AUGUST 2018 # 45
Official society partner of The Pathologist
In My View In Practice Profession Sitting Down With The health economics Maintaining wellness What led you Master of efficiency of liquid biopsy and resilience to pathology? John Goldblum
15 – 16 32 – 33 46 – 49 50 – 51
Tell Me, Doctor…
Are you communicating adequately with your non-pathologist physician colleagues?
18 – 26
www.thepathologist.com Copyright © 2018 PerkinElmer, Inc. 400378_04 All rights reserved. PerkinElmer® is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners. www.perkinelmer.com/Phenoptics Multiplex Biomarker ImagingSystems inForm Vectra PHENOPTICS Opal COMPLEXITY INTO CONTEXT PUT WHEN YOU UNDERSTANDING STARTS ® ® ™ Image Analysis Software 3and Vectra MultiplexStaining ™ SOLUTIONS ® Polaris For research useonly. Not for useindiagnostic procedures. in – microenvironment its and tumor the in cells other and immune between relationships the understand enable you tobetter solutions Phenoptics™ research Our now. –until impossible nearly was context morphological and relationships spatial cellular maintaining while cells Butphenotyping growth. totumor contribute types cell different Many We’re looking inside for the next big cancer breakthrough. big cancer next forthe We’re inside looking solutions: research Phenoptics research. fortranslational of cases stratification and mechanisms cancer therapystrategies Our bodies’naturaldisease-fightingcapabilitiesjust mightleadtonew context . So you can visualize and identify biomarkers, leading to better understanding of disease of disease understanding tobetter leading biomarkers, identify and visualize . Soyou can in situ , in intact FFPE sections, Case of the Month
A 48-year-old woman presented with a left ventricular mass, diagnosed by CT scan, approximately 20 years prior to resection. Over the previous few months, she complained of worsening tinnitus in the left ear, headaches, and increasing ddizziness. After resection, the tumor was grossly described as multiple fragments of calcified red/black tissue and was submitted after decalcification.
What is your diagnosis?
a Papillary meningioma
b Choroid plexus papilloma
c Choroid plexus carcinoma
d Metastatic carcinoma
Answer to last issue’s Case of the Month…
A. Androgen This is a salivary duct carcinoma, a highly aggressive malignant tumor resembling high-grade ductal carcinoma of the breast. Approximately 70 percent of all salivary duct carcinomas express androgen receptors, which can be demonstrated immunohistochemically in the nuclei of this tumor.
To register your guess, please go to http://tp.txp.to/0818/case-of-the-month We will reveal the answer in next month’s issue!
www.thepathologist.com ContentsContentss
111
10 In My View
14 Hayley Pincott talks about using public engagement to change 03 Case of the Month Upfront how pathology is perceived, and the value of engaging young 10 Recognizing and Reacting people in science and medicine. 09 Editorial to PID A Perfect Partnership 15 When exploring the potentialential By E. Blair Holladayay 11 The Gentle Fetal Genome of liquid biopsy, Ilan Danielianieli thinks those in industryy must 12 A Change of Heart (Genetics) consider the health economicsonomics of their options. On The Cover 12 FluorescenceFluore Macroscopy
45 171 feelsels thathatt AUGUST 2018 # Jason Heikenfeld
Official society partner of The Pathologist
In My View In Practice Profession Sitting Down With The health economics Maintaining wellness What led you Master of efficiency Inter-specialty collaborationaboration of liquid biopsy and resilience to pathology? John Goldblum 13 Qu Quickick HitsHits wearable technologygy may bee thethe
14 32 – 33 46 – 49 50 – 51
Tell Me, Doctor…or…
Are you communicatingg adequately with yourr nonnon-patholologigist physician colleagues?es? 18 – 26 represented by a stylizeded subwaysubway next wave of advancementsncements in map of specialties connectinging diagnostics and thehe provisionprovissioon oof
www.thepathologist.com two hands. contextual patientnt data. THE COMPLETE PICTURE
FOR TISSUE DIAGNOSTICS WORKFLOW
ROUTINE STAINS | SPECIAL STAINS | IMMUNOHISTOCHEMISTRY
Learn more about our QHZFRPSOHWHZRUNɠRZVROXWLRQDW SigmaAldrich.com
j0HUFN.*D$'DUPVWDGW*HUPDQ\DQGRULWV DɡOLDWHV0HUFNDQGWKHYLEUDQW0DUHWUDGHPDUNVRI 0HUFN.*D$'DUPVWDGW*HUPDQ\RULWVDɡOLDWHV$OORWKHU WUDGHPDUNVDUHWKHSURSHUW\RIWKHLUUHVSHFWLYHRZQHUV 'HWDLOHGLQIRUPDWLRQRQWUDGHPDUNVLVDYDLODEOHYLDSXEOLFO\ DFFHVVLEOHUHVRXUFHV
2018-13175
7KHOLIHVFLHQFHEXVLQHVVRI0HUFN RSHUDWHVDV0LOOLSRUH6LJPDLQWKH 86DQG&DQDGD
ISSUE 45 – AUGUST 2018
Editor - Michael Schubert [email protected] Associate Editor - William Aryitey [email protected] Content Director - Rich Whitworth [email protected] Publisher - Lee Noyes [email protected] Business Development Executive - Sally Loftus [email protected] Head of Design - Marc Bird [email protected]
Designer - Hannah Ennis [email protected] Junior Designer - Charlotte Brittain [email protected] Digital Team Lead - David Roberts [email protected] Digital Producer Web/Email - Peter Bartley [email protected] Digital Producer Web/App - Abygail Bradley [email protected] Audience Insight Manager - Tracey Nicholls 36 50 [email protected] Traffic & Audience Database Coordinator- Hayley Atiz [email protected] Traffic and Audience Associate- Lindsey Vickers [email protected] Traffic Manager Jody- Fryett Feature NextGen [email protected] Traffic Assistant Dan- Marr [email protected] 18 Tell Me, Doctor… 36 The Inside Story Events Manager - Alice Daniels-Wright How can we guarantee that At the intersection of pathology, [email protected] Marketing Manager - Katy Pearson pathology remains visible imaging, and analytical science, [email protected] and earns the respect of the Maastricht MultiModal Financial Controller - Phil Dale other disciplines – while Molecular Imaging Institute [email protected] Accounts Assistant - Kerri Benson simultaneously ensuring the best is taking new steps in disease [email protected] possible care for our patients? research and diagnostics. Chief Executive Officer - Andy Davies Tim Allen and his non- [email protected] Chief Operating Officer - Tracey Peers pathologist physician colleagues [email protected] share their views. Senior Vice President, North America - Fedra Pavlou Profession [email protected]
Change of address: 46 Your Origin Stories – in Tweets [email protected] Hayley Atiz, The Pathologist, Sponsored Feature One simple question – how Texere Publishing, Haig House, Haig did you find your way to Road, Knutsford, Cheshire, WA16 8DX, UK 28 Childhood Cancers pathology? – prompted many General enquiries: www.texerepublishing.com Are Different of you to tell your stories in [email protected] +44 (0) 1565 745200 your own words on Twitter. [email protected]
Distribution: The Pathologist (ISSN 2055-8228), is published monthly by Texere Publishing, In Practice Haig House, Haig Road, Knutsford, Cheshire WA16 8DX, UK Sitting Down With Single copy sales £15 (plus postage, cost available 32 Wellness: A New Kind on request [email protected]) Non-qualified annual subscription cost is of BBest Practice 50 John Goldblum, Chairman, £110 plus postage
TiTipsps anda tricks for making sure Department of Pathology, Reprints & Permissions – [email protected] The opinions presented within this publication are those of the authors and do youryour pathologypath residents have Cleveland Clinic; Professor of not reflect the opinions of The Pathologist or its publishers, Texere Publishing. Authors are required to disclose any relevant financial arrangements, thethe wellbewellbeinging and resilience to Pathology, Cleveland Clinic which are presented at the end of each article, where relevant. © 2018 Texere Publishing Limited. All rights reserved. take good care ofo themselves Lerner College of Medicine, Reproduction in whole or in parts is prohibited. and their patients.patients. Cleveland, USA. NEW
THE RIGHT RESULTS, THE FIRST TIME Avoid inefficiencies with a 93% first-pass yield1
When important patient care decisions are on the line, you need results you can count on—the first time. The DxH 900 hematology analyzer first-pass yield enables predictable costs and maximizes staff time by:
› Delivering accurate results with fewer reruns using near native-state cellular characterization and DataFusion technology—a unique combination of multiple testing methods for precise, high-resolution analysis in a single run
› Ensuring predictable costs through industry-leading 93% first-pass throughput1 for accurate flagging and a reduced number of slide reviews
› Maximizing staff time by reducing the time and supply costs related to managing systems with higher repeat rates, and simplifying workflow through a lean reagent portfolio
Learn more about how laboratories can achieve Lean practices and minimize repeat rates with the DxH 900 analyzer.
Visit www.beckmancoulter.com/dxh900-TP
1. Percentage of samples with numerical results that do not require additional intervention or handling, such as manual smear review, spun hematocrit, dilution, or other repeat/reflex testing. DxH series side-by-side results documentation. © 2018 Beckman Coulter, Inc. All rights reserved. Beckman Coulter, the stylized logo and the Beckman Coulter product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries. For more information, visit www.beckmancoulter.com/contact AD-127451 A Perfect Partnership Spreading the word and giving a voice to pathologists Editorial and laboratory professionals everywhere
ince the American Society for Clinical Pathology’s inception in 1922, our organization has worked to provide excellence in education, certification, and advocacy on behalf Sof patients, pathologists, and medical laboratory professionals. All of our activities are designed to feed into ASCP’s four pillars – knowledge, advancement, global community, and collaboration. The National Pathology Quality Registry helps pathologists improve quality and patient care; the ASCP Foundation raises money to provide scholarships and increase laboratory visibility; and the Center for Global Health’s work with the President’s Emergency Plan for AIDS Relief and our Partners for Cancer Diagnosis and Treatment in Africa initiative improve the diagnosis, care, and treatment of people all around the globe. Our portfolio of publications addresses the educational and academic research needs of our members, but what about the application of that research? And how do we explore the increasingly global aspect of pathology in ways that are relevant to our members today?. That’s where The Pathologist comes in. By bringing the magazine to our members, we’re increasing their access to world-class material while satisfying all four of our tent pole values. An interview with Richard M. Linnehan, a veterinarian who also happens to be an astronaut, provides insight into the importance of comparative pathology. Articles such as “Stromal Secrets” and “Instant Raman” examine non-invasive tests for diseases such as endometriosis and inflammatory bowel disease, respectively. The Case of the Month represents a bite-sized way to test your knowledge. And when you’re having a bad day, articles such as Kamran Mirza’s “Our Secret Language” provide the inspiration you need to persevere. The Pathologist is committed to publishing informed opinion pieces and articles covering cutting-edge technology that facilitate conversation among the world’s leaders in pathology and laboratory medicine. It seemed only natural to bring this resource to our members, so that they are better equipped to meet the demands of today, while paving the way for the future. As we approach our 100th anniversary, we must continue to evolve to maintain our place as the world’s largest organization for pathologists and laboratory professionals. As the authority on education, certification, and advocacy for the field, we must act as a guardian for the profession. This partnership with The Pathologist accomplishes all of that – and more. My best to you all.
E. Blair Holladay CEO, American Society for Clinical Pathology
www.thepathologist.com 10 Upfront
of patients with primary immune Recognizing and deficiency – a true collaborative effort Upfront from clinicians across the four nations,” Reacting to PID said Buckland. “For rare diseases, this is Reporting on research, the only way that we can collect reliable innovations, policies and On its 10th anniversary, the information that informs standard and UK Primary Immunodeficiency novel approaches to treatment or cure.” personalities that are (UKPID) registry aims to raise As awareness of PID has increased, shaping pathology today. awareness and improve care so has the number of patients diagnosed, which is why the UKPID Do you want to share Where can you find almost 10 years’ team emphasize the importance worth of data collection on primary of a valid authority on primary some interesting research immune deficiency (PID), representing 97 immunodeficiency. Thanks to our or an issue that will percent of immunology centers across the growing understanding of PIDs, impact pathology? UK and nearly 4,800 patients? Answer: screening for one type of the disorder the UK Primary Immunodeficiency (severe combined immunodeficiency, (UKPID) registry’s second report on or SCID) on newborn blood spots will Email: the rare syndrome (1). The new report be trialed this year, hopefully allowing [email protected] includes data from more than twice as healthcare teams to support patients many cases as their first publication in from a much earlier stage. 2014 (2). “It was more than four years Data in the new report covers disease since our last report,” says Matthew prevalence, delays in diagnosis, age of Buckland from the University College onset, and different treatments, such as London’s Centre for Immunodeficiency. hematopoietic stem cell transplantation “In that time, there has been a change of (HSCT) and gene therapy, all of platform, re-validation of original data, which can help doctors faced with and improved diagnostic criteria applied. unfamiliar symptoms or a rare diagnosis. With a significant increase in patient “Contributing centers now have new tools numbers approaching UK prevalence, we for the self-interrogation of data, which felt it was time to re-analyze the data.” helps feasibility assessment for specific PID affects only one in 16,000– studies on patient subpopulations,” says 50,000 people, and with more than Buckland. “The next stage is to implement 300 types of PID (3) – some of which new ‘level 3’ projects – studies that answer have been diagnosed in fewer than 10 questions on specific diseases or their patients – the condition can be difficult traits, such as inflammatory lung disease to spot. Consequently, patients often in common variable immune deficiency.” experience significant delays in having symptoms recognized and receiving the References correct treatment. 1. B Shillitoe et al., “The United Kingdom The national registry for structured Primary Immune Deficiency (UKPID) data on PID syndromes aims to combat registry 2012 to 2017”, Clin Exp Immunol, that diagnostic challenge by 192, 284–291 (2018). PMID: 29878323. providing and collating 2. JD Edgar et al., “The United Kingdom trustworthy Primary Immune Deficiency (UKPID) information for Registry: report of the first 4 years’ activity both doctors 2008-2012”, Clin Exp Immunol, 175, 68–78 and patients. (2014). PMID: 23841717. “It’s a unique 3. PIDUK, “Types of PID” (2017). Available at: data resource https://bit.ly/2zcxK8l. Accessed July 5, 2 The Gentle Fetal Genome
Can lab-on-a-chip technology enable extensive – yet noninvasive – prenatal screening?
