Just Say Know! From Mentoring to High Performance: A Resident Perspective

As pathologists, we are responsible for increasingly intricate anatomic pathology and clinical laboratory services in a continually changing healthcare landscape that requires us to integrate emerging technologies for improved quality of medical care while also being hypervigilant to cost control and efficiency. Hospital systems working under managed care business models seek to expand their coverage networks and boost the number of patients served, and as such, it is going to be very critical for the next generation of pathologists to develop and implement the management skills and techniques necessary to effectively advocate for investment in their departments and meet such goals.

The problem, however, is that we are largely shielded from these issues during our undergraduate and even graduate medical education experiences. We focus, of course, on the basic sciences and clinical skills, which are undeniably important; however, we get significantly less instruction or discussion on functioning within our health care system, addressing quality issues, or general leadership training that is indispensable and highly valuable for practicing physicians.

Earlier in the summer, I saw a number of pathology folks on Twitter promoting and strongly encouraging residents to apply for the two-day “Just Say Know! From Mentoring to High Performance” program, formed through collaboration between ASCP and USCAP, on an approach to leadership, management, and business for pathology. I was highly intrigued and had a feeling this program was the sort of experience for which I had been looking. Traveling to Palm Springs in the middle of the Chicago winter was not a bad deal either!

Drs. Blair Holladay and David Kaminsky assembled an impressive collection of speakers for the weekend, which was divided into four focus areas: leadership, management, business and policy, and change. After an engaging introduction by Drs. Holladay and Kaminsky, current trainees Drs. Kabeer Shah and Melissa Hogan set the stage by highlighting the increasing importance of “management” and “leadership” as reflected in the ACGME milestones as well as recent literature suggesting expectations for newly-trained pathologists include these very skills (Post et al. Arch Pathol Lab Med 2017;141: 193-202).Above all, they encouraged all of the thirty residents and fellows in attendance to “be honest, be open, and be vulnerable,” and ask the tough questions of themselves to gain the most from the weekend.

Lotte Mulder from ASCP led an enlightening discussion on the differences between emotional intelligence (EI) and conventional IQ, as well as the critical need to be self-aware of how our emotions can affect our performance and to understand the extent of our own abilities, strengths, and weaknesses. Dr. Karen Kaul followed with a very timely overview of strategies for identifying mentors. She discussed how our mentorship needs will evolve over the course of our careers and that fulfilling the mentor role for another junior individual while having your own mentors is key to the professional development necessary in leadership positions.

 After lunch, Dr. Dan Milner from ASCP took us through some very interesting global health case studies that forced our group to think critically about the role of pathology and the clinical laboratory in underserved settings as well as the major obstacles and economic disparities that must be considered. There were a number of important teaching points from Dr. Milner’s international cases that will be equally helpful for understanding the disparities we encounter right here in our backyard.

Dr .Yael Heher led off the afternoon management focus series with a really comprehensive look into how she has championed quality improvement and patient safety reviews at her institution to address root causes for laboratory errors, followed by a well-timed interactive session in which we divided into groups to use the six sigma methodology to work in concrete steps through a real-life laboratory error. It was a great opportunity to see people from different institutions and backgrounds bring unique perspectives to a common problem. The first day of the program concluded with a very unique session on art and leadership in which Dr. Kaminsky led us into Downtown Palm Springs to view the Palm Springs Babies art installation set up by David Cerny. Our powers of observation as pathologists were put to the test as we were asked to describe and interpret the meanings behind the exhibit in the same way that we often use visual evidence in our day-to-day work.

The second day of the program focused on business and policy with talks by Dr. Gary Procop on how pathologists can help integrate interventions into the laboratory to improve system-level metrics and by Khosrow Shotorbani on how laboratory data can be used to optimize laboratory services in the model of the rideshare service, Uber. The morning also included an interactive session on negotiation skills, in which each of us assumed the roles of departmental chair and owner of a private practice group negotiating with newly-hired pathologists. The weekend concluded with Dr. Nathan Johnson’s 18 steps to make change a part of an organizational culture, which was based on his experiences in academic research, military operational theory, and real-life lab experiences.

The weekend provided an incredibly impactful and high-yield array of discussions, so much so that I am already finding myself applying many of the strategies and techniques described over the weekend in my role as chief resident as well as to some of the changes and initiatives that I am hoping to bring to our department. Most important, though, were the opportunities to interact with my peers from around the country. We all face similar challenges as residents, and the opportunity to learn each other’s perspectives and approaches to similar issues was just as illuminating as the structured portions of the program. I hope that the ASCP and USCAP continue to offer the Just Say Know! Program and enthusiastically join all those pathology folks on social media promoting the program last summer with my own strong recommendation to challenge yourself and be open to new ways of learning by considering participating in this event!

From Twitter, @Blair_Holladay, December 12, 2018
Photo by Imran Uraizee

-Imran Uraizee, MD, is currently chief resident and a third-year anatomic and clinical pathology resident at the University of Chicago. He also manages the Department of Pathology Twitter account, @UChicagoPath. He majored in Biology at Duke University before earning his MD at the University of Rochester School of Medicine and Dentistry. Dr. Uraizee can be followed on Twitter at @IUraizee3MD.

Hematopathology Case Study: A 43 Year Old Man with Difficulty Breathing

Case History

43 year old man presented with symptoms of superior vena cava syndrome including swelling of the head and neck and difficulty breathing. He was found to have a 9 cm anterior mediastinal mass on imaging.

