroat • Maria A. Friedlander Journey to a Full Digital Workflow Molecular Diagnostic Service, Department of Pathology Radhanglie Seenauth • Lorraine Corsale • Shirley Vargas • Christine England • Jennifer Samboy • Chris Attard • Jamaal Spencer • John Mcdonough • Cindy McCollum

Goals and Objectives: Paper-based Personnel File Management System Key features • Transition to paperless-based Available and customizable when Background Root Cause Analysis personnel files designing the Employee Files Problem Statement - In 2015, pathology’s clinical workflow was introduced to Digital Scanning. Common Themes: • Minimize misfiled HR records Management Portal: -DIRECTLY IMPACTS PATIENT CARE Barcodes on Slide Labels Review with The Pathology department’s scan operations Print record Place signed Placement of Labels Complete required record (ex. employee & • Enhance HR file access for relevant Retrieve personnel file record in file Return file to consists of many manual steps resulting in ample Reprinting of Barcoded Labels competency assessment) obtain signature storage unit staff while maintaining security and delays. In an 8 hour shift Digital Scanning Scan Operations 2019 YTD Volume - Monthly Scan Updates Scan Volume Totals: Quality Control (Pre & Post Scan)  confidentiality Assistants spend 50% of the time adjusting and Scanner Software Limitations 2019 Current Archive Total LIS (CoPath) Limitation reprinting labels adding non-value added time to  • Engage alert notifications for records Jan 38,774 29,082 67,856 Lack of Education the process. Labeling issues prevent streamlined Inception - 2018 830,262 associated with expiration dates Feb 34,614 27,955 62,569 scan operations which limits the pathologists’ Mar 30,353 23,802 54,155 Propose & Test • Utilize current available resources (no License Alert Dashboard ability to consult more quickly on complex cases, Apr - Jan - YTD 2019 184,580 (e-mail alerts also sent) additional software cost) correlate outside diagnoses to a patient’s MSK May - Solutions Organize files by sub-sections • Enhance compliance with HR- diagnoses, and support the department’s transition Totals 103,741 80,839 184,580 Examples: Department, Lab Grand Total: 1,014,842 personnel records maintenance Section, Manager / Supervisor Create/upload specific records to full digital sign-out. with easy access links (records are auto-saved to selected employee’s file) Current State Smart Goal Click to open employee’s profile

Reduce percent of current clinical slides that require relabeling by 50% and increase the Impact to MSK: number of current clinical slides submitted weekly from 8,000 slides to 10,000 slides per week by • Positive feedback from April 30th, 2019. managers/supervisors using the portal

Basic Employee Information to maintain personnel files In each section, upload / fill out • Enhanced compliance with HR Profile Sections corresponding forms Benefits Examples: regulatory, accreditation & institutional Implement & Sustain Lab Test A • Training requirements • Use of Digital Pathology to Support OR Implementation steps: • Competency assessment Lab Test A Operations • Designed user-friendly employee (initial or annual) • Gain in physical space previously used for file storage • Telecommunication profile template on MSK’s SharePoint • Improvement in Pathology Material platform • Potential use and customization by Management • Employee profile tailored to include other MSK departments challenged • Opportunity for Savings in Vendor Services dedicated areas to archive various HR with HR personnel file management record requirements with current available platform • Sparking joy • Secure and access controlled site Paperless Personnel File Management System Long Term Goal • Incorporated email alert notifications # of slides generated by the Histology Lab daily = approx. 3,000 slides/day for relevant records Sustainability/Green Impact: Lab Scanner DIGITAL IMAGES Pathologist Diagnosis • • Trained lab managers/ supervisors in a 15,000 pages saved per ~116 use of the new portal employees • • Solicited user feedback and modified Complete required Review with Elimination of plastic binders the portal accordingly Go to Employee profile record (ex. competency employee & obtain Signed record stored and dividers used to store assessment) digital signature in employee profile. paper HR records