Invasive testing on a fetus is never desirable but can be unavoidable, which is why so many researchers are working on new and improved noninvasive prenatal tests (NIPT). One such research team is using inertial microfluidics within a lab-on-a-chip device to collect is a more elusive goal – but one that could extremely gentle, rapid, and cost-effective circulating fetal trophoblasts in maternal have a huge impact on prenatal screening. way to enrich rare cells. None of the peripheral blood (1). Here, we speak standard enrichment approaches have with Marnie Winter, first author and How far are you from having such been clinically useful in circulating fetal research associate at the University of an impact? cells because to their extreme rarity and South Australia, to find out how the Our work thus far demonstrates the stringent sample requirements. method differs from existing NIPT. potential for inertial microfluidics to enrich circulating fetal cells. The isolation of What’s next? What is the origin of your work? these cells from blood has been attempted For the test to be clinically viable, we need We have been working in the field of many times in the past, but is extremely fully integrated technology that requires rare cell isolation for a number of years, challenging, so the field has stagnated. minimal user input. We are currently with a particular interest in the isolation However, modern technologies (ours working on creating technology to address of circulating tumor cells, which poses included) give us hope that we can reliably this. At the same time, we are working with a similar technical challenge to the isolate these cells from all pregnancies. industry partners and geneticists to develop isolation of circulating fetal cells from By combining our cell isolation (and the genetic analysis techniques specifically for pregnant women’s blood. Recently, the whole fetal genome contained within) with low-number or single circulating fetal cells. field of prenatal screening has been cutting-edge genomic technology, we can Our research is supported by the revolutionized by the introduction of offer much more comprehensive prenatal Australian Research Council Centre NIPT based on circulating cell-free fetal screening. We believe that cell-based of Excellence in Convergent Bio-Nano DNA. The technique has now gained NIPT will form a part of the prenatal Science and Technology, and also by the broad clinical acceptance for the detection screening landscape in the near future. National Health and Medical Research of a number of common genetic disorders; Council (Australia). There are a number of however, the technology is limited. By How do you see your lab-on-a- key collaborators for this project, including relying on fragments of DNA in the chip technology fitting into the Majid Warkiani from the University of maternal blood stream, such tests are pathologist’s workflow? Technology Sydney, Tristan Hardy from unable to provide information on the full In general, lab-on-a-chip concepts SA Pathology, and Dierdre Zander-Fox range of potential genetic abnormalities. enable the manipulation of clinical from Monash IVF group. Our experience in rare cell isolation specimens with very high accuracy and and the great diagnostic potential of efficiency – and can often be completely Reference circulating fetal cells, which provide a automated. As a result, these technologies 1. M Winter at al., “Isolation of circulating fetal whole intact genome, prompted us to have a high potential to simplify and trophoblasts using inertial microfluidics for refocus our efforts towards the isolation facilitate a pathologist’s workflow. In our noninvasive prenatal testing”, Adv Mater of those cells. From our perspective, that specific case, inertial microfluidics is an Technol, 3 (2018).
www.thepathologist.com 12 Upfront
in young individuals and genome editing A Change of could possibly be could provide a explained by genetic personalized approach Heart (Genetics) mutations in channelopathy- to drug therapy for patients related genes,” says Wu. “However, with congenital long QT syndrome A new model system may clinical management is still hindered and other inherited conditions associated help personalize cardiac for most of these disorders because of with cardiac arrhythmias.” channelopathy diagnosis insufficient knowledge of the functional For the time being, the Wu lab will and treatment consequences of genetic mutations.” continue to establish and validate Wu blames the problem on the potential of iPSCs as a model for As genetic testing gets faster and cheaper, inadequate model systems for research accurately decrypting the pathogenicity people are increasingly having their own – but there is a solution. “The recent of unknown variants in cardiac disorders. genomes examined for all manner of emergence of induced pluripotent stem In the future, their approach, which variation. Much of this scrutiny is focused cell (iPSC) technology has provided combines genome editing and iPSC on disease risk. “Could I be in danger an unprecedented opportunity for techniques, may be used to accelerate of a heart attack? Will I suffer the same generating and studying iPSC-derived progress toward precision medicine in problems as my grandmother? How long cardiomyocytes from channelopathy cardiology. “We are very excited about am I likely to live a healthy life?” But not patients,” says Wu. “These cells can our data,” Wu says. “With the increasing every gene variant affects disease risk – accurately recapitulate human disease usage of next generation sequencing, and even for those that do, the increase electrophysiology in vitro, allowing many unknown functional variants will could be statistically meaningless. investigation of patient- and mutation- undoubtedly appear. We believe this Joseph Wu and his research team at specific disease mechanisms.” iPSCs approach will be a common method to Stanford Medicine set out to dispel can be used to study the pathogenicity decipher VUS in the future.” the mystery of variants of unknown of not only channelopathies, but other significance (VUS) in patients at potential cardiac disorders as well. And the story Reference risk of heart problems. In particular, doesn’t end there; Wu is optimistic that 1. P Garg et al., “Genome editing of induced they focused on a family of disorders his group’s investigations could lead pluripotent stem cells to decipher cardiac known as cardiac channelopathies (1). to precision diagnosis and treatment. channelopathy variant”, J Am Coll Cardiol, 72, “About 30 percent of negative autopsies “Future studies based on human iPSCs 62–75 (2018). PMID: 29957233.
methods to interrogate biological believe our macro-scanner can find Fluorescence systems in vitro, there are a limited applications in profiling tumors and number of ways to explore samples in in determining surgical margins. We Macroscopy vivo, especially when they’re large.” should also note that the exploration of To overcome this difficulty, the tumors in this case is based on the Using a macro-scanner to image Shcheslavskiy and colleagues from observation of intrinsic fluorophores larger samples with the detail Russia developed a system that allows that are present in it, so it is a virtually of fluorescence microscopy users to boost fluorescence laser scanning label-free approach to the monitoring microscopy to image samples as large as of samples.” Their “macroscopic” “Fluorescence microscopy is considered a 18 mm² – where the previous limit was technique can also examine tumor minimally invasive optical technique to less than 1 mm². But what separates this response to different therapeutics, and address a number of biological questions technology from mainstream imaging can be combined with other imaging that cannot be answered by other means techniques for large samples? systems to expand its scope of use. in a fast and relatively inexpensive way,” “Currently, there are systems on the Shcheslavskiy adds, “Of course, before says Vladislav Shcheslavskiy, a senior market that allow you to do whole- they can enter routine use in clinics, research scientist at Becker & Hickl. body imaging, but they lack molecular all results obtained by optical methods “Although there are a lot of powerful sensitivity,” explains Shcheslavskiy. “We have to go through independent checks Upfront 13
Shcheslavskiy concludes by highlighting the collaborative scope of the project, saying, “This work would be impossible without our collaboration with biologists. I would like to take the opportunity to express my appreciation to my colleagues from Privolzhsky Research Medical University, Nizhniy Novgorod, especially Elena Zagaynova and Marina Shirmanova. who were the main driving forces in the experiments carried out with the developed system.”
Reference by biochemical and other common system more user-friendly and updating 1. VI Shcheslavskiy et al., “Fluorescence methods for clinical labs.” As well, his the software and hardware to increase its time-resolved microimaging”, Opt Lett, 43, group’s next steps include making the flexibility and compactness. 3152–3155 (2018). PMID: 29957804.
breath has found that they act as novel The findings showed that associated Quick Hits biomarkers to detect the disease (2). gene mutations were found in 33 GC/MS analysis of exhaled air can percent of first-degree relatives and Pre-emptive Liver Protection allow diagnosticians to identify patients 24 percent of second-degree relatives with pancreatic cancer with 81 percent (4), meaning that relatives of patients One in 50 patients who take an sensitivity. diagnosed with sporadic NS-TAD interferon-ȕ (IFN-ȕ) biologic to treat would benefit from genetic screening. multiple sclerosis have adverse side A Swallowable Substitute effects that cause liver injury; up to The standard protocol for diagnosing References 60 percent present with abnormal small intestinal bacterial overgrowth 1. K Kowalec et al., “Common variation near biochemical liver tests. Although the and similar gastrointestinal tract IRF6 is associated with IFNȕinduced liver treatment benefits many, the detriment disorders requires a breath test that injury in multiple sclerosis”, Nat Genet, 50, to these patients cannot be overlooked evaluates intestinal gases – but the test 1081–1085 (2018). PMID: 30013178. – so a group of researchers hope to help often lacks accuracy. A swallowable 2. SR Markar et al., “Profile of exhaled-breath with new biomarkers for liver injury capsule measured hydrogen volatile organic compounds to diagnose caused by IFN-ȕ (1). These biomarkers concentration – associated with GI pancreatic cancer”, Br J Surg, [Epub ahead of may make it possible to predictict didiseasesse – over 3,000 times higher print] (2018). PMID: 30019405. whether a patient is susceptible too thanthan a bbreath test, resulting in 3. KJ Berean et al., “The safety and sensitivity of liverli injury. a higher signal-to-noise a telemetric capsule to monitor ratior and subsequently a gastrointestinal hydrogen production in vivo JustJ a Breath Away more precise diagnosis (3). in health sbjects: a pilot trial comparison to A new diagnostic for pancreaticatic concurrent breath analysis”, Aliment cancerca may come from aann FamilialFa Heart Care Pharmacol Ther, [Epub ahead of print] unlikelyu source: yourur A review of existing scientific (2018). PMID: 30067289. breath! A study of literaturelit on non-syndromic 4. G Mariscalco et al., “Systemic review of studies volatile organicic ththoracic aortic disease (NS- that evaluated screening tests in relatives of compounds in TATAD) has shown that familial patients affected by nonsyndromic thoracic aortic screeningscr may benefit populations. disease”, J Am Heart Assoc, 7, e009302 (2018).
www.thepathologist.com 14 In My View
are we to blame for this? Are we taking Changing part in public engagement or career talks In My in schools to change that perception? the Perception With the concern of a shortfall in workforce in the future, I feel we need to View of Pathology act to engage young people in pathology and biomedical science. I’m an avid Pathologists need to reach out watcher of the BBC2 fly-on-the-wall In this opinion section, to the general public – and the documentary Hospital. On the show, experts from across the earlier, the better “the lab” is referenced quite often, but world share a single the term “pathology” is never used. Why not? And could a small change like strongly held view or using the word “pathology” start the key idea. ball rolling in making others aware of how much we are involved in healthcare? About 18 months ago, I became a Submissions are welcome. STEM ambassador because I really Articles should be short, wanted to showcase my job and make focused, personal and students aware of pathology as a possible career choice. I also wanted passionate, and may to highlight our role in patient care to deal with any aspect of the public. I’ve visited a few schools to laboratory medicine. demonstrate pathology as much as I can; By Hayley Pincott, Associate Practitioner with students, I’ve stained cheek cells to They can be up to 600 in Oral Pathology at University Dental view in a microscope, grown bacterial words in length and Hospital, Cardiff, UK cultures, and demonstrated infection written in the first person. control. As part of British Science Week, I’m fortunate enough to have found a I spent the day at a primary school career that I completely love and feel where the theme was “exploration and Contact the editors at respected in. As a department, my discovery.” I had the opportunity to [email protected] colleagues in oral pathology and I are teach different classes about body maps, very rare. Why? Firstly because oral including the circulatory system, which pathology is so specialized that the let me talk about the structure of blood services we provide make us the only one of our kind in Wales; secondly, I feel, because our extreme specialization has led to a great working relationship with other healthcare professionals. However, “I feel we there is still a large pathology workforce whose situation is vastly different, and I need to act to know that not everybody in laboratory medicine feels that they are recognized engage young in the service they provide to patients and the impact they have on patient care. people in pathology The question we need to ask ourselves is, “Are we doing enough to change this?” and biomedical We are relatively unknown to the public – and, in some cases, even misunderstood science.” by other healthcare professionals – but In My View 15
and why it’s important to us in pathology. through their education. in the concourse of University Hospital The students were really excited about I’ve also recently competed in an online of Wales to raise awareness of laboratory extracting DNA from their cheek cells, project called I’m a Scientist, Get Me medicine, as well as visit schools) and which opened up a channel to talk Out of Here, which connected students National Pathology Week (November about the role of genetics. Another visit with scientists. It was an incredible 5–11), when we’ll be inviting primary to a primary school was about healthy experience and I can’t recommend it schools to visit on Friday and offering lifestyles, and that allowed me to talk highly enough – you don’t even need drop-in educational sessions to the about hemoglobin and the importance to leave the lab or office, so it’s great public on Saturday. of iron in carrying oxygen. I showed the for those who lack time or work in Not sure where to begin with public students how iron was found in a healthy remote areas. engagement? Organizations like diet by chasing bran flakes around a In general, I really enjoy public the Royal College of Pathologists, petri dish of water with a magnet! It engagement, showcasing and discussing IBMS, and STEM Learning have was a really fun way to introduce them what we do as clinical scientists, amazing ideas and resources online to hematology. One child even told me anatomical pathology technicians, for activities. Taking part is great fun that they thought science was meant to biomedical scientists, medical lab and has the potential to change lives. be boring, but what we were doing was assistants, associate practitioners, and the If each institution committed to just really fun. I think that if you engage many other roles involved in pathology. one science event a year, it would be children at a young age, their interest I have organized events for Biomedical a huge but achievable way to promote in science can potentially follow them Science Day (in which we’ll place a stand laboratory medicine.