Excisional Biopsy

Top: H&E morphology of diffuse large cells infiltrating through fibrotic tissue.
Bottom: Small lymphocytes with scattered large multinucleated Hodgkin and Reed-Sternberg (HRS) cells.
Left: CD30 showing dim/variable staining in the diffuse large cell component.
Right: CD30 highlighting Hodgkin and Reed-Sternberg cells with a golgi and membranous staining pattern.
Left: CD15 showing golgi staining in the diffuse large cell component.
Right: CD15 highlighting Hodgkin and Reed-Sternberg cells with a golgi and membranous staining pattern.
Left: CD20 diffusely highlighting the large cell infiltrate.
Right: CD20 highlighting small B-cells surrounding a negative HRS cell.
Left: PAX5 diffusely highlighting the large cell infiltrate.
Right: PAX5 showing bright staining in small B-cells surrounding a dimly stained HRS cell.
Left: Ki-67 showing a high proliferation index (90%) in the diffuse large cell component.
Right: Ki-67 showing increased staining in the HRS cells.

Diagnosis

Sections show fragments of fibrotic tissue with crush artifact. Two distinct morphologies are seen in different tissue fragments. Some tissue fragments show infiltration by cords and aggregates of abnormal large lymphoid cells with irregular nuclear contours, somewhat vesicular chromatin, small nucleoli and small to medium amounts of cytoplasm. Frequent apoptotic cells and mitotic figures are seen. In other tissue fragments, the large cell component is absent and there are focally vague nodules. The nodules are composed of small mature appearing lymphocytes, rare eosinophils and scattered medium and large mononuclear and multinucleated cells with prominent nucleoli consistent with Hodgkin cells and Reed-Sternberg cells, respectively. Admixed histiocytes are also seen.

By immunohistochemistry, the areas with different morphologies also show different staining patterns. The areas with the large cell infiltrate are immunoreactive for CD20, BCL6, and MUM1, dimly positive or negative for CD45 and negative for CD10. CD30 is variably positive in the large cell population and CD23 is largely negative. CD15 shows a golgi staining pattern. The Hodgkin and Reed-Sternberg (HRS) cells present in the areas without the large cell infiltrate are brightly immunoreactive for CD30 and CD15 (membranous and golgi pattern), dim positive for PAX5 and are negative for CD20. CD20 and PAX5 highlight small B-cells present in aggregates surrounding the HRS cells. By Ki-67 staining, the proliferation index is high (90%) within the diffuse large cell component and also highlights the HRS component.

Overall, the findings are of a composite lymphoma composed of both a diffuse large B-cell lymphoma (DLBCL) and a classic Hodgkin lymphoma (CHL).  

Discussion

Composite lymphomas occur when two morphologically and immunophenotypically distinct lymphomas occur at the same anatomical site. They are most commonly composed of two Non-Hodgkin B-cell lymphomas (NHL), however rare cases of composite CHL with NHL have been reported. In a review of the literature, Goyal et. al. documented 20 previously reported cases of composite lymphoma with CHL and DLBCL components. The median age at presentation was 51 years with 12 men and 9 women. Fifteen of the cases presented with nodal involvement and of those, three had mediastinal disease. The most common subtype of CHL was nodular sclerosis. Evaluation for IGH gene rearrangements was performed on both components of 6 cases, with either a complete or partial clonal relationship between the components seen in all of the cases tested. This suggests a shared origin from a common B-cell precursor.1

A review of literature by Wang et. al. documented 10 previously described composite lymphomas consisting of DLBCL and CHL. The most common site of occurrence was in lymph nodes, followed by three cases seen in the stomach, one case in the small intestine and one case in the anterior mediastinum. CHL is more commonly associated with EBV infection than NHL In the reviewed cases, 6 showed positivity for EBV infection in both the DLBCL and CHL components. This suggests that the lymphomas shared a common EBV-infected progenitor cell, and are also clonally related as seen in the Goyal review. 2

Composite lymphomas must be distinguished from another WHO defined entity called B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma. This entity has previously been referred to as “grey-zone lymphoma.” These lymphomas tend to present as mediastinal masses and can cause superior vena cava syndrome. They show a wide spectrum of histologic appearances within a single tumor and often show sheet-like growth of pleomorphic cells. Some areas may resemble CHL while others resemble DLBCL. The neoplastic cells typically do not show the characteristic immunophenotype of either CHL or DLBCL. Areas that may resemble CHL will show preservation of B-cell markers, while areas more characteristic of DLBCL might lose B-cell markers and express CD30 and CD15. These tumors will show clonal rearrangement of the immunoglobulin genes. They tend to have a more aggressive clinical course and worse outcome than either CHL or DLBCL. 3

This case was ultimately diagnosed as a composite lymphoma (CL) because it consisted of separate areas with the morphologic and immunophenotypic features of both classic Hodgkin lymphoma and diffuse large B-cell lymphoma. Patients tend to have a poor prognosis with short survival. There is no standardized treatment for composite lymphomas due to their rare occurrence; however cases with a component of DLBCL are generally treated with aggressive chemotherapy such as R-CHOP.

References

  1. Goyal, G. et al. “Composite Lymphoma with Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma Components: A Case Report and Review of the Literature.” Pathology – Research and Practice vol. 212,12(2016):1179-1190. http://www.ncbi.nlm.nih.gov/pubmed/27887763.
  2. Wang, Hong-Wei et al. “Composite diffuse large B-cell lymphoma and classical Hodgkin’s lymphoma of the stomach: case report and literature review” World journal of gastroenterology vol. 19,37(2013):6304-9.
  3. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoetic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017.

