MSK PATHOLOGY Initiatives Innovations REVIEW Accomplishments 1st Quarter 2020

Harnessing the Diagnostic Power of Proteins Memorial Sloan Kettering is committed to fulfilling the promise of protein-based diagnostics. Commentary from the Department Chair Case of the Quarter

CASE HISTORY Pan-CK E-Cadherin 21 year old female who presented with increasing abdominal distention and The current issue of the MSK Pathology Review continues our series pain. Transvaginal ultrasound showed of faculty research profiles, with Mauri Scaltriti, Jen Sauter, and a 15 cm mid-pelvic mass reaching to MLH1 P53 Misha Roshal sharing their interests. We also examine our efforts in the periumbilical region. Ca-125 was protein-based diagnostics, which have evolved from conventional within normal limits. She underwent immunohistochemical stains to multiplexed immunomorphology assays unilateral salpingo-oophorectomy, pelvic to mass spec-based protein detection and profiling. The new leadership and para-aortic lymph node dissection, of the autopsy program by Dilip Giri and Raj Murali is featured, as is our omentectomy and appendectomy. The Ovary Immunohistochemistry rejuvenated Grand Rounds program being led by Natasha Rekhtman and ovary consisted of a predominantly cystic Hikmat Al-Ahmadie. These are all important topics that I hope will be mass with a solid mural nodule. Images of broad interest. are from the ovarian mass. But of course, over the past three months, our attention has been The next issue of the focused on a topic of much broader impact to our patients, our staff, “ and our community–namely, the pandemic caused by SARS-CoV-2 MSK Pathology Review Scan the QR code to view and our response to the resulting illness, COVID-19. This disease has will be devoted to the digital slides available on mskcc.pathpresenter.com impacted everyone in some way, and our Department has been working Pathology Department’s IMPACT Mural Nodule continuously to adapt our activities, developing new workflows that response to the COVID allow for social distancing, experimenting with fully digital sign-out and pandemic and will telepathology, and piloting ways to work remotely. We have had to modify The correct the close interactions we enjoy with our fellows, and we have had to devise highlight how some of our diagnosis will be new ways to ensure a robust educational experience for them. While new processes are actually provided in the next most of the modifications to our processes are difficult to see as positive helping us move forward issue of the MSK changes, the pressures of adapting to the pandemic have allowed some initiatives like digital Pathology Review innovations that will hopefully persist beyond the immediate health pathology and remote and on Twitter emergency. The next issue of the MSK Pathology Review will be devoted @MSKPathology connectivity Ovarian Tumor Ovarian Mural Nodule to the Pathology Department’s response to the COVID pandemic and will ” Ovary Cyst Wall highlight how some of our new processes are actually helping us move forward initiatives like digital pathology and remote connectivity. But for now, we can take a break from the ongoing pressures of responding to this illness to enjoy stories that reflect an earlier time–which seems rather distant right now–when coming to work, looking at slides and data, conducting research, and teaching our fellows were the greatest challenges we had to consider! DIAGNOSIS: LAST ISSUE

- David Klimstra, MD Metaplastic (spindle cell) carcinoma arising from a malignant adenomyoepithelioma.

MSK PATHOLOGY MSK PATHOLOGY 2 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 3 Research Profile

MAURIZIO SCALTRITI, PHD

working or stops working offers researchers use, the tumor finds them. We were able to an opportunity to try new strategies. take this finding and go back to the patients who were resistant and then give them DELVING DEEPER a targeted therapy to turn off the MAPK Dr. Scaltriti and his colleagues use a pathway, and to reinstate a response to the variety of genetic and molecular techniques treatment. That’s the kind of personalized to understand how tumors cope with medicine that has a lot of clinical relevance.” pharmacological pressure, or the consistent use Dr. Scaltriti has also studied the of a drug over time. It is challenging work, he relationship of other pathways to treatment said—mostly because tumors are “very smart.” resistance in lung and breast cancers. “Tumors evolve quickly, and can adapt “Identifying these possible genetic causes to pharmacological pressure—really, to of resistance is something that is very useful anything clinicians do to try to fight it— to the clinic,” he said. “It can help doctors especially in cases of metastasis,” he said. develop the best possible treatment plans Identifying these “Sometimes we outsmart them, sometimes for each patient.” they outsmart us. But to be in a better possible“ genetic position to outsmart them, we need to A TEAM EFFORT understand, at the molecular level, how the While some may be surprised that Dr. causes of resistance tumor is adapting to the drug, radiation, or Scaltriti finds himself as part of the pathology chemotherapy. There may be more than one department at MSK, he said it was a good is something that mechanism of resistance. That’s why it’s so place for him to land. “When you do a lot of is very useful to the Maurizio Scaltriti, PhD, The research career of Maurizio Scaltriti, resistance in the people who do not respond important to find ways that we can reliably translational work, you need a lot of samples,” PhD, has been guided by one overarching to the drug? And what can we do about it so identify each tumor’s Achilles’ heel, or heels.” he said. “For the kind of research I do, I need clinic,” he said. “It can Dives Deep to Solve question: Why do some tumors respond they can be more effectively treated?” By recognizing the vulnerabilities of all types of specimens, from cell-free DNA to better than others to specific therapies? Dr. Scaltriti and his team spend their certain cancer cells as well as the strengths tumor biopsies.” help doctors develop the Problem of Treatment resistance is a persistent days trying to understand the wily ways that allow them to resist treatment, Dr. He said his successes are due to strong the best possible Treatment Resistance challenge in addressing different forms of solid tumors and the mechanisms of Scaltriti aims to provide new targets for collaborations with clinicians and other MSK of cancer. Some drugs simply don’t work resistance. The importance of this work can’t more refined drugs, as well as increasingly staff—as well as working in an institution that treatment plans for for every patient, even though, in theory, be understated. While some patients may personalized therapeutic strategies. His sequences the DNA of almost every patient By Kayt Sukel they should, said Dr. Scaltriti, principal not respond to a given drug immediately, research has led to several breakthroughs who walks through its doors. each patient.” investigator of the Human Oncology and others will show modest improvements on that front. As published in a 2019 Nature “Having this kind of information available Pathogenesis Program (HOPP) at Memorial and then build up resistance over time. Medicine paper, he and his colleagues found is invaluable in getting to know a tumor and Sloan Kettering Cancer Center (MSK). Once resistance to the go-to drug for a type that activation of the MAPK pathway is understanding what its vulnerabilities might “Many patients with the same genomic of cancer occurs, there’s not much clinicians important in inducing resistance to TRK be,” he said. “In finding the mechanisms of abnormalities should respond to a drug that can do, at least for the moment, to continue inhibitor drugs, commonly used to treat resistance, we can offer more benefits to works on those targets,” he explained. “Yet fighting the disease. several cancer types. patients who may no longer be responding even when the science tells us a group of “Too often, the problem is not that we “These drugs usually work very well for to a particular treatment. Also, we may be patients with these characteristics should don’t have an active drug to use. It’s that it almost all patients,” he said. “In some cases, able to help future patients avoid resistance be sensitive to a given therapy, we often see stops working at some point, allowing the the use of the drug activates other pathways. by selecting a therapy that they are more that some are, and some are not. That begs disease to progress unchecked,” Dr. Scaltriti These are pathways that were not important likely to respond to. This is our goal for every the questions: What are the mechanisms of said. Understanding why a drug is either not to the tumor before, but once the drug is in project in my lab.”

MSK PATHOLOGY MSK PATHOLOGY 4 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 5 Research Profile

MIKHAIL ROSHAL, MD, PhD

The sheer numbers of samples that “are available for study means we can not only look for things that may help us better tailor treatments for an individual patient, but also search for common factors that can help larger groups.”

LOOKING FOR A NEEDLE treated the first time around—avoiding cases are handled in the service each year— IN A HAYSTACK potentially deadly recurrences altogether. and many patients consent to have those Dr. Roshal explained that trying to detect samples used in research projects like Dr. specific biomarkers that can be used to develop WORKING TOWARD A Roshal’s. The more samples available to new targeted therapies for those patients COMMON GOAL Dr. Roshal and his colleagues, the more most likely to remit is a challenge. The main Dr. Roshal credits his extensive opportunities they have to identify the reason? Leukemia is a heterogeneous disease collaborations with other researchers at MSK critical molecular markers they seek. by nature. Finding different genetic markers or and scientists at outside institutions with “We see things here that are rarely seen The American Cancer Society estimates is most likely to fail the initial therapy, and proteins that might be an effective treatment helping to identify some of those markers. at other institutions,” he said. “The sheer Mikhail Roshal, MD, that more than 60,000 new cases of monitor them to figure out how their bodies target is a bit like looking for a very tiny needle In fact, some of their work has initiated numbers of samples that are available for PhD, Looks for a leukemia, or cancers of the marrow are responding to that therapy, and what other in a very messy haystack. the development of a targeted antibody study means we can not only look for things and blood-forming organs, will be diagnosed types of treatment might be of benefit, could “We tend to think about AML, for example, therapy that may one day be used to help that may help us better tailor treatments for an “Needle in a Haystack” in 2020. Traditionally, patients with this help us reduce the number of patients who go as a single disease. We even talk about it treat AML patients. The ability to form those individual patient, but also search for common diagnosis are treated with chemotherapy— on to relapse after remission.” that way clinically,” he said. “But it’s really collaborations is one of the reasons why he is factors that can help larger groups.” to Treat Recurring and approximately 70% will achieve a To find the patients who may need a large mixture of different diseases with happy he came to MSK eight years ago. Dr. Roshal enjoys his work immensely— Blood Cancers complete remission after completing a further treatment, Dr. Roshal is trying to heterogenous behaviors—and heterogenous “There are plenty of strong research and is driven by the stimulation that comes course of treatment. Unfortunately, said correlate low levels of disease, which is outcomes. Developing therapies for AML and institutions,” he said. “But MSK’s research from working with innovative technologies By Kayt Sukel Mikhail Roshal, MD, PhD, a member of often referred to as measurable or minimal even just looking for biomarkers that can help resources are exceptional. I have spectacular that allow more precise molecular and protein- the Memorial Sloan Kettering Cancer residual disease (MRD) and is detected us detect residual disease is difficult due to colleagues, both in hematopathology and in the based characterization of MRD cells. Center (MSK) Hematopathology Service, by flow cytometry and other molecular the number of different entities all grouped medical oncology service here. But MSK also “Progress will always be incremental—and relapse will happen for about half of those tests, with patient outcomes. MRD is the together. We want to find biomarkers and offers us a cooperative and supportive research it will always require a team approach,” he said. individuals. Worse, they’ll often end up small number of lingering cancer cells that approaches that suit the largest number of environment. It’s an atmosphere that really “But with such spectacular collaborators and suffering with a much more aggressive form remain in the body after treatment and into patients—but it takes time.” facilitates new ideas and people trying to work resources, I’m able to investigate novel targets of leukemia or other cancerous disease. remission. It’s now established that the Many patients who relapse or develop to the highest level of their fields.” that I might not be able to otherwise. In doing “Those 50% are the patients who need risk of relapse is proportional to the level other forms of cancer after AML treatment It is also a benefit that MSK’s so, I get to play a role in helping better treat additional therapies,” said Dr. Roshal. of MRD in the body—and, as such, it is the face a bleak prognosis. With more targeted hematopathology service runs such a high patients with leukemia in the future.” “Unfortunately, it’s difficult to identify them major cause of relapse in diseases like acute therapies available, said Dr. Roshal, those volume of samples. Tens of thousands of upfront. Finding ways to understand who myeloid leukemia (AML). patients are more likely to be successfully hematological biopsies and flow cytometry

MSK PATHOLOGY MSK PATHOLOGY 6 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 7 Jessica Chapman, PhD Director, Clinical Proteomics

of interest were commonly used but Ahmet Dogan, MD, PhD mostly in a research setting. Today Attending Pathologist HARNESSING the mostly monoclonal antibodies we Chief, Hematopathology Service use in these tests are sensitive tools which are able to distinguish different molecules, mostly proteins, which enable the pathologist THE DIAGNOSTIC to differentiate different tumor types,” he Laboratory explained. “With classical chemical staining now offers the methods such as hematoxylin/eosin, there is first clinical laboratory in only so much you can say about a tumor. But New York State to do comprehensive tumor research reveals that certain types of POWER OF PROTEINS proteomic phenotyping of human cancer tumors express certain types of proteins—so tissues. Ahmet Dogan, MD, PhD, chief of an ‘in-situ’ protein expression analysis done on hematopathology, argued the addition a tumor section can give you a lot of information Travis Hollmann, MD, PhD Memorial Sloan Kettering is committed to fulfilling the of proteomic results to more traditional to further define the tumor and put a clear label Associate Attending Pathologist promise of protein-based diagnostics. diagnostic methods has the strong potential on what disease is actually there on the slide.” to enhance patient care—and provide the With so many potential proteins or other kind of precision medicine clinicians and molecules of interest that can be detected By Kayt Sukel patients seek. by antibodies in different cancers, Dr. “Protein-based diagnostics identify the Jungbluth said “specificity is key.” He and Over the past decade, the medical and data on RNA, protein data has been more to proteins. There’s a mutation in a gene, consequences of genetic changes related to his team are working to create specialized scientific communities have been working difficult to assess—and that’s the type of that mutation makes it into the RNA, and cancers,” he said. “Precision medicine drugs protocols so only the appropriate and to promote truly personalized precision data that could make our diagnoses and then that produces a mutated protein,” he could target those proteins, not the genes, for desired proteins are stained. In doing so, medicine. At the completion of the Human subsequent treatments more precise.” explained. It was presumed that an amount of a better result.” they can move such tests more quickly Genome Project, the hope that oncologists Proteomics, the large-scale study of RNA is correlated with the amount of protein from the bench to the bedside. would be able to examine the genetic changes proteins, is an emerging field with much to offer but, he added, “that doesn’t really hold up. We IMPROVED DIAGNOSTIC METHODS “The most important thing is to in a patient’s cancer and then select the best in terms of pathology and cancer diagnostics. now understand that trying to predict which One area in which a more make sure the method you use is actually Achim Jungbluth, MD, PhD Attending Pathologist treatments to address those changes grew. For more than a century, physicians have used genetic aberrations at the DNA/RNA level comprehensive understanding of proteins detecting the proteins it’s supposed to Yet genes alone can’t tell the whole story of different proteins as simple diagnostic markers actually make it into the protein domain can assist with diagnosis is in improved be detecting,” he said. “My lab’s goal a tumor, said Travis Hollmann, MD, PhD, in a variety of medical conditions, including is quite difficult. But since these proteins immunohistochemistry techniques. is to establish standardized, reliable Director of Advanced Immunomorphology various types of cancer. Yet despite the millions actually carry out the biochemistry, those Pathologists all over the globe rely on this immunohistochemical protocols that can be Platforms at Memorial Sloan Kettering of protein molecules estimated to be housed in functional things that happen in a cell, and technique, which utilizes antibodies to used in our clinical immunohistochemistry Cancer Center (MSK). a single cell, it has been a challenge to expand ultimately, in the processes that lead to identify antigens of interest in a tumor labs to provide the kind of specificity True precision medicine, both at the this important portfolio of biomarkers into a cancer, these are the components we to make accurate diagnoses, said Achim required for accurate diagnosis.” diagnostic and treatment levels, will require higher level of precision care. Michael Roehrl, need to track in order to understand what is Jungbluth, MD, PhD, an attending taking a closer look at proteins. MD, PhD, gastrointestinal pathologist and driving disease.” pathologist at MSK. PROTEOME PROFILING “A protein is the functional end product director of MSK's PPBC, said identifying the That’s why MSK’s pathology department “The rise of immunohistochemistry as a With advances in proteogenomics, of a gene. It’s the part that is essentially doing proteins that may be most useful for diagnostic is committed to developing and validating robust diagnostic method only began in the late Dr. Roehrl's lab studies how proteome a gene’s business in the majority of cancer purposes remains a challenge. innovative protein-based diagnostic tests seventies with the introduction of monoclonal signaling in cancer changes over time. Those Michael Roehrl, MD, PhD cases,” he said. “While we have accrued a lot “People thought for a long time there using state-of-the-art methods and tools. antibody technology by Kohler and Milstein. biomarkers can then better inform diagnosis Associate Attending Pathologist of data on genomics, as well as expression was a direct relationship from DNA to RNA The department’s new Clinical Proteomics Earlier, animal sera containing the antibodies and treatment selection. Director, Precision Pathology Biobanking Center (PPBC)

