2020: Lessons Learned in Lab Safety

2020 will be a year for many to remember, no matter your profession. If you worked in a laboratory, though, you know many things happened along the way which were both difficult and unexpected, and much of the year was consumed with work surrounding the COVID-19 pandemic. Changes and challenges came along which would test the resiliency of any lab safety professional. With luck, though, there were good lessons learned and new ideas about how to face certain lab safety issues in the future.

The Fear of Biohazards

One of the earliest challenges many lab leaders faced this year was dealing with the fears of staff who would have to work with COVID-19 patients and specimens. With the news reporting daily death tolls and unscientific data (like mortality rates when the total number of cases could not be determined), the amount of fear that was generated for some people became obvious at work. Staff members became afraid of handling any specimens, and people began unnecessary practices like double-bagging swabs or wearing gloves when transporting specimens.

Getting employees to deal with those fears and to continue to work became a priority for many very quickly. Many lab leaders conducted meetings and educational sessions. It was important to remind staff that they usually handled specimens every day which contain bacteria and other viruses that could be as harmful to them. They had to remember that if they used Standard Precautions with all samples, they could remain safe. In some locations COVID-19 FAQ newsletters were used to address hot-button issues and answer common questions about PPE, high-touch surfaces, and aerosol generating procedures. It was a good lesson to learn, lab staff need regular information about the proper handling of the hazards they work with and knowledge about how to remain safe on the job.

PPE Changes

Another challenge that arose was trying to keep up with the changes in recommendations for PPE use in the lab and for those who collected COVID-19 swab specimens. In the beginning of the year, masks were not required in the workplace, but that changed. Then cloth masks were not allowed in some organizations. The use of face shields or goggles was mandated, in some locations they were even required in break rooms and hallways. Phlebotomists who once wore only gloves now had to wear gowns, masks and face shields, and in some instances N95 respirators were used. These changes required education, training and an explanation for staff as to why the extra PPE was necessary.

Changes also came to how laboratorians would utilize PPE. Because of international shortages of supplies, the CDC provided information about extended use and re-use of the equipment. Organizations moved from using disposable lab coats and gowns to reusable ones. Hospitals had to set up methods for reprocessing and disinfecting gowns and N95 respirators for reuse using UV lighting or a hydrogen peroxide vapor treatment. Laboratorians and other healthcare workers learned how to extend the normal wear time of N95 respirators, masks, and other disposable PPE and how to store items rather than toss them out. While PPE supply issues seem to have calmed down, labs learned many lessons about how to handle such shortages in the future.

New Testing

As the pandemic progressed, many labs were asked to bring on board new COVID-19 testing. This testing typically had to be brought on board quickly, and in some cases new laboratory space had to be found. Many considerations had to be discussed such as room ventilation, safety equipment (BSCs, eyewash stations, spill kits, etc.), and proper specimen transport.

The best approach for this (as with any new process in the lab) is to conduct a complete risk assessment. One method is to identify the risks associated with the new testing, rate the likelihood and consequences of potential hazards in the process, and then implement steps to mitigate those hazards. Performing these assessments routinely and reviewing them will help to keep your staff safe as work continues in the department all year.

The COVID-19 pandemic affected other areas of work in the laboratory. Accreditation agencies delayed inspections, and now they are trying virtual auditing. Staffing levels are affected by virus exposures in the community or within the department, and while organizations do their best to follow national safety guidance, many have different approaches. The pandemic is not over, and soon healthcare workers will be offered a vaccine. What new lessons will we continue to learn as the situation continues to develop? Time will tell. The important thing for lab leadership is to stand for what keeps those in their department safe. Continue to follow standard precautions, and escalate issues when the unusual occurs. Remember, we will get through this, but as we do, take the opportunity to learn from the experience this year and when moving ahead!

Dan Scungio, MT(ASCP), SLS, CQA (ASQ) has over 25 years experience as a certified medical technologist. Today he is the Laboratory Safety Officer for Sentara Healthcare, a system of seven hospitals and over 20 laboratories and draw sites in the Tidewater area of Virginia. He is also known as Dan the Lab Safety Man, a lab safety consultant, educator, and trainer.

The Pathology Value Chain and Global Health

When Michael Porter conceptualized the Value Chain in 1985, histology as an idea was at least 184 years old and the use of a microtome to cut sections was 155 years old. Now 35 years into value chain as an established lens for markets and firms to approach those markets, numerous publications and reports discuss the value chain of diagnostics, of digital pathology, and of laboratories as profit centers from a variety of sources and as a profitable business model. With the core tool—histology—being such an old technology, easily duplicated, and standardized for skill, quality, and output, can it create competitive advantage or be part of a firm’s value chain? The framework of diagnostic anatomic pathology services (for example, a histology diagnosis for cancer) as a profit model creates ethical questions around what the true value of these services are when the tool is so common. No one chooses to have cancer. Therefore, no one chooses to have a diagnostic procedure for cancer. Stated another way, the consumer’s choice for the product is a potential matter of life and death—that is not true of breakfast cereal. One of the most important features of a capital market is free choice by consumers to choose or not choose products and services. Today, there are people that get by with a flip phone that only makes phone calls and perhaps sends text messages while other people choose essentially supercomputers to carry around in their pocket; however, no one is going to die if they don’t have a telephone on their person. Without a diagnostic procedure for cancer—with histology serving as the primary tool—patients will commonly die from that disease; but with a diagnosis they have a chance of cure, a chance which increases greatly the more rapidly and the earlier in the course of disease the diagnosis is made. One paradigm of healthcare that differs from actual business sectors is an inverse relationship of cost to supply. As competition increases in business, prices are driven downward and reach a level barely above margin which sustains the supply of the goods but often requires the business to diversify or innovate to reach higher margins. In healthcare, costs for the same procedures which are standard of care have gone up, year over year, even while new innovations emerge at higher costs. From a business perspective, creating a feasible value chain around healthcare and, specifically histology, seems unlikely to be sustainable in the long run. However, patients are the center of healthcare and there is high value to patients in having services that meet their medical needs. In applying the concept of “value” and established value chain concepts to anatomic pathology, we shall assume that the maximum value the system can achieve is the shortest time interval from development of cancer in the patient to cure. Fortunately, this value lens mirrors the most efficient pathology laboratory system which would process and sign out large volumes of small biopsies. Coincidentally, that is also the best profit model.