Chelsea Marcus, MD is a Hematopathology Fellow at Beth Israel Deaconess Medical Center in Boston, MA. She has a particular interest in High-grade B-Cell lymphomas and the genetic alterations of these lymphomas.

Dead Wrong About Forensic Pathology

(•_•)         ( •_•)>⌐■-■       (⌐■_■)

[Puts my sunglasses on dramatically]

[Won’t Get Fooled Again by The Who plays]

Image 1. Looks like this medical lab science blogger made quite the … shady… joke. CSI: Miami’s Lt. Horatio Caine (played by David Caruso) donned his shades at pivotal plot times. (Source: CBS)

Okay-okay, I couldn’t resist that. How many times have you just wanted a CSI-style joke on here? No? Just me? That’s fine…

Hello again everybody! Welcome back! Last month I talked a bit about “Just Culture,” a sort of bridge between the values we tout as clinical leaders in our laboratories and the medical culture’s evolving and value-informed paradigm shift. There was a little in there about the lessons paralleled in LMU and the benefits of interdisciplinary teamwork. This month, on the subject of interdisciplinary collaboration, I’d like to talk about our colleagues who often are secluded or in more remote areas in our hospitals, offices, and academic centers. Not here to stereotype; I’m talking about our friends in forensic pathology!

Before I get there, let me go back a bit. I’ve already written several times about the stereotypes that surround our field of lab medicine and there are two times when that is glaringly present: when you’re a medical student or when you’re in forensics. I got the chance to meet someone who falls into both categories.

I’ve just finished up my OB/GYN rotation. But before my last day, I went to the lab at our hospital and followed up on some pending biopsy results. Okay, I can’t lie to you guys: they wanted me to see if I could rush “my lab friends” to expedite the process of fixing, setting, cutting, staining, and reading/reporting—because that’s possible. So, I went to the lab and had a pleasant chat with the staff explaining the situation and they were happy to help. While I was there, however, I happened to see another short white coat (ironically from my same school) who was helping some lab personnel with some grossing. Turns out she wants to match into a pathology residency—just like me—and specifically was interested in forensic path, a field which I don’t know much about. After talking more, I asked if she’d like to share some information. Here’s my conversation with Kyla Jorgenson, a 3rd year medical student at AUC-SOM from Toronto, Canada:

I get lots of hassle when I say I want to become a pathologist. People often ask me, “what’s your back up choice” or “don’t you like patients?” It can be a challenge. What’s your experience been like?

You want to do autopsies, so you want to be a mortician, right? Not quite. Many times, I’ve been faced with blank stares when I say I want to be a forensic pathologist. Other times I get the other end of the spectrum, that’s so cool! Clearly, they’ve seen a few crime-shows and think that I’ll get to go to crime scenes in stiletto high heeled shoes with a song by The Who playing in the background as I arrive. Even today when talking with a dermatopathologist I got a, “well when you realize that hanging out with dead bodies every day isn’t the greatest, you might consider surg path.” Then after hearing my experience as an autopsy assistant and that I’m sure this is what I want to do it was the resigned sigh signalling that I was a lost cause already.

A “lost cause,” that’s frustrating. A lot of specialities rag on other ones, it seems to be part of the culture of medicine—hopefully not forever, but still can’t we all just get along?

So, my background leading to pathology involved me working for several years between college, graduate school, and medical school; in hospitals of various sizes. I have personal experiences in these fields and sort of feel “at home” when I’m dealing with hematopathology, transfusion medicine, cell therapy—that sort of thing. What piqued your interest in forensics?

I started my undergraduate degree in forensic biology at the University of Toronto in the fall of 2008 just as a major review of pediatric forensic pathology in Ontario was being released. After numerous issues came to light, the inquiry looked at policies, procedures, practices, accountability and oversight mechanisms, quality control measures and institutional arrangements within the field in Ontario from 1981 to 2001. Ontario Court of Appeal’s Honourable Justice Stephen T. Goudge developed 169 recommendations on how pediatric forensic pathology in Ontario needed to address and correct its systemic failings to restore public confidence.

(Read more about these inquiries here: https://www.attorneygeneral.jus.gov.on.ca/inquiries/goudge/index.html)

After studying the cases that prompted the inquiry and its recommendations in class, what left the greatest impression was the importance of having medicolegal autopsies performed by those trained in not just pathology, but specifically, forensic pathology. What I took away from the cases of accidental deaths falsely attributed as homicides due to lack of experience on behalf of the pathologist and other such issues, is that forensic pathology isn’t something to be dabbled in. While our patients are no longer alive, there are lives that can be affected by the work we do. In Ontario, false convictions not only stemmed from “junk science” but also from inadequacies in the training of pathologists working in a forensic capacity and also a general shortage of forensic pathologists.

Seems like a lot of us (of the few of us) who enter medical school knowing we want to go into pathology have to sort of wait their turn, as it were, collecting experiences which help make us competitive for residency matching—what keeps your “commitment algorithm” going?

Since discovering that forensic medicine is a career path as a high school student, I’ve geared my education towards training in forensics. First my undergraduate degree and then a side trip for my master’s degree in Forensic Death Scene Investigation and a job as a pathology technician at the Medical Examiner’s office on my way to medical school. I have in each step along the way, confirmed that both medicine and forensics fascinate me. Scroll through my Netflix account and you’ll find crime dramas (with the British shows being my favourite) or my podcast app filled with true crime shows; I am enraptured using science to figure out what happened.