MSK PATHOLOGY MSK PATHOLOGY 8 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 9 Cover Story

“Once you start treating a patient, you are basically perturbing coexpression and proximity,” said Dr. Hollmann. “Much of this Jessica Chapman, PhD, director of MSK’s Clinical Proteomics the protein network,” he said. “So if you can measure the proteins and technology is reliant on new digital detection devices using more Laboratory, said this protein typing test, using formalin-fixed see what happens to them quantitatively, their chemical activation sophisticated microscopes than what pathologists use today. The paraffin embedded (FFPE) tissue, can identify the protein state, and how they are interacting with one another, both before The pathologist can then use digital tools on their computer to assess responsible for amyloidosis before too much damage has been and after treatment, you can get a better idea of whether or not that images, quantify, and make the diagnosis.” done—and can help clinicians better select the right course of treatment is working.” Reaching that point, however, will require more work. Dr. treatment for patients. Using a variety of biochemical tools including high-resolution mass Hollmann said pathologists interested in furthering protein-based “Amyloidosis is underdiagnosed because it comes with a tricky set spectrometry, he and his lab colleagues have discovered novel proteins diagnostics need to study results from tissues used in prior clinical of symptoms. This test can help,” she said. “It starts when a pathologist in colorectal cancer that correlate with its propensity to metastasize, trials to associate proteomic discoveries with patient outcomes, reviews a case and considers it suspect for amyloid deposits. We then and his lab is developing pan-proteome profiling of cancers. as well as do more comparability projects with the current gold- review it to see how much material we need for the test and I work "Understanding the dynamics of the proteome requires precise standard being conventional immunohistochemistry. with the surgical pathology labs to get the specimens in the way we quantitative measurements," he said. "Our technologies have “This is a good time to expand our digital pathology tools to need them. Then a clinical proteomics technologist will perform the potential to transform pathology and bring proteome-driven include the analysis of protein-based tests. This will certainly improve laser microdissection, protein extraction and then analyze those on diagnostics and treatment monitoring to patients." quantitation in diagnostic pathology. These advances should ease a the mass spectrometer.” pathologist’s job so they can accomplish more in less time, freeing When Dr. Chapman first came on board at MSK, her primary role DIGITAL PATHOLOGY them up to do more clinical or translational work,” he said. “It also was to get the test validated for clinical use, a task that took significant With so many proteins circulating in a single cancer cell, it can reduces the subjective element in diagnosis, which can improve our time and effort. She and her colleagues instituted comprehensive be difficult to identify which have the most clinical relevance. Today, accuracy and reproducibility.” quality-control systems and standard operating procedures to meet diagnostic pathologists generally assess 1-2 proteins on a single slide New York State’s vigorous regulations. and sometimes between 10-20 slides per patient to fully interrogate the A PROTEIN-BASED TEST FOR AMYLOIDOSIS “It’s just a mix of 15 peptides but there’s a certain way they look expression of proteins in a tumor and the tumor’s microenvironment Unfortunately, cancers often travel with other conditions which when they come off the instrument,” she said in reference to the daily (the blood vessels, immune cells, fibroblasts, and other signaling can directly affect a patient’s outcomes. One of those disorders is quality standard they run on the mass spectrometer. “We make sure molecules that surround the tumor) for a diagnosis. amyloidosis, a condition in which misfolded protein is deposited that we are running these tests under the correct parameters, so Dr. Hollmann’s laboratory is examining ways to simplify that extracellulary, displacing healthy tissue. A subset of patients with we know we are giving pathologists the right information to make work so that pathologists can do these assays on a single tissue slide, blood cancers will develop amyloidosis, which is quite difficult to decisions.” reducing the time, effort, and valuable patient tissue used to derive diagnose. Recently, however, MSK developed and validated the first While the amyloidosis test was the first validated in the Clinical the information required for diagnosis. clinical assay to diagnose amyloidosis. This is highly significant, Proteomics Lab, Dr. Dogan said it will not be the last. They hope to “The benefit of having many markers on a single slide is that says Dr. Dogan: “It is the first time such an assay has been clinically validate a novel assay to assess minimal residual disease (MRD) in Dr. Travis Hollmann you retain co-localization and the subsequent quantification of implemented in New York State and the Northeast.” myeloma after treatment, to replace invasive bone marrow biopsies. They are also developing tests for diagnostic biomarkers in rare carcinomas and comprehensive typing of immunoglobin repertoires combination therapy. We can use proteomics to direct the patient to to assess the tumor microenvironment in different cancers. the correct clinical trial at the correct time in their therapy. We can “It is hoped that these novel assays will have broad applications, use it to find new proteins we may not have considered before in drug not only in the diagnosis of cancer but in predicting a patient’s development. There’s a lot of potential there.” response to therapy,” Dr. Dogan said. Dr. Chapman agreed. “Protein-based diagnostics is an area where we can have a lot of impact on clinical care,” she said. “At the end of MOVING FORWARD the day, I think that’s why most of us do what we do here.” Dr. Chapman said that finding ways to integrate proteomics into The protein-based diagnosis team at MSK has been fortunate validated diagnostic tools will be a challenge. But with its addition and grateful to receive generous grant support from the Farmer to information pathologists currently collect regarding DNA, RNA, Family Foundation. and other clinical features of disease, it should allow for more precise diagnoses and more informed evidence-based clinical decisions regarding treatment. “Being able to give the most accurate diagnosis is the foundation to making sure that a patient is getting the proper care,” she said. “There are a lot of challenges to both developing and then validating these tests. But when we can give clinicians relevant information, they This is a good time to expand our have the ability to make sure patients aren’t having to try different treatment protocols or go through extra procedures.” digital“ pathology tools to include the As research in proteomics progresses and leads to the identification of new biomarkers, it is likely to also play a role in the analysis of protein-based tests. This development of newer, more precise treatment regimens, added will certainly improve quantitation in Dr. Hollmann. Current drugs don’t affect genes, they affect targeted proteins. By knowing what proteins have changed in the tumor or diagnostic pathology.” the tumor microenvironment, there is the potential to develop more effective pharmacological interventions. “Many patients will receive some type of combination therapy,” he said. “But a lot of the current combinations that are being pushed Drs. Makiko Ogawa, Atsushi Tanaka, Michael Roehrl, and Kei Namba through are not necessarily based on the specific biomarker profile of the tumor. In the future, we can use this technology to guide

MSK PATHOLOGY MSK PATHOLOGY 10 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 11 those advances, the MSK Pathology Department has grown by large department, with such diversified specialties and backgrounds, Grand Rounds are Back, leaps and bounds over the past few years. With so many new faces, a Grand Rounds program that looks at the bigger picture, so to speak, there was also a need for new ways to bring people together in a is something that we hope will appeal to everyone.” and Better Than Ever collegial, educational atmosphere. “Beyond our faculty, a robust Grand Rounds relaunched in September. Since then, said Dr. Al- Memorial Sloan Kettering Cancer Center’s Pathology Grand Rounds program is tremendously beneficial to our fellowship Ahmadie, the sessions have been a “resounding success,” with both Department relaunched its grand rounds program to program. It exposes our trainees to different perspectives held by attendance and engagement high. The first few gatherings featured experts from other institutions and provides fellows an opportunity invited speakers from outside institutions, but Dr. Al-Ahmadie said better meet the needs of its trainees and faculty. to engage with them directly during the dedicated slide session or some of them had a connection to MSK. “Some were former trainees By Kayt Sukel fellow lecture later in the day." said Dr. Rekhtman. or colleagues who went on to become experts in their particular field,” By organizing regular, ongoing presentations, at a more he said. “They set the bar quite high for the content and quality of their Medicine evolves constantly, and continuing education is a key way convenient time of day, pathologists, pathology trainees as well as presentation, which is something we want to continue. If we are asking clinicians can keep abreast of the latest advances in methods,tools, other interested clinicians outside the department would be more our colleagues to give up an hour of their time, we want to make sure practice-based guidelines, and clinical trial results. And while likely to be able to fit the sessions into their busy schedules and it is worth it.” physicians and other medical staff subscribe to academic journals and directly benefit from attendance. Dr. Rekhtman agreed. With the Grand Rounds team’s new means attend conferences to stay on top of new developments, few options With logistical support from Sarah B. Virgo, the department's of soliciting and vetting speaker nominations, however, she is not for continuing education parallel Grand Rounds programs. These Education & Communications Manager, Drs. Rekhtman and worried about finding qualified candidates. And as they move forward events—formal presentations of thought-provoking medical content Al-Ahmadie worked to revamp the department's Grand Rounds with the program, she and Dr. Al-Ahmadie are already thinking about by prominent experts in the field coupled with active discussions— program to provide regularly scheduled monthly talks. Grand rounds ways to improve it for the department and the larger MSK community. offer physicians, trainees, scientists, and medical students another speakers were selected after soliciting recommendations from “Attendees’ feedback has been overwhelmingly positive,” avenue to gain critical knowledge. That's why, David Klimstra, MD, members across the department. The new program also moved the she said. “It’s been a great way for the whole department to come the Pathology Department Chair, requested volunteers to reboot the sessions to a larger space and scheduled the talks at midday, with food together at a regular time and learn about what’s new and exciting in program to better reflect the evolution of the field. Natasha Rekhtman, provided for attendees, to make it easier for more people to attend. our field. In the future, we hope to include internal speakers as well Natasha Rekhtman, MD, PhD MD, PhD, a thoracic pathologist and cytopathologist, and Hikmat Al- “We asked each sub-specialty team to propose the names of as to develop educational seminars. The last few months are just the Associate Attending Pathologist Ahmadie, MD, a genitourinary pathologist, gladly heeded the call. The people who are doing interesting and important work relevant to start. It’s the foundation that we hope to keep building upon to make new team was charged with coordinating the Grand Rounds program our field—and we reviewed those recommendations in an ordered, Grand Rounds indispensable for everyone.” as well as the nominations for the annual Gerald and Stewart awards, systematic way to coordinate a great program,” said Dr. Rekhtman. with Dr. Rekhtman as a lead for the Grand Rounds and Dr. Al-Ahmadie “The goal is to invite people who are great educators or who are doing for the award nominations. groundbreaking research.” Future Grand Rounds Lectures Clinicians in the Pathology Department can derive huge benefit The field of pathology has evolved pretty dramatically over the from regular Grand Rounds presentations. “There are so many past decade, added Dr. Al-Ahmadie, with new methods and tools doctors and scientists who really are working at the cutting edge regularly coming online. Pathology team members wanted more Justin Bishop, MD John Hart, MD of their fields,” Al-Ahmadie said. “When we can learn more about ways to keep up with those innovations. “With so many new advances Director, Anatomic Professor of Pathology, that work—what they’ve done, how they are approaching medicine’s in medicine in general, as well as in pathology and genomic medicine, Pathology Professor of Medicine bigger problems, and how it might apply here at Memorial Sloan the way we understand how to diagnose and characterize disease has Kettering Cancer Center (MSK)—it really is of great benefit.” Beyond changed and will likely continue to change,” he said. “With such a University of Texas University of Chicago Southwestern Medical Center Brooke Howitt, MD 2019 Grand Rounds Lectures Assistant Professor of Jon Aster, MD, PhD Pathology September 24 December 3 Professor, Harvard Stanford University Characterizing and Targeting Epigenetic Three Reasons You Should Care About Breast Medical School Medical Center Dysfunction in Malignant Glioma Myoepithelial Cells Associate Pathologist, Jason T. Huse, MD, PhD Stuart Schnitt, MD Brigham and Women’s Andrew Folpe, MD The University of Texas, MD Anderson Cancer Center Chief of Breast Oncologic Pathology, Dana-Farber Brigham Hospital Director, Bone and Soft Departments of Pathology, Anatomical and Translational and Women's Cancer Center Tissue Pathology Richard Torres, MD, MS Mayo Clinic Hikmat Al-Ahmadie, MD Molecular Pathology Associate Director, Dana-Farber Cancer Institute-Brigham Associate Attending Pathologist and Women's Hospital Breast Oncology Program Assistant Professor of November 5 Professor of Pathology, Harvard Medical School Laboratory Medicine Sook-Bin Woo, MD Artificial Intelligence & Cytopathology and Lecturer in Associate Professor of Oral Liron Pantanowitz, MD January 21 Molecular Biophysics Medicine, Infection and Professor of Pathology and Biomedical Informatics Where are We Going? One Person's View of a and Biochemistry , Immunity University of Pittsburgh Medical Center Future for Molecular Diagnostics in Cancer Director, Flow Cytometry Harvard School of Neal Lindeman, MD Laboratory, Director, Medicine Associate Professor, Harvard Medical School Immunology Laboratory Yale School of Medicine