MSK PATHOLOGY MSK PATHOLOGY 46 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 47 Park–International Society of Neuroendocrine Neoplasms– Zhou, Tanaka, Hendrickson, Basturk–Pancreas Pathology. MSKCC@USCAP 2019 Gynecological Pathology. Landscape and Horizon Wang, Roehrl–Techniques. Field Risk (“Field-Effect”/ HPV- Independent Cervical Developing a Robust Sample “Field-Defect”) in the Adenocarcinomas (Including Travis–Pulmonary Pathology Preparation Procedure for Gallbladder and Biliary Tree: PLATFORMS Arcila–Practical Molecular Fine–Large Gland Lesions of Biological Significance and Relationship to Silva Classification Society. Lung Adenocarcinoma: Depp Fourier- Transform Mass An Under-Recognized Diagnostics for the Practicing the Prostate on Needle Biopsy Clinical Implications and Molecular Abnormalities) Emerging Histologic Patterns Spectrometric Profiling of Phenomenon with Major Agaram, Zhang, Antonescu– Surgical Pathologist Formalin-Fixed Paraffin- Implications for Management Bone and Soft Tissue Pathology. Fine, Al-Ahmadie, Chen, Ho–HematoPathology. Rekhtman–Pulmonary Travis–Pulmonary Pathology. Embedded Clinical Tissue and Carcinogenesis GLI1-Amplified Soft Tissue Basturk–Surgical Pathology Gopalan, Sirintrapun, Tickoo, Clinico- Pathologic and Pathology Society. Update Importance of Distinguishing Specimens Neoplasm: A Novel Entity and CytoPathology of the Genitourinary Pathology. Genetic Characterization Reuter– on SMARCB4 Deficient Adenocarcinoma and Squamous Benayed, Ladanyi, Hechtman– Showing Morphologic Overlap Pancreas and Ampulla Practice Patterns in Report- of non-AML NPM1-Mutated Lung Tumors Cell Carcinoma in Assessment Pathobiology. NTRK Fusion with Tumors with GLI1 Gene ing Tertiary Grades at Radical Myeloid Neoplasms of Pathologic Response After POSTERS Detection Across Three Assays Boroujeni, Arcila, Ladanyi, Fusions Prostatectomy: Survey of a Reuter–Arthur Purdy Stout Neoadjuvant Chemotherapy and 29,000 Tumors Dogan–Pathobiology. Large Group of Experienced Jungbluth, Katabi, Xu– Society of Surgical Pathologists. Al-Ahmadie–Genitourinary Genitourinary Genomic Profiling of Mucinous Genitourinary Pathology. Al-Ahmadie– Urologic Pathologists The Disease Doesn’t Know Travis, Sauter–Pulmonary Pathology. Urothelial Carcinoma Bhanot, Roehrl–Informatics. Pathology Society. Pathology Adenocarcinomas Can Assist in Expanded Characterization of Your Age: Adults and Children Pathology. Pericardial in Situ Versus Early High-Grade Digital Imaging for Systematic Dynamic Evolution in and Molecular Features with Determination of Site of Origin Fine– the Immune Microenvironment with the “Wrong Affliction”? Mesothelioma: A Multi- Papillary Urothelial Carcinoma: Validation of Spatially Annotated Prostate Cancer Diagnosis and Clinical Implications: Lower in High-Grade Urothelial GU Pathology Institutional Study of A Survey of Pathologist and Mirror-Image Simultaneous Chen–­­ International Society Tract Urothelial Tumors Reporting: What the Pathologist Carcinoma of the Bladder 61 Cases Urologist Interpretations Flash Frozen and FFPE Tissue of Urological Pathology. The Needs to Know Soslow–Gynecologic Pathology. Banking for Research Al-Ahmadie, Fine, Gopalan, Importance of Pathologic Katabi, Jungbluth, Xu– ClinicoPathologic Analysis of Vakiani, Shia, Klimstra– Antonescu–Bone and Soft Evaluation in Active Surveillance International Society Quality Assurance. Inter- Sirintrapun, Tickoo, Chen, Fuchs– MMR-Deficient Endometrial Gastrointestinal Pathology. Tissue Pathology. Pericytoma Boroujeni, Al-Ahmadie, Genitourinary Pathology. of Small Renal Masses of Breast Pathology. Artificial and Intra-Observer Reuter– Carcinosarcomas Massive Parallel Sequencing with t(7;12) and ACTB-GLI1 Reuter, Gopalan, Arcila, Fine, Revisiting Prognostic Significance Intelligence (AI) in Breast Agreement of PD-L1 Scoring of Neuroendocrine Carcinomas Fusion Involving the Ladanyi, Yao–Pathobiology. Chen–International Society of ClinicoPathological Features Pathology in Hypopharyngeal Squa- Shia, Gopalan, Chen, Fine, of the Large Bowel Reveals Musculoskeletal System and Genomic Profiling of Prostate of Urological Pathology Special in Type 1 Papillary Renal Cell mous Cell Carcinoma (HSCC), Sirintrapun, Arcila, Tickoo, Distinct Molecular Subsets and Ovary: A Report of Three Cases Cancer with EGFR Family Gene Conference on Molecular Fine, Tickoo, Al-Ahmadie, Carcinoma Urothelial Carcinoma (UC), Berger, Reuter, Al-Ahmadie– Patterns of Genomic Evolution Alterations-Potential of Clinical Pathology of Urogenital Chen, Sirintrapun, Ladanyi, and Breast Carcinoma (BC) Genitourinary Pathology. Arcila, Nafa, Ho, Roshal– and Therapeutic Implications Antonescu–International Genitourinary Cancers–Molecular Pathology Reuter, Gopalan– Detailed Morphologic and Weigelt–Molecular Diagnostic HematoPathology. Sensitive Society of Bone and Soft Kidney Cancer Working Group. Pathology. Immunohistochemical Kezlarian, Dogan, Lin– Genetic Features of Urothelial & Genomic Applications in and Ultra-Rapid BRAF V600E Boroujeni, Arcila, Ladanyi, Tissue Pathology. Epithelioid Eosinophilic Solid and Cystic Detection of Androgen Receptor CytoPathology. CytoPathologic Carcinoma in Patients with Cancer: A Primer for the Mutation Assessment in Hairy Soslow, Chang–Gynecologic Hemangioendothelioma– in Metastatic Castrate Resistant Renal Cell Carcinoma and Characterization of SMARCB1- Lynch Syndrome Pathologist Cell Leukemia from Stained Pathology. Evaluation of Copy Histologic and Clinical Spectrum Renal Tumors Associated Prostate Cancer Deficient Malignancies of the Smear Slides, Blood and Bone Number Alterations of MYC and New Genetic Variants with TSC-mTOR Pathways; Head and Neck Region Sigel, Basturk–CytoPathology. Weigelt–Molecular Advances Marrow without Pre-Extraction Family of Genes, RB1 Gene Grabenstetter, Brogi–Breast Distinguishing Papillary Renal Fine Needle Aspiration Find- in Gynecologic Pathology: and AURKA in Endometrial Antonescu–Pathobiology. Pathology. Flat Epithelial Atypia Klimstra–Acini, Islets, and Cell Carcinoma and Mucinous ings in Pancreatoblastoma An Update for the Anatomic Askan, Olca Basturk–Pancreas Carcinomas Genomic Progression in PDG- (FEA) in Breast Core Needle Tubular Spindle Cell Carcinoma Associated Pancreatic Neoplasia: (PBL): An Analysis of 10 Cases Pathologist Pathology. Do We Still Really FRA-Mutant Gastrointestinal Biopsy (CNB): Is Excision A Journey of Technological Reveals Helpful Cytologic Need to Count Mitoses for Pan- Brogi, Pareja, Murray, Weigelt, Stromal Tumors (GISTs) Diagnostic Approach to Necessary? Evolution in Research and Chen– Criteria in Their Distinction Wen–Uncommon Histologic NETs? Proper Ki67 Counting Reis-Filho, Wen–Breast Renal Tumors with Papillary Diagnostics from Common Mimics Subtypes of Triple Negative Negates the Need for the Pathology. Secretory Carcinoma Antonescu–Genitourinary Hechtman–Incorporating TRK Architecture: Updates Using Breast Cancer Cumbersome and Problematic of the Breast: ClinicoPathologic Pathology. BCOR-Overexpressing Inhibition into the Treatment Nafa, Hameed–Bone and 2016 WHO Classification Sirintrapun–Association for Mitotic Count Required in the Profile of 14 Cases Emphasizing Malignant Renal/Perirenal Paradigm: The Pathologist’s Soft Zissue Pathology. Xu–Genitourinary Pathology. Pathology Informatics. Robotic Current WHO-2017 Grading Distant Metastatic Potential Solitary Fibrous Tumor: A Chen, Fine, Gopalan, Role–What Methods are Comprehensive Genomic Protein and Transcriptomic Telecytology for Remote Scheme Close Mimic of Clear Cell Appropriate for Detecting TRK Profiling of the Primary Sirintrapun, Tickoo, Reuter, Diagnosis Characterization of the Brogi, Murray–Breast Pathology. Sarcoma of the Kidney Al-Ahmadie–Genitourinary Fusion Cancer in Daily Practice Craniofacial Osteosarcomas Immune Milieu of High-Grade Basturk–Pancreas Pathology. Core Needle Biopsy Diagnosis of Pathology. Expression of Soslow–GYN Pathology. Bladder Cancer Frequency of Dysplasia/ Fibroepithelial Lesions: Features Arcila–Biocartis–Potential of Hechtman, Vakiani, Klimstra, Pareja, Jungbluth, Giri, Insulinoma-Associated Protein 1 The Evolving Landscape of Carcinoma and Foveolar Atypia Predictive of Upgrade to Ultra-Rapid Mutational Analysis Shia–Gastrointestinal Weigelt, Reis-Filho, Zhang, Antonescu–Bone and (INSM1) in Small Cell Carcinoma Endocervical Adenocarcinoma, Associated with Gallbladder Phyllodes Tumor at Excision in Oncology-Based Applications: Pathology. Inter-Tumoral Brogi–Breast Pathology. Soft Tissue Pathology. Novel of the Bladder What Matters? Cancer Risk: Comparative Ultra-Rapid Mutational Analysis Discordance in Mismatch Immunohistochemical Analysis Recurrent PHF1-TFE3 Fusions Analysis in Mapped/Totally Chan, Lewis, Arcila, Zhang, Complementing NGS Workflows D’ Alfonso–Challenging Frozen Repair Protein Expression in of IDH2 R172 Hotspot in a Subset of Ossifying Tang–Pancreatobiliary Sampled Gallbladders from High- Roshal, Xia–HematoPathology. in High-Volume Laboratories Sections: When Do I Stick My Synchronous or Metachronous Mutations in Breast Papillary Fibromyxoid Tumors Pathology Society. Pancreatic Risk Versus Low-Risk Regions Blast to Plasmacytoid Neck Out…and How Far? Gastrointestinal Tumors: Neoplasms