of our healthcare environment. Most The Economics people are familiar with the statistic (ostensibly) stating that 90 percent “Much like diabetes of Personalized of a patient’s healthcare costs are incurred during the last six months of patients constantly Medicine their life. We also know that the value derived from that spend – as measured monitor their blood Can companies investing by patient quality of life during that in innovative liquid biopsy period – is often questionable. Yet sugar levels [...], technologies continue to companies continue to develop products ignore healthcare economics? and services that feed into and worsen cancer patients that statistic, rather than attempting to improve it. We routinely hear of a should constantly new “miraculous” chemotherapy drug that costs US$100,000 per regimen and be on the lookout extends patients’ lives by an average of about three months. This leads us for genetic changes to a complex question: How do we balance clinical, emotional, moral, and in their disease.” economic considerations? Are we, as By Ilan Danieli, Chief Executive Officer a society, directing our resources in a of Precipio, New Haven, USA sensible manner? one easy way to keep an eye on those The field of liquid biopsy is one of the changes: they shed DNA “ breadcrumbs” As an economics-trained executive of most exciting and promising areas in into the bloodstream. The ability to a cancer diagnostics company, I often cancer diagnostics. As we have learned, detect tumor-based genetic changes struggle to rationalize the business the biology of malignant tumors is via a simple, noninvasive blood test (a model and economic considerations constantly evolving – but they give us liquid biopsy) provides critical insight
www.thepathologist.com 16 In My View
into the patient’s current clinical state. changes may present in the blood between the technology’s ability and its Companies have seized on this concept, stream for “early warning” detection applicability. Payers realize this and are raising hundreds of millions of dollars via liquid biopsy. reluctant to reimburse for these large to develop sophisticated technologies Timing is everything. Catching panel tests; this is part of the reason that identify these changes and aid these changes early is critical, so it many of these companies raise such clinicians in treating patients. Some of is imperative to constantly monitor vast sums of money, with investors the leading players have spent millions the patient – both during treatment essentially subsidizing the payment of to develop broad panels with hundreds to quickly spot genetic changes that these tests because the market will not. of genes, running on sophisticated next might render chemo ineffective and The other disconnect revolves around generation sequencers with complex after remission in case the cancer the actionability of the tests’ results. bioinformatics platforms. As a result, returns. Much like diabetes patients Every piece of diagnostic information these tests are expensive – $5,000– constantly monitor their blood sugar is useless if it doesn’t drive a clinical 8,000 per test. levels to identify spikes and drops, decision. A panel of hundreds of There are two key applications of cancer patients should constantly be on genes may be relevant as a “catch-all, liquid biopsies, each with very different the lookout for genetic changes in their fire in all directions” tool for patients target audiences, clinical needs, usage disease so that doctors can respond seeking to turn over every stone in patterns, and related economics. before it’s too late. their genetic footprint. But for specific The first application is screening. One cancer patients with a diagnosed of the key factors in a successful battle disease, the universe of genetics-driven against cancer is early detection. Just treatments available – and thus, the as in other areas where preventative actual number of relevant, actionable medicine plays a prominent role, the “Every piece of genes to be interrogated – is limited. ability to identify genetic abnormalities So, for monitoring, large panels present that may cause cancer – before the diagnostic a tremendous overkill. disease ever arises – is an attractive Therefore, for the purpose of patient concept. As a once-in-a-lifetime information is monitoring, we need targeted liquid test, clinicians treating patients may biopsy solutions with panels that recommend that they and their family useless if it doesn’t deliver focused, clinically actionable members get screened using large panel information at a cost that enables tests to identify potential risk. Payers drive a clinical regular monitoring. Panels consisting may agree to cover the cost, balancing of a small subset of clinically actionable the high price against the potential decision.” genes relevant to the specific patient’s benefit of early detection; indeed, it’s type of cancer, using less complex and likely that patients who can afford costly technologies, result in tests at such prices themselves will want to a fraction of the price point of other “purchase” this insight into their future The problem is, these sophisticated broad NGS panels. As in many areas, health risks. tests are very expensive. A clinician, there is no one-size-fits-all technology. The second application is monitoring. payer, or even a patient may be able to Though some players focus on broad Science has taught us that cancer stomach a one-time $5,000 screening panels that provide exciting tools for constantly evolves – whether based test. But there is no doctor, and certainly patient screening, others take into on genetics, outside factors (such as no payer, who, in the current economic consideration economic factors, creating smoking or sunshine), or the very environment (which is unlikely to low-cost tests that are economically chemotherapy intended to battle it. A improve in the near future), will agree feasible for repeat testing. treatment that works today may become to pay for this test more than once. With the skyrocketing costs of ineffective tomorrow. And even patients And so, although this technology is healthcare, I believe solutions that fortunate enough to achieve remission sustainable for screening, it’s far outside embrace, rather than ignore, economic still face the terrifying possibility of the realms of economic reality as a considerations will play a prominent the cancer’s return. The good news is tool for ongoing cancer monitoring. In role in patient monitoring through that, in either scenario, those genetic that sense, there is a major disconnect liquid biopsies. In My View 17
Imagine personalized therapeutics, molecule drugs). Proteins and antibodies Coming Soon: where the dosing is adjusted in real time are larger and therefore more challenging based on each individual’s unique rates because they are highly diluted in sweat, Third-Wave of absorption and metabolism and their but we can now pre-concentrate such treatment responsiveness. Or something analytes by several orders of magnitude – Diagnostics even simpler: knowing for certain that also continuously and within minutes. the patient is actually taking the drug The need for continuous and at all. Imagine a complete, continuous contextual biochemical data biochemical view of lifestyle choices for a is clearer than ever – and cardiac patient, measuring potassium and “Our goal is enabling technology may be brain natriuretic peptide continuously on just around the corner. both good and bad days. Imagine mental something even or stress disorders without the need for biased self-reporting, with treatment based more powerful instead on quantitative cortisol responses to daily stressors. Or imagine a workforce than continuous safety system in which chemical toxin exposure is reliably recorded as internal biochemical data exposure and organ loading, not just in By Jason Heikenfeld, Professor at the terms of what volume of toxin may have for a patient; we University of Cincinnati and Chief breached protective clothing. Science Officer at Eccrine Systems Inc., Imagination may soon become reality want that data to Cincinnati, USA with the third wave of diagnostics – one that allows patients to take the laboratory be contextual.” When is it appropriate to attach the with them in the form of wearable moniker “stone age” to a previous era of biochemical monitoring systems. That’s science and medicine? You could easily what prompted our research group (in argue that pathology was in just such partnership with Air Force Research Labs) With this device, we hope to ride the crest a stone age before biofluid- and tissue- to seek not a technological solution, but of that third wave. Our goal is something based diagnostics came of age. So when rather to first uncover the fundamental even more powerful than continuous will our present-day capabilities be questions and challenges that would face biochemical data for a patient; we want similarly relegated? such diagnostics. It led us to a biofluid that that data to be contextual. As doctors, you The last century produced the first was at the time underused, but arguably had know just how limited a single data point wave of modern diagnostics based on the highest upside potential: eccrine sweat. can be – and you know that, in many cases, collected biosamples that had to be sent to Seven years after that first inspiration, you would find it more powerful to trade a laboratory for analysis. More recently, we we have now demonstrated a wearable absolute concentration accuracy for the have seen a second technological wave of device that can locally stimulate sweat for ability to closely monitor relative changes point of care diagnostics that put the lab multiple days, wick a tiny sweat sample in chemical analytes. Measuring such right in the hands of the doctor. This second up off the skin surface, and transport it changes can be particularly powerful when wave brings added convenience and can within minutes to a Bluetooth-connected they are placed into context. Coming back even allow the doctor to validate a diagnosis array of sensors that can continuously to the cardiac patient from earlier – was while in the presence of the patient. Despite report analyte concentrations. In essence, the spike in blood pressure due to eating these advances, the remaining gaps in we are extracting blood-level information a cheesesteak sandwich or because of a patient care are so significant that – one continuously and noninvasively, with less daily stress event? Or did the patient day not too far in the future – we may agree than five-minute time stamps. And it works simply stop taking their statins? For many that pathologists in 2018 were in the “stone exceptionally well for small, hydrophobic diseases, the coming wave will make age” of medical diagnostics. To visualize the analytes that partition readily through the current diagnostics look like interpreting gaps, it may help to start thinking about tissue layers between blood and the sweat a connect-the-dots picture before the what might soon be possible… glands (such as steroid hormones or small- connecting lines have been drawn.
www.thepathologist.com 18 Feature Feature 19
TELL ME, DOCTOR…
To keep pace with medicine’s future, pathologists need to develop much better communication skills – with great urgency
By Timothy Craig Allen
www.thepathologist.com 202 FeatureFeeature
“The single biggest problem in communication is the illusion “OUR INABILITY TO that it has taken place.” INTERACT EFFECTIVELY —George Bernard Shaw AND EFFICIENTLY “It is not what you say that matters but the manner in whichhich you say it; there lies the secret of the ages.” WITH OUR PATIENTS, —William Carlos Williams ADMINISTRATORS, AND Communication is everything – whether via a pathologygy report, NON-PATHOLOGIST a test result, a phone call or email to a colleague, a chance PHYSICIAN COLLEAGUES meeting with an administrator in the hall, or a coconferencenference room discussion. Communication is written words, eeyeye contact, IS TODAY’S GREATEST RISK tone of voice, body language, dress and appearance,ce, and much TO OUR PROFESSION.” more – and it’s something all physicians shouldould strive to improve. For pathologists – traditionally office-bound,ce-bound, glass glass slide-reading diagnostic physicians – improvedd communication is unquestionably the key to our future successuccess in today’s evolving world of molecular medicine, team-focusedam-focused patient FeatureFeature 21
care, and payment for quality. Iff we don’t do these things, we will not be ppartart of the future We pathologists must become better communicators to off medicine.medicine. ItIt’s’s a stronstrongg assertion to mamake,ke, butbut itit’s’s one I trulytruly meet our new responsibilities as more engaged medical team believeelieve – and we need to take eequallyqually strong action to remedy the players. Indeed, it’s becoming increasingly obvious that our situation.tuation. I ddon’ton’t tthinkhink it wiwillll bbee ooff any surprise to tthehe majority ofof traditional approach to communication (primarily sitting pathologistsathologists that communication is a problem, and yet we have notnot in our offices generating electronic pathology reports and evenven begunbegun to graspgrasp thethe solution.solution. LetLet’s’s use thesethese concerns not to making the occasional phone call) is our likely path to failure stokeoke fear, but to energize ourselves and other pathologists. TheThe as a profession. timeme fforor ddiscussioniscussion is nonow.w. Yet we resist even discussing how we might become better PathologistsPathologists oftenoften talktalk aboutabout whatwhat we thinkthink our non-pathologistnon-pathologist communicators. We seem to poke our heads out every now colleaguesolleagues want but, all too often, we don’t hear what they actualactuallyly and then to point out the need to improve our professional need.eed. WWhy?hy? Because we are not tatalkinglking to tthem.hem. We interinterpretpret or communication skills, before sticking our heads back into the divine among ourselves what we believe they need, often leaving sand and hoping it will all just go away. them unsatisfied when we are wrong. These are our professional The issue won’t go away. But we might disappear. Right now, colleagues – people who want good relationships with pathologists we are the physicians who hold intimate knowledge of the – and they are frustrated when those relationships don’t happen. details of molecular diagnostics and immunotherapy testing; They fall all over themselves trying to communicate with us until, we are the experts in cancer staging; we are the authorities on eventually, they give up, discouraged that they are not getting the pathophysiologies of diseases. But our industry colleagues what they need. There’s only one way to fix this problem: we must have become so frustrated with our reluctance – or even refusal speak to them. We need them to tell us what they want, what they – to engage with them that they are beginning to bypass us expect, how well we are delivering our services to our patients, and altogether. Instead, they take their testing questions and what we can do to improve. Strong, focused conversations with needs to interventional radiologists and treating physicians. our colleagues will help guide us in providing better patient care. According to other professionals with whom I’ve personally We must develop better, necessary, expected, and appreciated spoken, bypassing pathologists is quickly becoming a trend communication skills; we really have no choice. – a chilling circumstance that we need to begin changing right away. “IMPROVING Conversations with colleagues Our resistance to fully addressing communication comes, COMMUNICATION SKILLS I think, from a widespread sense of discomfort about the DOESN’T JUST MEAN issue. Nobody wants to be considered a deficient or inferior communicator, and the idea brings about a vague sense of ‘TALKING MORE.’” shame. Many of us even fear that we could become the subject of mmockeryoc if we openly confess to the elephant in the room: thatthat we areare notno as skilled at communication as we ought to be.be. Professional ccommunicationom is difficult, and it is hard to admit that it is difficult.difficult. An And yet, our inability to interact effectively and efficiently withou r ourpa patients, administrators, Finding time for culture change and non-pathologist physician colleagucolleagueses isis today’s greatest Changing the way pathologists communicate will require no riskrisk to our proprofession.fession. less than a cultural shift for all of us. Why? Because improving communication skills doesn’t just mean “talking more.” It isn’t WhatWhat do we need to ddo?o? limitedlimi to specific situations, such as when working intraoperatively withwith a surgeon. We are endeavoring to be efficient and effective • Ac Activelytively engage with the healthcare team and get a seaseatt professionalprof communicators in any situation that may arise as at thethe tatableble witwithh tthemhem wwhenhen ddecisionsecisions are bbeingeing mamade.de. we conduct our professional responsibilities. It’s not something • Routine Routinelyly anandd cocollegiallyllegially interact withwith our non- pathologistspa are incapable of doing; a few days spent at any pathologistpathologist physicianphysician colleaguescolleagues andand our aadministrators.dministrators. pathologyp conference will demonstrate just how communicative • Invo Involvelve ourselvesourselves in patient decision-making.decision-making. we can be in the right circumstances. Critically, what we need is more of our most precious resource – time.