Many countries and large segments of the population in general do not have access to diagnostic histology services due to a range of barriers and challenges that are specific to each site. In some instances, these systems simply do not exist, for example, on many island nations and some nations that are less than 2 million people. The reason for this absence in such settings is due to a massive cost of such services because economies of scope and scale cannot be achieved without a particular threshold of case volume which results in excessively expensive—and thus, unsustainable–services. In larger yet low-resourced countries, private diagnostic histology services with variable quality exist with the main barriers being the out-of-pocket costs of those services to patients although quality could be considered the more important barrier. In high income countries, impoverished patients and patients with insufficient insurance coverage may never be able to access services while others who can access services initially may be inundated with bills related to cancer care that lead to financial disaster. However, all of these “gloom-and-doom” anecdotal observations are not solving the large range of problems that can be found across the patient’s pathology value chain. In order to approach this in the spirit with which Michael Porter intended but framed for a patient, let’s look at the pathology value chain with our value being maximum benefit to the patient, frame it in the context of global health, and assign solutions based on the original Porter activities. This is part 1 of a 4-part series dissecting value chain and pathology in global health. The activities are inbound logistics, operations, outbound logistics, marketing & sales, and service. Let us look at inbound logistics in this part.

Inbound Logistics – This activity encompasses the “receiving, warehousing, and inventory control of a company’s raw materials.” For the lens of maximum value to the patient, from the moment a biopsy is taken until delivery to the laboratory should be minimized and, when the sample arrives, it should be able to be processed immediately with all reagents available. For anatomic pathology, this portion of the value chain includes controlled and uncontrolled raw materials. The controlled raw materials are all of the purchased reagents, supplies, and other consumables that are used in the process of histology and include hazardous materials, flammable materials, and bulky materials such that inventory control should be optimized for both maximum efficiency and value but also maximum safety of staff. “Stock outs”, which are relatively rare in high-income settings, on the laboratory side can include lack of any of the essential reagents and tools to process samples including formalin, alcohol, xylene, paraffin, glass slides, cassettes, etc. Stock outs are the most common challenge in LMICs followed by complete lack of supply chain or lost supply chain. In HIC, bulk purchases, long-term contracts, and volume pricing reduce the cost of the controlled raw materials and can create slight competitive advantage.

Uncontrolled raw materials are the inbound patient tissue samples which can range from minute to whole bodies (in the special case of autopsy) and may be “packaged” by a diverse set of suppliers (i.e., clinical teams) with variable resources. These materials are also “precious” in that they are unique to each customer, cannot be easily reobtained, do not have a fiscal loss value that is easily quantifiable, and may have a large impact on the patient from which they are derived. These materials are also “flawed” because the pre-analytic collection of them by individuals that are not part of the laboratory may create inadequate, insufficient, inappropriate, or damaged materials. In HIC, considerable effort goes into educating clinical teams on collection, creating referral networks, providing collection vessels, etc.; yet laboratories still receive inadequate or insufficient samples. When we consider low- and middle-income countries, observed delays/deficiencies in this part of the value chain are quite common. “Stock outs” on the clinical side can include lack of supplies of clinicians for obtaining biopsies from a specific patient such as sterile biopsy tools, surgical services, and adequate formalin. “Skill lacks” include insufficient training or understanding of the laboratory operations by the clinical team to obtain a biopsy from a patient or properly prepare it for delivery to the laboratory. “System lacks” include an absent or poorly functioning specimen transportation and/or communication system which delays or prevents samples from reaching a laboratory. For a given patient or even population of patients that are to be served by a clinical health system feeding to a specific laboratory, the value chain can be massively depreciated if these inbound logistics are not rectified. When encountered and depending on the specific gap in controlled or uncontrolled raw materials, the solutions can include training of clinical staff; local production of reagents; supplier contract negotiations; bulk ordering; collaborative ordering; cost cross-subsidization; public-private partnerships; capital investment in transportation; and coordination with other convenient transportation networks.

To summarize this part, inbound logistics for a pathology laboratory include controlled and uncontrolled raw materials that have variable costs, safety, inherent value, and flaws that must be considered when planning laboratory operations. With rare exception, these inbound logistics are standardized which leaves little opportunity for major competitive advantage. In LMICs, stock outs (complete or delayed) can invalidate the work of a pathology laboratory by creating significant time delays in diagnosis which make the final diagnosis useless to the individual patient and erode the clinical confidence in the overall system.

In part 2, we will look at operations.

References:

Porter, M. (1985). The value chain and competitive advantage, Chapter 2 in Competitive Advantage: Creating and Sustaining Superior Performance. Free Press, New York, 33-61.