MSK PATHOLOGY MSK PATHOLOGY 12 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 13 Research Profile

JENNIFER L. SAUTER, MD

behave more aggressively to help clinicians this disease, but outcomes have been better stratify patients .” mixed. PD-L1, for example, is a biomarker used across a variety of tumor types to PINPOINTING MOLECULAR help select immunotherapies. But that MARKERS same pathway may not work as well for Going beyond the classic subtyping pleural mesothelioma. Dr. Sauter and her of mesothelioma and providing more colleagues recently studied V-domain Ig- information, including the nuclear grade of containing suppressor of T-cell activation the tumor, may change the way a patient is (VISTA), a protein that is highly expressed treated. Dr. Sauter added that identifying in mesothelioma tumors and may be a more unique histologic patterns, as pathologists do apt target for this disease. for lung adenocarcinomas, has the potential “We now have anti-VISTA antibodies to better inform clinical decision-making. that can be used to target tumors that What we’re doing “For example, patients with epithelioid express VISTA,” she said. “Alternative now is helping us to mesotheliomas with a lower nuclear grade targets, beyond PD-L1, may be more useful “ have a better prognosis than those with a in treating mesothelioma since the majority understand tumor higher nuclear grade, whereas epithelioid of mesotheliomas do not express PD-L1 and mesotheliomas with a pleomorphic mesotheliomas generally have a low mutation biology in a much component tend to behave more burden. VISTA may be a better target for aggressively,” she said. This information is immunotherapy in pleural mesothelioma. more detailed way, Just over three years ago, Jennifer projects. It felt like coming to MSK would put useful to oncologists in making management Here at MSK we recently started a clinical which will one day Jennifer Sauter, MD Sauter, MD, finished her fellowship work me in a good position to study the pathology decisions for these patients. But there is still trial that utilizes a combined anti-PD-L1 Puts Mesothelioma and embarked on a position in thoracic of mesothelioma in a really comprehensive much to learn. and anti-VISTA regimen for patients with help our clinicians pathology at Memorial Sloan Kettering way—and to advance the field.” “Currently, there are some subtypes of mesothelioma.” Under the Microscope Cancer Center (MSK). As someone driven Mesothelioma affects approximately mesotheliomas where the data are unclear, Dr. Sauter discusses her ongoing work develop or utilize new by delving deeper into histologic factors 3,000 people, mostly men, each year and particularly with rare features that we do with a mixture of hope and enthusiasm. At targeted therapies By Kayt Sukel involved with pleural mesothelioma, an is an aggressive disease with very poor not often encounter, so it will be important the end of the day, she’s genuinely excited to aggressive tumor that effects the lung’s overall survival. Dr. Sauter is committed to accrue more data to determine what be at her microscope learning about thoracic for these hard-to- pleura, she knew MSK had unparalleled to discovering microscopic clues that can they may mean for the patient. The hope tumors and trying to find ways to improve resources to help her in that mission. improve clinical management for patients is that by including more histologic data in cancer care for our patients. treat patients.” “There are so many phenomenal with mesothelioma. our reporting we can help clinicians better “It’s thrilling to be able to actively resources at MSK that it seemed like a natural “Traditionally, mesothelioma is diagnosed manage patients.” participate in collaborative work with our fit for me,” she said. “MSK Pathology houses by histologic subtype. We identify the tumor as colleagues throughout the institution that a large number of archival cases we can either epithelioid or sarcomatoid, or biphasic, BETTER BIOMARKERS can be translated into improving cancer care study and learn from. We have tremendous tumors that contain both epithelioid and Dr. Sauter’s research is also directed for our patients,” she said. “The work we are assets like next-generation sequencing sarcomatoid components,” she explained. “But toward identifying more effective biomarkers doing will help us better understand tumor (NGS) technologies so we can obtain robust we are finding we can become more granular that can be used for targeted immunotherapy biology in a more detailed way and can help molecular data and active clinicians who in our histologic reporting to identify tumors in mesothelioma. Oncologists are beginning our clinicians develop or utilize new targeted want to collaborate on innovative research within the epithelioid subtype that will likely to utilize immunotherapy to combat therapies for these hard-to-treat tumors.”

MSK PATHOLOGY MSK PATHOLOGY 14 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 15 Service Spotlight

We are trying to increase offer researchers new molecular pathways to explore, and “ these may lead to future novel treatment.” awareness, among both doctors There are many other research questions that can be and patients, about the importance investigated with autopsy-harvested samples, from why AUTOPSY of autopsy and what it offers to some patients never respond at all to treatment to how tumors metastasize in the body. Dr. Murali added that potential research studies.” autopsy samples offer researchers the ability to directly PROGRAM compare different tissues or tumors in a single patient as the harvested samples provide them a lot more material to “Many patients may have received different work with than what can be obtained through biopsies or 12,000 types of treatments over several years,” said Dr. Giri. other clinical means. “They may have developed complications from such “Autopsy samples allow researchers to be much more treatments. There are a lot of complicating factors comprehensive and clinically effective in their studies,” he that may have contributed to a patient’s death. An explained. “We can take multiple pieces of tissue from the Over the past autopsy can help pinpoint some of those factors tumor, from other tumors that may be also present in the five years, by closely examining the different tissues. The body, and then from other organs or tissues as well. Studying the Last Wish autopsy findings can better inform future clinical these samples can help us understand how cancer develops, Program has management of patients. Physicians appreciate progresses and spreads. We can even look at how each of conducted over having that information, especially as they make those individual sites respond to different treatments. It 150 autopsies, decisions about how best to treat the patients.” really expands what kinds of questions researchers can ask which have Dr. Murali agreed. “Autopsies can also inform us about and what they are able to do in their studies.” yielded around what a particular drug may be doing besides targeting the 12,000 tissue tumor. For example we may see, during autopsy, that a drug MAKING A LAST WISH samples. These given to treat a patient’s cancer had an unusual effect on the Under the leadership of Christine Iacobuzio-Donahue, samples have liver. Then, we connect that liver injury back to the drug. MD, PhD, MSK launched an initiative in 2015 aimed at gently contributed to That is important information which can help clinicians encouraging more patients, and their families, to donate research that their bodies for autopsy. Over the past five years, the Last make optimal treatment decisions for their patients. has received Wish Program has conducted over 150 autopsies, which have over $19 million yielded around 12,000 tissue samples. Those samples are NEW AVENUES FOR RESEARCH in grant funding. Autopsies don’t just offer clues to the cause of death—they carefully stored in a tissue bank, a tremendous resource that also provide tissue samples critical to innovative research scientists can tap for a variety of research purposes. projects. Clinical biopsies only provide small amounts “It is a tremendous resource,” said Dr. Murali. “We Rajmohan Murali, MBBS, MD, FRCPA Dilip Giri, MD, FACP Associate Attending Pathologist Attending Pathologist of tissue, which limits the types of tests or experiments are trying to increase awareness, among both doctors and Director, Last Wish Program Director, Clinical Autopsy Program researchers can perform. For example, Dr. Giri said one big patients, about the importance of autopsy and what it offers Co-Director, Clinical Autopsy Program Co-Director, Last Wish Program question for cancer researchers is why treatment response to potential research studies.” for a certain drug or intervention may change over time in a That said, broaching the subject of autopsy with Modern medical knowledge is built upon us determine how to better manage cancer care in single patient. patients can be a challenge, said Dr. Murali. But he feels Clinical discoveries revealed by autopsy, the external and the future. Many of those insights would simply “Very often, for patients, the initial treatment response that awareness of programs like Last Wish is important internal examination of a cadaver to determine the not be available to us without performing this kind is great. They go into remission and have a good life for because it has the potential to bring about new discoveries Insight: the cause and manner of death. In fact, before the advent of examination.” several years,” he said. “But then the cancer comes back and regarding how cancer should be both diagnosed and treated. Ultimate Gift of innovative imaging technologies, autopsy was the treatments no longer work on that recurring disease. “It is an extraordinary program that offers so much the only way clinicians could unravel the mysteries NOVEL CLINICAL INSIGHTS Why is that?” potential for discovery,” he said. The Autopsy Program of the of human anatomy or track the physiological Dilip Giri, MD, FACP, who directs the Clinical The question can be better answered when researchers “Our patients are agreeing to give us the ultimate gift Department of Pathology consequences of different disease states. Autopsy Program, said the program provides both can access tissue from both biopsies and autopsies. The of their bodies at one of the most difficult times in their provides clinicians and Rajmohan Murali, MBBS, MD, FRCPA, Director of clinical and research autopsies to support different tissue samples harvested from autopsies provide more of the lives, to help further cancer research. These donations have researchers with unique, the Last Wish Program and Co-Director of the Clinical needs and programs at MSK. For example, clinicians vital material scientists require to follow the progression of already revealed new insights into the biology of tumors. invaluable insights into the Autopsy Program at Memorial Sloan Kettering Cancer may request an autopsy after a patient passes away disease, as well as to use innovative investigative methods We are immensely grateful for the generosity and altruism nature of cancers. Center (MSK), emphasizes the great value to science of to understand the exact cause and circumstances like genetic and molecular approaches to understand what of the patients who consent to donate their bodies. It really performing these posthumous procedures. Autopsies of death. pathways a certain treatment acted upon—and where that is fundamental to enabling us to carry out groundbreaking aren’t only of use to reveal the cause of a suspicious “The doctor may not know what exactly led to treatment may have failed. research that will help other patients in the future.” By Kayt Sukel death. The development of innovative genetic and a patient’s demise,” he said. “Often, we are able to “It offers us a whole new way of exploring the treatment molecular tools make autopsy a remarkable tool to provide that answer by doing a complete autopsy. of cancer,” said Dr. Giri. “That autopsy tissue may potentially help clinicians and scientists better understand how We then present those cases in a multidisciplinary different cancers and their treatments affect the conference so the requesting physician, as well as human body. other clinicians, can better understand if the death “Over the last 150 years, we’ve seen the number resulted from clinical progression of cancer or from of autopsies decline significantly for a variety of some other unsuspected or undetected factor.” For more information on how to donate to the Last Wish Program please call reasons,” said Dr. Murali. “But autopsy, especially Such information is of huge help to clinicians and in cancer patients with disease-and treatment- can bring up new issues that they should consider in 646-888-3253 or email us at [email protected] related changes, can provide insights that can help order to better manage the care of similar patients.

MSK PATHOLOGY MSK PATHOLOGY 16 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 17 Faculty Publications