www.thepathologist.com 22 Feature
Communicating successfully while still managing to allocate TheThe problemproblem cannot cannot be be solved solved by by aa coucoupleple ofof enough of our time to signing out cases or managing the classesclasses on howhow to tatalklk to otothers.hers. We neeneedd our bbestest laboratory is a significant, and often underestimated, challenge. minds workinworkingg on wwaysays to achieve the necessarynecessary To overcome it, we will have to change the way we spend our cultureculture changechange – takingtaking us out ofof our comfortcomfort zones days – doubly hard given that we are currently paid for the withoutwithout impactingimpacting our abilityability to getget the (paid)(paid) work done. The behaviors and actions that have guided us into our traditional balancebalance can bbee acachievedhieved – some ppathologistsathologists are succeedingsucceeding world of inefficient and infrequent communication. It’s a factor exceptionallyexceptionally wewell.ll. Now, we neeneedd tthemhem to ssharehare ttheirheir secrets we can’t ignore as we step up our efforts to communicate in andand act as rolerole momodelsdels to tthehe rest ofof us. ways that don’t directly lead to payment. But it’s also a factor we must learn to overcome. PhysiciansPhysicians ffirstirst In discussions with my ppathologistathologist colleagues,colleagues, I’ve discovered thatthat manmanyy of us see ourselves as jjustust that – ppathologists,athologists, rather “WE NEED TO than physicians.physicians. It’s vital for us to realize that, just like otheotherr medicalmedical pprofessionals,rofessionals, we neeneedd to constantconstantlyly workwork to bebe betterbetter UNDERSTAND THAT communicators.communicators. In our non-non-pathologistpathologist pphysicianhysician colleagues’ FOCUSED MENTORING world,world, itit’s’s simpsimplyly ununheard-ofheard-of not to speaspeakk witwithh a patient – and that’s the mindset we pathologists need to adopt. If the OR EDUCATION IN expectationexpectation fforor ototherher phphysiciansysicians is robust,robust, ddirect,irect, timely,timely, anandd COMMUNICATION clearclear communication, then whywhy shouldn’t it be the same for us? IfIf otherother phphysiciansysicians are taughttaught to communicate effectivelyeffectively d urinduringg IS NOTHING TO residencyresidency anandd bbeyond,eyond, tthenhen whywhy shouldn’tshouldn’t we ddoo tthehe samsame?e? BE ASHAMED OR Our jobs have changed significantly in recent years as science anandd tectechnologyhnology hhaveave aadvanceddvanced byby leapsleaps andand bounds.bounds. EMBARRASSED ABOUT – More and more, we practice “team medicine,” which means we AND CERTAINLY NOTHING needneed to interact witwithh ototherher doctors,doctors, nursenurses,s, bbioinformaticians,ioinformaticians, geneticists,geneticists, researchers… the list goesgoes on. This brave neneww TO SHY AWAY FROM.” worldworld into which we have been thrust can be disorienting, FeatureFeature 23
but it’s also giveng us the need – and the opportunity – to develop A COMMUNICATION communicationcommunica skills of the same professional level as our non- pathologistpathologist colleagues.c Practice makes perfect; if we pay consistent PROFESSIONAL’S attentionattention to developing those skills, we will quickly become PERSPECTIVE muchmuch more comfortable speaking with not only our professional counterparts,counterpart but with administrators, patients, and families as well. Soon, we’ll be having these interactions on a daily basis or Patrick Smith is Professor of Family eveneven more ooften, just as our non-pathologist colleagues do. Medicine, Chief Faculty Affairs Officer, We can non longer envision ourselves solely as laboratory and School of Medicine Associate Dean dwellers,dwellers, examiningex slides. Our prior communication training of Faculty Affairs at the University of (or lack thethereof,r especially for older pathologists) did not prepare usus for todtoday’say communication needs. But let me repeat: those Mississippi Medical Center, Jackson, USA. pathologistspathologists who cannot communicate and collaborate effectively He has a PhD in psychology with expertise willwill findfind it it in increasingly difficult – eventually even impossible – to in communication. be a meanimeaningfullyn contributing member of the increasingly broad medicalmedical teteamsam responsible for patient care. I propose that the discipline should reduce variability The iintroversionntr myth in communication patterns to ensure that all There is a widespread belief that many pathologists are communication is precise, clear, concise, and timely. To introvertedintroverted – one perpetuated through assumptions and improve, pathology needs to create curricula that focus jokes,jokes, somsomee even told by pathologists themselves. We need on communication. Other disciplines have extensive toto see this sstereotype for what it is – a corrosive generalization experience in creating a curriculum as an infrastructure thatthat arose ata least in part because of our discipline’s longtime for the communication competency dimension within lacklack ooff focus on our communication skills. The time graduate medical education. Perhaps adapting curricula isis ripe now to step out of our comfort zones and from other disciplines for application to pathology erasee that myth – for our patients’ sake and for our would be a way forward. It may sound daunting, but own.o We must work together to teach our residents help is available; many family medicine and primary betterb communication skills, building upon what care departments hire behavioral science faculty to do they learn as medical students; at the same time, (or at least assist with) this work. Good training leads we must assist our practicing pathologist colleagues who to good communication, and good communication struggle to enter the new world of medicine. We must help leads to good patient care! those pathologists who have generally not spoken with patients nor actively and routinely communicated with non-pathologist physician colleagues and administrators – while remaining sensitive to their needs, experiences, and priorities.
“PATHOLOGISTS ARE NOT POOR COMMUNICATORS BY NATURE; WE ARE SIMPLY OUT OF PRACTICE IN THE PROFESSIONAL SENSE.”
www.thepathologist.comwww.thepathologist.com 24 Feature
Perhaps most importantly, we need to understand almost from the ground up. Our challenge is greater,reater, butbut that focused mentoring or education in communication the principle remains the same: we are simply joiningoining our is nothing to be ashamed or embarrassed about – and colleagues on their quest for better communication.n. certainly nothing to shy away from. We cannot let the To fully develop and maintain superior professionalofessional introversion myth stop us or impact our participation communication skills, we must use them frequently.requently. in multidisciplinary medical care. In fact, we should embrace continuous communication training as a team. Even our role models – those pathologists who are already visible and interactive – could benefit from continuing “PATHOLOGISTS HAVE education. Strong communication skills are taught in TRADITIONALLY MET medical school, but in my experience, pathology residents have traditionally let those skills fall into disuse, as they EVERY CHALLENGE have not been necessary for us to practice successfully as THAT HAS ARISEN IN physicians. Forging communicative relationships and getting out of our comfort zones as pathologists means we must OUR PROFESSION; THIS IS rethink who we are. MERELY THE
No shame, no blame NEXT IN LINE.” We must recognize that pathologists are not poor communicators by nature; we are simply out of practice in the professional sense. I expect that pathologists communicate as well as anyone else in everyday situations – with family and friends, while running errands, or even as patients! And I suspect that most pathologists Communicating well once every six weeks misses the mark. were reasonably skilled communicators in medical school. Despite We must habitually communicate efficiently and effectively the stereotypes, most of us didn’t choose pathology because with the administrators in the C-suite, the surgeon in the we lacked the ability or inclination to interact with others! operating theater, the nurse in the hospital room, and the Unfortunately, many of us have passively allowed our professional patient in the clinic. We should build frequent practice into communication skills to wither from lack of use. If we make a our communication goals – not every six weeks, but every six point of starting to use them regularly, I anticipate that they will hours or even every six minutes. rapidly return and improve. Our charge is clear, and the risks of not heeding the call One thing I want to make extremely clear is that pathologists are just as clear. Pathologists have traditionally met every shouldn’t consider less-than-perfect communication a failing. challenge that has arisen in our profession; this is merely the Instead, we should acknowledge that it’s not a skill with which we next in line. We should have every confidence that we can are all equally comfortable – and when we hear other pathologists develop and maintain excellent professional communication say things like, “I don’t want to talk to patients,” or, “I don’t feel skills – and we can start by talking amongst ourselves about comfortable speaking to colleagues,” we should encourage them it. We all know the names of pathologists who are strong to find ways of overcoming their discomfort. Risk managers will advocates and advertisers of the discipline – so we should be readily tell us that the biggest risk for medical malpractice among asking them: how do you do it? What is your advice? How physicians is poor communication. We need to jump feet-first should we be talking to one another, to other health care into the challenge of getting out of our offices and meeting our professionals, to patients? In this way, we can progress in the colleagues’ and our patients’ needs. brave new medical world from the “doctor’s doctor” to the “patient’spatient s doctordoctor.”. Our challenge is greater WhoWho knows?knows? OOnene ddayay soon, we couldcould bebe thethe doctorsdoctors whomwhom Our non-pathologist physician colleaguesgues othersothers considerconsider rolerole modelsmodels forfor professionalprofessional communication! communicate many times a day, often momentnt to moment, so even those less comfortable with it rapidlypidly TimothyTimothy CraigCraig Allen is Professor and Chair of thethe develop and maintain a good set of skills. As a result, DepartmentDepartment of Pathology,Pathology, TheThe UniversiUniversityty ooff improvement typically involves little more than “brushingrushing MississippiMississippi Medical Center, up” on those skills. We, in contrast, must developlop ours Jackson, USA. Feature 25
FROMROM THETHE section may alter the course of an operation is important. Along those lines, it’s similarly vital to tell the surgeon what is needed to make decisions – even though the pathologist can’t make the HORSEORSE’S MOUTH “official” call themselves. An example of this from my career was a late night/early morning operation in a patient with primary sclerosing Non-pathologistNon-pathologist medical professionals cholangitis. There was little imaging evidence or gross evidence give us their thoughts on communicating that the distal bile duct would be involved with tumor. However, my pathology colleague made sure he understood the clinical with pathology situation and the decision to be made based on the frozen. He clearly told me that he couldn’t officially call it positive, but Inter-specialty communication is vital – that’s a given. But it’s that he was very concerned, and that more tissue would likely not enough to simply be aware of its importance; pathologists, not help him make a better call. Based on his concern, we like all other disciplines, must play an active role in ensuring that extended our resection to include a pancreaticoduodenectomy the lines of communication are open. Too often, pathologists (something we would not have done as a matter of course, guess at the needs of other specialties instead of asking directly, because it increased the risk of postoperative complications). which could lead to better information and, ultimately, more Ultimately, the margin in question was positive and the final productive conversations. So what do surgeons, radiologists, margins were negative. This collaborative discussion in the and other non-pathologist physicians need? Two other medical middle of the night had a huge impact on the outcome of the professionals share their views… patient, who is now eight years post-op. Another important area in which surgeon-pathologist The surgeon communication is important is the identification and marking Christopher Anderson is Professor and of margins. Having my colleague come and ink a specimen James D. Hardy Chair of Surgery, in the operating room is a great pleasure. We both know that Chief of the Division of Transplant and we are on the same page moving forward, and it humanizes Hepatobiliary Surgery, and Medical our interactions, making further communication easier. Director of Abdominal Transplant at the Independent of how a particular specimen is marked, having University of Mississippi Medical Center. the surgeon-pathologist team on the same page is important, and poor communication here can lead to inappropriate patient What is the current state of pathologist communication? care decisions down the line. Highly variable. I think pathologists who specialize in a focused area naturally develop relationships with surgical and medical How can pathologists get from where they are now to where they colleagues in the same area. An example is transplant medicine, need to be? in which the nephropathologist or hepatopathologist is integral I think specialty-focused teams can really facilitate this. Interactions to the team. Communication on such teams is often quite good, in tumor boards, specialty multidisciplinary clinics, or other which is a real bonus for patient care. However, in general, conferences help break down the physical and logistical pathology communication can be hit-or-miss. Often, the only divide that often exists between hospital operating suites and direct communication between pathologist and surgeon is during pathology labs. Phone calls or emails with questions about a a frozen section report. There is great opportunity to improve case should be encouraged (in both directions). Finally, the communication – from both sides. pathologist-surgeon relationship is important and special. I encourage pathologists to come to my OR and talk, ink What is the necessary landscape for pathologist communication? specimens, or just visit. Equally important, surgeons should be Ideally, I think that pathologists and surgeons should have a encouraged to visit the frozen area to review slides and discuss very collaborative relationship that fosters clear, timely, and cases with pathologists. Too often nowadays, the locations of focused communication to guide patient care. Understanding pathology departments and OR suites do not easily facilitate the clinical picture is paramount. Quick communication these activities, but that’s an obstacle we need to overcome to of results (whether positive or negative) and asking clarifying establish and maintain collaborative relationships. It takes a questions about the clinical picture are always welcome. In the team to achieve the best patient outcomes, and pathologists operative setting, understanding how the results of a frozen are important and integral members of that team.