Histology. Wikipedia. https://en.wikipedia.org/wiki/Histology#:~:text=In%20the%2019th%20century%20histology,by%20Karl%20Meyer%20in%201819.

Thorpe A et al. The healthcare diagnostics value game. KPMG International. Global Strategy Group. https://assets.kpmg/content/dam/kpmg/xx/pdf/2018/07/the-healthcare-diagnostics-value-game.pdf

Digital Pathology Market CAGR, Value Chain Study, PESTEL Analysis and SWOT Study|Omnyx LLC, 3DHISTECH Ltd, Definiens AG. https://www.pharmiweb.com/press-release/2020-06-30/digital-pathology-market-cagr-value-chain-study-pestel-analysis-and-swot-study-omnyx-llc-3dhistec

Friedman B. The Three Key Components of the Diagnostic Value Chain. Lab Soft News. January 2007. https://labsoftnews.typepad.com/lab_soft_news/2007/01/the_three_eleme.html

XIFIN. The Evolution of Diagnostics: Climbing the Value Chain. January 2020. https://www.xifin.com/resources/blog/202001/evolution-diagnostics-climbing-value-chain

Sommer R. Profiting from Diagnostic Laboratories. November 2011. Seeking alpha. https://seekingalpha.com/article/305931-profiting-from-diagnostic-laboratories#:~:text=The%20three%20year%20average%20operating,current%20operating%20margin%20of%2012.9%25.

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-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.

Solving Complex Clinical Puzzles: A Memorable Autopsy Experience

I walked into the autopsy suite, trembling and drenched in sweat, even though the atmospheric temperature was as cool as it could ever be. It was my second autopsy experience as a pathology resident and I could not make out exactly how I was feeling. My first session had exposed me to the critical role of pathologists in solving complex clinical puzzles and had left me shaken for days. And, I still wasn’t sure how the second session was going to be. But, one thing I was sure of was the fact that I still felt uncomfortable.

Not uncomfortable because of the task that had been given to us to find out the cause of death of the person I was going to meet. But I felt very uneasy with the fact that I did not know what to expect, yet again. The first session had been that of a middle-aged woman. This was going to be a case of a young man. Two different scenarios and diagnoses. I did not know what to expect. My stomach turned and churned and I could also feel my heart thumping loudly in my chest.

I looked up at my senior resident, with my attending physician observing our every move. He looked very comfortable with what we were about to do. He seemed to approach the entire situation like it was a routine procedure for him. I questioned myself, “would I ever get comfortable with doing autopsies like him?”

I listened attentively as the senior resident walked me through the process of performing an autopsy and what our duties as pathologists was supposed to be. I tried to listen as my senior colleague who was obviously very familiar with the process gave me a detailed lecture. I felt my mind wandering away, even though it seemed as though I was paying attention to what he was saying. My attention drifted back and forth as I couldn’t help thinking about so many other things including the complexities surrounding life and death.

As we went through the organs and finally began working on the lungs and heart were his primary pathologies were supposed to be, I was amazed at the pathology I was being exposed to. His bilateral lungs were severely fibrotic, encased with numerous calcified nodules that eventually turned out to be non-caseating granulomas. He also had calcified hilar nodules also confirmed histopathologically as non-caseating granulomas and his heart was markedly enlarged, with hypertrophy of biventricular walls, more prominent on the right side. His pulmonary arteries also showed signs of severe vascular disease with hyalinization and fibrosis. He had disseminated sarcoidosis, with his heart and lungs more severely affected. The sarcoid granulomas had spared the other organs and had domiciled in the lungs, with downstream effects on the heart. He fit the stereotypical case of cor-pulmonale-right sided heart failure from severe lung disease. The facts of the case suddenly began to make a lot of sense to me. I thus had a better understanding of why the patient had progressed so rapidly with his disease course with a fatal outcome.

I realized later that all my prior apprehension about performing the autopsy had been replaced by an interesting curiosity to find out more about his disease. My initial trepidation about performing that autopsy was quickly replaced by a determination to answer the “why” question. I became more involved and present with the procedure that by the time we left the autopsy suite, I thought I had learned something new that day.

That experience of being able to solve a clinical puzzle from autopsy findings made a huge impact on me. Therefore, the role of pathology and laboratory medicine in the advancement of medicine and patient care can never be overstated.

-Evi Abada, MD, MS is a Resident Physician in anatomic and clinical pathology at the Wayne State University School of Medicine/Detroit Medical Center in Michigan. She earned her Masters of Science in International Health Policy and Management from Brandeis University in Massachusetts, and is a global health advocate. Dr. Abada has been appointed to serve on the ASCP’s Resident’s Council and was named one of ASCP’S 40 under Forty honorees for the year 2020. You can follow her on twitter @EviAbadaMD.

Critical Values: The Burden, Promise and Realization of Virtual Interviews for Pathology Residency During a Pandemic

The SARS-CoV-2 virus continues to cause increased infections and deaths around the world with considerable impact on clinical and laboratory medicine communities. Meanwhile, medical students and the medical community are also undertaking the yearly tribulation of residency interview season. Following the May announcement by the Coalition for Physician Accountability’s Work Group on Medical Students,1 the 2020 interview season will be entirely conducted utilizing virtual interviews. In pointed response to this change in format, residency programs rapidly scrambled to bolster websites, increase their social media presence, add virtual tours and prepare for the virtual interview format prior to the start of interview season. Now, at the midpoint of interview season, it is evident that some burdens of traditional on-site interviews are indeed being alleviated. Whether or not online resident socials and virtual tours can sufficiently substitute for all aspects of on-site visits and if the promise of increased spread of geographic and cultural diversity can be realized remains to be accurately assessed. The survival of the virtual format may even depend on this assessment.