Sidebar: at this point Kyla showed me a first-author published piece in the Journal of Forensic Sciences from 2017 that talked about law enforcement-involved firearm related deaths in Oklahoma, where she worked at the time. Basically, it showed through metadata analysis that gun-related deaths were on the rise. Not just over time, but number of times being shot. Remember when we talked about pathology’s role in the #StayInYourLane/#ThisIsOurLane discussion? Well which pathology speciality do you think works with this stuff directly? Chemistry? Cytology? Last time I checked GSWs don’t get screened for lead poisoning and you can’t FNA a bullet. Forensic pathology has often been tasked with seeing trends in morbidity and mortality and translating that to effective social and public health change: think seatbelts, stents, and maybe someday gun-related legislation changes.

Image 2a. Monthly aggregates of gun-related deaths over a 16-year period in OK. (Source: Jorgenson, K et al (2017) Trends in Officer-Involved Firearm Deaths in Oklahoma from 2000-2015, Journal of Forensic Sciences, doi: 10.1111/1556-4029.13499)
Image 2b. Number of gun shot wounds per victim over time. (Source: Jorgenson, K et al (2017) Trends in Officer-Involved Firearm Deaths in Oklahoma from 2000-2015, Journal of Forensic Sciences, doi: 10.1111/1556-4029.13499)

I was interested when I shadowed at the Cook County ME’s office a few years ago—I saw some cool things. I also remember learning a lot from the first real autopsy I saw in a hospital, ultimately it seems like a totally different field that maybe gets underappreciated even within the pathology umbrella. AP/CP residents have to do a certain number of autopsies to graduate, but the attitude I’ve noticed around the topic is a “necessary evil” and most are working towards not having to do that. So let me ask you definitively, why forensic pathology?

Medicine is science being applied to find out what happened in the body and how we can change or manipulate those variables to diagnose, prevent, treat and manage disease. Each diagnosis is solving a crime occurring within the cells in the body, if you will. In forensic medicine, not only do you get to do all that but add in the crime solving element and you get to be “Dr. Nancy Drew.” While medicolegal systems are different all over the US and Canada, chances are that as a forensic pathologist you won’t only be working on your stereotypical “forensics” cases, the gunshot wounds, stab wounds and other nefarious causes of deaths many associate with that term. You could get the generic, “cause of death atherosclerotic cardiovascular disease, manner of death natural,” for a large proportion of cases.

It’s not glamorous, you could spend your day with a two-week-old decomposing decedent that has a pulsating maggot mass devouring its torso or documenting 51 stab wounds or signing out your cases after reviewing your histology and toxicology reports or testifying on a homicide case you worked on. But for me, those all sound like pretty interesting ways to spend the day, sign me up. As a pathology technician assisting with the autopsies and external exams, I was never required to think about what was happening in the body, but I wanted to understand it all. Now as I progress through medical school and look towards residency and fellowship, I eagerly await the chance to perform my first autopsy as a physician, to put all the knowledge and experience I’ve gained towards helping move Ontario and forensic pathology forward.

Image 3. Kyla M. Jorgenson is a 3rd year medical student at the American University of the Caribbean School of Medicine with prior undergraduate and graduate studies in the field of forensic pathology, professional experience as an autopsy technician, as well as a vested interest in pursuing a career in the field moving forward in residency and fellowship. (Source: Kyla M. Jorgenson)

I’d like to thank Kyla for her time in talking with me and her willingness to share her insights with all of you. I wish her all the best of luck as she continues through her training with electives and core rotations both in the UK and state-side. If you have any questions to relay to her, please feel free to comment below and I will forward appropriately. And as always, don’t forget to share with your colleagues across every discipline!

Thanks for reading, I’ll see you next time where I’ll be writing from the Mayo Clinic Hospital in Rochester, Minnesota, conducting a formal rotation in Anatomic and Clinical Pathology! Don’t miss it, I’ll have lots to share while learning at one of the nation’s top institutions!

Until next time!

–Constantine E. Kanakis MSc, MLS (ASCP)CM graduated from Loyola University Chicago with a BS in Molecular Biology and Bioethics and then Rush University with an MS in Medical Laboratory Science. He is currently a medical student actively involved in public health and laboratory medicine, conducting clinicals at Bronx-Care Hospital Center in New York City.

Microbiology Case Study: A Male in his Early 20s with Generalized Body Aches

Clinical History

An African American male in his early 20s presented to the emergency department (ED) with complaints of a sore throat, headache, generalized body aches, and fatigue for the past week. He also noted intermittent fever and chills as well as some nausea with a decrease in his appetite. He had been seen multiple times in the ED recently for similar symptoms. His past medical history was non-contributory and he noted no significant travel or exposure history with the exception of attending a local party 10 days ago. His temperature was 100.5°F and vitals were otherwise normal. His physical exam was normal with the exception of dry mucous membranes indicating mild dehydration. Initial laboratory testing showed a leukopenia (white blood cell count of 1.5 TH/cm2) with 39% lymphocytes and rapid antigen testing for group A Streptococcus, influenza, and infectious mononucleosis were negative. The patient was admitted for further work up due to the prolonged nature of his symptoms.   

Laboratory Identification

Results from additional infectious disease testing are in the table below.

This pattern of results is most consistent an acute HIV infection.