www.thepathologist.com 26 Feature
The radiologist WhatWhat is the necessary landscape for pathologist communicationcommunication?? Harpreet Talwar is Assistant Pathologists,Pathologists, as specialists,specialists, must bebe more communicative Professor of Radiology and Chiefief ofof with referring physicians. In the age of personalized medicine Breast Imaging at the University of and multi-specialty patient care, I believe it is judicious for each Mississippi Medical Center. specialty to recognize the significance of their role in the care of each patient. We are encountering increasing numbers of medically What is the current state of pathologist complex patients (thanks to factors like longer lifespan and greater communication? obesity), making it more important than ever that we take a unique In my opinion, the current state of pathologist communication approach to each patient’s diagnosis and treatment. It behooves is, at best, decent. I have personally interacted with pathologists each specialty, including pathology, to participate as actively in both academic institutions and private practice. To me, it as possible by interacting with referring physicians. Rigorous seems that pathologists in private practice seem to have a better communication between specialists also avoids unnecessary grasp of the need (or perhaps a more deep-seated desire) to medico-legal pitfalls. Personally, I am a big fan of a quick phone be more communicative with referring physicians for results call or email when I encounter a problem or an unexpected result and other critical findings. Are they keeping the referring in a breast biopsy. I try to include pertinent patient history and my physicians happy to retain their business, or do they have a own best guess (even if it’s just “benign” or “malignant”) in these greater sense of responsibility in patient care? I believe it may brief points of contact, but in more complicated cases – for instance, be a combination of the two. To maintain strong business amyloidosis of the breast – I prefer a discussion amongst all team with referring physicians, I believe private pathologists may members to select and implement the best treatment pathway. want to keep them up to date with their patients’ details – but In multi-specialty tumor board meetings, I definitely rely very I also believe that, in the process, they may achieve greater much on the pathologist’s input to ensure concordance of results, satisfaction in patient care. As far as academia goes, perhaps markers, and margins so that we can optimize the patient’s care. greater patient volume and/or the burden of other duties, such as teaching, may not give academic pathologists the luxury How can pathologists get from where they are now to where they of time private practitioners enjoy. It is also possible that need to be? pre-established referral patterns instill a sense of security in Pathologists have to get out of their comfort zone and be the academic pathologist, making them think that a phone call recognized as active physicians in patient care. Multi-specialty (or lack thereof) will not necessarily have much effect. Unlike tumor boards have defined the roles of each specialty and forced those in pprivaterivate ppractice,ractice, theythey have no additional incentive to the traditionallytraditional “paraclinical” specialties, such as radiology and keepkeep ttheirheir referringreferring physiciansphysicians “happy.”“happy.” pathology,pathology, to beb more involved in the decision-making process. PhysiciansPhysicians hahavev higher job satisfaction if they feel more involved inin ppatientatient care – and the job description of a pathologist is moving towardtoward ever mmore active participation. “PATHOLOGISTS I am not awawarea of any referring physician who would get annoyed HAVE TO GET atat a ppathologistathologis who took the time to phone them about a patient. After all, whowho likes to log in to the EMR for test results when OUT OF THEIR COMFORT you can ddiscussiscus them with the pathologist directly? I believe there ZONE AND BE areare no situatisituationso where it’s better to hedge and include a broad differential “just“ju in case” than to have a conversation, however RECOGNIZED AS brief,brief, aaboutbout ttheh patient’s symptoms and the referring physician’s ACTIVE PHYSICIANS IN thoughtthought processes.proces PATIENT CARE.” Join in the conversation or submit a question to Timothy Craig Allen by using #PathComm and tagging @pathologistmag on Twitter. Our author will be answering all questions on September 5th at 9:30am CT / 3:30pm GMT+1. Official society partner of The Pathologist
We are proud to announce our groundbreaking partnership with the American Society for Clinical Pathology (ASCP) the world’s largest professional membership organization for pathologists and laboratory professionals.
Register now at www.thepathologist.com/register to get The Patholoigist in print delivered direct to your door
As a fully registered user you will benefit from:
• Unlimited access to ALL articles • Full access to digital and archived copies of every issue of The Pathologist • Print (and PDF) copies delivered direct to you • Email news alerts • Networking opportunities • Application Notes and Product Profiles
Empowering pathologists to build a better future for pathology 28 Sponsored Feature
How useful is genomic Childhood data in supporting advances in diagnosis, Cancers Are prognosis, and treatment selection? Different Genomic data have changed everything. The features that drive pediatric When we started cancers are vastly different to doing genetic analysis those in adult disease – so how of childhood cancer, can we ensure that children are we were assaying accurately diagnosed and treated? single alterations with tools like PCR and An interview with Tim Triche, Co-Director Sanger sequencing of the Center for Personalized Medicine at because we didn’t Children’s Hospital Los Angeles, USA have the knowledge or the technology to do How do childhood cancers differ from anything more broadly. For those in adults? example, when poor prognosis Adults acquire a mutational burden over childhood neuroblastoma was the course of a lifetime; the longer you PMROIHXSXLIEQTPM½GEXMSRSJE live, the more mutations you acquire and gene called MYCN, it quickly the greater the probability that you will became obvious that we needed develop cancer at some point. This growing to develop an assay for that load of mutations is why cancer in adults EQTPM½GEXMSR8IWXHIZIPSTIVW increases over time. scrambled to create one (and and gene fusions are not easily In contrast, infants and children have succeeded) – but, of course, that was detected by DNA sequencing; had no opportunity to accumulate only one of multiple disease features we they can be seen much more readily at mutations, so it’s not possible that acquired needed to examine. And so, for years, we the RNA level. Ideally, a pediatric cancer mutational burden causes disease. Clearly, kept developing one assay after another, panel should look at both RNA and DNA pediatric cancers arise from a different each of which was critical to allocating to detect the entire spectrum of common process. It comes as no surprise, then, patients to high- or low-risk treatment abnormalities in children. At the RNA XLEX[I½RHZIV]JI[EGUYMVIHQYXEXMSRW protocols, but none of which provided level, it should detect gene fusions and in childhood cancer; instead, we see a enough information in isolation. For expressed gene abnormalities; at the large number of patients with inherited example, patients with MYCNEQTPM½GEXMSR DNA level, copy number alterations and gene defects and unusual features QE]EPWSLEZIGSEQTPM½GEXMSRSJALK, for sequence abnormalities, including insertions like copy number alterations, gene which we have targeted inhibitors – but and deletions (InDels). Next generation EQTPM½GEXMSRWSVGLVSQSWSQEPFVIEOW with a single-gene MYCN copy number sequencing (NGS) platforms can look at leading to gene fusions – alterations that assay, you wouldn’t have that information. both to spot multiple abnormalities in one are much less common in adult cancer. The solution? A platform for all of the large, comprehensive panel, so they have Adult cancers usually have mutational necessary analysis – MYCN copy number, been a huge boon to diagnostic accuracy HVMZIVWQER]SJ[LMGLEVIMHIRXM½EFPI c-Myc expression, and all of the unique and treatment selection. so the pharmaceutical industry focuses on JIEXYVIW[I½RHMRGLMPHLSSHGERGIV%W therapies that target those drivers – but we’ve discussed previously, childhood What can we achieve in the future by because most childhood cancer is closely cancer is fundamentally different to cancer using this technology more broadly? related to genomic alterations caused by in adults – and a major factor affecting its Although pediatric oncologists and development gone awry, the treatments accurate diagnosis is that we see different pathologists are a collaborative group, it that work for adult cancers are often not drivers, like copy number variation and GERFIZIV]HMJ½GYPXXSGSQTEVIVIWYPXW appropriate for pediatric disease. chromosomal breaks. Chromosomal breaks when each physician performs different Sponsored Feature 29
assays in different institutions in different been an extraordinary What distinguishes ways with different content. One of the success. Over 60 ICON from other QSWXWMKRM½GERXSTTSVXYRMXMIWSJJIVIHF] percent of the patients such databases? a standardized panel that incorporates the we examined (more than The biggest difference important features seen in childhood cancer 200 in the past six months) is that ICON is intended MWXLEXJSVXLI½VWXXMQIRSQEXXIV[LIVI had at least one actionable to be a clinically relevant, you run the assay, you’ll get the same results mutation – something nobody multiple-contributor, – so, in theory, you can compare your data expected. Now, in addition to our multiple-user, real-time database to that of someone at another institution conventional tumor board, we have a that contains both genomic and clinical or across the globe. This is essential for bi-weekly molecular tumor board in data on the included patients. Many cancer in children, which is far less common which we discuss an average of six to 10 existing databases have very little clinical than in adults. Learning what is and is not patients and make treatment decisions information linked to the genomic data, common – and, even more importantly, based on the childhood cancer panel ERHIEGLMWX]TMGEPP]JSGYWIHSREWTIGM½G what is and is not clinically relevant – is test results. X]TISJXYQSVSVXYQSVWERHEWTIGM½G GSVVIWTSRHMRKP]QSVIHMJ½GYPX analysis platform. These can range from NGS methods generate many What is ICON? older microarrays to whole exome candidate abnormalities, It occurred to us early on sequencing, commercial panels, custom or variants of unknown that if researchers at panels, or advanced research methods WMKRM½GERGI :97 FYX multiple institutions like epigenetic analysis of methylation, knowing which ones are all running the LMWXSRIWGLVSQEXMRQSHM½IVWERHXLIPMOI matter is an ongoing same assay and Although each is useful in its own right, challenge that can be accruing the same none necessarily leads to direct clinical met only by increasing data, it provides utility; in contrast, a comprehensive, all- our knowledge about a rich opportunity inclusive database can at least document which ones relate to for collaboration. MRGMHIRGIERHPMROEKIXSWTIGM½GXYQSV disease onset, progression, Why wouldn’t we types. When combined with a core treatment, or outcome. share that information so HEXEFEWISJWTIGM½GKIRIXMGHIJIGXW that everybody learned a little PMROIHXSWTIGM½GTEXMIRXWMRGSVTSVEXMRK bit more? That idea was formalized common data elements representing the in the creation of the International content of the panel, it becomes possible ±*SVXLI½VWX Childhood Oncology Network (ICON), to decide – for instance – d whether or which allows us all to share data, best RSXEKMZIR:97MWPMOIP]GPMRMGEPP]VIPIZERX time, no matter practices, and potentially linkage to Alternative methods like statistical analysis clinical treatment protocols matched to of how often a given polymorphism where you run the WTIGM½GKIRIHIJIGXW8LMWFIKER[MXLSYV occurs in a given population are useful own institutional database of Children’s guides, but fail to capture whether those assay, you’ll get the Hospital Los Angeles cases, but has now variants are associated with disease. With grown to include multiple databases of larger numbers of cases, we acquire the same results.” childhood cancer from published studies power to decide based on statistical from around the world. Not only can analysis linked to combined clinical and oncologists and pathologists compare genomic data – a very powerful approach each new result they obtain to previous that is not possible without a database Science and medicine are moving ever ones from around the world, but the new like ICON. more toward collaborative approaches result also adds to the existing database, and shared data, and standardized increasing its content and relevance. How can others join ICON ? results (or “common data elements”) ICON is a mechanism to share that It’s easy – just contact Thermo Fisher ensure that we’re all sharing the same information – and it’s our hope that it will 7GMIRXM½GERHXLI][MPPKYMHI]SY-XSRP] information. At our institution we have foster more and better clinical research requires signing a simple document and implemented an NGS panel that has into childhood cancer than ever before. using the standardized testing solution.
www.thermofisher.com ECP Booth 60
Get Comfortable Prevent Neck and Back Pain with an Ergonomic Upgrade
Working at the microscope for long periods without the correct ergonomic setup can quickly lead to back and neck pain. Now you can ensure continuous comfort and protect against health issues with a simple upgrade to our ergonomic tilting tube.
∙ 3D adjustments for optimal eyepiece positioning ∙ Easy camera integration for fast sample documentation and archiving ∙ Available for all Olympus BX microscopes*
If you plan to visit ECP 2018 (8–12 September in Bilbao, Spain), an expert will be present at the Olympus booth (no. 60). Visit us for a free consultation on how to minimize pain and discomfort when working long hours at the microscope.
www.olympus-lifescience.com
Postbox 10 49 08, 20034 Hamburg, Germany | Phone: +49 40 23773-0 | www.olympus-europa.com In Practice Technologies and techniques Quality and compliance Workflow
32-33 Wellness: A New Kind of Best Practice Pathologists are at high risk of burnout, so what can we do – institutionally and individually – to increase resilience and wellness? 32 Inn PPracticeractice
A dangerous situation spend time with them brainstorming ideas Wellness: Data on physician burnout in the United to better our department, and then – most States overwhelmingly points to a national importantly – we act on those suggestions. A New Kind of crisis. Being a physician is, in fact, We already have requested several changes considered a risk factor for suicide – with (such as new microscopes to make work Best Practice an incidence rate previously reported as 1.8 easier and more comfortable), and we intend times the national average (1,2). Pathology, to continue developing and passing on new To give patients the highest unfortunately, is no exception to this ideas. And, finally, we all have responsibility level of care, we must make rule; the burnout risk for pathologists is for our own individual wellbeing – so we’ve sure that we ourselves are reported at about 42 percent (3). Not many started a series of Wellness Talks to teach our happy, healthy, and engaged departments of pathology and laboratory trainees about different approaches to stress medicine address this issue, and even fewer and burnout, including physical and mental By Marisa Saint Martin pathology residency programs offer formal health, mindfulness techniques, and more. resilience training to help those at risk As physicians, our practice goes beyond alleviate the strain. The burnout dilemma Talking about wellness merely what we do at the microscope or takes a multidimensional form: it involves Initially, we conducted a survey of our in the clinical laboratory. It’s well known the individual, the group, and the system. pathology residents that indicated an that patient satisfaction is constructed In the case of pathology, this means the overall need for wellness and resiliency on a foundation of healthcare provider individual pathologists, the laboratory or training. After some discussion as to the wellness and satisfaction. When department, and the hospital or institution. best approach, we settled on monthly providers are engaged and happy, The burden extends to all colleagues in talks (including a free lunch!), which we the result is safer and more efficient the laboratory and the healthcare arena; supplement with additional education. encounters with our patients. But is that although the individual burnout statistics I organize the talks myself, but the how we always feel? And if not, what may be different for nurses, technologists, residents drive them. Each meeting starts can we do to ensure that our patients laboratory scientists, or clinicians, the fact with a moment to celebrate and be grateful (be they cells on a slide, blood in a test remains that it is a systemic issue with no for something, followed by a short talk on a tube, or human beings in a hospital) are single easy solution. specific subject, such as burnout symptom receiving our best care? There is hope, though. Wellness and recognition, suicide prevention, physical resilience can be taught, and groups and health, the benefits of sleep, or the effects institutions can put formal training into of gratitude on mental health. After the place to help those who work there to didactic portion of the meeting, we move into At a Glance weather the storm. In our department action items and brainstorm what we can do • Pathologists, like all physicians, at Loyola University Medical Center, next to improve the department’s wellbeing. constantly face the challenge we are approaching the issue with our We accomplish a lot with each session, but of burnout and other mental residents using a comprehensive tri- I think the biggest driver of attendance is health issues dimensional strategy. Our goal? To that the attendees feel free to express their • To seek a resolution, we must provide them with tools to maintain opinions in a non-judgmental environment. approach the problem using a tri- the joy, humanity, and satisfaction of Because I want to respect the confidentiality dimensional strategy that considers practicing pathology and laboratory of what is discussed at the meetings and give three angles: institutional, group, medicine throughout their careers. people a space to express themselves freely, and individual The tri-dimensional approach involves only our trainees are invited to attend – and • It’s especially effective to target strategies for the institution, the group, and I make it clear to them that everything we trainees – often at a high risk the individual. At the institutional level, we discuss is private, except for action steps that of burnout – who can then take try to improve working conditions for all they permit me to bring up with the people what they have learned to their physicians. The administration at Loyola and who can enact change. future workplaces at the Gottlieb Memorial Hospital plays a Based on the success of these talks, we • Practical tips and tricks can help key role in this. In our case, the “group” refers are now in the process of formalizing a institutions implement resilience to pathology department trainees (residents, wellness curriculum that will focus on and wellness training fellows, rotating observers, and students). We stress prevention, management, treatment, Anonymous responses to the six-month and one-year surveys on Loyola’s wellness talks. and professional and life purpose. Our or it can include all of your faculty • Consider working with other ultimate goals are to increase wellness members. Our institution pairs first- departments to develop an among our pathology residents to prepare year residents with senior residents in institutional resilience resource. them for a high-stress environment before first-time rotations, and each resident This grants easy search access entering the workforce, and to increase chooses a faculty mentor during their to volunteer activities and their ability to bring the tools they have first year. interdepartmental networking – learned to their new workplaces • Provide opportunities to learn activities that contribute to many mindfulness and meditation people’s overall wellness. Tips and tricks techniques. We discuss and practice We have implemented a number of those techniques during the wellness There is no one-size-fits-all solution. initiatives to assist our residents, many talks, so people receive regular Each one of us may have a different way of which are applicable to all of our refreshers and can ask for assistance of achieving balance and managing the colleagues. What can other institutions if needed. multitude of demands in our personal and take away from our approach? • If you are able to provide discounts professional lives. But remember: we don’t to other resources, such as your have to travel this path alone. Together, • Ensure that your residents have access institution’s fitness center (or even we can create an environment where our to sessions with trained resilience a nearby gym or wellness facility), personal goals and our love for medicine coaches. We provide this service in this can create opportunities for can coexist and thrive. addition to standard psychological your colleagues to pursue wellness help, an Employee Assistance on their own time. For instance, Marisa Saint Martin is Assistant Professor Program, a Care for the Care Giver pathology residents at Loyola receive of Pathology at Loyola University Medical Program, and chaplaincy services. discounted admission to the school’s School, Maywood, Associate Director of • Have a portal on your internal Fitness Center. the Residency Program, and Laboratory network that allows your staff • Stay abreast of how well your Medical Director at Gottlieb Memorial members to access wellness and initiatives are working and how your Hospital, Melrose Park, USA. resilience resources, such as those faculty and staff are feeling. We named above. At Loyola, our conducted a brief pulse survey to References residents and faculty can find identify one positive, one frustration, 1. LB Andrew, BE Brenner, “Physician suicide” these programs by tapping into and one thing that needs to be (2015). Available at: https://bit.ly/2AWxbAo. our website’s Resilience Page, changed at the beginning of our Accessed August 9, 2018. so accessing them is quick study, then ran separate wellness 2. S Kishore et al., “Breaking the culture of silence on and convenient. surveys at the six-month point physician suicide” (2016). Available at: https:// • Foster a successful mentorship and after one year. Results showed bit.ly/2OqK1ZB. Accessed August 9, 2018. program within the department. a significant trend toward better 3. T Parks, “Report reveals severity of burnout by This can focus on partnering new individual stress control and a more specialty” (2017). Available at: https://bit. residents with those further along, positive overall environment. ly/2kz5UrH. Accessed August 9, 2018.