MSK PATHOLOGY MSK PATHOLOGY 48 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 49 Dendritic Cell Ratio is Predictive Reuter–Genitourinary Pathology. Muller, Rekhtman–CytoPathology. Sequencing Analyses of Three Soslow, Jia, Chiang–Gynecologic Wen, Xu, Ross, Brogi–Breast Xu–Quality Assurance. Zeng, Edelweiss, Ross, of Progression in Low Grade In Organ-Confined Prostate Sclerosing Pneumocytoma of Cases Pathology. Evaluation of Criteria Pathology. Impact of the 2018 The Impact of Pre-Analytical Brogi, D’ Alfonso–Breast Myelodysplastic Syndromes Cancer at Radical Prostatectomy, Lung: CytoMorphologic Find- for Distinguishing Uterine ASCO/CAP HER2 Guideline Parameters on PD-L1 Pathology. Triple-Positive Breast neither Total Tumor Volume nor ings and Immunoprofile of a Pareja, Xu, Ghossein, Weigelt, Smooth Muscle Tumors of Updates on HER2 Assessment Immunohistochemistry: Carcinoma: A HistoPathologic Chen, Al-Ahmadie, Fine, Go- Maximum Tumor Diameter of the Rare Entity Reis-Filho, Katabi–Head and Uncertain Malignant Potential in Breast Cancer with HER2 Concordance Across Four and Clinical Study of Patients palan, Sirintrapun, Tickoo, Index Lesion Aids in Prediction Neck Pathology. Histologic (STUMP) from Mimics and Immunohistochemistry Tissue Processing Protocols Treated with Neoadjuvant euter–Genitourinary Pathology. of Biochemical Recurrence Muller, Agaram–CytoPathology. Spectrum of Polymorphous Improved Prediction of Patient Equivocal Results Using Two PD-L1 Clones in Chemotherapy SMARCB1 Alterations and Fine Needle Aspiration Cytology Adenocarcinoma of the Salivary Outcome: A Multi-Institutional Multiple Tumor Types Protein Expression in Fine, Reuter–Genitourinary of Benign and Malignant Soft Gland Harbor Genetic Alterations Study of 51 Cases Xiao, Kumar, Arcila, Zhang, Zhang–HematoPathology. Non-Medullary Renal Cell Pathology. Reporting Practices Tissue and Bone Tumors: An Affecting PRKD Genes Roshal–HematoPathology. Xu, Katabi, Ghossein– An Integrative Approach Carcinoma and Resource Utilization in Institutional Experience Over Tashkandi, Xiao, Roshal, Abnormal Immature Endocrine Pathology. Reveals Genetic Complexity the Era of Intraductal Carcinoma a 10-Year Period Reis-Filho, Mandelker, Weigelt– Zhang, Arcila, Benayed, Sen, B-Lymphoblast Population The Prognostic Impact of and Epigenetic Perturbation in Chen–Genitourinary Pathology. of the Prostate (IDCP): A Gynecologic Pathology. Are Ho, Dogan, Petrova-Drus– in MDS and Non-CML MPN: Percentage of Papillae in Acute Promyelocytic Leukemia Clear Cell Renal Cell Carci- Survey of Genitourinary Murray, Pareja, Weigelt, Brogi, Endometrial Cancers Arising HematoPathology. PICALM- Diagnostic Implications Unifocal Encapsulated noma with a Poorly-Differen- (GU) Subspecialists Reis-Filho, Zhang–Breast in BRCA1/BRCA2 Germline MLLT10 Fusion Commonly Papillary Thyroid Carcinoma: Zhang, Hameed, Yagi– tiated Component: A Novel Pathology. Recurrent MED12 Mutation Carriers True BRCA1/ Presents with Extramedullary Xu–Genitourinary Pathology. Implications for Noninvasive Informatics. 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Deep Proteomics PD-L1 Expression and Using a Confocal Whole Slide Reuter–Genitourinary Pathology. and High-Grade Forms of Tumors: 3-Dimensional of Colorectal Cancer Liver Xu–Genitourinary Associated Immune Alterations Image Scanner and Image TFEB Expression Profiling in Jungbluth, Zhang, Zhang, Polymorphous Adenocarcinoma Morphometric Analysis of Metastases Uncovers Prognostic Pathology.ClinicoPathologic in High-Grade Urothelial Analysis Software Renal Cell Carcinomas Chen, Tickoo, Fine, Gopalan, are Underpinned by Genetic Spread Through Air Spaces Factors and Highly Promising and Transcriptomic Predictors Carcinoma of the Bladder Al-Ahmadie, Sirintrapun, Alterations Affecting PRKD (STAS) Therapeutic Targets of Fast Urothelial Carcinoma Zhou, Tanaka, Roehrl– Dogan, Xu, Vanderbilt, Berger, Arcila, Ross, Ladanyi, Genes Relapse Post-Radical Cystectomy Xu, Brogi, Ross, Wen–Breast Pathobiology. Understanding Berger–Head and Neck Reuter–Genitourinary Pathology. Roehrl–Informatics. Machine Tanaka, Zhou, Roehrl– Pathology. ClinicoPathologic the Metastatic Process by Pathology. Genomic Analysis JAK2/PD-LI/PD-L2 (9p24.1) Pareja, Brogi, Wen, Weigelt, Learning-Based Natural Language Pathobiology. Deep Proteomics Xu–Genitourinary Pathology. Features of Breast Cancers Deep Proteomic Analysis of of 134 Squamous Cell Amplified Renal Cell Carcinoma: Reis-Filho–Pathobiology. Are Processing for Automated of Gastrointestinal Cancers Morphologic Features in with HER2/CEP17 Ratio <2, Primary Colon Cancers and Carcinomas Arising in the Implications for Clinical Metaplastic Breast Carcinomas Extraction and Standardized an Distinguish Tumor Location, Urothelial Carcinoma Correlate HER2 Copy Number >4 and Matched Liver Metastases Base of Tongue Diagnosed Management and Uterine Carcinosarcomas Annotation of IHC Results from Histology, and New Post- with Intrinsic Molecular Subtypes <6 Signals/Cell Using Clinical FFPE Tissues from 1985 to 2017 Genetically Related Free Text Pathology Reports Genomic Subtypes Jia, Al-Ahmadie, Fine, Gopalan, Xu–Breast Pathology. Mammary Xu, Antonescu, Ghossein, Zhu, Hechtman, Arcila, Dogan, Arcila, Katabi, Sirintrapun, Tickoo, Reuter, Pareja, Wen, Jungbluth, Salagean, Grabenstetter, Tickoo–Genitourinary Pathology. Adenoid Cystic Carcinoma: Jungbluth, Katabi–Head and Vanderbilt–Gastrointestinal Ladanyi, Benayed– Chen–Genitourinary Pathology. Brogi, Weigelt, Reis-Filho– Brogi–Breast Pathology. ClinicoPathological Findings in A Multi-Institutional Canadian Neck Pathology. Utility of Pathology. Appendectomy Head and Neck Pathology. Expanding the Morphologic Breast Pathology. Atypical Ductal Hyperplasia End Stage Kidneys Resected Study Pan-TRK Immunohistochemistry Status is Associated with NovelRearrangements in Salivary Spectrum of Sporadic Immunohistochemical Assess- (ADH) in Breast Core Needle for Mass Lesions: A Single (IHC) as an Ancillary Tool in Distinct Molecular and Gland Tumors Detected by an Renal Cell Carcinoma (RCC) ment of HRAS Q61R Mutations Biopsies (CNB): Is Excision Institution Experience Xu, Dogan, Ghossein, Katabi– Diagnosing Secretory Carcinoma Microbiota Profiles in RNA-Based Targeted Next- Harboring Somatic TSC or in Breast Adenomyoepitheliomas Always Warranted? Review of Head and Neck Pathology. (SC) of Salivary Gland and Colorectal Carcinomas Based Generation Sequencing Assay MTOR Alterations: Analysis of the Experience at a Tertiary Vyas, Vakiani, Hechtman, ClinicoPathologic Features and Detecting ETV6-NTRK3 Fusion on Comprehensive Molecular 8 Cases with Clear Cytoplasm Pareja, Murray, Giri, Weigelt, Care Center Klimstra, Shia–Gastrointestinal Outcome of Head and Neck Testing by Hybridization Dogan, Ghossein, Reis-Filho, and Leiomyomatous Stroma Reis-Filho, Brogi–Breast Pathology. Residual Neoplasia Spindle Cell Squamous Cell Xu, Vanderbilt, Berger, Dogan– Capture Next-Generation Xu, Katabi–Head and Neck Pathology. Recurrent MED12 Sigel–CytoPathology. Limited to the Mucosa in Carcinoma (SpC-SCC) Head and Neck Pathology. Sequencing Pathology. Inter-Observer Kezlarian, Sauter, Travis, Exon 2 Mutations in Benign Biliary Tract Involvement Rectal Resections for The Mutational Profile of 50 Variation in the Histologic Ladanyi, Breast Fibroepithelial Lesions by Hepatocellular Carcinoma Adenocarcinoma Post- Xu, Vanderbilt, Berger, Dogan– Squamous Cell Carcinomas Classification of Polymorphous Rekhtman–Pulmonary Pathology. in Adolescents and Young (HCC): An Under-Appreciated Neoadjuvant Therapy: Head and Neck Pathology. of the Soft Palate Adenocarcinoma (PAC) and Evaluation of H3K27me3 Adults Phenomenon and Potential Frequency, Morphological Integrative Clinical and Cribriform Adenocarcinoma Expression as a Marker of Diagnostic Pitfall in the Spectrum and Potential Genomic Analysis of Tonsillar of Salivary Gland (CASG) EZH2 Activation in SMARCA4/ Pareja, Chiang, Reis-Filho, Evaluation of Bile Duct Clinical Implications Squamous Cell Carcinoma SMARCA2-Deficient Tumors Weigelt–Gynecologic Pathology. Brushings (T-SCC) Fine, Al-Ahmadie, Chen, and Candidate Biomarker for Uterine Rhabdomyosarcomas:

Gopalan, Sirintrapun, Tickoo, Trials of EZH2 Inhibitors Targeted Capture and RNA

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Two well-differentiated Benfante NE, Sjoberg DD, Yoshimi A, Lee SC, Inoue D, Liu Miller DV, O'Malley D, Qiu J, Rosai J, Suster S, Thompson Spiczka AJ, VandeHaar MA, van MP, Chang JC, Wolff AC, Krop IE, Urology. 2019;134:42-4. pancreatic neuroendocrine Eastham JA, Scardino PT, Fine B, Zhang XJ, Mato AR, Dogan Salama ME, Schaberg KB, LDR, Wenig BM. Interobserver Zante A, Sauter JL, American Fuqua SAW, Prat A, Hilsenbeck tumor mouse models. Cell Death SW, Oya M, Touijer KA. Extensive A, Kharas MG, Chen Y, Wang D, Schwartz RA, Shia J, Summers variability in the histopathologic Society of Cytopathology SG, Weigelt B, Reis-Filho JS, Wang S, Mondal S, Zhao C, Differ. 2020;27(1):269-83. disease among potential Soni RK, Hendrickson RC, Prieto TA, Jr., Wu Y. Predictive markers assessment of extrathyroidal Clinical Practice C. 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Tsuda Y, Dickson BC, Dry SM, for Tumor Staging. Thyroid. patterns. J Am Soc Cytopathol. and trastuzumab without auto-inhibitory residues that Dogan A, Jaffe ES. Recurrent Tashkandi H, Petrova-Drus K, Federman N, Suurmeijer AJH, 2019;29(5):619-24. 2019;8(6):333-41. chemotherapy in patients with control its transforming activity. somatic JAK3 mutations in Batlevi CL, Arcila ME, Roshal Tchekmedyian V, Sherman EJ, Swanson D, Sung YS, Zhang L, HER2+ breast cancer. Ann Oncol. JCI Insight. 2019;4(12). NK-cell enteropathy. Blood. M, Sen F, Yao J, Baik J, Bilger Dunn L, Tran C, Baxi S, Katabi Healey JH, Antonescu CR. Clinical van der Kwast TH, Helleman J, Varma M, Srigley JR, Brimo 2019;30(6):927-33. 2019;134(12):986-91. A, Singh J, de Frank S, Kumar N, Antonescu CR, Ostrovnaya and molecular characterization Nieboer D, Bruinsma SM, Roobol F, Comperat E, Delahunt B, Wang T, Askan G, Adsay V, Allen A, Aryeequaye R, Zhang Y, I, Haque SS, Pfister DG, Ho AL. of primary sclerosing epithelioid MJ, Movember Foundation's Koch M, Lopez-Beltran A, Viny AD, Bowman RL, Liu Y, P, Jarnagin WR, Memis B, Sigel C, Xiao W, Petrova-Drus K, Roshal Dogan A, Xiao W. Divergent Phase II study of lenvatinib fibrosarcoma of bone and Global Action Plan Prostate Reuter V, Samaratunga H, Lavallee VP, Eisman SE, Xiao Seven IE, Klimstra DS, Basturk O. M. Optimal measurable residual clonal evolution of a common in patients with progressive, review of the literature. Genes Cancer Active Surveillance C, Shanks JH, Tsuzuki T, van der W, Durham BH, Navitski A, Intraductal oncocytic papillary disease testing for acute precursor to mantle cell recurrent or metastatic adenoid Chromosomes Cancer. 2019 Trock B, Ehdaie B, Carroll P, Filson Kwast T, Webster F, Grignon Park J, Braunstein S, Alija B, neoplasms: Clinical-pathologic myeloid leukemia. Surg Pathol lymphoma and classic hodgkin cystic carcinoma. J Clin Oncol. [E-pub ahead of print]. C, Kim J, Logothetis C, Morgan D. Dataset for the reporting of Karzai A, Csete IS, Witkin M, characterization of 24 cases, Clin. 2019;12(3):671-86. lymphoma. Cold Spring Harb 2019;37(18):1529-37. T, Klotz L, Pickles T, Hyndman E, urinary tract carcinoma-biopsy Azizi E, Baslan T, Ott CJ, Pe'er with an emphasis on associated Mol Case Stud. 2019;5(6). Tsuda Y, Dickson BC, Swanson Moore CM, Gnanapragasam V, and transurethral resection D, Dekker J, Koche R, Levine RL. invasive carcinomas. Am J Surg Xu B, Dogan S, Haroon Al Tomasetti C, Poling J, Roberts D, Sung YS, Zhang L, Meyers Van Hemelrijck M, Dasgupta P, specimen: Recommendations Cohesin members STAG1 and Pathol. 2019;43(5):656-61. Rasheed MR, Ghossein R, Taskin OC, Akkas G, Memis NJ, London NR, Jr., Pittman P, Healey JH, Antonescu CR. Bangma C, Roobol M, Villers A, from The International STAG2 display distinct roles Katabi N. Androgen receptor B, Seven IE, Basturk O, Jang ME, Haffner MC, Rizzo A, Baras Ewing sarcoma with FEV Rannikko A, Valdagni R, Perry Collaboration on Cancer in chromatin accessibility and Wang T, Drill E, Vakiani E, immunohistochemistry in KT, Roa JC, Araya JC, Bellolio A, Karim B, Kim A, Heaphy gene rearrangements is a rare A, Hugosson J, Rubio-Briones J, Reporting (ICCR). Mod Pathol. topological control of HSC self- Pak LM, Boerner T, Askan G, salivary duct carcinoma: A E, Losada H, Sarmiento J, CM, Meeker AK, Hruban RH, subset with predilection for Bjartell A, Hefermehl L, Shiong 2019 [E-pub ahead of print]. renewal and differentiation. Cell Schvartzman JM, Simpson retrospective study of 188 Balci S, Pehlivanoglu B, Iacobuzio-Donahue CA, extraskeletal locations and LL, Frydenberg M, Kakehi Y, Stem Cell. 2019;25(5):682-96 e8. AL, Jarnagin WR, Sigel CS. cases focusing on tumoral Reid MD, Koshiol J, Adsay V. Vogelstein B. Cell division rates aggressive behavior. Genes Chung BH, van der Kwast T, Vasan N, Razavi P, Johnson Distinct histomorphological heterogeneity and temporal Sarcomatoid carcinomas of the decrease with age, providing Chromosomes Cancer. 