Abou-Alfa GK, Mayer R, Venook Argani P, Reuter VE, Eble Bhatia A, Hatzoglou V, Ulaner Cercek A, Dos Santos Fernandes Da Cruz Paula A, da Silva EM, Fagan-Solis KD, Simpson DA, Gao J, Chen YH, Mina A, Grabenstetter A, Brennan S, AP, O'Neill AF, Beg MS, LaQuaglia JN, Vlatkovic L, Yaskiv O, G, Rampal R, Hyman DM, G, Roxburgh CS, Ganesh K, Ng S, Segura SE, Pareja F, Bi R, Selenica Kumar RJ, Martelotto LG, Mose Altman JK, Kim KY, Zhang Y, Salagean ED, Morrow M, Brogi E. M, Kingham PT, Kobos R, Basturk Swanson D, Dickson BC, Abdel-Wahab O, Durham BH, Sanchez-Vega F, Yaeger R, Segal P, Kim SH, Ferrando L, Vahdatinia LE, Rashid NU, Ho AY, Powell Lu X, Jennings L, Sukhanova M. Flat Epithelial Atypia in Breast Core O, Brennan C, Yopp A, Harding JJ, Antonescu CR, Matoso A, Dogan A, Ozkaya N, Yabe M, NH, Reidy-Lagunes DL, Varghese M, Soslow RA, Vidal A, Gatius S, SN, Wen YH, Parker JS, Reis- Unique morphologic and genetic Needle Biopsies With Radiologic- Leong S, Crown J, Hoti E, Leonard Gagan J, Palsgrove DN. Biphasic Petrova-Drus K, Panageas AM, Markowitz A, Wu C, Szeglin Przybycin CG, Abu-Rustum NR, Filho JS, Petrini JHJ, Gupta characteristics of acute myeloid Pathologic Concordance: Is G, Ly M, Bradley M, Valentino E, Hyalinizing Psammomatous KS, Reiner A, Rosenblum M, B, Sauvé CG, Salo-Mullen E, Tran Matias-Guiu X, Rubin BP, Reis- GP. A P53-Independent DNA leukemia with chromothripsis: a Excision Necessary?. Am J Surg Markowitz D, Zukiwski A, Ren K, Renal Cell Carcinoma (BHP RCC): Diamond EL. Neurologic and C, Patel Z, Krishnan A, Tkachuk Filho JS, DeLair DF, Weigelt B. Damage Response Suppresses clinicopathologic study from a Pathol. 2020;44(2):182-190. Gordan JD. Phase II Multicenter, A Distinctive oncologic features of Erdheim- K, Nash GM, Guillem J, Paty Genomic profiling of primary Oncogenic Proliferation and single institution [E-pub ahead of Gris-Oliver A, Palafox M, Open-Label Study of Oral Associated With Somatic NF2 Chester disease: a 30-patient PB, Shia J, Schultz N, Garcia- and recurrent adult granulosa Genome Instability. Cell Rep. print, 2020 Feb 21]. Hum Pathol. Monserrat L, Brasó-Maristany ENMD-2076 for the Treatment Mutations [E-pub ahead of print, series [E-pub ahead of print, Aguilar J, Diaz LA, Goodman K, cell tumors of the ovary [E-pub 2020;30(5):1385-1399.e7. 2020;98:22-31. F, Òdena A, Sánchez-Guixé M, of Patients with Advanced 2020 Mar 25]. Am J Surg Pathol. 2020 Jan 17]. Neuro Oncol. Saltz LB, Weiser MR, Smith JJ, ahead of print, 2020 Mar 12]. Mod Farris AB, Moghe I, Wu S, Hogan Goebel EA, Hernandez Bonilla Ibrahim YH, Villacampa G, Grueso Fibrolamellar Carcinoma [E-pub 2020;10.1097/PAS. 2020;noaa008. Stadler ZK. Mismatch Repair- Pathol. 2020;10.1038/s41379- J, Cornell LD, Alexander MP, Kers S, Dong F, Dickson BC, Hoang J, Parés M, Guzman M, Rodriguez ahead of print, 2020 Mar 10]. 0000000000001467 Deficient Rectal Cancer and 020-0514-3. Bolton KL, , Ptashkin J, Demetris AJ, Levenson RM, LN, Hardisson D, Lacambra MD, O, Bruna A, Hirst CS, Barnicle A, Oncologist. 2020;10.1634/ Zehir A Resistance to Neoadjuvant , Taylor J, Garcia JS, RN, Patel M, Gupta D, Sidlow de la Fuente MI, Rosenblum MK, Tomaszewski J, Barisoni L, , Lu FI, Fletcher CDM, Crum CP, de Bruin EC, Reddy A, Schiavon theoncologist.2020-0093. Aypar U Chemotherapy [E-pu ahead of Yagi Y Diamond EL, Tabar VS, Omuro A. Momeni-Boroujeni A, Gao Q, R, Papaemmanuil E, Berger print, 2020 Mar 6]. Clin Cancer Solez K. Banff Digital Pathology Antonescu CR, Nucci MR, Kolin G, Arribas J, Mills GB, Caldas C, Erdheim-Chester disease among Al-Ahmadie HA, Netto GJ. Baik J, Londono D, Benayed R, MF, Levine RL. The Clinical Res. 2020;10.1158/1078-0432. Working Group: Going digital DL. Uterine Tumor Resembling Dienstman R, Prat A, Nuciforo neuroinflammatory syndromes: Updates on the Genomics of Sigler A, Haddadin M, Penson AV, Management of Clonal CCR-19-3728. in transplant pathology [E-pub Ovarian Sex Cord Tumor P, Razavi P, Scaltriti M, Turner Bladder Cancer and Novel Arcila ME, Mullaney K, Sukhadia Hematopoiesis: Creation of a the case for precision medicine ahead of print, 2020 Mar 17]. (UTROSCT): A Morphologic and NC, Saura C, Davies BR, Oliveira Molecular Taxonomy. Adv Anat P, Quesada AE, Roshal M, Cullen Clonal Hematopoiesis Clinic Chernichenko N, Omelchenko T, [E-pub ahead of print, 2020 Am J Transplant. 2020;10.1111/ Molecular Study of 26 Cases M, Serra V. Genetic alterations Pathol. 2020;27(1):36-43. N, Lako A, Rodig SJ, Goldberg [E-pub ahead of print, 2020 Jan Deborde S, Bakst RL, He S, Chen Mar 2]. Neurol Neuroimmunol ajt.15850. Confirms Recurrent NCOA1- in the PI3K/AKT pathway and AD, Zhang Y, Xiao W, Ho C. 18]. Hematol Oncol Clin North CH, Gusain L, Vakiani E, Katabi N, Neuroinflamm. 2020;7(3):e686. 3 Rearrangement. Am J Surg baseline AKT activity define Almassi N, Pietzak EJ, Sarungbam P2RY8-CRLF2Fusion-Positive Am. 2020;34(2):357-367. Hall A, Wong RJ. Cdc42 Mediates Galateau Salle F, Le Stang N, Pathol. 2020;44(1):30-42. AKT inhibitor sensitivity in Entenberg D, Oktay MH, D'Alfonso J, Tickoo SK, Reuter VE, Solit Acute Myeloid Leukemia With Cancer Cell Chemotaxis in Tirode F, Courtiol P, Nicholson breast cancer patient-derived Carlsson S, Benfante N, Alvim T, Ginter PS, Robinson BD, Xue Gonzalez RS, Mukhopadhyay S, DB, Al-Ahmadie HA. Inverted Myelodysplasia-Related Changes: Perineural Invasion [E-pub ahead AG, Tsao MS, Tazelaar HD, Churg xenografts [E-pub ahead of print, R, Sjoberg DD, Vickers A, X, Rohan TE, Sparano JA, Jones , Jiang XS. Conducting urothelial papilloma and urothelial Response to Novel Therapy. JCO of print, 2020 Feb 21]. Mol Cancer A, Dacic S, Roggli V, Pissaloux Fine SW 2020 Mar 27]. Clin Cancer Res. , , Vargas HA, JG, Condeelis JS. Validation of an a Pathology Research Study, carcinoma with inverted growth Precis Oncol. 2020;4:152-160 Reuter VE Fine SW Res. 2020;10.1158/1541-7786. D, Maussion C, Moarii M, Beasley 2020;clincanres.3324.2019. Automated Quantitative Digital are histologically and molecularly Wiseman M, Mamoor M, Ehdaie B, MCR-19-0726. MB, Begueret H, Chapel DB, From Start to Finish: A Guide for distinct entities [E-pub ahead of Bale TA. FGFR- gene family Laudone V, Scardino P, Eastham Pathology Approach for Scoring Copin MC, Gibbs AR, Klebe Residents and Fellows [E-pub Gupta S, Fine SW, Chang print, 2020 Feb 28]. J Pathol. alterations in low-grade J, Touijer K. Risk of Metastasis Comen EA, Bowman RL, Selenica TMEM, a Prognostic Biomarker S, Lantuejoul S, Nabeshima ahead of print, 2020 Jan 20]. Arch J, Tickoo SK, Chen YB, Al- 2020;250(4):464-465. neuroepithelial tumors. Acta in Men with Grade Group 2 P, Kleppe M, Farnoud NR, Pareja for Metastasis. Cancers (Basel). K, Vignaud JM, Attanoos R, Pathol Lab Med. 2020;10.5858/ Ahmadie HA, Sirintrapun SJ, Neuropathol Commun. 2020; Prostate Cancer Managed with F, Weigelt B, Hill CE, Alon 2020;12(4):846. Published 2020 Brcic L, Capron F, Chirieac LR, arpa.2019-0490-RA. Abida W, Ladanyi M, Reuter Alpert L, Al-Sabti R, Graham RP, 8(1):21. Published 2020 Feb 21. Active Surveillance at a Tertiary A, Geyer FC, Akturk G, Reis- Mar 31. Damiola F, Sequeiros R, Cazes A, VE, Gopalan A. Morphologic Pai RK, Gonzalez RS, Zhang X, Goyal A, , Pirog Cancer Center [E-pub ahead Filho JS, Norton L, Levine RL. Damotte D, Foulet A, Giusiano- Ellenson LH and Immunohistochemical Smith V, Wang HL, Westbrook L, , , Etay Z, Buonocore D, Prasad EC. p16 Positive Histologically Bale TA Benhamida J of print, 2020 Jan 7]. J Urol. Evaluating Clonal Hematopoiesis Courcambeck S, Hiroshima K, Assessment of CDH1 Loss of Goldblum JR, Bakhshwin A, Shetty Roychoudury S, Villafania L, A. Histology subtyping from Bland Squamous Metaplasia 2020;203(6):1117-1121. in Tumor-Infiltrating Leukocytes Hofman V, Husain AN, Kerr K, Function Alterations in Prostatic S, , , Askan G, Wrzolek MA, Bouffard JP, Bapat core needle biopsy [E-pub of the Cervix: What does It Klimstra DS Shia J in Breast Cancer and Secondary Marchevsky A, Paindavoine Adenocarcinoma. Am J Surg Robert ME, Thomas C, Frankel K, , . Caso R, Jones GD, Bains MS, Hsu ahead of print, 2020 Jan 29]. Signify?. Am J Surg Pathol. Ladanyi M Rosenblum MK Hematologic Malignancies. J Natl S, Picquenot JM, Rouquette I, Pathol. 2020;44(3):420-422. WL, Alsomali M, Hagen C, Mostafa Infarction with associated M, Tan KS, Feldman DR, Funt Ann Thorac Surg. 2020;S0003- 2020;44(1):129-139. Cancer Inst. 2020;112(1):107-110. Sagan C, Sauter JL, Thivolet F, ME, Feely MM, Assarzadegan N, pseudosarcomatous changes SA, Reuter VE, Bosl GJ, McHugh 4975(20)30088-6. Gupta S, Vanderbilt C, Abida W, Brevet M, Rouvier P, Travis WD, Goyal G, Heaney ML, Collin Misdraji J, Shih AR, Agostini-Vulaj mimics anaplasia in otherwise D, Huang J, Molena D, Amar D, Cordeiro PG, Ghione P, Ni A, Hu Fine SW, Tickoo SK, Al-Ahmadie Eveillard M, Rustad E, Roshal Planchard G, Weynand B, Clozel M, Cohen Aubart F, Vaglio A, D, Meis JM, Tang S, Chatterjee D, grade I meningiomas [E-pub Fischer G, Rusch VW, Jones DR. Q, Ganesan N, Galasso N, Dogan HA, Chen YB, Sirintrapun SJ, M, Zhang Y, Ciardiello A, Korde T, Wainrib G, Fernandez-Cuesta , Hershkovitz-Rokah Kang LI, Hart J, Lee SM, Smith T, ahead of print, 2020 Feb 11]. Outcomes After Multidisciplinary A, Horwitz SM. Risk of breast Durham BH Chadalavada K, Nanjangud GJ, N, Hultcrantz M, Lu S, Shah U, L, Pairon JC, Rusch V, Girard O, Girschikofsky M, Jacobsen Yantiss RK, Hissong EM, Gao ZH, Mod Pathol. 2020;10.1038/ Management of Primary implant associated anaplastic Bialik A, Morris MJ, Scher HI, Hassoun H, Smith E, Lesokhin N. Comprehensive Molecular ED, Toyama K, Goodman AM, Wu J, Resnick MB, Wu EY, Pai s41379-020-0491-6. Mediastinal Germ Cell Tumors large cell lymphoma (BIA-ALCL) Ladanyi M, Reuter VE, Gopalan A, Mailankody S, Landgren O, and Pathologic Evaluation Hendrie P, Cao XX, Estrada- RK, Zhao L, Doyle LA, Chopra [E-pub ahead of print, 2020 in a cohort of 3546 women A. Immunohistochemistry-based Beca F, Sebastiao APM, , Thoren K. Comparison of MALDI- of Transitional Mesothelioma Veras J, Shpilberg O, Abdo A, S, Panarelli NC, Hu S, Longacre Pareja F Jan 21]. Ann Surg. 2020;10.1097/ prospectively followed long assessment of androgen receptor Dessources K, Lozada JR, Geyer TOF mass spectrometry analysis Assisted by Deep Learning Kurokawa M, Dagna L, McClain TA, Raghavan SS, Lauwers SLA.0000000000003754. term after reconstruction with status and the AR-null phenotype F, Selenica P, Zeizafoun N, Wen of peripheral blood and bone Approach: A Multi-Institutional KL, Mazor RD, Picarsic J, Janku GY, Ghayouri M, Cooper HS, textured breast implants [E-pub in metastatic castrate resistant HY, Norton L, , marrow-based flow cytometry Study of the International F, Go RS, Haroche J, Diamond Nagarathinam R, Bellizzi AM, Kakar Brogi E Weigelt ahead of print, 2020 Jan 20]. prostate cancer [E-pub ahead , . Whole-Exome for tracking measurable residual Mesothelioma Panel from the E. Erdheim-Chester disease: S, Hosseini M, Rong J, Greenson B Reis-Filho JS J Plast Reconstr Aesthet Surg. of print, 2020 Feb 24]. Prostate Analysis of Metaplastic Breast disease in patients with multiple MESOPATH Reference Center Consensus recommendations JK, Lamps LW, Dong Z, Bronner 2020;S1748-6815(20)30001-2. Cancer Prostatic Dis. 2020;10.1038/ Carcinomas with Extensive myeloma [E-pub ahead of print, [E-pub ahead of print, 2020 Mar for the evaluation, diagnosis, MP. Smooth muscle tumors of s41391-020-0214-6. Osseous Differentiation [E-pub 2020 Feb 5]. Br J Haematol. 9]. J Thorac Oncol. 2020;S1556- and treatment in the the gastrointestinal tract: an ahead of print, 2020 Feb 11]. 0864(20)30174-X. molecular era [E-pub ahead , Horvai AE, Jordan analysis of prognostic features 2020;10.1111/bjh.16443. Hameed M Histopathology. of print, 2020 Mar 18]. Blood. RCK. Soft Tissue Special Issue: in 407 cases [E-pub ahead of 2020;blood.2019003507. Gnathic Fibro-Osseous Lesions print, 2020 Feb 12]. Mod Pathol. and [E-pub ahead 2020;10.1038/s41379-020-0492-5. of print, 2020 Jan 16]. Head Neck Pathol. 2020;14(1):70-82.