www.thepathologist.com Oncomine solutions for clinical research—answers at your fingertips
One NGS workfl ow enabling you to provide comprehensive answers from any sample type
With Ion Torrent™ Oncomine™ solutions for clinical research, you will be able to fl exibly generate comprehensive and relevant profi les for every clinical research case—from initial biomarker profi ling of FFPE tissue, to alternative analysis from a liquid biopsy in the absence of suffi cient tissue, to mutational load assessment for immunotherapy research insights—all in one streamlined and automated workfl ow that includes end-to-end informatics and reporting tools.
Find out more at thermofi sher.com/oncomine-oncology
For Research Use Only. Not for use in diagnostic procedures. © 2018 Thermo Fisher Scientifi c Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientifi c and its subsidiaries unless otherwise specifi ed. COL32344 0418 NextGen Research advances New technologies Future practice
36-43 The Inside Story How the Maastricht MultiModal Molecular Imaging Institute aims to improve the diagnosis and understanding of disease. 36 NextGen
The Inside Story
The Maastricht MultiModal Molecular Imaging Institute (M4I) continues to break new ground in mass spectrometry imaging – providing pathologists with better diagnostic tools, and giving us a close-up view of the complex molecular machinery that underpins health and disease
By Ron Heeren
Breaking boundaries is a key theme of my work, and pivotal to all fields of science. The motivating force of most scientists is to break through boundaries of knowledge – seeing something that no one has seen before is On a more down-to-earth level, puzzle. It’s clear to me that the future an awe-inspiring experience. Whether they breaking boundaries between disciplines of medicine lies in clinicians’ gaining are building better microscopes to visualize is a crucial facet of our work. We need much more detailed information about molecules in a cell, or better telescopes to to make sure that our knowledge crosses the patient to deliver more personalized detect far-away stars, scientists have the the boundaries of our own disciplines to treatment with a better outcome. same drive – they want to see what they answer the big questions society faces. This personalized medicine – or, as cannot yet see. Whether it is in life science, food, scientific visionary Leroy Hood terms water or energy, input is needed across it, personal, predictive, preventive and the boundary of mathematics, physics, participatory (P4) medicine – is where At a Glance chemistry, biology, and medicine. I focus my work. • Cutting-edge research in mass I have always been driven by curiosity; To make personalized medicine a spectrometry imaging (MSI) I just love figuring out how the world reality, we must find a way to resolve the development, informed by detailed around me works. If the switch on incredible complexity of the human body molecular data, can advance the field my bike light stops working it’s not and apply it in clinical decision-making. of precision medicine enough to simply replace it; I want And that involves gathering as much • Researchers at the Maastricht to understand the problem and try to information as possible at the genome, Multimodal Molecular Imaging fix it. The same curiosity that sees me proteome, and metabolome level and Institute are improving MSI to dismantling my bike light also motivates coupling it to disease manifestation, quickly differentiate between isomers my work, albeit the questions I ask treatment choices and, ultimately, patient and identify changes over time are much bigger! At the Maastricht outcome. After we gather all of this data, • Integrated MSI tech in intelligent MultiModal Molecular Imaging we can start building complex clinical tools like the iKnife could become Institute (M4I), we seek to visualize decision-making models. Developments an invaluable tool to increase the fundamental molecular processes, in information technology, machine accuracy of tumor resection and and apply that knowledge to improve learning and artificial intelligence have reduce the invasiveness of surgery human health. already started to play an increasingly • Growing interest in MSI across Clinicians often have very sparse important role in this process, as the multiple fields will hopefully lead information to work with – they sheer volume of the available personal to the creation of revolutionary are forced to make life-and-death data becomes too daunting to interpret targeted diagnostic aids decisions without all the pieces of the for an individual clinician (or researcher, Particle-based
History of Mass Spectrometry
Imaging Laser-based
There are three main categories of mass Reproduced from: RMA Heeren, “Getting the picture: The coming of age of imaging MS”, spectrometry imaging (MSI): Int J Mass Spectrom, 377, 672-680 (2015). secondary ion MS, ambient MSI, and laser-based MSI this century for a suitable ionization even within a single class, is still technology to be conceived – and unsurpassed. Spatial resolution has In the 1960s, secondary ion mass desorption electrospray ionization evolved over the years from hundreds spectrometry (SIMS) appeared as one (DESI) is still one of the main ambient of micrometers to just 1–5 micrometers, of the first surface analysis technologies. imaging technologies for non-vacuum- making the technology compatible Researchers employed energetic ion beams compatible surfaces. It deploys a with morphological features of interest to generate secondary ions that would tell supersonic jet of charged droplets that to pathologists. them something about the properties impact the surface and pick up surface All three types of imaging, whether of a surface. At first, they focused on molecules. Like SIMS, it involves particle- or photon-based, have benefited elementary surface composition, but charged particles that impact a surface, from the technological advances in they quickly realized that SIMS could but the desorption and ionization mainstream mass spectrometry. MSI can be deployed to study surface chemistry, mechanisms are markedly different. The now be routinely performed on modern which piqued the interest of physical development of DESI resulted in a new hybrid high-resolution instruments. In chemists. Modern SIMS instruments can field of imaging research and is used to addition, developments in time-of-flight study organic surfaces in unprecedented directly study plant surfaces, hydrogels, (ToF) mass spectrometry have provided detail. Recent advances have included the water-containing polymers, drying paint new high-throughput approaches that implementation of gentle Ar-cluster beams and bacterial colonies on agar plates, to allow us to screen a tissue section in that sputter surface without any organic name just a few. It is also widely used in 10–15 minutes, dependent on size and subsurface damage, allowing us to build biomedical tissue imaging, as it requires required spatial resolution. These two full three-dimensional molecular models little to no sample preparation. methods combined – high-throughput of single cells. Equally revolutionary Though SIMS and ambient techniques MS with high-resolution MS – are was the implementation of tandem mass have been valuable, the laser-based the cornerstones of MSI-based clinical spectrometry for structural identification, technologies have arguably had the biggest diagnostics. At M4I, we routinely use which moved the field from “pretty pictures” impact on MSI. In particular, MALDI- them back to back – high-throughput of individual m/z values to interpreted MSI has revolutionized MS-based MALDI-ToF-MSI to screen tissues from biological images. These technologies have molecular pathology. The key advantage large patient cohorts, complemented with found their way into application domains over the other two technologies is that high-resolution FT-based MSI on selected ranging from material sciences, catalysis, MALDI-MSI can offer information samples to identify the molecular profiles forensic sciences, semiconductor sciences, on a much wider variety of compounds, found. New methods are surfacing fast; coating technology and, of course, biology including metabolites, lipids, peptides, three years from now, the MSI field will and biomedicine. proteins, and intact polymer molecules undoubtedly look very different to today. Ambient MSI was developed when directly from complex surfaces. Even As more and more disciplines adopt (and researchers realized that not all samples though every molecular class requires adapt) our technologies, I believe we will were suitable for the vacuum of a a different sample preparation protocol, move from evolutions to revolutions in mass spectrometer. It took until early the breadth of molecular coverage, the years to come.