2019 Obbink H, van der Linden W, JL, Shao H, Shah H, Antoine Vokes NI, Liu D, Ricciuti B, features are associated with concordance. Hum Pathol. gallbladder: Clinicopathologic a potential explanation for the [E-pub ahead of print]. Hulsen T, de Jonge C, Kattan M, A, Ladewig E, Gorelick A, Lin Jimenez-Aguilar E, Rizvi H, IDH1 mutation in intrahepatic 2019;93:30-6. characteristics. Virchows Arch. age-dependent deceleration in Xinge J, Muir K, Lophatananon A, TY, Toska E, Xu G, Kazmi A, Dietlein F, He MX, Margolis cholangiocarcinoma. Hum 2019;475(1):59-66. cancer incidence. Proc Natl Acad Tsui DWY, Barnett E, Scher Fahey M, Steyerberg E, Nieboer Chang MT, Taylor BS, Dickler CA, Elmarakeby HA, Girshman Pathol. 2019;91:19-25. Xu B, Ghossein R. Critical Sci U S A. 2019;116(41):20482-8. HI. Toward standardization of D, Zhang L, Guo W, Benfante MN, Jhaveri K, Chandarlapaty S, J, Adeni A, Sanchez-Vega F, prognostic parameters in the Taskin OC, Bellolio E, Dursun preanalytical procedures for cell- N, Cowan J, Patil D, Tolosa E, Rabadan R, Reznik E, Smith ML, Schultz N, Dahlberg S, Zehir A, Wang T, Lee LH, Vyas M, Zhang anatomic pathology reporting N, Seven IE, Roa JC, Araya JC, Toska E, Castel P, Chhangawala free DNA profiling. Clin Chem. Kim TK, Mamedov A, LaPointe Sebra R, Schimmoller F, Wilson Janne PA, Nishino M, Umeton R, L, Ganesh K, Firat C, Segal NH, of differentiated follicular cell- Villaseca M, Tapia O, Vance C, S, Arruabarrena-Aristorena A, 2019 [E-pub ahead of print]. V, Crump T, Kimberly-Duffell TR, Friedman LS, Cantley LC, Sholl LM, Van Allen EM, Hellmann Desai A, Hechtman JF, Ntiamoah derived thyroid carcinoma. Saka B, Balci S, Bagci P, Losada Chan C, Hristidis VC, Cocco E, J, Santaolalla A, Nieboer D, Scaltriti M, Baselga J. Double MD, Awad MM. Harmonization P, Weiser MR, Markowitz AJ, Cancers (Basel). 2019;11(8). H, Sarmiento J, Memis B, Sallaku M, Xu G, Park J, Minuesa Tuncel D, Basturk O, Bradley Olivier JT, Rancati T, Ahlgren H, PIK3CA mutations in cis increase of tumor mutational burden Vakiani E, Klimstra DS, Stadler Pehlivanoglu B, Basturk O, Reid G, Shifman SG, Socci ND, Koche KT, Kim GE, Xue Y, Reid MD, Mascaros J, Lofgren A, Lehmann oncogenicity and sensitivity quantification and association ZK, Shia J. Colorectal carcinoma Xu B, Haroon Al Rasheed MR, MD, Koshiol J, Cheng JD, Kapran R, Leslie CS, Scaltriti M, Baselga Balci S, Erbarut I, Adsay V. K, Lin CH, Hirama H, Lee KS, to PI3K inhibitors. Science. with response to immune with double somatic mismatch Antonescu CR, Alex D, Frosina Y, Adsay V. Non-neoplastic J. PI3K inhibition activates SGK1 Poorly cohesive (signet ring Jenster G, Auvinen A, Bjartell A, 2019;366(6466):714-23. checkpoint blockade in non- repair gene inactivation: Clinical D, Ghossein R, Jungbluth polyps of the gallbladder: A via a feedback loop to promote cell) carcinoma of the ampulla Haider M, van Bochove K, Carter small-cell lung cancer. JCO and pathological characteristics AA, Katabi N. PAN-TRK clinicopathologic analysis of 447 chromatin-based regulation of of vater. Int J Surg Pathol. 2019 B, Gledhill S, Buzza M, Bangma C, Vasan N, Toska E, Scaltriti M. Precis Oncol. 2019;3. and response to immune immunohistochemistry is a cases. Am J Surg Pathol. 2019 ER-dependent gene expression. [E-pub ahead of print]. Roobol M, Bruinsma S, Helleman Overview of the relevance of checkpoint blockade. Mod sensitive and specific ancillary [E-pub ahead of print]. Cell Rep. 2019;27(1):294-306 e5. J. Consistent biopsy quality and PI3K pathway in HR-positive Vyas M, Hechtman JF, Zhang Pathol. 2019;32(10):1551-62. tool for diagnosing secretory Turashvili G, Fix DJ, Soslow RA, Gleason grading within the global breast cancer. Ann Oncol. Y, Benayed R, Yavas A, Askan carcinoma of the salivary gland Taylor J, Haddadin M, Upadhyay Touijer KA, Michaud L, Alvarez Park KJ. Wilms tumor of the active surveillance global action 2019;30(Supplement_10):x3-x11. G, Shia J, Klimstra DS, Basturk Won E, Basunia A, Chatila WK, and detecting ETV6-NTRK3 VA, Grussie E, Mehta-Shah N, HAV, Gopalan A, Kossatz S, ovary: Review of the literature plan 3 initiative: A prerequisite O. DNAJB1-PRKACA fusions Hechtman JF, Chou JF, Ku fusion. Histopathology. 2019 Brunner AM, Louissaint A, Jr., Gonen M, Beattie B, Sandler and report of 2 cases. Int J for future studies. Eur Urol Oncol. occur in oncocytic pancreatic GY, Chalasani SB, Boyar MS, [E-pub ahead of print]. Lovitch SB, Dogan A, Fathi AT, I, Lyaschenko S, Eastham JA, Gynecol Pathol. 2020;39(1):72-8. 2019;2(3):333-6. and biliary neoplasms and are Goldberg Z, Desai AM, Tuvy Y, Stone RM, Tallman MS, Rampal Scardino PT, Hricak H, Weber not specific for fibrolamellar Berger MF, Tang L, Kelsen DP, RK, Neuberg DS, Stevenson KE, WA. Prospective study of the Turashvili G, Park KJ. hepatocellular carcinoma. Mod Schattner M, Ilson DH, Capanu M, Horwitz SM, Lane AA. Multicenter radiolabeled GRPR antagonist Cervical glandular neoplasia: Pathol. 2019 [E-pub ahead of Solit DB, Schultz N, Janjigian YY. analysis of outcomes in blastic BAY86-7548 for positron Classification and staging. Surg print]. Efficacy of combined VEGFR1-3, plasmacytoid dendritic cell emission tomography/computed Pathol Clin. 2019;12(2):281-313. PDGF alpha/beta, and FGFR1-3 neoplasm offers a pretargeted tomography imaging of newly blockade using nintedanib for therapy benchmark. Blood. diagnosed prostate cancer. Eur esophagogastric cancer. Clin 2019;134(8):678-87. Urol Oncol. 2019;2(2):166-73. Cancer Res. 2019;25(13):3811-7.