MSK PATHOLOGY MSK PATHOLOGY 18 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 19 Hellmann MD, Nabet BY, Rizvi H, Kao YC, Lee JC, Zhang L, Sung Kossatz S, Pirovano G, Demétrio Li GZ, Okada T, Kim YM, Agaram Maloney N, Smith SM, Peters McHugh DJ, Funt SA, Silber D, Mondello P, Tadros S, Teater M, Pareja F, Brown DN, Lee JY, Da Chaudhuri AA, Wells DK, Dunphy YS, Swanson D, Hsieh TH, Liu De Souza França P, Strome AL, NP, Sanchez-Vega F, Shen Y, SB, Batistatou A, Evangelou Z, Knezevic A, Patil S, O'Donnell Fontan L, Chang AY, Jain N, Yang Cruz Paula A, Selenica P, Bi R, MPS, Chabon JJ, Liu CL, Hui AB, YR, Agaram NP, Huang HY, Sunny SP, Zanoni DK, Mauguen Tsubokawa N, Rios J, Martin AS, Harms PW, Chan MP, Antonescu D, Tsai S, Reuter VE, Sheinfeld H, Singh S, Ying HY, Chu CS, Ma Geyer FC, Gazzo A, da Silva Arbour KC, Luo J, Preeshagul IR, Dickson BC, Antonescu CR. A, Carney B, Brand C, Shah V, Dickson MA, Qin LX, Socci ND, CR, Linos K. Expanding the J, Carver BS, Motzer RJ, Bajorin MCJ, Toska E, Alig S, Durant M, EM, Vahdatinia M, Stylianou AA, Moding EJ, Almanza D, Bonilla Recurrent YAP1 and KMT2A Ramanajinappa RD, Hedne N, Singer S. Rb and p53-Deficient differential of superficial tumors DF, Bosl GJ, Feldman DR. de Stanchina E, Ghosh S, Mottok Ferrando L, Wen HY, Hicks J, RF, Sauter JL, Choi H, Tenet M, Gene Rearrangements in a Subset Birur P, Sihag S, Ghossein RA, Myxofibrosarcoma and with round-cell morphology: Adjuvant Chemotherapy With A, Nastoupil L, Neelapu SS, Weigelt B, Reis-Filho JS. Whole- Abu-Akeel M, Plodkowski AJ, of MUC4-negative Sclerosing Gönen M, Strome M, Suresh A, Undifferentiated Pleomorphic Report of three cases of Etoposide Plus Cisplatin for Weigert O, Inghirami G, Baselga Exome Sequencing Analysis of Perez Johnston R, Yoo CH, Ko Epithelioid . Am J Molena D, Ganly I, Kuriakose MA, Require Skp2 for CIC-rearranged sarcoma, a Patients With Pathologic Stage J, Younes A, Yee C, Dogan A, the Progression from Non-Low RB, Stehr H, Gojenola L, Wakelee Surg Pathol. 2020;44(3):368-377. Patel SG, Reiner T. Validation of Survival [E-pub ahead of print, potentially under-recognized II Nonseminomatous Germ Cell Scheinberg DA, Roeder RG, Grade Ductal Carcinoma In Situ HA, Padda SK, Neal JW, Chaft JE, the use of a fluorescent PARP1 2020 Mar 11]. Cancer Res. entity [E-pub ahead of print, Tumors [E-pub ahead of print, Melnick AM, Green MR. Selective to Invasive Ductal Carcinoma Kao YC, Sung YS, Argani P, Kris MG, Rudin CM, Merghoub inhibitor for the detection of oral, 2020;10.1158/0008-5472.CAN- 2020 Jan 10]. J Cutan Pathol. 2020 Feb 28]. J Clin Oncol. Inhibition of HDAC3 Targets [E-pub ahead of print, 2020 Swanson D, Alaggio R, Tap W, T, Li BT, Alizadeh AA, Diehn M. oropharyngeal and oesophageal 19-1269. 2020;47(6):535-540. 2020;38(12):1332-1337. Synthetic Vulnerabilities and Mar 27]. Clin Cancer Res. Wexler L, Dickson BC, Circulating Tumor DNA Analysis Antonescu epithelial cancers [E-pub ahead Activates Immune Surveillance 2020;clincanres.2563.2019. . NTRK3 overexpression in Lin AL, Rosenblum M, Mellinghoff Malouf GG, Flippot R, Dong Y, Meeks JJ, Al-Ahmadie HA, to Assess Risk of Progression CR of print, 2020 Mar 12]. Nat Biomed in Lymphoma [E-pub ahead of undifferentiated with IK, Tabar VS, Ogilvie S, Schaff L, Dinatale RG, Chen YB, Su X, Faltas BM, Taylor JA 3rd, Flaig , da Silva EM, Frosina after Long-term Response to PD- Eng. 2020;4(3):272-285. print, 2020 Jan 8]. Cancer Discov. Pareja F YWHAE and BCOR genetic Yang TJ, Young RJ, Taylor BS, Compérat E, Rouprêt M, Mano TW, DeGraff DJ, Christensen D, Geyer FC, Lozada JR, Basili (L)1 Blockade in NSCLC [E-pub 2020;10(3):440-459. alterations [E-pub ahead of Laughney AM, Hu J, Campbell NR, Jonsson P, Bale TA. Prognostic R, Blum KA, Yao H, Mouawad E, Woolbright BL, McConkey T, Da Cruz Paula A, Zhong E, ahead of print, 2020 Feb 11]. Clin print, 2020 Feb 7]. Mod Pathol. Bakhoum SF, Setty M, Lavallée and radiographic correlates R, Spano JP, Khayat D, Karam DJ, Dyrskjøt L. Genomic Mueller JJ, Dauer LT, , Derakhshan F, , Wen Cancer Res. 2020;10.1158/1078- Murali R D'Alfonso T 2020;10.1038/s41379-020- VP, Xie Y, Masilionis I, Carr AJ, of a prospectively collected JA, Ho TH, Tickoo SK, Russo heterogeneity in bladder Iasonos A, Pandit-Taskar N, Abu- HY, Giri DD, Hayes MM, Krings G, 0432.CCR-19-3418. 0495-2. Kottapalli S, Allaj V, Mattar M, molecularly profiled cohort of P, Hsieh JJ, Tannir NM, Hakimi cancer: challenges and possible Rustum N, Grimm J. Positron Bhargava R, Palazzo JP, Rakha Hodgson A, Vesprini D, Liu SK, Rekhtman N, Xavier JB, Mazutis IDH1/2-wildtype astrocytomas AA. Molecular characterization solutions to improve outcomes lymphography via intracervical EA, Hoda SA, Sanders ME, Collins Kelly CM, Antonescu CR, Bowler Xu B, Downes MR. Correlation L, Poirier JT, Rudin CM, Pe'er [E-pub ahead of print, 2020 Feb of sarcomatoid clear cell renal [E-pub ahead of print, 18F-FDG injection for pre- LC, Schnitt SJ, Chen YY, Weigelt T, Munhoz R, Chi P, Dickson of mismatch repair protein D, Massagué J. Regenerative 12]. Brain Pathol. 2020;30(3):653- cell carcinoma unveils new 2020 Mar 31]. Nat Rev Urol. surgical lymphatic mapping B, Jungbluth AA, Reis-Filho JS, MA, Gounder MM, Keohan ML, deficiency, PD-L1 and CD8 lineages and immune-mediated 660. candidate oncogenic drivers. 2020;17(5):259-270. in cervical and endometrial Brogi E. Immunohistochemical Movva S, Dholakia R, Ahmad H, expression in high-grade pruning in lung cancer metastasis Sci Rep. 2020;10(1):701. malignancies [E-pub ahead of analysis of IDH2 R172 hotspot Biniakewitz M, Condy M, Phelan Linxweiler M, Kuo F, Katabi N, Lee urothelial carcinoma of the [E-pub ahead of print, 2020 Feb Merino DM, McShane LM, print, 2020 Jan 10]. J Nucl Med. mutations in breast papillary H, Callahan M, Wong P, Singer M, Nadeem Z, Dalin MG, Makarov Mao N, Gao D, Hu W, Gadal S, bladder [E-pub ahead of print, 10]. Nat Med. 2020;26(2):259-269. Fabrizio D, Funari V, Chen SJ, 2020;jnumed.119.230714. : applications in the S, Ariyan C, Bartlett EK, Crago V, Chowell D, Dogan S, Ganly I, Hieronymus H, Wang S, Lee 2020 Jan 9]. J Clin Pathol. White JR, Wenz P, Baden J, diagnosis of tall cell carcinoma A, Yoon S, Hwang S, Erinjeri León-Castillo A, Gilvazquez E, Hakimi AA, Wong RJ, Riaz N, YS, Sullivan P, Zhang Z, Choi D, Navarrete-Dechent C, Aleissa S, 2020;jclinpath-2019-206256. Barrett JC, Chaudhary R, Chen L, with reverse polarity [E-pub Nout R, Smit VT, McAlpine JN, Ho AL, Chan TA, Morris LGT. Rosen N, Sawyers CL, Gopalan JP, Qin LX, Tap WD, D'Angelo Chen WS, Cheng JH, Cyanam D, Cordova M, Liopyris K, Lee EH, ahead of print, 2020 Jan 2]. Mod McConechy M, Kommoss S, The Immune Microenvironment A, Chen Y, Carver BS. Oncogenic Hong DS, DuBois SG, Kummar SP. Objective Response Rate Dickey JS, Gupta V, Hellmann M, Rossi AM, Hollman T, Pulitzer Pathol. 2020;10.1038/s41379- Brucker SY, Carlson JW, Epstein and Neoantigen Landscape ERG Represses PI3K Signaling S, Farago AF, Albert CM, Among Patients With Locally Helman E, Li Y, Maas J, Papin A, M, Lezcano C, Busam KJ, 019-0442-2. Rohrberg KS, van Tilburg CM, Advanced or Metastatic Sarcoma E, Rau TT, Soslow RA, Ganesan R, of Aggressive Salivary Gland through Downregulation of Patidar R, Quinn KJ, Rizvi N, Tae Marghoob AA, Chen CJ, Nehal Nagasubramanian R, Berlin JD, Treated With Talimogene Matias-Guiu X, Oliva E, Harrison Carcinomas Differ by Subtype IRS2 [E-pub ahead of print, H, Ward C, Xie M, Zehir A, Zhao C, KS. Incompletely excised Park KJ. Cervical adenocarcinoma: Federman N, Mascarenhas L, Laherparepvec in Combination BT, Church DN, Gilks CB, Bosse [E-pub ahead of print, 2020 2020 Feb 3]. Cancer Res. Dietel M, Stenzinger A, Stewart maligna is associated integration of HPV status, Geoerger B, Dowlati A, Pappo With Pembrolizumab: A Phase T. Clinicopathological and Feb 14]. Clin Cancer Res. 2020;80(7):1428-1437. M, Allen J; TMB Harmonization with unpredictable residual pattern of invasion, morphology AS, Bielack S, Doz F, McDermott 2 Clinical Trial [E-pub ahead molecular characterisation of 2020;10.1158/1078-0432.CCR- Consortium. Establishing disease: clinical features and and molecular markers into Maynard H, Stadler ZK, Berger R, Patel JD, Schilder RJ, Tahara of print, 2020 Jan 23]. JAMA 'multiple-classifier' endometrial 19-3758. guidelines to harmonize tumor the emerging role of reflectance classification. Histopathology. MF, Solit DB, Ly M, Lowery MA, M, Pfister SM, Witt O, Ladanyi M, Oncol. 2020;6(3):402-408. carcinomas [E-pub ahead of mutational burden (TMB): in confocal microscopy [E-pub 2020;76(1):112-127. Luzar B, Ieremia E, Antonescu Mandelker D, Zhang L, Jordan Rudzinski ER, Nanda S, Childs BH, print, 2020 Jan 12]. J Pathol. silico assessment of variation ahead of print, 2020 Feb 7]. J Kim SH, Da Cruz Paula A, Basili T, CR, Zhang L, Calonje E. E, El Dika I, Kemel Y, Ladanyi M, Piris A, Sanchez DF, Fernandez- Laetsch TW, Hyman DM, Drilon A. 2020;250(3):312-322. in TMB quantification across Eur Acad Dermatol Venereol. Dopeso H, Bi R, , da Silva Cutaneous intravascular Robson ME, O'Reilly EM, Abou- Nestosa MJ, Cañete-Portillo S, Larotrectinib in patients with TRK Pareja F diagnostic platforms: phase 2020;10.1111/jdv.16272. EM, Gularte-Mérida R, Sun Z, Li BT, Michelini F, Misale S, Cocco epithelioid hemangioma. Alfa GK. Germline alterations Campagnoli T, Gonzalez Stark fusion-positive solid tumours: a I of the Friends of Cancer Fujisawa S, Smith CG, Ferrando E, Baldino L, Cai Y, Shifman S, A clinicopathological and in patients with biliary tract Navarrete-Dechent C, L, Zarza P, Oneto S, pooled analysis of three phase Research TMB Harmonization Busam Lezcano L, Martins Sebastião AP, Bykov Tu HY, Myers ML, Xu C, Mattar molecular study of 21 cases cancers: A spectrum of , Markova A. Facial Erythema , Rodriguez I, Velazquez 1/2 clinical trials [E-pub ahead Project. J Immunother Cancer. KJ C Y, Li A, Silveira C, Ashley CW, M, Khodos I, Little M, Qeriqi B, [E-pub ahead of print, 2020 Feb significant and previously in an Elderly Man [E-pub EF, Mihm M, Cubilla AL. of print, 2020 Feb 24]. Lancet 2020;8(1):e000147. Stylianou A, Selenica P, Samore Weitsman G, Wilhem CJ, Lalani 24]. Mod Pathol. 2020;10.1038/ underappreciated findings. ahead of print, 2020 Mar 25]. Topographical Evaluation of Oncol. 2020;21(4):531-540. WR, Jungbluth AA, Zamarin AS, Diala I, Freedman RA, Lin NU, s41379-020-0505-4. Cancer. 2020;126(9):1995- Momeni-Boroujeni A, Chiang S. JAMA Dermatol. 2020;10.1001/ Penile Lichen Sclerosus Reveals Hoon Tan P, Ellis I, Allison K, D, Abu-Rustum NR, Helin K, Solit DB, Berger MF, Barber PR, 2002. Uterine mesenchymal tumours: jamadermatol.2020.0123. a Lymphocytic Depleted Variant, Maleki Z, Muller S, Layfield Brogi E, Fox SB, Lakhani S, Soslow RA, Reis-Filho JS, Oliva Ng T, Offin M, Isbell JM, Jones DR, recent advances. Histopathology. Preferentially Associated With L, Siddiqui MT, Rekhtman N, Nguyen J, Singh N, Afifi S, Giralt Lazar AJ, Morris EA, Sahin A, E, Weigelt B. Identification of Yu HA, Thyparambil S, Liao WL, 2020;76(1):64-75. Neoplasia: A Report of 200 Pantanowitz L. Pulmonary S, Lacouture ME, , Salgado R, Sapino A, Sasano H, recurrent FHL2-GLI2 oncogenic Bhalkikar A, Cecchi F, Hyman DM, Busam KJ Cases [E-pub ahead of print, sclerosing pneumocytoma: Hassoun H. Vitiligo Following Schnitt S, Sotiriou C, van Diest P, fusion in sclerosing stromal Lewis JS, Buonocore DJ, Ho AL, 2020 Jan 22]. Int J Surg Pathol. Cytomorphology and Autologous Hematopoietic White VA, Lokuhetty D, Cree IA; tumors of the ovary. Nat Makker V, Reis-Filho JS, Razavi 2020;1066896920901333. immunoprofile [E-pub ahead Stem Cell Transplantation WHO Classification of Tumours Commun. 2020;11(1):44. P, Arcila ME, Kris MG, Poirier JT, of print, 2020 Feb 5]. Cancer [E-pub ahead of print, 2020 Jan Editorial Board. The 2019 WHO Shen R, Tsurutani J, Ulaner GA, Cytopathol. 2020;10.1002/ 9]. Clin Lymphoma Myeloma classification of tumours of the de Stanchina E, Rosen N, Rudin cncy.22251. Leuk. 2020;20(4):e171-e173. breast [E-pub ahead of print, CM, Scaltriti M. HER2-Mediated 2020 Feb 13]. Histopathology. Internalization of Cytotoxic Agents 2020;10.1111/his.14091. in ERBB2 Amplified or Mutant Lung Cancers [E-pub ahead of print, 2020 Mar 25]. Cancer Discov. 2020;10(5):674-687. MSK PATHOLOGY MSK PATHOLOGY 20 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 21 Prasad M, Jagadeeshan S, Prockop S, Doubrovina E, Suser Sakamoto H, Attiyeh MA, Gerold Simeon-Dubach D, Roehrl Suurmeijer AJH, Dickson BC, Taylor AS, McKenney JK, Vaghjiani RG, Takahashi Y, Yoshida KI, Machado I, Motoi Scaltriti M, Allon I, Elkabets S, Heller G, Barker J, Dahi P, JM, Makohon-Moore AP, Hayashi MH, Hofman P, Puchois P. Swanson D, Sung YS, Zhang L, Osunkoya AO, Chan MP, Al- Eguchi T, Lu S, Kameda K, T, Parafioriti A, Lacambra M, M. In Vitro Establishment of a Perales MA, Papadopoulos E, A, Hong J, Kappagantula R, Enhancing Cooperation Antonescu CR. Variant WWTR1 Ahmadie HA, Spratt DE, Tano Z, Dozier J, Tan KS, Jones Ichikawa H, Kawai A, Antonescu Genetically Engineered Murine Sauter C, Castro-Malaspina Zhang L, Melchor JP, Reiter JG, Between Academic Biobanks gene fusions in epithelioid Fullen DR, Chinnaiyan AM, DR, Travis WD, Adusumilli CR, Yoshida A. NKX3-1 Is a Useful Head and Neck Cancer Cell Line H, Boulad F, Curran KJ, Giralt Heyde A, Bielski CM, Penson and Biomedical Industry: hemangioendothelioma-A Brown NA, Mehra R. PAX8 PS. Tumor Spread Through Immunohistochemical Marker of using an Adeno-Associated S, Gyurkocza B, Hsu KC, AV, Gönen M, Chakravarty D, Better Mutual Understanding genetic subset associated with expression and TERT promoter Air Spaces Is a Predictor of EWSR1-NFATC2 Sarcoma and Virus-Cas9 System. J Vis Exp. Jakubowski A, Hanash AM, O'Reilly EM, Wood LD, Hruban and New Collaborative Models cardiac involvement [E-pub mutations in the nested variant Occult Lymph Node Metastasis Mesenchymal . 2020;(155):10.3791/60410. Kernan NA, Kobos R, Koehne RH, Nowak MA, Socci ND, Taylor Are Needed [E-pub ahead of ahead of print, 2020 Mar 20]. of urothelial carcinoma: a in Clinical Stage IA Lung Am J Surg Pathol. [E-pub Published 2020 Jan 9. G, Landau H, Ponce D, Spitzer BS, Iacobuzio-Donahue CA. The print, 2020 Feb 11]. Biopreserv Genes Chromosomes Cancer. clinicopathologic study with Adenocarcinoma [E-pub ahead ahead of print, 2020 Jan 16]. B, Young JW, Behr G, Dunphy Evolutionary Origins of Recurrent Biobank. 2020;18(2):144-149. 2020;59(7):389-395. immunohistochemical and of print, 2020 Jan 30]. J Thorac 2020;44(6):719-728. Poirier JT, George J, Owonikoko M, Haque S, Teruya-Feldstein J, Pancreatic Cancer [E-pub ahead molecular correlates [E-pub Oncol. 2020;15(5):792-802. TK, Berns A, Brambilla E, Byers Siu J, Fuller K, Nadler A, Suurmeijer AJH, Dickson BC, Yoshimi A, Trippett TM, Zhang Arcila M, Moung C, Hsu S, Hasan of print, 2020 Mar 19]. Cancer ahead of print, 2020 Jan 13]. Pugash R, Cohen L, Deutsch K, Swanson D, Zhang L, Sung YS, N, Chen X, Penson AV, LA, Carbone D, Chen HJ, A, O'Reilly RJ. Off-the-shelf EBV- Discov. 2020;10.1158/2159-8290. Mod Pathol. 2020;10.1038/ Xu B, Chang K, Folpe AL, Kao Arcila Enepekides D, Karam I, Husain Fletcher CD, Antonescu CR. , Pichardo `J, Baik J, Sigler Christensen CL, Dive C, Farago specific T cell immunotherapy CD-19-1508. s41379-020-0453-z. YC, Wey SL, Huang HY, Gill AJ, ME Z, Chan K, Singh S, Poon I, A morphologic and molecular A, Harada H, Fajgenbaum AF, Govindan R, Hann C, for rituximab-refractory EBV- Rooper L, Bishop JA, Dickson Sato H, Schoenfeld AJ, Siau E, Higgins K, , Eskander A. reappraisal of myoepithelial Travis WD. Lung Cancer DC, , Abdel-Wahab Hellmann MD, Horn L, Johnson associated lymphoma following Xu B BC, Lee JC, Antonescu CR. Dogan A Lu YC, Tai H, Suzawa K, Kubota Metastasis to gastrostomy sites tumors of soft tissue, bone, and Pathology: Current Concepts. O, . Genetic basis for JE, Ju YS, Kang S, Krasnow transplantation. J Clin Invest. Head and Neck Mesenchymal Xiao W D, Lui AJW, Qeriqi B, Mattar M, from upper aerodigestive tract viscera with EWSR1 and FUS Clin Chest Med. 2020;41(1):67-85. iMCD-TAFRO [E-pub ahead of M, Lee J, Lee SH, Lehman J, 2020;130(2):733-747 Neoplasms With GLI1 Gene Lok B, Lovly C, MacPherson Offin M, Sakaguchi M, Toyooka malignancies: a systematic gene rearrangements [E-pub Alterations: A Pathologic print, 2020 Feb 12]. Oncogene. Travis WD, Dacic S, Wistuba I, D, McFadden D, Minna J, Oser Razavi P, Dickler MN, Shah PD, S, Drilon A, Rosen NX, Kris MG, review and meta-analysis ahead of print, 2020 Feb 7]. Entity With Distinct Histologic 2020;39(15):3218-3225. Sholl L, Adusumilli P, Bubendorf M, Park K, Park KS, Pommier Toy W, Brown DN, Won HH, Li Solit D, De Stanchina E, Davare [E-pub ahead of print, 2020 Genes Chromosomes Cancer. Features and Potential for L, Bunn P, Cascone T, Chaft J, Yuan L, , , Y, Quaranta V, Ready N, BT, Shen R, Vasan N, Modi S, MA, Riely GJ, Ladanyi M, Somwar Jan 8]. Gastrointest Endosc. 2020;59(6):348-356. Distant Metastasis [E-[ub ahead Katabi N Antonescu CR Chen G, Chou TY, Cooper W, Golden A, , Sage J, Scagliotti G, Sos ML, Jhaveri K, Caravella BA, Patil S, R. MAPK Pathway Alterations 2020;91(5):1005-1014.e17. of print, 2020 Jan 12]. Am J Surg Travis WD Rekhtman Tanaka A, Zhou Y, Shia J, Erasmus JJ, Ferreira CG, Goo N. Pulmonary Myoepithelial Sutherland KD, Travis WD, Selenica P, Zamora S, Cowan Correlate with Poor Survival and Pathol. 2020;44(6):729-737. Soliman MM, Aguado A, Sutton Ginty F, Ogawa M, Klimstra JM, Heymach J, Hirsch FR, Tumors With Exuberant Vakoc CR, Wait SJ, Wistuba I, AM, Comen E, Singh A, Covey A, Drive Resistance to Therapy in C, Hameed M, Hwang S, Healey DS, Hendrickson RC, Wang JY, Horinouchi H, Kerr K, Kris M, , . Noninvasive Reactive Pneumocytes: Wong KK, Zhang H, Daigneault Berger MF, Hudis CA, Norton L, Patients with Lung Cancers Xu B Ghossein RA JH, Maybody M. Technical Roehrl MH. Prolyl 4-hydroxylase Jain D, Kim YT, Lopez-Rios F, Lu Follicular Thyroid Neoplasm with Proposed Reclassification J, Wiens J, Rudin CM, Oliver Nagy RJ, Odegaard JI, Lanman Driven by ROS1 Fusions [E-pub and nidus-specific factors alpha 1 protein expression S, Mitsudomi T, Moreira A, Motoi Papillary-Like Nuclear Features of So-called Pneumocytic TG. New Approaches to SCLC RB, Solit DB, Robson ME, ahead of print, 2020 Mar 2]. Clin associated with adequacy of risk-stratifies early stage N, Nicholson AG, Oliveira R, (NIFTP): An Update [E-pub Adenomyoepithelioma. Am J Therapy: From the Laboratory Lacouture ME, Brogi E, Reis- Cancer Res. 2020;10.1158/1078- intraprocedural biopsy samples colorectal cancer. Oncotarget. Papotti M, Pastorino U, Paz-Ares ahead of print, 2020 Mar 2]. Head Surg Pathol. 2020;44(1):140-147. to the Clinic [E-pub ahead of Filho JS, Moynahan ME, Scaltriti 0432.CCR-19-3321. preceding radiofrequency 2020;11(8):813-824. L, Pelosi G, Poleri C, Provencio Neck Pathol. 2020;14(2):303-310. print, 2020 Feb 1]. J Thorac M, Chandarlapaty S. Alterations , Hwang S, Schnitt SJ, Brogi E, Chen YY, ablation of M, Roden AC, Scagliotti G, Zhang L Benayed Oncol. 2020;15(4):520-540. in PTEN and ESR1 promote Tang YW, Lozano L, Chen X, King TA, Lakhani SR. American [E-pub ahead of print, 2020 Jan Swisher SG, Thunnissen E, Tsao Xu G, Chhangawala S, Cocco E, R, Zhu GG, Mullaney KA, Rios clinical resistance to alpelisib Querec TD, Katabi N, Moreno- Razavi P, Cai Y, Otto JE, Ferrando KM, Sukhadia PY, , Prat A, Pascual T, De Angelis C, Registry of Pathology Expert 9]. Clin Imaging. 2020;61:27-32. MS, Vansteenkiste J, Weder W, Agaram N plus aromatase inhibitors. Nat Docón A, Wang H, Fix D, De L, Selenica P, Ladewig E, Chan , Bridge JA, Healey Gutierrez C, Llombart-Cussac A, Opinions: The Spectrum of Yatabe Y. IASLC Multidisciplinary Zhang Y Cancer 1, 382–393 (2020). Stolnicu S, Segura S, Parra- Brot L, McMillen TA, Yoon JY, C, Da Cruz Paula A, Witkin M, JH, Athanasian EA, . Wang T, Cortés J, Rexer B, Paré Lobular Carcinoma in Situ: Recommendations for Hameed M Herran C, Horn LC, Hoang L, Torroba A, Wang Y, Unger Cheng Y, Park J, Serna-Tamayo Myositis ossificans-like soft tissue L, Forero A, Wolff AC, Morales Rekhtman N. "Napoleon Hat" Diagnostic Features and Clinical Pathologic Assessment of Lung Terinte C, Pesci A, Aviel-Ronen ER, Park KJ. An Isothermal, C, Zhao H, Wu F, Sallaku M, Qu aneurysmal bone cyst: a clinical, S, Adamo B, Brasó-Maristany Sign: A Distinctive Cytologic Implications [E-pub ahead of Cancer Resection Specimens S, Kyokawa T, Alvarado-Cabrero Multiplex Amplification Assay X, Zhao A, Collings CK, D'Avino radiological, and pathological F, Vidal M, Veeraraghavan J, Clue to Reactive Pneumocytes print, 2020 Feb 15]. Ann Diagn After Neoadjuvant Therapy I, Oliva E, Soslow RA, Park for Detection and Genotyping AR, Jhaveri K, Koche R, Levine study of seven cases with Krop I, Galván P, Pavlick AC, [E-pub ahead of print, 2020 Pathol. 2020;45:151481. [E-pub ahead of print, 2020 KJ. Invasive Stratified Mucin- of Human Papillomaviruses RL, , Kadoch C, COL1A1-USP6 fusion and a Bermejo B, Izquierdo M, Rodrik- Jan 23]. Arch Pathol Lab Med. Jan 28]. J Thorac Oncol. Reis-Filho JS Schoenfeld AJ, Chan JM, Kubota producing Carcinoma (ISMC) in Formalin-Fixed, Paraffin- Scaltriti M, Leslie CS, Baselga novel ANGPTL2-USP6 fusion Outmezguine V, Reis-Filho 2020;144(4):443-445. 2020;15(5):709-740. D, Sato H, Rizvi H, Daneshbod of the Cervix: A Study on Embedded Tissues [E-pub J, Toska E. ARID1A determines [E-pub ahead of print, 2020 Mar JS, Hilsenbeck SG, Oliveira M, . Measurable disease Y, , Paik PK, Offin M, Morphologic Diversity [E-pub ahead of print, 2020 Jan 22]. J Tsui DWY, Blumenthal GM, luminal identity and therapeutic 10]. Mod Pathol. 2020;10.1038/ Dieci MV, Griguolo G, Fasani R, Roshal M Chang JC evaluation in patients with , Davare MA, Shinde U, ahead of print, 2020 Mar 31]. Mol Diagn. 2020;22(3):419-428. Philip R, Barrett JC, Montagut C, response in estrogen-receptor- s41379-020-0513-4. Nuciforo P, Parker JS, Conte P, Arcila ME myeloma. Best Pract Res Clin Pe'er D, Rekhtman N, Kris MG, Am J Surg Pathol. 2020;10.1097/ Bramlett K, Ladanyi M, Ghosh S. positive breast cancer. Nat Genet. Schiff R, Guarneri V, Osborne Tashkandi H, Dogan A. Haematol. 2020;33(1):101154. Somwar R, Riely GJ, Ladanyi M, PAS.0000000000001480. Development, Validation, and 2020;52(2):198-207. CK, Rimawi MF. HER2-Enriched Histiocytic sarcoma arising Yu HA. Tumor Analyses Reveal Regulatory Considerations for Subtype and ERBB2 Expression Suurmeijer AJ, Dickson BC, in patient with history of , Gao Q, Ozkaya N, Huet S, Squamous Transformation and a Liquid Biopsy Test. Clin Chem. Yabe M in HER2-Positive Breast Cancer Swanson D, Sung YS, Zhang clonally-related germ cell , Pichardo JD, Moskowitz Off-Target Alterations As Early 2020;66(3):408-414. Lewis N Treated with Dual HER2 L, . Novel SRF- tumour and myelodysplastic Resistance Mechanisms to Antonescu CR AJ, Horwitz SM, Dogan A, Roshal Blockade. J Natl Cancer Inst. ICA1L Fusions in Cellular Myoid syndrome. Br J Haematol. First-line Osimertinib in EGFR- Turashvili G, Fix DJ, Soslow RA, M. Bright PD-1 expression by flow 2020;112(1):46-54. Neoplasms With Potential For 2020;188(4):482. Mutant Lung Cancer [E-pub Park KJ. Wilms Tumor of the cytometry is a powerful tool Malignant Behavior. Am J Surg ahead of print, 2020 Jan 7]. Clin Ovary: Review of the Literature for diagnosis and monitoring Pathol. 2020;44(1):55-60. Cancer Res. 2020;10.1158/1078- and Report of 2 Cases. Int J of angioimmunoblastic T-cell 0432.CCR-19-3563. Gynecol Pathol. 2020;39(1):72-78. lymphoma. Blood Cancer J. 2020;10(3):32.