Discussion

Human immunodeficiency virus (HIV) is an enveloped, single stranded RNA virus which belongs to the family Retroviridae. HIV is most commonly sexually transmitted via body fluids such as blood, semen, and vaginal secretions directly contacting mucosa membranes. HIV can also be transmitted due to needle stick injuries, blood transfusions, and transplacentally from infected mother to fetus or by breast feeding. Acute HIV illness presents as a mononucleosis-like syndrome with fever, pharyngitis, arthralgias, malaise, and weight loss. During this acute illness, the HIV RNA viral load is extremely high. After a period of clinical latency, which on average is approximately 10 years, there is a deterioration of the immune system, the CD4 count drops, and the patient is at risk for opportunistic infections and neoplastic diseases.

Based on the 2014 CDC/APHL guidelines, the initial screening test for HIV is an antigen-antibody combination assay. These immunoassay based tests detect the p24 antigen and antibodies to HIV-1 and HIV-2 (see image below). By testing for the p24 antigen in addition to HIV antibodies the time to a positive patient result is decreased (window period) as p24 is one of the first viral proteins to appear, even before antibodies are present.    

If the antigen-antibody test is repeatedly positive, the second step in the testing algorithm is an antibody differentiation assay. This test has taken the place of the Western blot and Western blot is no longer recommended in the diagnosis of HIV. If the antibody differentiation test is positive, the diagnosis of HIV-1 or HIV-2 is confirmed. As this step only detects the presence of antibodies, the differentiation test will be negative in an acute HIV infection.

If there is a discrepancy between the first two steps in the testing algorithm or an indeterminate result is obtained, the final step involves nucleic acid amplification testing (NAAT) to detect viral RNA. Viral RNA is the first HIV-1 specific marker to appear following infection. In the case of an acute or untreated long term infection, the viral load can approach levels up to 100 million copies.  

When additional history was obtained from our patient, he said he was sexually active with a new male partner in the past few weeks and did not use protection. He stated he had been treated with Chlamydia in the past. Further testing for CD4 count, other opportunist & sexually transmitted infections, and HIV genotype testing was performed and outpatient HIV care was arranged for the patient. 

-Lisa Stempak, MD, is an Assistant Professor of Pathology at the University of Mississippi Medical Center in Jackson, MS. She is certified by the American Board of Pathology in Anatomic and Clinical Pathology as well as Medical Microbiology. She is the Director of Clinical Pathology as well as the Microbiology and Serology Laboratories. Her interests include infectious disease histology, process and quality improvement, and resident education.

Global Health Narratives Interview Series: Meet Dr. Blair Holladay

In my short career in pathology, I’ve had the opportunity to meet some amazing laboratory medicine specialists working in global health. I’ve been curious to know their personal stories of how they got involved in global pathology and their suggestions of how we can also contribute.

In my first article for Lablogatory, I detailed my recent experience participating in ASCP’s Trainee Global Health Fellowship in Addis Ababa, Ethiopia. It was incredibly exciting, and I was thrilled to be involved with what ASCP is accomplishing there. I thought it would be fascinating to hear from the CEO and the driving force behind the global health initiatives at ASCP – Dr. Blair Holladay. He was kind enough to reserve some time for me to interview him. I felt inspired after talking with him, and even more excited about the future of pathology in leading the way to success in global health! In the following, I share our conversation. I hope it will also leave you inspired to go out and change the world!

Dr. Holladay during a recent trip to Tanzania with ASCP.

Q: Dr. Holladay, how did you get started working in global health through laboratory medicine?

A: Beginning in the late-1980’s while working as a professor at the Medial University of South Carolina in Charleston, I directed a clinical trials cancer research center focused on developing better diagnostic test methods with the goal of improving access. My interest was focused on creating innovative pathways to diagnostics for people who don’t currently have access to testing, including those in developing countries. We sought alternative diagnostic methods, such as molecular biomarkers, that could act as screening tools and as targets for drug therapies.

Through the course of this work, what became interesting to me is that I found that a lot of low- and middle-income countries didn’t have an essential toolkit for population screening and were seeking to mirror the US in their broad test menus. This goal is realistically impossible, and unnecessary. This led me to the next step in my global health career, which was to work with companies around the world to develop alternative screening techniques and diagnostics that are more feasible to be used in low- and middle-income countries. To try to apply the same tests used in the US around the world is not possible and not helpful. You cannot retrofit a square test into a round hole — meaning that every country, every culture, every population, will have unique epidemiological issues and different access to healthcare. Considering this, I worked to develop individual diagnostic tool kits for each country – for each unique population, each unique financial setting, in order to bring the best diagnostics to populations without access. It is important to bear in mind that any test is better than no test. 

Q: How did you start working with ASCP and expanding the global health initiatives?

A: I started working as the Vice President for Scientific Activities for ASCP in 2005, but in the early 2000’s, ASCP’s global outreach was limited to only as distant as Canada. We worked to expand our outreach around the globe, with a strategy to look at where the need was the greatest, and next to focus on individual opportunities where the yield would be the greatest. This was, in our opinion, in Sub-Saharan Africa. We first started working with a [U.S. President’s Emergency Plan for AIDS Relief] PEPFAR grant to provide access to testing for HIV. With infectious disease, namely HIV, being the most problematic issue at the time, we focused our work to build capacity and infrastructure around this epidemic – our goal was to train the trainer, build a self-sustaining diagnostic system, and move on to the next country and do it all again. This was very successful until we ran into the next big problem – cancer. Suddenly people were living longer and developing cancer and other non-communicable diseases [NCDs]. One memory stands out – It was around 2012-13, while serving as ASCP’s CEO and working  with the Clinton Global Initiative,  I remember visiting Botswana where I walked into the main hospital ward to find beds upon beds full of women, laying there dying of cancer, while their young children sat on the floor around them.  The waiting areas were also full of children and their grandmothers, while their mothers were either dying or had already died of cervical cancer. We, at ASCP, realized then that we needed to do something about this growing epidemic, and we realized the need to focus on creating strategies for the prevention and intervention of NCDs.