The average cost of traditional on-site pathology interviews has continued to increase for medical students from a per person average of $3400 in 2015 to $4000 in 2020.2 Much of this expense comes from travel/transportation while some pathology programs provided accommodations. Additionally, interview season required about 20 total days away from medical school. To cover these expenses, about half (49%) of medical students borrow money for interviews . Not surprisingly, the majority of them agree that travel (79%) and lodging (65%) are overly burdensome components of interview season.2 Beyond accounting, the salient impact of these time and financial investments is that they were influencing the majority (58%) of interview decisions.

While the rising time and financial burdens of traditional on-site residency interviews were well-known and there was and continues to be a myriad of ideas3 on how to best address these concerns and the match overall, a small burgeoning literature on virtual resident interviews was available prior to the pandemic that showed promise for addressing these concerns.4,5 That is, in the 2020 – 2021 residency interview season, medical students are estimated to spend about 3.5 hours on an average virtual interview day instead of the 8 hour day of a traditional interview and through the elimination of travel time they may spend 7 less days on the interview trail. Thus, the cost of interviewing is also projected to be skeletonized to that of necessary professional clothing and computer hardware. Additional promising data from this small body of research suggests that 85% of virtual interviewees were satisfied with their understanding of the program and their ability to present themselves to residency programs.6 Furthermore, the fact that the residency program’s rank list showed no significant impact based on whether candidates interviewed virtually or in-person suggests that residency programs may feel capable of fairly assessing candidates.7

Beyond time and financial savings for pathology residency applicants and the assessment of candidates by residency programs and vice versa, the measurability of additional outcomes may be critical to the continuation of virtual resident interviews. In particular, there is great interest in online social events and interview day resident panels as a sufficient substitute for the naturally evolving casual conversations that occur during the dinners, lunches and tours available with on-site visits. Also, whether or not these socials combined with interviews with a small subset of faculty can accurately portray a pathology residency program’s culture. In prior surveys that compared in-person, virtual or a combined approach to interviews, candidates always favored in-person assessment when given the choice. The present circumstance will perhaps be the best attempt at an unbiased assessment of the perception of culture through virtual interviews. Last but not least, given the turbulent nature of race relations and culture in the United States over the last year combined with the ability of applicants to virtually interview without travel or financial restrictions, it will be absolutely critical to understand if virtual interviews portend to increase the spread of geographic and cultural diversity among applicants to pathology residency programs. That is, if current trends in resident recruitment can be altered from the current rate of 40 – 60% intraregional resident matriculation or whether the needs of financial and family assistance and/or intraregional familiarity are insurmountable.8 For if the potential for greater diversity is attainable in a significant manner that can be perpetuated into the future, it will be hard to argue for a return to the traditional format. That said, there will likely be bias in the data as an increasing number of pathology residency programs have heard the call to arms and are marching towards diversity, inclusion and equity through greater promotion, recruitment and retention efforts.9

In a tumultuous year that has included race relations reminiscent of the Civil Rights Era combined with a total number of worldwide pandemic deaths similar to the 1957 or 1968 influenza pandemics, medicine continues its steady progression toward improved healthcare and education for all. Following the May 2020 recommendations to implement virtual residency interviews, pathology residency programs moved expeditiously to bolster their websites, increase their social media presence, add virtual tours and prepare for the virtual interview format. Amid this tumult, the virtual interview format has already served to lessen the burdens of time and cost while also serving the practical needs of interview assessments for both medical students and residency programs. Yet, only time and methodical assessment will tell if the virtual interview format eliminates the impact of these burdens on residency decisions, allows both parties to adequately assess cultural fit and if the format and its advantages are here to stay. Regardless, it is imperative that the emphasis on diversity, inclusion and equity remains irrespective of future format.

References

  1. The Coalition for Physician Accountability’s Work Group on Medical Students in the Class of 2021 Moving Across Institutions for Post Graduate Training Final Report and Recommendations for Medical Education Institutions of LCME-Accredited, U.S. Osteopathic, and Non-U.S. Medical School Applicants.
  2. Pourmand, A., Lee, H., Fair, M., Maloney, K. & Caggiula, A. Feasibility and usability of tele-interview for medical residency interview. Western Journal of Emergency Medicine 19, 80–86 (2018).
  3. Hammoud, M. M., Andrews, J. & Skochelak, S. E. Improving the Residency Application and Selection Process: An Optional Early Result Acceptance Program. JAMA – Journal of the American Medical Association 323, 503–504 (2020).
  4. Chandler, N. M., Litz, C. N., Chang, H. L. & Danielson, P. D. Efficacy of Videoconference Interviews in the Pediatric Surgery Match. J. Surg. Educ. 76, 420–426 (2019).
  5. Vining, C. C. et al. Virtual Surgical Fellowship Recruitment During COVID-19 and Its Implications for Resident/Fellow Recruitment in the Future. Ann. Surg. Oncol. 1 (2020). doi:10.1245/s10434-020-08623-2
  6. Healy, W. L. & Bedair, H. Videoconference Interviews for an Adult Reconstruction Fellowship: Lessons Learned. Journal of Bone and Joint Surgery – American Volume 99, E114 (2017).
  7. Vadi, M. G. et al. Comparison of web-based and face-to-face interviews for application to an anesthesiology training program: a pilot study. Int. J. Med. Educ. 7, 102–108 (2016).
  8. Shappell, C. N., Farnan, J. M., McConville, J. F. & Martin, S. K. Geographic Trends for United States Allopathic Seniors Participating in the Residency Match: a Descriptive Analysis. J. Gen. Intern. Med. 34, 179–181 (2019).
  9. Ware, A. D. et al. The “Race” Toward Diversity, Inclusion, and Equity in Pathology: The Johns Hopkins Experience. Acad. Pathol. 6, (2019).