MSK PATHOLOGY MSK PATHOLOGY 22 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 23 Reis-Filho–Problematic Breast Xu, S. Dogan, Katabi, Ghossein– Baine, Travis Buonocore, Chang, Beech, Tang, Klimstra, Shia–Gas- MSKCC@USCAP 2020 Tumors Reassessed in Light of Nov- Endocrine Pathology. Dissecting Rekhtman, Sauter–Pulmonary trointestinal Pathology. Esoph- el Molecular Data Anaplastic Thyroid Carcinoma Pathology. Histologic Patterns of ageal Adenocarcinoma Show- (ATC. Comprehensive Clinico- Lung Adenocarcinoma Report- ing Extensive Neuroendocrine Reuter–Hot Topics in Pathology Pathologic, Immunophenotypic, ed on Biopsy Accurately Predict Differentiation after Induction 01–GU Pathology–The Testis: From and Molecular Studies of 357 Cases Composition of Resected Tumor Chemo-Radiation: The Molecu- Grossing to Reporting lar View of a Poorly Understood Phenomenon PLATFORMS Chiang–International Society of Grabenstetter, D’Alfonso, Wen, Maldonado, Momeni-Boroujeni, Yang, Chang, S. Dogan, Travis, Baine, Travis, Klimstra, Sauter– Gynecological Pathology. S100 and Brogi, Tan–Breast Pathology Benayed, Ladanyi, Park, Soslow, Schwartz, Brogi, Pareja, Weigelt, Arcila, Ladanyi, Rekhtman– Pulmonary Pathology. Histologic Pulmonary Pathology. Multifocal Features of Desmoplastic Meso- Caniello, Chan, Roshal, Lin– Agaram–International Society of NTRK Staining to Report NTRK Morphologic and Immunohisto- Chiang–Gynecologic Pathology. Reis-Filho, Wen–Breast Pathol- Invasive Mucinous Adenocarcino- thelioma (DMM) Cytopathology. Role of Flow Bone and Soft Tissue Pathology. Fusion Sarcoma of the Cervix chemical (IHC) Features of Car- Frequency of Molecular Alter- ogy. Adenoid Cystic Carcinoma mas Involving Different Lobes are Cytometry Studies in the Diagno- Soft Tissue Spindle Cell Neo- cinoma Involving Microglandular ation Using a Targeted RNA Se- of the Breast: A Single Institution Clonally Related and Represent sis of Classical Hodgkin Lympho- plasms: Emerging Entities D’Alfonso, Hanna, Grabenstetter, Adenosis (MGA) of the Breast quencing Approach in Uterine Experience with Emphasis on Sol- Baine, Travis, Sauter, Chang, Buono- Intrapulmonary Spread as De- ma in Cytology Specimens Tan–Informatics. Machine Learning Following Neoadjuvant Therapy Mesenchymal Neoplasms id Variant with Basaloid Features core, Jungbluth, Rekhtman– Pul- fined by Molecular Profiling monary Pathology. Novel Biologic Agaram, Y. Zhang, Antonescu– as an Ancillary Tool in the As- Subsets of Small Cell Lung Carci- Chan, Roshal, Lin–Hematopa- Bone & Soft Tissue Pathology. sessmentof Shaved Margins Klimstra–Gastrointestinal Mata, Benhamida, Ferguson, Shia, Klimstra, Basturk– Pancreas C. Yang, Sarungbam, Al-Ahmadie, Defined by ASCL1 and Neu- thology. Breast Implant-Associ- A Molecular Reappraisal of Glo- for Breast Carcinoma Excision Pathology. Gastrointestinal Stromal Benayed, Rosenblum, Arcila, Pathology. Solitary Fibrous Tumor Gopalan, Sirintrapun, Fine, Tick- roD1: Immunohistochemical and ated Anaplastic Large Cell Lym- mus Tumors (GT. A Study of 93 Specimens Tumors Arising in Uncommon Ladanyi, Bale–Neuropathology. of the Pancreas oo, Reuter, Y. Zhang, Chen–Gen- Histopathological Characterization phoma Diagnosis: Role of Flow Cases with a Focus on NOTCH Locations: Clinico-Pathologic Fea- Associations between FGFR3 itourinary Pathology. Homozy- Cytometry Studies Gene Fusions Ferguson, Momeni-Boroujeni, tures and Risk Assessment of Activating Fusions, Molecular Soslow, Park–Gynecologic Pa- gous Loss of CDKN2A/B and Zheng, Ho, Arcila, Ross, S. Dogan– Esophageal, Appendiceal, and Genetic Profiles, and Epigenetic thology. Clinical and Pathological Basturk–Pancreas Pathology. Is It Colonic Tumors Methylation Signatures in Glio- Complex Genomic Alterations Justifiable to Move the Grade-1 Chang, Sauter, Buonocore, Basturk, Klimstra–New Con- Head & Neck Pathology. HER2 Determinants of Outcome in In- blastomas Observed in Locally Advanced/ Ki67 Index Cut-Off from 3% to Vanderbilt, Arcila, Travis, Ladanyi, cepts and Controversies in the Gene Amplification and Protein vasive Stratified Mucinous Carci- Metastatic Mucinous, Tubular, and 5% for Pancreatic Neuroendo- Rekhtman–Pulmonary Pathology. Diagnosis of Pancreatobiliary Expression Assessment in 44 Sal- Klimstra–Pancreatobiliary Pathol- noma (iSMILE) of the Cervix: An Spindle Cell Carcinoma (MTSCC) crine Tumors as Has Been Pro- Histologic Challenges in Dis- and Gastrointestinal Tract Neu- ivary Duct Carcinomas ogy Society. Mucinous Cystic & Momeni-Boroujeni, Vanderbilt, International Multicentric Study posed? The Cases that Fall to tinguishing Separate Primary Lung roendocrine Neoplasms Intraductal Neoplasms of the Murali–Gynecologic Pathology. L. Zhang, Nafa, Hameed–Bone 3-5% Category Have Clinicopath- Carcinomas from Intrapulmonary Fine–Large Gland Lesions of the Pancreatobiliary Tract Alterations in Chromatin Re- Tang–Increasing Importance of modeling Genes in Endometrial & Soft Tissue Pathology. A Next ologic Characteristics Closer to Metastases Using Broad Next- Benhamida, Basturk, Weigelt, Prostate on Needle Biopsy HER2 Testing in the Context of Epithelial Tumors are Associat- Generation Sequencing Study of Those >5% Generation Sequencing as a Gold Reis-Filho, Klimstra–Pancreas Kuba, Xu, Antonescu–Breast an Expanding Targeted Therapies ed with Prognosis Seven Primary Central Chondro- Standard for Determining Tumor Pathology. Pancreatoblastomas Fine, Magi-Galluzzi–Dynamic Pathology. The Impact of MYC Landscape–Gastrointestinal Can- sarcomas in the Pediatric Pop- Basturk–Pancreas Pathology. Ep- Clonal Relationships and Acinar Cell Carcinomas Evolution in Prostate Cancer Amplification on Clinico-Patho- cer: Latest Updates and Practical ulation Showed Recurrent IDH ithelial Inclusions in the Gallblad- Share Epigenetic Signatures Diagnosis and Reporting: What logic Features and Prognosis of Park, Soslow–Gynecologic Guidelines for Pathologists Mutations and a Novel EWSR1- der: Cytoisospora belli Organisms Chapman-Lim, A. Dogan, D’Al- Distinct From Other Neoplasms the Pathologist Needs to Know Radiation-Associated Angiosar- Pathology. International Endo- SMAD3 Fusion or Degenerative Intracytoplasmic fonso–Breast Pathology. Mam- of the Pancreas comas of the Breast cervical Adenocarcinoma Crite- Weigelt, Chiang–Gynecologic ria and Classification (IECC. An PAS-Positive Hyaline Globules mary Amyloidosis: An Uncommon Ghossein–North American Pathology. Epigenetic Signatures Independent Cohort with Clini- Entity that May Present as Brogi–The Never-Ending Saga Society of Head and Neck Lin, Pantanowitz–Short Course of Synchronous and Metastatic cal and Molecular Relevance Basturk–Pancreas Pathology. Mammographic Microcalcifications of Papillary Lesions of the Breast Pathology. Latest Advances in #49: Telecytology for Rapid On- Endometrioid Adenocarcinomas POSTERS Whipple-Ables: Clinico-Pathologic the Diagnosis of NIFTP Site Evaluation: From Implemen- tation to Clinical Challenges Perron, Brogi, Murray–Breast Pa- Comparison of 1032 Cancers Chui, Soslow– Gynecologic Chen–Diagnostic Approach to Wen–Uncommon Histologic Sub- thology. Local Recurrence of Be- Al-Ahmadie, Reuter–Genitourinary Removed by Pancreatoduo- Pathology. TP53-Wildtype High- Renal Tumors with Papillary Gopalan–Genitourinary Pathology. types of Triple Negative Breast nign and Borderline Phyllodes Tu- Pathology. Urothelial Dysplasia: denectomy Based on Patho- Grade Serous Tubo-Ovarian Architecture: Updates Using Reporting Trends, Practices, and Liu, Mata, Arcila, Y. Zhang, Cancer mors: Analysis of Margin Status and Diagnostic Value in Clinical Prac- logic Re-Review Using Refined Carcinomas 2016 WHO Classification Resource Utilization in Neuroen- A. Dogan, Roshal, Xiao– Clinico-pathologic Features tice 20 Years Since the 1998 Site-Specific Criteria docrine Tumors of the Prostate Hematopathology. Erythroid/ Xu–Endocrine Pathology Society. Megakaryoblastic Leukemia WHO/ISUP Consensus Dahoud, Imam, Tang–Gastro- Chen–Genitourinary Pathology Gland: A Survey of Genitourinary Anaplastic Thyroid Carcinoma: with TP53 and RUNX1 Muta- Basturk–Pancreas Pathology. A intestinal Pathology. Heterogeneity Society. Molecular Stratification (GU) Pathologists Perron, Wen, Hanna, Brogi, Ross– Everything the Pathologist Needs tions Frequently Occurs in Breast Pathology. HER2 Immu- Baine, Buonocore, Chang, Proposal for Improved T-Staging of Signet Ring Cell Carcinoma at of Kidney Cancer: Clinical Rel- to Know Blast Transformation of Phila- nohistochemistry in Invasive Mi- Rekhtman, Sauter, Travis– of Pancreatic Ductal Adenocar- Different Primary Sites–Human evance of Molecular Types Em- Gopalan, Fine, Chen, Al-Ahmadie, delphia Chromosome-Negative cropapillary Breast Carcinoma: Pulmonary Pathology. The Dis- cinoma by Using Microscopic Observation Precedes Artificial phasized Sarungbam, Tickoo, Reuter– Xu, Antonescu–Head & Neck Pa- Myeloproliferative Neoplasms: Complete Assessment of an In- tinction Between Spread Thru Examination as the Basis for Intelligence Genitourinary Pathology. Prostate thology. Head and Neck (H&N) A Single-Institution Experience complete Pattern Air Spaces (STAS) and Artifacts Determining Size and T-Stage Gynecologic Pathology. Cancer with Germline DNA Dam- Malignant Mesenchymal Neo- Chiang– with 56 Cases in Selected Images is Highly Re- Recurrent Chromatin Remodel- age Repair Gene Alterations: A plasms with GLI-1 Alterations: A International Society of producible ing Pathway Mutations Identi- Clinical and Pathologic Assessment Reis-Filho– Pathologic Entity with Distinct Breast Pathology. Rare Types of fied in Ovarian Juvenile Granu- Histologic Features and Potential Breast Carcinomas losa Cell Tumors for Distant Metastasis