As we set forth, one problem that we discovered was that the World Health Organization had undervalued malignancy as a global health threat – largely because the cancers were going undiagnosed and the cancer registries to generate data were anemic to non-existent. Realizing the urgency of the situation, we began working with the US federal government and other groups to enhance diagnostic access.

In 2014, I met with the Obama administration to urge them to place value on developing outreach to address cancer and other non-communicable diseases in low- and middle-income countries, particularly in Sub-Saharan Africa. Emphasizing the urgency that because NCDs are the inevitably worsening epidemic in Africa, with a population approaching 1 billion, 800 million people or more who had little to no access to diagnostics and were clearly at risk for developing cancer. This will serve to threaten their rapidly growing economies and the ability for their economies to continue to grow.

The Obama administration agreed to let ASCP work with them to develop a program for the prevention, diagnosis, and treatment of NCDs in Africa. I was able to also garner the support of the Clinton Foundation and we brought in significant partners (such as Paul Farmer with Partners in Health) with cohorts such as the pharmaceutical industry, diagnostic industry, people in the public health sector, and key members in Pathology. ASCP proposed the Partners for Cancer Diagnosis and Treatment in Africa initiative and together we launched this program from the White House in October of 2015.

This was the first time that any pathology association had ever launched a large-scale initiative of this kind to bring pathology and laboratory medicine to the forefront of the global health solution.

We began our work by partnering with the ministries of health in each country to establish disease registries. We forged a partnership with the World Health Organization and the Center for Global Health at the NIH to develop pathology-led early detection testing so that early intervention strategies could then be developed.

The Partners Initiative has grown into a 150-million-dollar operation run through the ASCP Center for Global Health which functions to first survey the disease prevalence in the country, next to build pathology and laboratory medicine capacity with the help of technology and pharmaceutical vendors, and to supplement the diagnostics with alliances with the interventionalists who can provide appropriate treatment.

Q: What about sustainability? How will these systems stay in place when ASCP leaves?

A: Before ASCP launches to build capacity and create the necessary partnerships for treatment, we ensure that there is government buy-in for long term sustainability. There is a ten-year exit strategy for each site – we aim to create turn-key facilities, where we can walk away and begin work in the next country. We do this by requiring each country to contractually prioritize diagnostics and develop a plan to financially sustain these systems. They must train enough laboratory and medical staff to run the facilities – and they must have a plan to train and retain pathologists to do the work.

We’ve also focused on the prevention of diseases and invested in a lot of education and training to teach the population about preventive medicine. We also support vaccination programs that lead to prevention of NCDs. For instance, in Rwanda, one hundred percent of the girls there have been vaccinated against HPV – a rate not seen even in the US. We’ve also had great success in dispersing laboratories throughout the country and the government has responded to support this by increasing the training of laboratory medicine specialists to nearly a 1000-fold increase since when ASCP first began working there.

Q: What are some ways laboratory members can contribute their skills to this cause?

A: Anyone that is willing to volunteer time is welcomed and needed, and there are opportunities available no matter your specialty. We try to match each person to their specific interest.

  • On the clinical side, we have many opportunities to volunteer with our PEPFAR initiatives around the world working in the microbiology and infectious disease space.
  • Much of our telepathology diagnostics are provided by our board-certified Anatomic Pathologist members that take time to remotely review cases.
  • We need the help of forensic specialists, for example in Puerto Rico, where we are working to go through the back-log of victims from the 2018 hurricane.
  • For residents and fellows, we have the ASCP Trainee Global Health Fellowship where they have the opportunity to spend a month at one of our global partner sites.
  • We’ve also started a Global Health Ideation Challenge that is an opportunity for anyone to contribute solutions to challenges uniquely faced by low- and middle-income countries.
  • There’s also ample opportunity for anyone to help us with our global education initiatives. We need people to work with institutions to help with educating and training laboratory members, build curriculums, and develop educational systems.

Q: Why is Global Health something that Pathology as a field needs to prioritize?

A: All you have to do is look at the world’s population – 80% of the population lives in developing countries. These are all our brothers and sisters and they deserve the same access to care and the same standard of care as we do in the US. At ASCP, we fervently believe health care for is a universal right.  How can we stand by and let children die of preventable diseases?

The Obama administration had initially raised the point that we in the US have our own health related issues to deal with – and they queried the incentives to prioritize the health of those in sub-Saharan Africa. I explained that if you consider that the US is currently the largest distributor of global aid – and that a threat such as the enormous burden that uncontrolled NCDs will place on the fast-growing economies of sub-Saharan Africa – then you must consider this situation a priority.

The US National Security Council shared these concerns and recognized that if even if only one of the booming African economies crumbles under the looming healthcare crisis, it is our economy that is ultimately affected.  We will be the ones to pay the price.

One must realize that the world is fluent – we are all connected now, and we work not only for altruism but also to ensure global health security. Compared to the scale of the HIV crisis, NCDs are the health threat that gone unchecked, will go far beyond in affecting huge proportions of the global population.