-Josh Klonoski, MD, PhD, is a chief resident at the University of Utah, Salt Lake City, Utah, with a focus in neuroinfectious disease and global health. He has completed the first year of a neuropathology fellowship (out of sequence) and is in his final year of an anatomical and clinical pathology residency. Dr. Klonoski will return to the second neuropathology fellowship year in 2021 – 2022 and apply for a mentored clinical scientist research career development award (K08). The focus of his laboratory research is influenza and active projects include flu pneumonia, super-infections, encephalitis and oncolytic virotherapy.

A Closer Look at “Inside the Lab”

Hello everyone and welcome back!

If you’re as “plugged in” to the pathology and laboratory medicine community as I am, then you’ve been absolutely swimming in the explosion of new content and novel delivery this past year alone! A lot of it is a result of our unfortunate pandemic circumstance, but the pathology media-train has been gaining speed for quite a while now.  Whether you’re a podcast addict, an enthusiastic virtual annual meeting participant (which is still open!), or if you’ve spent way too much time on Path Twitter, I’m right there with you!

Image 1. Awesome Title. Awesome Topics. Awesome Podcast. Subscribe today!

I’ve talked here before about the power and impact of social media in our community, and I could drone on and on about its impressive potential and warn you about pitfalls, give you tips, or just celebrate success stories. But that’s boring. You may or may not have a social media presence, in which case I’d either be pandering to the choir, or putting you sound asleep. Well, I didn’t match into anesthesia, so let me give you the readers’ (tweeters’?) digest. ASCP has (yet again) taken a huge stride in making a presence in today’s increasingly digital age. Catalyzed by many things—pandemic included—many of the projects I have heard about among ASCP colleagues have started to magically materialize; enter the podcast. Among podcast media, ASCP’s Inside the Lab absolutely nails the archetype of what good podcasting is today! It’s a wonderfully curated series, highlighting super relevant topics, and is hosted by a fantastic team. But that’s not all! (wait, this sounds like a commercial, I’m drafting an email about promotional royalties right now…) Kidding. Sort of. Along with the topics, discussions, and guest panelists in the 7 episodes thus far, you can get continuing education credits!

Let me stop there. For emphasis. Imagine you’re driving to work. Sipping your coffee, sitting through traffic on the Dan Ryan Expressway (to those not in Chicago, we name them—we can talk more about this later). You suddenly remember you need CME/CMLE credits for your continuing ed maintenance. Great, you’ll just go hunting online for some boring QA/QC module about something somewhat related to your interests. Or… you could pop in those air pods and turn this podcast on for 1 AMA PRA credit a piece! Leave the murder mystery podcast for the drive home and spend the morning Inside the Lab! But I promised the readers’ digest, right? The following are highlights from a few of the currently available episodes for your listening and CE registering pleasure…

Image 2. Can’t have a good show, without good hosts. Dr. Milner, Dr. Mulder, and Kelly Swails are just that: excellent hosts and fantastic conversationalists who bring up interesting topics that go deeper into pathology and laboratory medicine. It makes for easy listening, easier CE, and provides the listener with a nice peek Inside the Lab. (Oh man, see what I did there?)

Hosted by Dr. Danny Milner (ASCP Chief Medical Officer and Global Health Champion), Dr. Lotte Mulder (ASCP Leadership and Empowerment extraordinaire), and Lablogatory’s very own Kelly Swails (digital managing editor in publications); the podcast has featured numerous amazing guests and topics ranging from testing logistics and interprofessional collaboration, to burnout and (obviously) COVID.

Episode 1: Disparities in COVID Cases Among Minorities

The inaugural episode featured Dr. Von Samedi (Associate Professor of Pathology at the University of Colorado School of Medicine), Dr. Valerie Fitzhugh (Associate Professor/Interim Chair of Pathology and Laboratory Medicine at Rutgers), and ASCP Social Media teammate Aaron Odegard (Infectious Disease MLS at Baptist Health Jacksonville). The inaugural topic (not a softball by any measure): how Black, Latinx, and minorities have suffered the brunt of COVID worse than other demographics. They discussed how COVID, at large, has uncovered swaths of long-standing, problematic disparities, and failures of our healthcare system. I gave a lecture on this topic when I was in New York as part of a CDC-funded, public health training seminar back in April of this (super long) year and things haven’t gotten any better—in fact from April to August when this episode aired, cases absolutely skyrocketed, especially in minority populations. The discussion’s bottom line: our community stands at a crossroads of education and delivery of results to both change the paradigm and improve the system. Good stuff. Listen here.

Episode 3: Online Teaching and Learning in Pathology and Laboratory Medicine

This cutting-edge episode featured our hosts talking to Dr. Sara Wobker (Assistant Professor in Pathology and Laboratory Medicine at UNC Chapel Hill), Dr. Natalie Banet (Assistant Professor of Pathology and Laboratory Medicine at Brown University), and Dr. Richard Davis (Regional Director of Microbiology for Providence Health Care in WA). The topic: how the pandemic has shunted all educational efforts into zoom meetings, virtual conferences, and online classes. Maybe this was happening already? The panelists talked about the old guard of education and the new way online learning has provided dynamic, flexible options for various students of all learning styles. Limitations, however, are clear when addressing pathology education—it’s not so easy to go virtual overnight and you can see the growing pains in every laboratory department. When you try to deliver old lessons across new platforms, things don’t work. So, in order to maintain relevance, engagement, and success educators must take into consideration different types of students, social determinants of learning, cultural backgrounds, accessibility, and inclusion for all. Highly relevant today. Listen here.