MSK PATHOLOGY MSK PATHOLOGY 66 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 67 New Pathology Faculty

Xu B, Jungbluth AA, Frosina Yang W, Lee KW, Srivastava RM, Yuan L, Katabi N, Antonescu CR, Zhang L, Walsh MF, Jairam S, D, Alzumaili B, Aleynick N, Kuo F, Krishna C, Chowell D, Golden A, Travis WD, Rekhtman Mandelker D, Zhong Y, Kemel Slodkowska E, Higgins K, Ho A, Makarov V, Hoen D, Dalin MG, N. Pulmonary myoepithelial Y, Chen YB, Musheyev D, Zehir Morris L, Ghossein R, Katabi N. Wexler L, Ghossein R, Katabi tumors with exuberant A, Jayakumaran G, Brzostowski The immune microenvironment N, Nadeem Z, Cohen MA, Tian reactive pneumocytes: E, Birsoy O, Yang C, Li Y, Somar and expression of PD-L1, PD- SK, Robine N, Arora K, Geiger H, Proposed reclassification J, DeLair D, Pradhan N, Berger 1, PRAME and MHC in salivary Agius P, Bouvier N, Huberman of so-called pneumocytic MF, Cadoo K, Carlo MI, Robson duct carcinoma. Histopathology. K, Vanness K, Havel JJ, Sims JS, adenomyoepithelioma. Am J ME, Stadler ZK, Iacobuzio- 2019;75(5):672-82. Samstein RM, Mandal R, Tepe J, Surg Pathol. 2020;44(1):140-7. Donahue CA, Joseph V, Ganly I, Ho AL, Riaz N, Wong Offit K. Fumarate hydratase Xu B, Serrette R, Tuttle RM, RJ, Shukla N, Chan TA, Morris Zaremba A, Murali R, Jansen P, FH c.1431_1433dupAAA Alzumaili B, Ganly I, LGT. Immunogenic neoantigens Moller I, Sucker A, Paschen A, (p.Lys477dup) variant is not Katabi N, Lora Hedrick Ellenson, MD Tallini G, How many derived from gene fusions Zimmer L, Livingstone E, Brinker associated with cancer including Ghossein R. Attending Pathologist M. Herman Chui, MD Pallavi Galera, MD papillae in conventional papillary stimulate T cell responses. Nat TJ, Hadaschik E, Franklin C, renal cell carcinoma. Hum Mutat. Director, Gynecologic Pathology Assistant Attending Pathologist Assistant Attending Pathologist carcinoma? A clinical evidence- Med. 2019;25(5):767-75. Roesch A, Ugurel S, Schadendorf 2020;41(1):103-9. based pathology study of 235 D, Griewank KG, Cosgarea I. unifocal encapsulated papillary Yang X, Sen F, Geyer MB. Clinical and genetic analysis of Zhang W, Rho JH, Roehrl MH, thyroid carcinomas, with Inotuzumab ozogamicin as melanomas arising in acral sites. Wang JY. A comprehensive emphasis on the diagnosis of chemotherapy-sparing salvage Eur J Cancer. 2019;119:66-76. autoantigen-ome of autoimmune noninvasive follicular thyroid in a 67-year-old man with liver diseases identified from neoplasm with papillary-like primary refractory B-cell acute Zauderer MG, Jayakumaran G, dermatan sulfate affinity nuclear features. Thyroid. lymphoblastic leukemia with DuBoff M, Zhang L, Francis JH, enrichment of liver tissue proteins. 2019;29(12):1792-803. high-risk genomic features. Leuk Abramson DH, Cercek A, Nash BMC Immunol. 2019;20(1):21. Res Rep. 2019;12:100186. GM, Shoushtari A, Chapman P, Xu J, Reznik E, Lee HJ, Gundem D'Angelo S, Arnold AG, Siegel Zhang W, Rho JH, Roehrl MW, G, Jonsson P, Sarungbam Yellapantula V, Hultcrantz M, B, Fleischut MH, Ni A, Rimner Roehrl MH, Wang JY. A repertoire J, Bialik A, Sanchez-Vega F, Rustad EH, Wasserman E, A, Rusch VW, Adusumilli PS, of 124 potential autoantigens for Creighton CJ, Hoekstra J, Zhang Londono D, Cimera R, Ciardiello Travis W, Sauter JL, Zehir A, autoimmune kidney diseases Brie Kezlarian, MD Alexander Chan, MD Andrea Moy, MD L, Sajjakulnukit P, Kremer D, A, Landau H, Akhlaghi T, Mandelker D, Ladanyi M, Robson identified by dermatan sulfate Assistant Attending Pathologist Assistant Attending Pathologist Assistant Attending Pathologist Tolstyka Z, Casuscelli J, Stirdivant Mailankody S, Patel M, Medina- M. Prevalence and preliminary affinity enrichment of kidney S, Tang J, Schultz N, Jeng P, Martinez JS, Arango Ossa JE, validation of screening criteria tissue proteins. PLoS One. Dong Y, Su W, Cheng EH, Russo Levine MF, Bolli N, Maura F, Dogan to identify carriers of germline 2019;14(6):e0219018. P, Coleman JA, Papaemmanuil A, Papaemmanuil E, Zhang Y, BAP1 mutations. J Thorac Oncol. E, Chen YB, Reuter VE, Landgren O. Comprehensive 2019;14(11):1989-94. Zhou J, Sanchez-Vega F, Caso Sander C, Kennedy SR, Hsieh detection of recurring genomic R, Tan KS, Brandt WS, Jones JJ, Lyssiotis CA, Tickoo SK, abnormalities: A targeted Zeng J, Piscuoglio S, Aggarwal GD, Yan S, Adusumilli PS, Bott Hakimi AA. Abnormal oxidative sequencing approach for G, Magda J, Friedlander MA, M, Huang J, Isbell JM, Sihag S, metabolism in a quiet genomic multiple myeloma. Blood Cancer Murray M, Akram M, Reis-Filho Molena D, Rusch VW, Chatila background underlies clear cell J. 2019;9(12):101. JS, Weigelt B, Edelweiss M. WK, Rekhtman N, Yang F, papillary renal cell carcinoma. Hormone receptor and HER2 Ladanyi M, Solit DB, Berger MF, Elife. 2019;8. Yoon EC, Schwartz C, Brogi E, assessment in breast carcinoma Schultz N, Jones DR. Analysis Ventura K, Wen H, Darvishian metastatic to bone: A comparison of tumor genomic pathway Maksym Misyura, PhD Judy Sarungbam, MD Xiao Jun Wei, MD, PhD Yagi Y, Aly RG, Tabata K, F. Impact of biomarkers and between FNA cell blocks and alterations using broad-panel Assistant Attending Molecular Geneticist Assistant Attending Pathologist Attending Pathologist Barlas A, Rekhtman N, Eguchi genetic profiling on breast cancer decalcified core needle biopsies. next-generation sequencing T, Montecalvo J, Hameed prognostication: A comparative Cancer Cytopathol. 2019 [E-pub in surgically resected lung M, Manova-Todorova K, analysis of the 8th edition of ahead of print]. adenocarcinoma. Clin Cancer Adusumilli PS, Travis WD. Breast Cancer Staging System. Res. 2019;25(24):7475-84. Three-dimensional histologic, Breast J. 2019;25(5):829-37. immunohistochemical and Zhu GG, Nafa K, Agaram N, multiplex immunofluorescence Yoshida H, Yokota H, Singh R, Zehir A, Benayed R, Sadowska analysis of dynamic vessel Kiyuna T, Yamaguchi M, Kikuchi J, Borsu L, Kelly C, Tap WD, co-option of spread through S, Yagi Y, Ochiai A. Meeting Fabbri N, Athanasian E, Boland air spaces (STAS) in lung report: The International PJ, Healey JH, Berger MF, adenocarcinoma. J Thorac Oncol. Workshop on Harmonization Ladanyi M, Hameed M. Genomic 2019 [E-pub ahead of print]. and Standardization of Digital profiling identifies association of Pathology Image, held on April IDH1/IDH2 mutation with longer Debyani Chakravarty, PhD Joachim Silber, PhD 4, 2019 in Tokyo. Pathobiology. relapse-free and metastasis- Angela Rose Brannon, PhD Assistant Attending Molecular Geneticist Assistant Attending Bioinformatician Assistant Attending Laboratorian 2019;86(5-6):322-4. free survival in high-grade chondrosarcoma. Clin Cancer Res. 2020;26(2):419-27.