We cannot turn our backs on our brothers and sisters in other countries who are just like us, who just want the same access to healthcare that we have. We must have the life-cycle of our patients in mind when we offer diagnostic testing – how sad it would be to treat a young woman’s HIV infection for example, only to the let her die of cervical cancer in her thirties. We at ASCP believe it is a fundamental fiduciary responsibility to provide access to healthcare – and is part of why our members join us.

What was the reason that we went into medicine in the first place? Wasn’t it to help patients? We have the obligation to help not only our local population of patients, but also all those around the world. The work is difficult, but immensely rewarding. We can help make a difference in a big way, we just need to TAKE ACTION.

-Dana Razzano, MD is a Chief Resident in her third year in anatomic and clinical pathology at New York Medical College at Westchester Medical Center and will be starting her fellowship in Cytopathology at Yale University in 2020. She was a top 5 honoree in ASCP’s Forty Under 40 2018 and was named to The Pathologist’s Power List of 2018. Follow Dr. Razzano on twitter @Dr_DR_Cells.

Lean Principles

Last month we touched on implementing lean principles to help improve efficiency within the lab, as opposed to relying strictly on physical changes. For example, purchasing a larger centrifuge as opposed to switching to a different methodology completely for your STAT testing needs. But what exactly does “lean” mean?

The overall focus of a “lean” laboratory is efficiency: optimizing delivery of results by efficiently utilizing resources, thereby reducing costs and improving speed (turnaround time). If a step or action does not add value, lean laboratories will seek to remove or minimize this perceived waste.

There are 8 key areas where lean processing can be applied to minimize waste, improve efficiency, and prevent unplanned downtime:

  1. Defects: This can apply to both your consumables (reagents, controls) as well as your instruments and equipment. QC reagents that are not as stable as the manufacturer claims them to be can lead to failures, repeats, and extra costs (and time). Older equipment may be more prone to failures and breaking down, leading to additional downtime. Ensure all maintenance tasks are completed on time to prevent these interruptions.
  • Overproduction: Performing testing that was not requested by the customer uses staff time and resources, and cannot be billed for. Evaluate your critical value policy – are you repeating and verifying every single critical result, even though the patient has been consistently running that way since admission? Consider tightening your delta check rules and only verifying values when the result is either new, or a significant change from the prior result.
  • Waiting: If a process is idle or stagnant, resources are being tied down that cannot be used to add value. There is value to batching certain tests due to QC requirements or cost (ELISA plates, electrophoresis gels); however waiting to batch CBC samples on an automated analyzer does not provide the same return value. Similarly, waiting until an instrument runs out of reagent completely before loading more on board can cause further delays if the reagent has special handling requirements (thawing, reconstituting) or has not yet been calibrated.

Evaluate your workload to ensure you have appropriate staffing levels that match your testing volume. If your laboratory receives a large drop off of samples from outpatient clinics at 5pm, consider staggering your work schedules so that you have coverage when you need it, while minimizing the amount of staff waiting for work to arrive.

  • Not engaging all employees: Your staff on the front lines are the experts – utilize this valuable resource by tapping into their creativity. Ask them what is working in your current process, and what they would like to see improved. You may be surprised by the innovative ideas they come up with, and they will have a vested interest in making the improvements work.
  • Transportation: Excessive movement of reagents or samples can lead to time wasted. Try to keep heavy or commonly used items stocked near the location they are used in. It is much easier to transfer a 5 gallon reagent cube from a storage shelf within the hematology department than to bring it up from a central supply room 3 floors below the lab. When possible, utilize automation to process samples and organize completed tubes ready for long-term storage.
  • Inventory: Determine appropriate par levels for each consumable, and avoid over ordering when possible. Excess inventory ties up capital budget, space, and depending on the product can risk wastage due to short expiration dates. For items requiring a long lead time (heavy reagent cubes traveling via ground shipping), plan accordingly to avoid excess rush delivery costs. Within your inventory management system, include all necessary information so that all staff can reorder supplies when the par threshold is exceeded: full description of the item, photo, physical location where it is stored, supplier, item #, par level, amount to order.
  • Motion/Distances: Reduce excess travel and motion of both your staff and your samples to improve efficiency. Strive to create a continuous process flow when designing your lab work areas. Work should move along the process path in a smooth and uninterrupted stream; rather than having to keep returning back to a different bench or department. If different departments frequently share specimens (CBC and HA1c on the same tube), consider colocation of these areas to reduce excess motion between them.
  • Extra processing: Performing non-value added work, having redundant paperwork, or overly complicated processing steps can lead to errors and wasted time. Focus on simplification and standardization. For example, consider implementing a barcode scanner to reduce transcription errors associated with manual entry of values.

When looking to implement lean processes within your lab, start small. Look to see which departments or processing steps are generating the most waste and focus your efforts in those areas first. Even small steps can yield a big return when executed well. Efficient labs lead to happy techs; happy techs lead to successful labs.

https://www.mt.com/us/en/home/library/guides/laboratory-division/1/lean_lab_guide.html

-Kyle Nevins, MS, MLS(ASCP)CM is one of ASCP’s 2018 Top 5 in the 40 Under Forty recognition program. She has worked in the medical laboratory profession for over 18 years. In her current position, she transitions between performing laboratory audits across the entire Northwell Health System on Long Island, NY, consulting for at-risk laboratories outside of Northwell Health, bringing laboratories up to regulatory standards, and acting as supervisor and mentor in labs with management gaps.