Episode 6: Pathology Research and Publication

Finally, I’ll end with a more recent episode. This one featured a panel that included (among their many other academic and clinical roles) Dr. Steven Kroft (Editor-in-Chief of the American Journal of Clinical Pathology), Dr. Roger Bertholf (Editor-in-Chief of Laboratory Medicine), and Dr. Sanjay Mukhopadyay (Associate Editor of the American Journal of Clinical Pathology). The topic for these well-published leaders in our field: how important it is to maintain a scientific standard, and how to get your paper published—yes you! They all talked about peer review, editing, submitting, and being able to tell whether paper’s are “good.” A seemingly subjective measure, but apropos of the year we’ve had which was filled with so many “bad” pieces of scientific literature. The benefits and limitations of peer-review are something we all have come to scrutinize as the digital age puts out clinical content ad nauseum on our social media feeds. But they all assert that one thing should be preserved as the future of scientific publication unfolds: the ability to create a standard by which professional societies, and medical subgroups and communities, collect and assess the science behind our work with purpose, accuracy, efficacy, and efficiency. It behooves editors as well as writers to enter a process that, ultimately, aims to improve the system as a whole—for the benefit of patients everywhere. Exactly how we are #StrongerTogether. Check it out here.

Image 3. You’re still here. It’s over. Go home. Go. Go listen to the podcast. Get your CE!

Check out these and the rest of the available episodes at www.ascp.org/insidethelab, Apple’s app store, Spotify, Google play, or wherever you listen to podcasts!

Thanks for reading, now go listen!

See you next time!

Constantine E. Kanakis MD, MSc, MLS(ASCP)CM is a first-year resident physician in the Pathology and Laboratory Medicine Department at Loyola University Medical Center in Chicago with interests in hematopathology, transfusion medicine, bioethics, public health, and graphic medicine. He is a certified CAP inspector, holds an ASCP LMU certificate, and xxx. He was named on the 2017 ASCP Forty Under 40 list, The Pathologist magazine’s 2020 Power List and serves on ASCP’s Commission for Continuing Professional Development, Social Media Committee, and Patient Champions Advisory Board. He was featured in several online forums during the peak of the COVID pandemic discussing laboratory-related testing considerations, delivered a TEDx talk called “Unrecognizable Medicine,” and sits on the Auxiliary Board of the American Red Cross in Illinois. Dr. Kanakis is active on social media; follow him at @CEKanakisMD.

Microbiology Case Study: Interesting Case of a Cavitary Lung Mass

Case History

A 50 year old male with a significant past medical history of poorly controlled type 2 diabetes mellitus, hypertension, hyperlipidemia, smoking tobacco abuse and obstructive sleep apnea was referred to our institution’s pulmonology clinic for cavitary lung mass. The lung mass was incidentally discovered on chest x-ray and has been clinically stable on serial imaging for over two years; however, a previous extensive laboratory workup including computed tomography (CT) guided biopsy was unrevealing to its etiology. The patient was noted to be largely asymptomatic at his initial office visit; repeat diagnostic workup was ordered. CT chest imaging revealed a 2.8 x 1.9 x 2.0 cm cavitary lung mass in the posterior left lower lobe that was unchanged compared to outside CT imaging from approximately 4 months prior.

Image 1. Cross section (left) and Sagittal (right) views from CT chest without contrast revealed a 2.8 cm transverse by 1.9 cm anteroposterior by 2.0 cm craniocaudal stable mass-like opacity in the left lower lobe superior segment broadly abutting the posterior pleura with a tiny internal focus of cavitation.

Given the chronicity of the lung mass, atypical infection (Nocardia, endemic fungi, mycobacterium) and primary pulmonary cancer were highest on the differential diagnosis. Blood tests including endemic fungal serologies, QuantiFERON-TB Gold, cryptococcal antigen, galactomannan and Fungitell (1-3)-B-d glucan assay were negative. Given the unrevealing non-invasive workup, a repeat CT guided biopsy was performed and core biopsy samples were sent for AFB, fungal and Nocardia cultures as well as for histopathological examination.

Histopathology revealed necrotizing granulomatous inflammation with empty spherules of Coccidioides suggestive of a remote infection of long duration (Images 2, 3). Additionally, no microorganisms were isolated from cultures. Based on these findings, an infectious disease (ID) consult was placed. The patient remained asymptomatic and revealed a long history of residing within areas of the Southwestern United States endemic to Coccidioides species (sp.) during his ID office visit. Repeat Coccidioides complement fixation was positive for IgG (Titer: 1:4) with negative IgM by immunodiffusion testing. Urine Coccidioides antigen tested by quantitative sandwich enzyme immunoassay was negative. These findings likely represent past history of coccidiomycosis and not active infection. Antifungal therapy was deferred due to the patient’s asymptomatic status. The patient was monitored with close clinical follow up and continued serial imaging.

Histopathology Images

Image 2. Hematoxylin and eosin stained sections of formalin fixed paraffin embedded (FFPE) tissue from core biopsy of cavitary lung mass. Necrotizing granulomatous inflammation at 40X (A) and 100X (B) with empty spherules of Coccidioides (C, D) at 600X.
Image 3. Special stains performed of formalin fixed paraffin embedded (FFPE) tissue from core biopsy of cavitary lung mass highlighting empty spherules. Grocott’s methenamine silver stain at 100X (A) and 400X (B). Periodic Acid Schiff for Fungus stain at 600X (C).