MSK PATHOLOGY MSK PATHOLOGY 68 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 69 Featured (Newly) Available IHC Protocols

DAXX MUC6 New Protocol: DAXX New Protocol: MUC6 Reagent: rabbit mA Reagent: mouse mAb Protein: DAXX (Death domain-associated protein 6) Protein: MUC6 (Mucin-6, oligomeric mucus/ gel-forming) Protein Description: Corepressor of transcription that interacts with several transcription factors. It is Protein Description: Mucins are carbohydrate rich part of the Histone remodeling complex ATRX/DAXX. glycoproteins with a protein backbone linked to a wide variety of oligosaccharide side chains; so far 20 Manufacturer: Abcam (ab32140) mucins have been identified, which are expressed in a Clone: E94 tissue-specific manner. MUC6 (pyloric type mucin) is Clinical Use: Loss of DAXX in pancreatic expressed in gastric pyloric glands, Brunner glands as neuroendocrine tumors is associated with DAXX well as in other tissues. mutations, alternative lengthening of telomeres, and Manufacturer: Santa Cruz (SC-33668) poor prognosis. Clone: CLH5 Reference: https://www.ncbi.nlm.nih.gov/pubmed/30747827 HGNC: MUC6 Syn.: Muc-6, Gastric mucin6 Clinical Use: Differential diagnosis of pancreatic MUC6 (mAb CHL5), stomach mucosa intraductal neoplasms; distinction of IPMNs from DAXX (mAb E94), llver biopy, DAXX-mutated pancreatic NET metastatic to the liver ITPNs (IPMNs usually positive for MUC5AC and References: negative for MUC6; ITPNs usually positive for MUC6 https://www.ncbi.nlm.nih.gov/pubmed/27984235 and negative for MUC5AC). https://www.ncbi.nlm.nih.gov/pubmed/28776573 MUC5AC New Protocol: MUC5AC EGFRvIIII Reagent: mouse mAb New Protocol: EGFRvIII Protein: MUC5AC (Mucin 5AC, oligomeric mucus/ Reagent: rabbit mAb gel-forming) Protein: EGFRvIII (Epidermal Growth Factor Protein Description: Mucins are carbohydrate rich Receptor deletion mutation vIII) glycoproteins with a protein backbone linked to a wide Protein Description: Deletion mutation of EGFR variety of oligosaccharide side chains; so far 20 mucins with loss of exons 2-7; also called EGFRd2-7. have been identified, which are expressed in a tissue- specific manner. MUC5AC is expressed in surface- Manufacturer: Cell Signaling Technologies epithelial (foveolar) mucin of the gastro-intestinal tract, (CST), (#64952) including the ampulla, as well as in other tissues. Clone: D6T2Q Manufacturer: Santa Cruz (SC-33667) HGNC: n/a Clone: CLH2 Syn.: EGFRd2-7 HGNC: MUC5AC Clinical Use: EGFRvIII is a common mutation in Syn.: MUC5, TBM, leB, mucin, mucin 5AC, oligomeric glioblastoma (GBM). It involves the deletion of exons 2-7 and is associated with protein overexpression; mucus/gel-forming EGFRvIII (mAb D6T2Q), EGFRvIII-positive glioblastoma it is thought to be a late event after amplification of MUCSAC (mAb CJJLZ), stomach mucosa Clinical Use: Differential diagnosis of pancreatic EGFR. The present antibody detects EGFRvIII. While intraductal neoplasms; distinction of IPMNs from ITPNs the pro-tumorigenic effects of EGFRvIII have been References: https://www.ncbi.nlm.nih.gov/pubmed/1584765 (IPMNs usually positive for MUC5AC and negative for References: demonstrated in several model systems of GBM, it can https://www.ncbi.nlm.nih.gov/pubmed/28776573 https://www.ncbi.nlm.nih.gov/pubmed/21170331 MUC6; ITPNs usually positive for MUC6 and negative also be rarely encountered in other tumor types, where for MUC5AC). https://www.ncbi.nlm.nih.gov/pubmed/27984235 https://www.ncbi.nlm.nih.gov/pubmed/25255959 its significance is less clear. https://www.ncbi.nlm.nih.gov/pubmed/16672372