Surgical Pathology Case Study: A 64 Year Old Man with History of Loose Stools and Abdominal Pain

Case History

A 64 year old male presented with a one year history of loose stools, lower abdominal crampy/gassy pain that improved with defection, and an unclear history of melena. A colonoscopy revealed a circumferential, villous, carpet-like lesion extending from 15 cm to the anal verge, with biopsies demonstrating fragments of a villous adenoma. A follow-up CT scan was negative for metastatic disease. The decision was then made to proceed with a low anterior resection with hand-sewn colo-anal anastomosis and diverting loop ileostomy.

Diagnosis

Upon opening the rectum, a 13.8 cm long circumferential, carpet-like lesion is identified, extending to the distal margin (Image 1). Sectioning demonstrated a lesion with a maximum thickness of 1.0 cm, which grossly appears to be confined to the mucosa. Due to the prior biopsy history of a villous adenoma, the entire lesion was completely submitted. This required 116 blocks to be submitted, which were then mapped out to show where each block would have been taken from (Image 2). Although there were many foci of intramucosal carcinoma present, clear cut submucosal invasion was not identified, and the specimen was signed out as a villous adenoma (Image 3).

Image 1. Opened rectum demonstrating the 13.8 cm-long carpet-like lesion.
Image 2. Mapping the lesion to show from where each block is taken.
Image 3. Photomicrograph showing the transition from normal mucosa (black arrow) to villous adenomatous tissue (red arrow).

Discussion

Polyps are an abnormal tissue growth that is a common occurrence within the colon, although they can also be found throughout the small intestine, stomach and esophagus. Polyps can be further classified as being neoplastic or non-neoplastic based on the histological pattern of the cells. The most common types of neoplastic polyps found within the GI tract are colonic adenomas, which are benign polyps that serve as precursors to the majority of colorectal cancers. Nearly half of adults in the Western world will develop adenomas by the age of 50, and there is no gender predilection. It is because of this that it is recommended that all adults get a colonoscopy by the age of 50 (even earlier when there is a family history of developing colorectal cancer).

Most polyps are small, measuring 0.5 cm or less, but can grow to be over 10 cm in size (as seen in this case). When a colonoscopy is performed, these polyps can appear as sessile, meaning flat, or pedunculated, meaning on a stalk. Due to the abnormal epithelial growth of the mucosa, the surface of an adenoma can have a velvety appearance, resembling that of a raspberry. Most patients will not demonstrate any symptoms from their polyps, with the exception of occult bleeding and anemia which are associated with larger polyps.

Dysplasia, which literally means “disordered growth”, occurs when the individual cells lose their uniformity and architecture, often resulting in cells with a hyperchromatic nuclei and a high nuclear to cytoplasmic ratio. The presence of dysplasia contained within the epithelium of a polyp is what classifies the polyp as an adenoma (Image 4). Based on their epithelial growth pattern, adenomas can be classified as either tubular adenomas or villous adenomas. Tubular adenomas tend to be smaller polyps, with a smoother surface and rounded glands on histologic examination. Villous adenomas, in contrast, tend to be larger polyps with long, slender villi noted on histology (Image 5). If an adenoma contains a mixture of tubular and villous elements, they are classified as tubulovillous adenomas. When a dysplastic cell is no longer contained within the epithelium, and instead breaches the basement membrane which separates the epithelium from the underlying tissue, it is termed invasive.

Image 4. Photomicrograph of the villous adenoma, demonstrating the dysplasia that is confined to the mucosa and not extending to the deeper tissue.
Image 5. Photomicrograph of the long, slender villi that are commonly seen in villous adenomas.

What makes this case so interesting is that there is a direct correlation between the size of an adenoma, and the risk of developing colorectal cancer. This is not true with most other cancers, however, as size plays no part in determining whether the tumor is cancerous or not. With colon polyps, the larger the polyp, the greater the chance of developing invasive carcinoma (i.e. cancer). This is why screening colonoscopies are so important. Studies have shown that regular colonoscopies, combined with the removal of the polyps found on the exam, reduce the incidence of colorectal cancer. Why this case is so interesting is that you could assume based on the size of this polypoid lesion, you would find some invasive component. However, after reviewing 116 blocks, not a single focus of invasion could be identified.

It should be stated that although there is a correlation between an adenomas size and the risk of developing cancer, the majority of adenomas will not progress to cancer, and in fact, there are no tools currently available that help to determine why one patient’s adenoma will progress to cancer, while another patient’s adenoma will not.

References

  1. Association of Directors of Anatomic and Surgical Pathology, adapted with permission by the American Cancer Society. Understanding Your Pathology Report: Colon Polyps (Sessile or Traditional Serrated Adenomas). cancer.org. https://www.cancer.org/treatment/understanding-your-diagnosis/tests/understanding-your-pathology-report/colon-pathology/colon-polyps-sessile-or-traditional-serrated-adenomas.html. Accessed February 14, 2019.
  2. Colon Polyps. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/colon-polyps/symptoms-causes/syc-20352875. Accessed February 14, 2019.
  3. Turner JR. Polyps. In: Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran Pathologic Basis of Disease, 8th edition. Philadelphia, PA: Elsevier, Inc; 2010: 815-820

-Cory Nash is a board certified Pathologists’ Assistant, specializing in surgical and gross pathology. He currently works as a Pathologists’ Assistant at the University of Chicago Medical Center. His job involves the macroscopic examination, dissection and tissue submission of surgical specimens, ranging from biopsies to multi-organ resections. Cory has a special interest in head and neck pathology, as well as bone and soft tissue pathology. Cory can be followed on twitter at @iplaywithorgans.