Discussion

Coccidioides sp. are dimorphic fungi with a mycelial (saprophytic) phase in the environment and a spherule (parasitic) phase in its host.1 It is the cause of coccidiomycosis, also known as valley fever, desert fever or San Joaquin fever, which has a wide range of clinical presentations from subclinical manifestations (~60%) to an influenza-like illness followed by skin lesions to the most pathological form, disseminated disease.1 It can also cause the development of cavitary lung masses, as described in this case.1 It is endemic to the Southwestern region of the United States where it prefers dry, arid conditions.2 Infections normally occur by inhalation of infective arthroconidia, which have matured from mycelium, following disruption of soil.1 Once inside the host, lungs spherules containing endospores develop (Image 4).1 These spherules rupture releasing the endospores which can continue to develop into spherules to maintain a continuous parasitic cycle or can be exhaled into the environment to continue its saprophytic phase.1

Image 4. High magnification images of hematoxylin and eosin stained sections of formalin fixed paraffin embedded (FFPE) lung tissue revealing multiple spherules containing endospores (left) consistent with active Coccidioides infection and a giant ruptured spherule releasing endospores (right) that will continue to propagate Coccidioides infection.

Two morphologically indistinct species exist (C. immitis and C. posadasii) that can only be definitively identified by molecular methods.3 C. immitis is predominantly found in central and southern California while C. posadasii can be found in other non-Californian southwestern US states and extending into western Texas and down throughout Mexico and South America.3 When cultured, it grows rapidly at both 25°C and 37°C into woolly white colonies that develop alternating barrel-shaped arthroconidia that can be seen on tape prep with lactophenol blue.4

References

  1. Donovan FM, Shubitz L, Powell D, Orbach M, Frelinger J, Galgiani JM. 2019. Early Events in Coccidiomycosis. Clinical Microbiology Reviews, 33, e00112-19, DOI: 10.1128/CMR.00112-19
  2. Hernandez H, Erives VH, Martinez LR. 2019. Coccidioidomycosis: Epidemiology, Fungal Pathogenesis and Therapeutic Development. Current Tropical Medicine Reports, 6, 132-144,  DOI: 10.1007/s40475-019-00184-z
  3. Kirkland TN, Fierer J. 2018. Coccidioides immitis and posadasii; a review of their biology, genomics, pathogenesis, and host immunity, Virulence, 9:1, 1426-1435, DOI: 10.1080/21505594.2018.1509667
  4. Love GL, Ribes JA. 2018. Color Atlas of Mycology, An Illustrated Field Guide Based on Proficiency Testing. College of American Pathologists (CAP), p. 234-235

-John Markantonis is the current Medical Microbiology fellow at UT Southwestern and will be completing his Clinical Pathology residency in 2022. He is also interested in Transfusion Medicine and parasitic diseases.

-Dominick Cavuoti is a Professor at UT Southwestern and specializes in Infectious Diseases Pathology, Medical Microbiology and Cytology.

-Clare McCormick-Baw, MD, PhD is an Assistant Professor of Clinical Microbiology at UT Southwestern in Dallas, Texas. She has a passion for teaching about laboratory medicine in general and the best uses of the microbiology lab in particular.

Hematology Case Study: A 20 Year Old with Anemia

Case History

A 20 year old Black male with a known history of HbS trait went to the primary care office for a pre-surgical evaluation for elective laparoscopic cholecystectomy for symptomatic cholelithiasis. All physical exam findings were negative. The patient had blood work completed and was found to have mild anemia with microcytosis. On previous imaging, the spleen was noted to be slightly enlarged. Further workup included a peripheral blood smear, finding target cells, microspherocytes, folded cells, and rod-shaped Hb C crystals (see image below). No sickled RBCs were noted.

Image 1. Peripheral blood smear with anemia, increased polychromatphilic RBCs, numerous target cells and rare HbC crystals

Discussion

Hemoglobin C disease is an intrinsic red cell disorder caused by Hemoglobin C (Hb C). Hb C is a variant of normal Hemoglobin A (Hb A) that results from a missense mutation in the β-globin protein, replacing the glutamic acid at position 6 with a lysine molecule. The disease can be either in the homozygous state (Hb CC) or in the heterozygous states (Hb AC or Hb SC). The origin of this mutation was traced back to West Africa and is found to confer protection against severe manifestations of malaria. In the United States, the Hb C allele is prevalent in about 1-2% of the African American population. There is an equal incidence between gender, and the incidence of the homozygous disease (i.e., Hb CC) is only 0.02%. Nevertheless, these statistics may be under-representative, since the disease is generally asymptomatic.

Heterozygous individuals with Hb AC usually show no symptoms, while homozygous individuals with Hb CC can have mild hemolytic anemia, jaundice, and splenomegaly. When Hb C is combined with other hemoglobinopathies, such as Hemoglobin S (Hb S), more serious complications can result. Hb S is similar to HbC in that it arises from a missense mutation; ie, a valine is substituted for the glutamic acid at the 6th position on the β-globin protein. As a result of this mutation, HbS abnormally polymerizes when in the presence of low oxygen tension, leaving the red blood cells (RBCs) rigid and irregularly shaped. Sickle cell disease (SCD) typically is a result of homozygous Hb S mutations (i.e., Hb SS), but the disease can also come from Hb SC.