www.thepathologist.comwwwwwww.thhepae thohologist.comoom 38 NextGen
spectrometryspectrometryr andand, more specifically,p mass spectrometryspectrometspectrometrsppectromettrytryry imaging (MSI)MMS is central to MassMass Spectro-Spe the endeavor.endedeeavor.ava o Mass spectrometryr alreadylread “To make providesprovidrovvideides insightsi into manyy of the molecularmole metry Imaging 101101 classesclclasslassesa seses foundf n in complex cclinicalcal samples, personalized suchsu as bloblood,oooo urine, cerebrospinalebbros fluid, ByB SShaneh Ellis andandmanymoreCombinedwithmodernd many more.mmoremo Combined CombiCbidithCCbibiidinenededdithddith withi h modernd medicine a chromatographicchchromatogrchr raphicr phichic separatiseparationra on technologies Mass spectrometry imaging iss a (GC,GC,C, CE, LC,L LLC×LC,LC×C aandnd so on) mass reality, we must find molecularol imaging technitechniquequue thatthatt spectrometryspectrrromomometro ryr is capableableble off unraveunravelingling tthehe exploitse a uniquen featureuree of eveeveryryy moleculararr ccocomplexityomplexityo pyp y thathatatt wew neeneed to form a way to resolve the moleculemom lecule – its weight. ByBy measuring thet input forfoor ouoour clinical ddecision-makingecision-makingecis thethe wewweightight (mass-to-chargech ratio) of models.models. MSMSISI tatakesakkes ththisis detaildete ail to thethe nextnext incredible complexity allall the moleculesmom lecules from a small region level,l,, withw analysesaannalysesn performedperfoperpe rmmedm inn tthehe sspatial of a samsample,ple,e we can determine the contextcontext ofo cellceell andand tissue.tissue. of the human body spatialspatiallocationsandconcentratatialti l locallocationstiiono s and concentratioconcentrationsconcentrations At M4I,M4I, wew havehbh ave broughtbr brougbroughouugghght cutting-edgecu cuttintting-g edge of molecules present in the sample. MS-based technologies together with and apply it in By sampling many points on a high-end cryo-electron microscopy. In sample, we can build detailed images doing so, it becomes possible to image clinical decision- (ion distribution maps) of hundreds biological processes at multiple scales: a of molecules simultaneously. This single molecule, the molecule in the context making.” allows us to see how the presence of of a cell, the cells in context of diseased and certain molecules alters others in the healthy tissue, and that tissue in the context surrounding environment, and how of the patient’s biological system. will facilitate the translation of our work localized chemical processes vary into personalized medicine, ultimately across a complex and heterogeneous Mass effort reducing diagnostic and treatment costs. sample. MSI involves a variety of My group at M4I is pushing the Whether it’s fundamental research, techniques, such as pulsed-UV laser boundaries of spatial resolution in MSI, instrument development, or clinical irradiation (MALDI), focused ion including developing new tools to resolve translation, an important bottleneck beam irradiation (SIMS), or charged molecular structures that have so far is our ability to deal with the ongoing solvent droplets (DESI). Each method proved elusive. We are currently working data tsunami. We need innovative data has strengths and weaknesses, and on combining ion chemistry with MSI sciences and bioinformatics to digest here at M4I, we combine all three to apply imaging in a completely new the data as rapidly as we can now to help us find answers to complex way (see page 40) – if successful, this generate it (see page 43). biomolecular questions. could result in a paradigm shift for I believe that the team at M4I has the the analytical application of mass vision and drive to help move healthcare Read more from Shane on page 40. spectrometry in structural biology. forward (read more about the work Throughput is another key area for us. of some of our “rising stars” in MSI provides orders of magnitude more the following sections). But to detailed information for clinical diagnostics achieve our goals, it’s crucial than conventional imaging techniques, but that our research is for that matter). Data scientists will the information needs to be available to embedded in the clinic lead clinicians, and will in turn be led clinicians quickly. A diagnostic approach – for example, our by clinicians, analytical scientists and that takes hours to complete will not be epidemiologists. It’s a nice example of adopted easily. We are working with the knowledge crossing borders to improve main MS vendors to deliver MSI-based healthcare on many levels. tissue diagnoses to surgeons, pathologists How do we gather the data needed and other healthcare professionals in a by modern medicine? For me, mass matter of minutes (see page 42), which collaboration examine it on exactly the same platform – Scratching the surface with a nearby allowing diagnosis to be based on much more The potential impact of MSI is hard to academic hospital, extensive molecular information. It also offers overstate. Everything we experience, MUMC+. M4I has the combination of targeted and untargeted invent, touch, eat, and use involves some developed several MS-based molecular diagnostics, which will be the true form of surface chemistry. MSI can help translational medicine projects paradigm shift in personalized medicine and us to better understand all of these surfaces together with the MUMC+ molecular pathology. and their chemical interactions with their Department of General Surgery and environment, provided we are careful to Pathology. After three years of building ask the right questions and design our bridges, these projects are now beginning experiments in the best way. to come to fruition – not only scientifically The most obvious impact will be in but also clinically, with the birth of several “MSI can be medicine. MSI can be employed to more novel diagnostic assays that are now being precisely define a tumor margin on a tissue validated for patient care. This type of employed to more section, determine the degree of ischemic interdisciplinary research is something damage in an organ for transplantation, I am passionate about – it is absolutely precisely define a classify the severity of a disease, and so crucial to advancing MSI, and science as much more. The pharmaceutical sector a whole. tumor margin on a will benefit from detailed information on A beautiful example is the recently local drug metabolism – researchers will published (1) result of a collaboration tissue section, be able to see if a drug reaches a target between M4I and Steven Olde- without the need for labels that could Damink’s group at MUMC+ on non- determine the degree interfere with its mode of action. Better alcoholic steatohepatitis (NASH). information on local drug metabolism Using a mass spectrometry-based of ischemic damage and pharmacokinetics will be crucial to tissue imaging approach we established innovation in drug development. a novel classification model for NASH. in an organ for The impact of MSI on science and society Importantly, we found that this is already tremendous and can only grow. classification was only possible when transplantation, If the number of published papers is an the spatial context of the molecules indication of the impact of MSI, the best is was taken into account; we could classify the severity yet to come! Read on to find out more about not establish the classifier on a tissue the young researchers breaking through homogenate in which the spatial of disease, and so scientific and technical barriers at M4I. context was lost. This study is a prime example of why MSI is needed for much more.” Ron Heeren is Director of Maastricht modern medicine. MultiModal Molecular Imaging Institute We are entering a new era of digital (M4I), Distinguished Professor and pathology, and MSI fits seamlessly with Limburg Chair at Maastricht University, innovative concepts in molecular MSI-based molecular pathology can be The Netherlands. pathology. In the future, a combined with MS-based intraoperative pathologist will order an MSI diagnostics, as is being done with rapid Reference assay with similar ease to evaporative ionization mass spectrometry 1. K Ščupáková et al., “Spatial systems lipidomics an immunohistological (REIMS), with the “i-Knife” sampling reveals nonalcoholic fatty liver disease assay – and device (see page 42). Our group has been heterogeneity”, Anal Chem, 90, 5130–5138 the first to take all of our molecular imaging (2018). PMID: 29570976. information and put it into models that 2. 2. Ron Heeren is the Director of the classify tissue during a surgical procedure. Maastricht MultiModal Molecular Imaging We are building the molecular operating Institute (M4I) and Division Head of room of the future to improve the quality Imaging Mass Spectrometry at Maastricht of care and treatment outcomes of patients. University, Maastricht, the Netherlands.
www.thepathologist.com 40 NextGenNextGeen Artist’s impression of MSI using laser-induced post-ionization (MALDI-2).
The Imaging almost every tissue studied with MSI, a signal. By breaking down an image into a heterogeneous spatial distribution of the isomeric contributors, we can begin to Innovator lipids is seen, and yet the underlying understand the biochemical origin of MSI reasons behind these distributions are data. By combining this with the power Shane Ellis is an assistant not known. More generally, very little of high-mass-resolving-power MSI using professor in imaging is known about the roles of individual FT-based analyzers to reduce the search innovation and structural lipids in cell metabolism and function – I space for structural assignments, we would imaging. We caught up with want to add to our knowledge. one day like to gain a cell-by-cell view of him to find out how M4I is all active metabolic processes and how they pushing imaging technology How are you improving MSI? are altered with disease. to its limits – and beyond As a chemist, I want to know exactly We are also working on adding what molecules we are seeing in MSI, but temporal data to MSI. With MSI, What is the aim of your research? this goal is complicated by the presence we acquire a static snapshot of a My group develops new instrumental of isomers. We are combining new heterogeneous sample – but in reality, methods and applications to improve MS/MS methods (such as selective gas the molecules we detect are the result the chemical information we can extract phase ion/molecule reactions) with imaging of a variety of dynamic processes. To from imaging data. I have a strong focus to resolve structural isomers and discover capture this change over time, we are on lipids and find it fascinating that, in exactly what molecules are contributing to infusing isotope labels into animals so “In almost every tissue studied with MSI, a heterogeneous spatial distribution of lipids is seen, and yet the underlying reasons behind these distributions are not known.”
Figure 1. Comparison of MALDI coupled with laser post-ionization (MALDI-2, black trace) and that we can monitor uptake of the isotope conventional MALDI (red trace) for MSI of lipids from mouse brain tissue. MALDI-2 dramatically improves label into biochemical processes. This the ionization efficiency sensitivity for many lipid classes. All lipid assignments are performed with a mass error means we can directly view the turnover tolerance of 2 ppm, and in the majority of cases supported with on-tissue MS/MS. Reproduced from (5). and synthesis of new molecules and differentiate new molecules (synthesized What’s next? momentum, moving towards true since label introduction) from old The typically low ionization efficiencies of molecular identification of signals molecules (synthesized before label many molecules mean that we may only observed in MSI. High mass resolution introduction). This provides a powerful detect one in every 10,000–1,000,000 has been a huge advance, but ultimately and as yet largely untapped resource occurrences of a given molecule – this this provides little structural information to image the kinetics of biochemical is the ultimate limitation in sensitivity. beyond elemental composition. For conversions within tissues. Work is ongoing at M4I and elsewhere to structure determination, MS/MS is Speed is also very important, especially finally overcome this key challenge, either needed. The challenge is that MS/MS for clinical applications of MSI. Modern using targeted derivatization methods is typically a targeted approach, and it’s ToF systems allow us to acquire data up to convert certain molecules into more not yet clear how best to combine this to 20 times faster than a few years ago, detectable forms (for example, by adding with the untargeted nature of MSI. but these methods are now at the physical a fixed charge), or using the MALDI-2 limits of conventional ToF technology. method, where a second laser is fired References M4I is heavily involved with the Medipix into the MALDI plume. Pioneering 1. SR Ellis et al., Angew Chem Int Ed, 52, consortium at CERN, working on semi- work by wthe University of Muenster (4) 11261–11264 (2013). PMID: 24039122. conductor-based detectors for stigmatic and later by M4I (5) has shown that this 2. S Ellis, J Soltwisch, RA Heeren, J Am Soc imaging. With the Timepix detector and method can enable up to two orders of Mass Spectrom, 25, 809–819 (2014). PMID: dedicated ion optics within stigmatic magnitude greater sensitivity for certain 24658803. imaging mass spectrometers, we can molecules and significantly improves the 3. J Soltwisch et al., Anal Chem, 86, 321–325 acquire thousands of pixels in parallel depth of molecular coverage for an MSI (2013). PMID: 24308447. (rather than one at a time). Instead of experiment (see Figure 1). 4. J Soltwisch et al., Science, 348, 211–215 one detector, we have 262,144 detectors, I also think the use of MS/MS (2015). PMID: 25745064. each capable of recording both ToF and methods (both conventional and 5. S Ellis et al., Chem Commun, 53, 7246–7249 impact position (1–3). new variants) will continue to gain (2017). PMID: 28573274.
www.thepathologist.com 42 NextGenNeN xtGen
Tell us about the iKnife… clinical staff and surgeons. The goal is The Clinical The technology behind the “iKnife” or to validate the databases that we are “intelligent scalpel” is rapid evaporative currently building ex vivo and work Collaborator ionization mass spectrometry (REIMS) with clinicians towards integration of – developed by Zoltan Takats for the the iKnife in clinical routine. Tiffany Porta, an assistant rapid classification of human tissue via professor at M4I, tells us how MS analysis. It analyzes aerosols released What developments lie ahead? the institute is translating during electrosurgical dissection using Recent developments have concentrated MSI technology into the electric scalpel or forceps. The smoke on miniaturization of the system and operating theater generated during electrosurgery is very making it minimally invasive. For rich in molecular information, including example, integration of REIMS with What is your goal? tissue-specific profiles that discriminate an endoscopic polypectomy snare to allow My research group focuses on translational between the tumor and surrounding in vivo analysis of the gastrointestinal research and clinical imaging. My tissue – data not available to the naked eye tract is a promising methodology to main interest is to provide new clinical of the surgeon. The electrosurgical aerosol explore internal structures in a minimally diagnostic tools, with a focus on collected in real time is compared with invasive way (1). High diagnostic accuracy intraoperative diagnostics. Therefore, I a reference model to determine, within for tumor type and known histological am strongly connected with the hospital seconds, the type of tissue being cut (for features of poor prognostic outcome in and working very closely with surgeons example, tumor versus non-tumor). In a colorectal cancer was reported, based on and pathologists. Our ultimate joint goal clinical setting, the data would be provided a multivariable analysis of the mucosal is to improve the clinical decision-making interactively to the surgeon as they cut the lipidome. The potential of this approach process (surgical and medical) that results tissue. Through this rapid, on-line analysis, for other minimally invasive procedures has in better patient outcome. This is what surgeons get immediate feedback to help also been demonstrated by combining real- drives me and my research. them resect the tumor accurately, leaving time MS with surgical laser systems where no cancerous tissue behind. The beauty aerosol is generated by thermal ablation. What problem do you hope to solve? of this approach is that existing surgical The molecular patterns generated are Surgery is the best hope of a cure in 80 devices need no modification to combine specific to the cellular phenotypes and can percent of diagnosed cancer cases. Whether them with REIMS, the surgical procedure easily distinguish benign from malignant a cure can be achieved usually depends remains the same, and surgeons need no regions in patient biopsies, which opens on the quality of the surgical resection of extra training. And for me, these are key the door for applications in a wide range the tumor. At the moment, it is hard for points to accelerate the translation of the of clinical areas. Additionally, the cavitron surgeons to find the edges of the tumor technique into clinical practice. ultrasonic surgical aspirator, which is widely and remove all the cancerous tissue. To Currently, reference models are built used for brain and liver surgery, can also be find out if any cancer remains, pathologists ex vivo, which permits the creation of combined with the REIMS technology for evaluate frozen cut tissue sections; results spectral databases for prospective use. intraoperative diagnostics (2). are often not available for several days, In Maastricht, we are currently building and sometimes prove inconclusive. There databases on breast, colorectal liver References is ample evidence that improving the metastasis, sarcomas, and head and neck 1. J Alexander et al., “A novel methodology for in accuracy of surgical resection would reduce tumors, which are validated histologically vivo endoscopic phenotyping of colorectal cancer the number of patients requiring further by expert pathologists. Our based on real-time analysis of the mucosal surgery and improve overall outcomes. next step is to move our lipidome: a prospective observational study of the This is where molecular profiling based work in vivo and go into iKnife”, Surg Endosc, 31, 1361–1370 (2017). on mass spectrometry comes in – by using the operating theater, PMID: 27501728. a tissue (disease)-specific database we can where we will 2. KC Schäfer et al., “Real time analysis of provide real-time and specific molecular work closely brain tissue by direct combination of ultrasonic analysis of tissue and assist the surgical with the surgical aspiration and sonic spray mass decision-making process. We can also use spectrometry”, Anal Chem, 83, rapid molecular pathology of resected tissue 7729–7735 (2011). PMID: to assist pathologists in their diagnosis. 21916423. The Big What are the challenges? bioinformatics groupsupupssfr frofrfromroroomm out outsidesiide ofof The analysis of MSI data is challengingchallenging our field have becomeme interestedi interestedd ini nin Data Explorer in many ways – ranging from ththee this type of data,, whichwh in turnrnn lleadss optimal processing of gigabyte-sizedgigabyte-sized to an accelerationion in tthee develdevelopmentvelopmentvel t Assistant professor Benjamin data to selecting the correct statisticastatisticall of useful tools for the analysisannalysisaly of MSII Balluff develops innovative analysis. The rapid advance of instrumeinstrumentnt data, including commercialcommerercialerciilall solutions.l is. I bioinformatics approaches capabilities has increased demands onon hope this widespreadad interesti e stst wwilllll helph p that allow M4I researchers to computational power and memory. us, as a communicommunity,nityity,ty, to achievee ourouur aimm master their data What’s more, this data delivers a degreedegree of making MSISI a robust diagnosticc tooltot l of detail that the human brain is unable toto in a clinicalal setting.se What is your goal? process without the help of algorithms andand Our focfocus is, of course, mainly on I develop advanced data analysis clever data visualization tools. I develop MSI, bubut there is a wider trend in life methods for MSI of cancer tissues new methods and algorithms that help science to integrate data on the same – revealing molecular heterogeneity to interpret the data and ultimately fifindnd subject from different modalities. We within apparently homogeneous tumors. answers to urgent bibiomedical di l questions. i havehkhihdiff to work together with different Intratumoral heterogeneity plays an Integration of different (imaging) data specialties and disciplines, and find a important role in therapeutic failures modalities is a prerequisite for successful way to combine heterogeneous data (of and progression of the disease. I want personalized medicine. different sizes and optical resolutions, to use MSI to pinpoint clinically at different scales, in different storage detrimental tumor subpopulations for What new advances excite you? formats, and so on) using tailored further in-depth investigation. With the rising popularity of MSI, more software solutions.
www.thepathologist.com Now CE Marked
The Panther FusionTM MRSA assay brings full automation, efficiency and excellent assay performance to MRSA screening enabling: • Accurate and comprehensive results • Cost-efficiencies • Improved patient management
Diagnostic Solutions | Hologic.com | [email protected]
ADS-022788-NOR-EN Rev 001 ©2018 Hologic, Inc. All rights reserved. HolHlogiog c,c Theh Scieni ce of Sure, Panther Fusion and associated logos are trademarks and/or registered trademarks of Hologic, Inc. and/or its subsidiaries in the United States and/or othot er countries. This inforormationio is inntente ded forrm medical professiss onanals and is not intended as a product solicitation or promotion where such activities are prohibited. Because Hologic materials are distributed through websites, eBroadcasts and tradeshows, it is noot always possible to control where such materials appear. For specific information on what products are available for sale in a particular country, please contact your local Hologic representative or write to [email protected].