MSK PATHOLOGY MSK PATHOLOGY 24 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 25 Dahoud, Momeni-Boroujeni, Hoda, Zehir, Brogi, Ladanyi, Ar- Kopach, Al-Ahmadie, Fine, Go- Momeni-Boroujeni, Benayed, Rekhtman, Travis, Yagi–Pulmo- Soslow–Gynecologic Pathology. X. Wu, Momeni-Boroujeni, Soslow, S-R Yang, Mata, Benayed, Rekht- Vanderbilt, Soslow–Clinicopath- cila, Wen, Ross–Breast Patholo- palan, Sarungbam, Sirintrapun, Antonescu, Ladanyi, Chiang– nary Pathology. The Roles of Evaluation of HPV RNA In-Situ Weigelt–Gynecologic Pathology. man, Ladanyi, Jungbluth, Hecht- ologic and Genomic Analysis of gy. Next-Generation Assessment Tickoo, Reuter, Chen–Genitouri- Gynecologic Pathology. High Whole Block Imaging with Mi- Hybridization (ISH) and p16 Im- Genetic Alterations in Mullerian man–Pathobiology & Techniques. Copy Number-High (CH-H) En- of Human Epidermal Growth Fac- nary Pathology. High Grade Un- NTRK3 Expression in High-Grade cro-Computed Tomography in munohistochemistry (IHC) Con- Adenosarcoma with High-Grade Detection of RET Kinase Fusions dometrial Carcinoma tor Receptor 2 (ERBB2) Status in classified Renal Cell Carcinoma Endometrial Stromal Sarcomas Lung Adenocarcinoma cordance in Endocervical Adeno- Sarcoma Components Using DNA, RNA, and Pro- Breast Cancer: A Focus on Group with NF2-Loss–Morphologic and (ESS) with BCRO Abnormalities carcinomas tein-Based Methods Dahoud, Momeni-Boroujeni, 4 Using the 2018 ASCO/CAP Molecular Analysis Reis-Filho, Weigelt–Gynecologic Umphress, Tang–Gastrointestinal Vanderbilt, Soslow–Gynecologic HER2 Testing Guideline Pareja, Reis-Filho–Breast Pathol- Pathology. The Chronology of Soslow, Park, Chiang, Reis-Filho, Pathology. Is Histologic Grade L. Zhang, Klimstra, Hameed, Pathology. Clinico-Pathologic and Kuba, Murray, Brogi–Breast ogy. NR4A3 Expression is Consis- Development of Endometrioid Zehir, Murali, Weigelt–Gyneco- Prognostically Important Among Roehrl–Bone and Soft Tissue Genomic Analysis of Copy Num- Imam, Dahoud, Nourbaksh, Va- Pathology. Morphologic Variants tently Absent in Acinic Cell Carci- Endometrial and Ovarian Tumors logic Pathology. Concordance of Goblet Cell Neoplasms Confined Pathology. Towards Biomarkers ber-High Endometrial Carcinomas kiani, Hechtman, Tang, Klimstra, of Lobular Carcinoma in Situ nomas of the Breast: A Potential in Patients with Synchronous p53 Immunohistochemistry and to the Appendix and Therapeutic Targets for De- Shia–Gastrointestinal Pathology. (LCIS) Diagnosed on Core Nee- Nosologic Shift Disease TP53 Mutation Status in Endo- differentiated Chondrosarcoma Ferguson, Mata, Brogi, Ladanyi, Mismatch Repair Deficiency in dle Biopsy: Clinico-Pathologic metrial Cancer Xu, Katabi, S. Dogan, Ghossein– Discovered by Fourier Transform Arcila, Benayed, Ross–Breast Squamous Cell Carcinoma of the Features and Findings at Fol- Pareja, Reis-Filho, Weigelt, Park– Ross, Zehir, Wen, Brogi, Weigelt, Endocrine Pathology. Should Mass Spectrometry Proteomics Pathology. Androgen Recep- Gastrointestinal Tract: Frequency low-Up Excision Gynecologic Pathology. Mesone- Reis-Filho, Pareja–Breast Pathol- Tickoo, Reuter–Genitourinary Medullary Thyroid Carcinomas tor Splicing Variant-7 in Breast and Clinical Implication phric and Mesonephric-like Car- ogy. Genetic Alterations Target- Pathology. Novel Biomarker for Be Graded? Zhu, Ho, Petrova-Drus, Nafa, Carcinoma: Clinical and Patho- Liu, Mata, Arcila, Nafa, A. Do- cinomas of the Female Genital ing KIT in Breast Cancer MiT Family Translocation Renal Quesada, A. Dogan, Arcila– logic Correlations Kennedy, Al-Ahmadie, Fine, Go- gan, Ho, Roshal–Hematopathol- Tract: Molecular Interrogation Cell Carcinoma. Xu, Katabi, Hameed, Ghossein, Pathobiology & Techniques. palan, Sarungbam, Sirintrapun, ogy. Minimal Residual Disease Including Three Cases Mixed with Salama, Momeni-Boroujeni, Yagi–Endocrine Pathology. De- Evaluation of T-Cell Receptor Grabenstetter, Jungbluth, Hoda, Tickoo, Reuter, Chen–Genitouri- Detection in B-ALL: Comparison Serous and Mucinous Neoplasms Vanderbilt, Soslow–Gynecologic Vakiani, Shia–Gastrointestinal fining Crucial Pathologic Param- (TCR) Repertoire by Next-Gen- Weigelt, Reis-Filho, H. Zhang, nary Pathology. Type 1 Papillary of a High-Sensitivity, Single-Tube, Pathology. Molecular Landscape Pathology. Processing Rectal eters in Thyroid Neoplasm Using eration Sequencing (NGS) Based Brogi, Wen–Breast Pathology. Renal Cell Carcinomas with High 13-Color Flow Cytometry Assay Pareja, Wen Brogi, H. Zhang, of HPV Negative Vulvar Squa- Cancer Resection Specimens: 3D Whole Block Imaging (WBI) TCR Gamma Chain Clonality PD-L1 Expression in Metaplastic Grade Features–Morphologic and an NGS-Based Assay Weigelt, Reis-Filho–Breast Pa- mous Cell Carcinoma Including A Comparative Evaluation of a with Micro-resolution CT Scanner Testing Breast Carcinoma (MBC) Using and Molecular Analysis thology. TERT Promoter Muta- NOTCH Alterations Cross Sectioning Approach with (MicroCT. A Proof of Concept PD-L1 SP142 Assay and Concor- Liu, Petrova-Drus, A. Dogan, tions in Metaplastic Breast Can- Wholemount Blocks and Slides dance Among PD-l1 Immunohis- Kennedy, Fine, Gopalan, Chen, Yabe–Hematopathology. Fre- cer Shia–Gastrointestinal Pathology. Versus the Regular Approach Xu, Sethi, S. Dogan, Ghossein, tochemical (IHC) Assays Sarungbam, Sirintrapun, Arcila, quent TET2 Mutations in Histio- Clinicopathologic Feature of Var- Katabi–Head & Neck Pathology. Tickoo, Reuter, Al-Ahmadie– cytic Neoplasms Pareja, Wen, Weigelt, Reis-Fil- icella Zoster Virus Infection of the Weigelt, Park, Murali–Gyne- Clinicopathologic Characteristics Hameed, Vakiani, Yagi, Shia– Genitourinary Pathology. Ge- ho–Breast Pathology.Genomic Upper Gastrointestinal Tract cologic Pathology Massively of Young Patients with Oral Squa- Gastrointestinal Pathology.Whole nomic Landscape of Non-Inva- Maldonado, Ross, Zehir, Wen, Analysis of Multifocal Ductal Car- Parallel Sequencing Analysis of mous Cell Carcinoma (OSCC) sive Urothelial Carcinoma of the Block Imaging (WBI) Utilizing Mi- Brogi, Weigelt, Reis-Filho, Pare- cinoma In Situ and Synchronous Shia–Gastrointestinal Patholo- Gastric-Type Cervical Adenocar- Bladder cro-Computed Tomography (Mi- ja–Breast Pathology. MET Gene Invasive Ductal Carcinoma gy. Metastases to the Stomach: cinomas Reveals Mutations in Yagi–Gastrointestinal Pathology. cro-CT) Reveals Pathologic Infor- Amplification in Breast Cancer Frequent Fliers and Unexpected Cell Cycle-Regulation Genes and Application of Whole Block Im- mation Not Detected on Regular Klimstra, Roehrl–Gastrointesti- Park, Soslow–Gynecologic Pa- Guests Rare Potentially Targetable aging (WBI) by Micro-Computed Histology: A Pilot Study of Rectal nal Pathology. Deep Proteomics Mata, Benayed, Agaram, Arcila, thology. FIGO (2018) Stage 1B ERBB2 Mutations Tomography for the Evaluation of Cancer Resection Specimens of Colorectal Carcinoma Liver Ladanyi, Hameed–Bone & Soft Endocervical Adenocarcino- Soslow, Murali–Gynecologic Endoscopic Submucosal Dissec- Metastases Uncovers New Tumor Tissue Pathology. Targetable Al- mas: A Detailed Study of Clin- Patholog. Cytologic Features of Wong, Brogi, Wen–Breast Pa- tion Specimens Subtypes and Therapeutic Targets Hoda, Brogi, D’Alfonso, terations and Rare Fusions in Sar- ical Outcomes Informed by Undifferentiated and Dedifferen- thology. Poor Response to Neo- Grabenstetter, Giri, Hanna, comas Identified by Custom RNA Clinico-pathological Parameters tiated Carcinomas of the Endo- adjuvant Chemotherapy in Meta- Yagi–Informatics. Mitosis Detec- Kuba, Murray, Vallejo, H. Zhang, Klimstra, Roehrl–Gastrointestinal Sequencing Including HPV Status metrium plastic Breast Carcinoma tion with Tiny-YOLO Reis-Filho, Wen–Breast Patholo- Pathology. Deep Proteomics gy. Interobserver Variation of PD- of Diffuse-Type Gastric Cancer Mata, S-R Yang, Ferguson, Liu, Raza, Travis, Buonocore, Chang, Soslow, Park, Chiang, Reis-Filho, Wong, Hanna, Edelweiss, Bro- C Yang, Ladanyi, Travis, Busam, L1 (SP142) Immunohistochem- Uncovers New Therapeutic Targets Sharma, Al-Ahmadie, Tickoo, Jungbluth, Rekhtman, Ladanyi, Zehir, Mandelker, Murali, Weigelt– gi, Hameed, Ross, Yagi–Breast Rekhtman–Pulmonary Pathology. istry Interpretation in Breast and Accelerates Drug Repositioning Reuter, Arcila, Ladanyi, Vander- Sauter–Pulmonary Pathology. Gynecologic Pathology. Con- Pathology.A Feasibility Study in UV Genomic Signature Classifies Carcinoma bilt–Genitourinary Pathology.As- Utility of Methylthioadenosine cordance between Immunohis- the Automated Quantification Lung of Unknown Kopach, Al-Ahmadie, Chen, Go- sociations of KIT Mutations with Phosphorylase (MTAP), 5-Hy- tochemistry for DNA Mismatch of HER2 Gene Amplification in Primary as Metastases from Oc- Hoda, Brogi, Grabenstetter, Wei- palan, Sarungbam, Sirintrapun, Concurrent RAS/MAPK Pathway droxymethyl cystosine (5-HMC) Repair Proteins and Next Gener- Breast Cancer Using Chromo- cult Cutaneous Melanomas gelt, Reis-Filho, Wen–Breast Pa- Tickoo, Reuter, Fine–Genitouri- Driver Alterations in Seminoma- and BAP1 Immunocytochemistry ation Sequencing for the Identifi- genic In Situ Hybridization Whole thology. PD-L1 Expression in Tu- nary Pathology. Quantification of tous and Non-Seminomatous (ICC) in Cytology Specimens for cation of Microsatellite Instability Slide Images mor-Infiltrating Lymphocytes of Pattern 4 in Patients with Highest Germ Cell Tumors the Diagnosis of Malignant Meso- in Endometrial Cancer Invasive Breast Carcinoma Needle Biopsy Gleason Score thelioma 4+4=8/Grade group 4 is Associ- ated with Radical Prostatectomy Downgrading