MSK PATHOLOGY MSK PATHOLOGY 70 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 71 Q&A Additional Opportunities

ERIC KLEIN Senior Financial Manager

By Kayt Sukel Fifth Annual

Symposium in The Pathology of What are you responsible for work done. If I’ve done my job well, it appears will further advance cancer insights and Translational Research Q in your current role? effortless to everyone else. But there’s an treatment in the future. I try to incorporate Neoplastic Diseases enormous amount of work involved, and a my personal interests in digital technology in Pathology My primary responsibility is ensuring large support structure to make sure that and efficiency when delivering support so A the fiscal health of the department. can happen. We work together closely to that we can ensure high quality of care and It may sound simple, but it involves being integrate finance, operations, clinical care, optimization of resources to reduce patient aware of all the different priorities from and research in a holistic way. costs and provide education for the different all the different services and stakeholders March 26, 2020 April 27-May 1 services in the Department of Medicine. here in Pathology and ensuring that they Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center Zuckerman Research Center The PathologyRockefeller Research Laboratories of have the resources they need to meet their What brought you to Another large part of my role is research. Q I help coordinate collaborations with www.mskcc.org/trs2020 www.mskcc.org/neoplasticdiseases2020 individual, departmental, and institutional Memorial Sloan Kettering? goals. I also oversee all of the research industry, which involves working with them administration within the department. My father worked in hospital to determine the scope of work, preparing That includes helping to prepare research A administration and I knew early on a budget, working with legal to review Neoplastic Diseases and grant applications for faculty, reporting that I wanted to work in a hospital setting contracts, and coordinating the logistics of Third Annual their progress to granting agencies, and where there was a strong mission to help a study. April MEDICAL29 - May 3, 2019 working with other departments to help people as well as advance the field of Warren Alpert Center for connect them with the right people in our medicine. MSK offers the pinnacle of cancer LABORATORY department to meet their pathology needs. treatment, research, and education. It’s an From your perspective, what Digital and Computational PROFESSIONALS internationally renowned institution and Q sets MSK apart from other Most people think my job is all about WEEK I’m proud to have joined it two years ago. Pathology Symposium numbers on a spreadsheet. But they don’t cancer centers? Pathology is a critical part of that mission. see the behind-the-scenes part where I work Without the clinical care going on in our It’s all about the translational science. with clinicians, investigators, lab managers, A We provide the best clinical care to our department, the rest of cancer treatment suppliers, and administrators to make sure patients. We also have a strong research June 24, 2020 falls apart. Pathology provides a unique April 19-25, 2020 that all of the pieces of the puzzle come program and some of the brightest minds Memorial Sloan Kettering Cancer Center way of understanding, identifying, and together in such a way that there’s a seamless Zuckerman Research Center optimizing the treatment of cancer. in the field. But our department is unique flow of resources when it’s time to get the in bridging the two together. And that’s important because one can’t grow without What’s the most enjoyable the other. Our work is helping to not only Q part of your work? advance the field through research or improving patient outcomes, but combining I get a lot of satisfaction out of working the two to advance the standards of cancer A hand in hand with clinicians, lab care across the industry. And in doing so, we managers, and investigators to understand create new and innovative technologies and DR. CHRISTINE IACOBUZIO-DONAHUE what resources they need to perform treatments and quickly move them from the was named as the 2019 recipient of the clinical care or conduct their research and bench to the bedside to help our patients. Ruth Leff Siegel Award delivering those resources seamlessly so that they may focus on their work and not the support structure behind it. I work The Pancreas Center of Columbia University has been entrusted closely with them to help them understand by the Siegel family to identify the investigator who has had the what they need to do their work to treat and most impactful contribution to the understanding/treatment/ cure cancer as well as generate results that advancement of pancreatic cancer over the past year. Their research can be in any field of pancreatic cancer research, including but not limited to basic biology, population biology, public health, and/or translational science. Not only must the investigator have a track record of high quality work in this field, but also must have contributed to our understanding of pancreatic cancer in the past year, and will continue to do so for years to come.

MSK PATHOLOGY REVIEW 4th Quarter 2019 73 Social Media

INQUIRIES about the MSK @MSKPathology is excited to announce that Pathology Review should be workshop proposals for ICLR 2020 entitled “AI for addressed to: Overcoming Global Disparities in Cancer Care” have been accepted! Congrats to @marciaedelweiss and Memorial Sloan Kettering Cancer Center MDs Dr. Ntiamoah for their contributions! ai4cc.org Attn: Sarah Virgo 1275 York Avenue who Department of Pathology, H-504 New York, NY 10065 #GrandRounds2019 First lecture of the 2019-2020 academic year @MSKPathology: Dr. Jason Huse of 212-639-5696 tweet @MDAndersonNews “Characterizing and Targeting [email protected] Epigenetic Dysfunction in Malignant Glioma” www.mskcc.org/departments/pathology @MSKPathology

Twitter & Instagram: @MSKPathology Twitter @MSKPathology

Congratulations to @MSKPathology faculty Twitter members Drs. Jorge Reis-Filho and Samson Fine Twitter @ (@rovingatuscap) for their inclusion in

Twitter @pathologistmag’s 2019 Power List which features Twitter @ 100 of the industry’s top trailblazers!! 1st Quarter 2020 Research Profile: Jennifer Sauter, MD

Research Profile: Maurizio Scaltriti, PhD Jackie Hechtman @JackieHechtman Jamal Benhamida @jamalbenhamida Our #liquidbiopsy test at @sloan_kettering has Research Profile: Mikhail Roshal, MD received NY State DOH approval for clinical use! Ahmet Zehir @ahmetz Ozge Birsoy @BirsoyOzge MSK-ACCESS captures 129 genes, selected from Service Spotlight: Autopsy Service Christine Iacobuzio- Donahue @ciacobu Meera Hameed @hameedm MSK-IMPACT, for high sensitivity, non-invasive cancer genomic profiling and disease monitoring in Cover: Protein Based Diagnoses Natasha Rekhtman @natasharekhtman DanaTsui @DNA_tsui plasma cell-free DNA #ASC019 Michael Berger @MFBerger1 Yukako Yagi @YukakoYagi Q & A with Jessica Chapman, PhD Ryma Benayed @RymaBenayed Matthew Hanna @MGHannaMD Samson Fine @rovingatuscap Wenbin Xiao @drwenbin_xiao Jennifer Sauter @JL_Sauter Yingbei Chen @Unclassified1 Marcia Edelweiss @marciaedelweiss Sahussapont Joseph Sirintrapun @sirints Thomas Fuchs @ThomasFuchsAI Ronald Ghossein @ghosseir1 Edi Brogi @EdiBrogi Nora Katabi @katabinmsk Bin Xu @BinXu16 Timothy D’Alfonso @tim_dalfonso Marc Ladanyi @MLadanyi Anne Grabenstetter @AGrabenstetter FOLLOW Hikmat Al-Ahmadie @h_alahmadie Melissa Murray @MelissaMurray17 us on Instagram Hannah Wen @HannahYWen Andrea Moy @aprimi Kay Park @KayParkMD Melissa Pulitzer @MPulitzerMD @MSKPathology Olca Basturk @OlcaBasturk Debyani Chakravarty@CDebyaniPhD

MSK PATHOLOGY MSK PATHOLOGY 74 REVIEW 4th Quarter 2019 REVIEW 4th Quarter 2019 75 76