Not for use in the U.S. Profession Your career Your business Your life
46-49 Your Origin Stories – in Tweets How did you find your way to pathology? We asked – and you answered! 46 ProfessionProfession
Your Origin Stories –
in Tweets David Larson (@dmlarsonpath1): Last rotation of med school. Had What got you started on the wanted to do IM, but realized during path to pathology? acting internship that it wasn’t for me. Friend suggested #pathology. Arranged Earlier this year, we featured an editorial for elective and loved it. Saw what on the “magic of mystery” and how it could #pathologists do day to day. Pathology lead to an interest – and possible career – class didn’t do that. Have been loving in science (1). We decided to follow up by it ever since. asking what inspiredins you – our readers – to pursue pathologypathology. And your responses Sara Jiang (@Sara_Jiang): came thick and fast! Here, with your I am that friend! And I think many permission, we’ve collectedcollecte the stories you of us on #pathologytwitter are told on social media abouabout your journey – both virtually and IRL! into pathology, and how youyo fell in love withwith tthehe fifield.eld.
Daniela Hermelin (@HermelinDaniela): My father was an ID doc with a mini-lab in his office, Maria Martinez-Lage (@mlage): including a microscope, where I would be found perched. As a third year Neurology resident, I Inspired by his love for medicine and humanity. Fell in love, sought a #Neuropath rotation and was with pathology that is, in medical school: mechanism of extremely lucky to spend two months disease, pictures, best teachers: received Path Award @MGHPathology. I went back to Spain, decided to become a neuropathologist. My love solidified after my first general pathology elective, 13 years later, the people who inspired and second, and third and then fourth… Graduated medical me are my colleagues and I made great school and then received a PhD in diapers, breast feeding friends @PennPathLabMed and sleep deprivation. Began my pathology residency with five kids and pregnant (again).
Pathology residency about to be completed in four days and ecstatic to be starting transfusion medicine fellowship at #SLUPath #grateful ProfessionProfession 47
Laura G. Pastrián (@DraEosina): Karra Jones (@BrainIsThePath): My moment was @fetalpath explaining I went into @KUMedCenter knowing I that pathologists were the ones that liked wanted to be a neurologist. One PhD first years of medicine and disliked the later during my third year back in med last ones. I felt so like that. school, I realized the thing I loved was my time spent under the microscope in my research years. Then David Gisselsson (@canceriswar): a neuropathologist – Kathy Newell – A summer elective at inspired me to pursue neuropath. @BrighamWomens Path under Chris Fletcher completely transformed my view. It planted a seed that hybridized with genetics to blossom into #pediatric #pathology. I have never looked back. Never a boring day.
Miguel Reyes-Mugica (@mreyesm): I wanted to become an internal Adriana Zucchiatti (@zucchiatti_): medicine physician. I started as I always wanted to be a pediatrician, an instructor of #histology on my basically because I love kids. Then I second year and then met my mentor worked one year in a peds little hospital #RuyPérezTamayo for my class of and I figure out practicing peds wasn’t Pathology. Started doing research under the most exciting for me. I just started him. That was enough. Experimental to read a lot about pathology and how it pathology and the beauty of histology! works and made the decision.
Now, I’m really, really happy with what I do, even in residency program . Jena Martin (@DrsDrMartin): The moral is that sometimes you have to During the second year of medical take the chance and take risks, and it is school when a retired pathologist possible everything turns out great. :) explained Potters syndrome. Seemed so intensely interesting!
www.thepathologist.comwww.thepathologist.com 48 ProfessionProfession
Irma Ramos (@iramos89): Mary Kinloch (@saskmary): When attending a pathology practice In despair on colorectal surgery rotation. on the third year of Medicine everyone Surgery seemed boring: you spend so much commented how boring that seemed to time to get it out & NOT GONNA LOOK them and I was like “Uoouu, have you INSIDE?! Then, walked into GI tumour seen that? *.*” boards where a well-dressed feller with a microscope was telling the surgeons what to do. I was like, I wanna be that guy.
Ashley Flaman (@ashleyflamanmd): Christine Salibay (@cjsalibay): First year med student at a lunch hour career Path profs suggested an elective. OB/ presentation about pathology. Pathology family were always on my mind but by the resident presents a case – 50s M single end of third year, when I finished path lung nodule removed for suspected cancer. elective, I was Path vs Peds – ultimately Resident puts up histo image & says, decided on a specialty that reminded me “it’s not a tumor, it’s a granuloma!” Me: I of how I like to think and why I loved wanna be her. That resident: @saskmary medicine in the first place –
– the basics: mechanism of disease and diagnosis. Plus, the lab people were amazing and reminded me of my awesome undergraduate research group :)
Ashley Stueck (@LiverPath): I was seven when The X-Files premiered, and Scully was a forensic pathologist. The path was set! Of course, this was followed by learning more, shadowing, working in a path research lab, and electives. Forensics (still love!) changed to liver, Mary Landau (@MPathyart): but I always wanted to be Standing in a gyn onc ward during a pathologist! my intern year in Ob/Gyn. I had just Alicia Pomata (@AliPomata): completed my gyn path rotation (and First year med school, wanted to stay in adored it), but even more pertinent, I the white, clean and cold lab forever had just completed 36 straight hours on looking to every single cell in the call and only faced 12 hours off before my next 36-hour penance. ProfessionProfession 49
Lara Pijuan (@lara_pijuan): At second year of medical school when I had my first contact with #histology. I Valerio Ortenzi (@ortens84): loved histological images and then at I guess when I was a little boy: my third year when I had my pathology parents gave me toys to play, instead I classes I realized it was done for me… used to disassemble them to understand or I was done for Pathology I what was going on inside… #Pathology
MaríaElena PérezMartín (@ElenPath): At second year of MD School, I had my first contact with #histology and I images (as Lara). And at third year, I Akinshipo Wariz (@AkinshipoWariz): had my path classes and I realized I knew I would be an oral pathologist pathology was amazing. We dived deep when the only textbook I bought in into the real diagnostics of the disease. Dental school was Neville and Damm At fourth year, I met Dr. Burnier, Eye Oral and Maxillofacial Pathology. Path and I fell in with #Pathology
Valerie Fitzhugh (DrFNA): I didn’t match orthopaedics. Pathology was the only other specialty I rotated through in medical school that I could see myself doing for the rest of my life. 14 years later and I haven’t looked back. #MyCalling #NoRegrets #Pathology Kalyani Bambal (@kriyer68): #BSTPath #Cytopath Loved histology in first year med school Tweets have been edited for readability only. and then reinforced by pathology in second year. Was a foregone conclusion ReferenceRef in itself. Went for MD Path in spite of 1. M SSchubert, “The magic of mystery”, The offers for medicine and ped to the sheer Pathologist,Pathologist 40, 7 (2018). Available at: consternation of my profs that time https://bit.ly/2us18Sk.https:p //bit.ly/2u
www.thepathologist.comwww.thepathoth logist.com A Natural Gift for Pathology Sitting Down With… John Goldblum, Chairman, Department of Pathology, Cleveland Clinic; Professor of Pathology, Cleveland Clinic Lerner College of Medicine, Cleveland, USA. Sitting Down With 51
What inspired you to pursue pathology? to take his place. I didn’t think I was in a I am hoping it’s not going to be that When I was a medical student, there was position to do it, but she said, “You can long before I can sign out my cases from a second-year course in pathology. The do it. I trust you.” And so I also wasn’t in anywhere, which I expect will really teachers were the best I’d had, so they a position to say no! It was the first time help those who struggle with work/ strongly influenced my choice. As part I had ever written a textbook, so it took life balance. I already do a number of of the course, we each had a microscope me about three years to finish. It was consults from China and other parts of and a pile of old, dingy slides on which good practice, though, because my friend the world digitally, and they’re only a we were supposed to identify disease Rob Odze had the idea of working on little more challenging than using the entities. Somehow, I ended up as one of the a GI textbook with me. Eventually, the microscope, so I think we’re inching students who went around explaining to powers that be at Elsevier asked me to closer. I hope that, in my lifetime, we everyone else what they were supposed to take over the 11th edition of the Rosai and get to that point – it’s my goal to sign be seeing. Whatever wiring is required to Ackerman textbook on surgical pathology. out cases from the beach! look at a microscope slide and understand You can imagine the scale of that task! I it, I seemed to have it – and liked doing it! gathered three other world-class people What do you consider the high points Within a week of starting my residency to help me and it took us about five years, of your career? at the University of Michigan, I decided but we did it. My biggest accomplishment is taking that the smartest people on the faculty my department from 15 people and were Henry Appelman, a world- a limited reputation to a very large famous gastrointestinal pathologist, subspecialty department with an and Sharon Weiss, a world-famous soft international reputation and about 70 tissue pathologist. I said, “Whatever “The most pathologists. It’s a job I only reluctantly they do, that’s what I’m going to do.” accepted, but I ended up really liking I didn’t know a thing about GI or soft important thing to it and building what I think is a tissue pathology, but I did know I tremendous department. wanted to learn from them. remember is to be a I’m also very engaged with organizational pathology. I got involved How did you get so involved in good colleague and with USCAP early in my career and pathology education? ended up running their education When I first began to speak publicly, I team player.” committee for six years and serving on was terrible at it. I was always nervous; I the committee for 14 years. Eventually, couldn’t catch my breath; I think I might I joined the board and became President even have taken a beta blocker the first of USCAP – and I’m still involved with time I had to get up in front of an audience! How do you maintain your them now. That’s the other thing that Eventually, though, I learned to like it, and work/life balance? makes me proud, because I believe that now I really enjoy it. I get a great deal of When I started at the Cleveland Clinic, I not only derived tremendous personal satisfaction from lecturing – even if the it was extremely busy – but I was a young and professional benefit from USCAP, listeners only take away a small amount parent who didn’t want to stay at work all but I feel I actually contributed to the of useful information. I try not to include day and night and never see my wife and organization’s progress at a critical time. too much, and I don’t expect people to children. My father was a hardworking remember all of it. When I’m sitting in dermatologist who rarely had time to What’s your advice for the audience, I’m happy to take away one spend at home, and although I admired young pathologists? or two valuable points; that’s what I would his dedication, I didn’t want to replicate The most important thing is to remember like others to be able to do when I teach. it – so I tried to become exceedingly is to be a good colleague and team player. With respect to textbooks, in 1997, efficient at multitasking. When I’m at That’s how you’re going to end up loving Franz Enzinger decided he was not up work, I run around like a maniac to your job – by working with people whose to working on the fourth edition of the get everything done. I keep breaks and company you enjoy. The people who are Enzinger and Weiss soft tissue pathology socializing to a minimum so that I can most successful in pathology are those book. Sharon Weiss asked me, as one of accomplish what I need and then go who really like both the profession and her former fellows, if I would be willing home to my family. the people they work with.
www.thepathologist.com IDYLLATM MSI ASSAY
THE IDYLLA™ ADVANTAGE
The fully automated Idylla™ MSI Assay provides fast and reliable information on MSI status.1-3
Idylla™ MSI Assay shows high concordance (> 95%) and lower failure rates compared to standard methods.2,3
Idylla™ MSI Assay provides accurate results for a variety of cancer types independent of ethnicities.1-4
Idylla™ MSI Assay performs directly on 1 FFPE sample.
biocartis.com
(1) De Craene et al. Detection of microsatellite instability (MSI) in colorectal cancer samples with a novel set of highly sensitive markers by means of the Idylla MSI Test prototype. Journal of Clinical Oncology 2018 36:15_suppl, e15639. Data obtained with prototype cartridge. (2) De Craene et al. Detection of microsatellite instability (MSI) with a novel panel of biomarkers in gastric cancer samples. Annals of Oncology (2017) 28 (suppl_5): v209-v268. Data obtained with pre-fi nal biomarker panel containing the 7 fi nal biomarkers and several additional biomarkers that were not retained in the fi nal product. (3) Maertens et al. Detection of microsatellite instability (MSI) with the Idylla™ MSI Test in colorectal cancer samples. Annals of Oncology (2017) 28 (suppl_5): v22-v42. (4) Data based upon internal research data.
Idylla™ MSI Assay is available for Research Use Only (RUO), not for use in diagnostic procedures. Biocartis and Idylla™ are registered trademarks in Europe, the United States and other countries. The Biocartis trademark and logo and the Idylla trademark and logo are used trademarks owned by Biocartis. Idylla™ platform is CE-marked IVD in Europe. Idylla™ is available for sale in EU, USA and some other countries. Please check availability with the local Biocartis sales representative. © Mik Man / fotolia.com 30th European Congress of Pathology Pathology: Path to Precision medicine 8 – 12 September 2018 Euskalduna Conference Centre, Bilbao, Spain
www.esp-congress.org