MSK PATHOLOGY MSK PATHOLOGY 26 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 27 Q&A $ Raised JESSICA CHAPMAN, PHD Director of Clinical Proteomics $1,371 By Kayt Sukel $3,928 $2,395 2020 Q What are you responsible We already have one NYS DOH approved Q What are some of the $4,193 for in your current role? clinical test. This test uses FFPE biopsy favorite parts of your $4,025 tissue to determine the causative protein. day-to-day work? A I came to Memorial Sloan Kettering Amyloidosis is a disease caused by the Pathology Teams $2,420 Cancer Center (MSK) in 2017 with deposition of a misfolded protein that A I’m always learning! When I came to the goal of taking mass spectrometry– displaces healthy tissue and can lead to MSK, I only knew the basics about based proteomics and moving it into a organ failure and even death. Determining pathology. I really enjoy interacting with Accesioning Team Captain: clinical setting. Proteomics, in general, is the causative protein is essential for proper the different people in the department. Jigar Patel the study of proteins. It is understood that treatment. My first major task as Director I get to learn what everyone does, from Gatekeepers $1,160 certain proteins are expressed differently of clinical proteomics was to get the test the pathologist to the histotechnologist $4,219 in healthy tissues as opposed to tumors. validated. Now, we have a streamlined preparing the samples, and what goes into 2019 Researchers can use mass spectrometry to process that includes coordination of the their jobs. I’ve also learned quite a bit on the $4,827 study the differences in proteomic profiles administrative side—all the moving parts hematopathology office coordinators, of malignant tissues and try to determine histotechnologists, myself, and the clinical that go into running a lab and the greater $1,683 how they might influence the development technologists in the proteomics laboratory. In pathology department here. It helps me do ARTIFICIAL Team Captain: and growth of those tumors. However, addition, I put a lot of effort into ensuring the my own job better. Christina Virgo the next step is to translate this wealth SPINTELLIGENCE instrumentation is kept in optimal condition Another large part of my role is research. I of information into clinically applicable which includes hands-on training of the have developed wonderful collaborations tests. My role involves identifying unmet $1,285 technologists. This is not instrumentation with pathologists, laboratory medicine needs in diagnostic, prognostic or disease or techniques that are common in clinical faculty, and SKI researchers. These tracking testing. Then developing, $1,502 laboratories so it is an opportunity to teach connections are very important in doing 2018 validating, and implementing those kinds someone something new. truly translational science. $2,710 of clinical assays that can be used by Team Captain: pathologists and clinicians. In the bigger What brought you to MSK? From your perspective, $1,600 picture, those tests could help doctors Q Fernando Garcia Q what sets MSK apart from choose more precisely targeted treatments I did my post-doctoral work at the FBI for their patients. A laboratory in Quantico, Virginia. Then other cancer centers? I went to work in the proteomics laboratory There’s a real sense of community here. $1,835 at NYU Medical Center. While I enjoyed that A I’ve gotten to know people across the work and learned a lot about building and LOGY institution such as members of the security HO $1,420 running a laboratory over my six years there, T 2017 department, environmental services, A I was ready to try something new. When I P Team Captain: $2,660 shipping and receiving, and others. Since my Sarah Virgo learned about this job, I was intrigued by desk and laboratory spaces are quite spread the prospect of using mass spectrometry- out I have a lot of opportunities to interact S based proteomics in a clinical setting. In A L with members of the MSK community P E D clinical settings, mass spectrometers are outside of Pathology as I walk between usually used for small molecule or single $1,827 buildings. It feels like family. I’m happy that 2016 protein target analysis. I wanted to be more I’m able to do truly interesting work but also $1,050 directly involved in the clinical community that, when I walk down the halls, everyone and hopefully play a role in establishing says hello and smiles. It really is a great place how these new assays and tests could be Team Captain: to work. BANK THIS Emily Lin effectively used in patient care. Total Raised (2016–2020)

Team Captain: Lorraine Corsale $45,110

IN LOVING MEMORY OF ROB PATERSON

MSK PATHOLOGY MSK PATHOLOGY 28 REVIEW 1st Quarter 2020 REVIEW 1st Quarter 2020 29 Social Media

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Our #PathIT Team addresses all of our information It was very humbling and an honor to have received You're welcome. Bread and butter pathology from @MSKPathology 69 y/o technology, LIS and digital technology needs. We're the Mario Luna awward from the Latin American #FeelGoodFriday #FanMail #HealthCareHeroes F, axillary LN FNA #cyto #cytology @cytopathology thankful for them and they're thankful for our laboratory Pathology Foundation @LatinAmericanPF, for my #MSKPathology professionals! Happy Lab Week!#PeopleofPathology project on fusions in uterine mesenchymal tumors @SarahCiang1 @AmirMom32351131 @KAyPArkMD @ RymaBenayed @MLadanyi @ MSKPathology @ USCAP2020

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