All clinical features of Hb SS can be seen in Hb SC, including painful vaso-occlusive crises, chronic hemolytic anemia, stroke, acute chest syndrome, etc. Nevertheless, Hb SC is generally a milder disease. The complications from HbSC disease are less severe and less frequent when compared to Hb SS. Fortunately, unlike those with Hb SS disease, patients with Hb SC disease do not experience autosplenectomy, but they can develop splenomegaly. There are two complications that occur in HbSC disease occur more frequently than in HbSS disease, and they include proliferative sickle cell retinopathy and avascular necrosis of the femoral head (the latter case presents especially in peripartum women). Therefore, patients with HbSC disease should follow up with ophthalmology and obstetrics to monitor these complications. Furthermore, patients with Hb SC disease can vary in the severity of symptoms and the resulting complications. For example, some patients may develop a severe anemia and require blood transfusions; whereas, other patients are minimally affected by the disease. Overall, patients with Hb SC disease tend to have a better life expectancy compared to those with Hb SS disease. Patients with Hb SS disease have an average life expectancy of 40 years, while those with Hb SC disease are expected to live into their 60s and 70s. In contrast to Hb SS and Hb SC disease, Hb CC disease does not have an increase in mortality. As mentioned earlier, Hb CC disease results only in mild anemia, asymptomatic splenomegaly, and largely absent clinical symptoms.

Pathologic features of Hb SC and Hb CC diseases can be seen on a peripheral blood smear (PBS). Hb CC disease does not show sickled RBCs, while Hb SC can show sickled RBCs though very rarely. More importantly, Hb C is prone to polymerize into characteristic crystals. Depending on the zygosity of the individual, the crystals take on a defining shape. In heterozygous individuals (Hb SC), the crystals are found as irregular, amorphous, or bent appearing, and the RBCs can take on a “spiked and hooked” appearance. In homozygous individuals (Hb CC), the crystals are elongate, straight, and uniformly dense (as seen in the case above). In addition to crystals, the PBS shows numerous target cells, scattered folded cells, and microspherocytes.

Ancillary studies for diagnosis of these diseases include Hb variant analysis, such as electrophoresis and high-pressure liquid chromatography. Cellulose acetate (alkaline) electrophoresis is a standard method used to separate Hb A, Hb A2, Hb F, Hb C, Hb S, and other variants according to charge. Some hemoglobin variants comigrate using this described method, so citrate agar (acid) electrophoresis can be used additionally to distinguish between these variants. In Hb CC disease, analysis shows nearly all Hb C with small amounts of Hb F (i.e., fetal hemoglobin) and HbA2 (i.e., a normal variant of Hb A, in which the hemoglobin molecule is made up of 2 α chains and 2 δ chains). In Hb SC disease, analysis demonstrates almost equal amounts of Hb S and Hb C.

References

  1. Aster JC, Pozdnyakova O, Kutok JL. Hematopathology: A Volume in the High Yield Pathology Series. Philadelphia, PA: Saunders, an imprint of Elsevier Inc.; 2013.
  2. Gao J, Monaghan SA. Hematopathology. Chapter 1: Red Blood Cell/Hemoglobin Disorders. 3rd edition. Philadelphia, PA: Elsevier; 2018.
  3. Karna B, Jha SK, Al Zaabi E. Hemoglobin C Disease. 2020 Jun 9. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. PMID: 32644469.
  4. Mitton BA. Hemoglobin C Disease. Medscape, 9 Nov. 2019, emedicine.medscape.com/article/200853-overview.
  5. Saunthararajah Y, Vichinsky EP. Hematology: Basic Principles and Practice. Chapter 42: Sickle Cell Disease: Clinical Features and Management. Philadelphia, PA: Elsevier; 2018.

-Amy Brady is a 4th-year medical student at the Philadelphia College of Osteopathic Medicine. She is currently applying to AP/CP pathology residency programs. Follow her on Twitter @amybrady517.

-Kamran Mirza, MD PhD is an Associate Professor of Pathology and Laboratory Medicine and Medical Education, and the Vice-Chair of Education in the Department of Pathology at Loyola University Chicago Stritch School of Medicine. Follow him on Twitter @KMirza.

Virtually Amazing

Hello everyone and welcome back!

I’ve appreciated some amazing feedback from my previous post discussing how doctors can sometimes be patients too, and the challenges one might face in different roles within our health care system. Not only a challenge of roles, but those that struggle with invisible illness have unique perspectives on patient care.

That said, this month let me take a break from all the fun content found between cases, concepts, and trends in pathology and laboratory medicine, and celebrate our amazingly successful (and virtual) Annual ASCP Meeting!

Image 1. Just look at this virtual lobby! Set aside that in-person connectivity dissapointment and just appreciate the quality put into this visually! More of my oggling to come in further images…

It was awesome. But don’t just take my word for it, we’re all people of science here, right? So let’s do it by the numbers!

  • 133 educational sessions
  • 3 general sessions
  • 4 named lectures
  • 36 round table sessions which included topics like wellness, problem-solving, collaborative solutions, and “birds of a feather” breakout discussions
  • 9 virtual video microscopy sessions
  • 8 session dedicated to laboratory professionals covering hematology, chemistry, microbiology, and blood banking
  • 6 resident board review sessions
  • 15 companion society sessions
  • 14 sessions related to wellness
  • 4 sessions discussing diversity and inclusion
  • 10 COVID-focused sessions
  • 20 grant funded sessions
  • 4 virtual patient symposia (more on this topic below…) and
  • And 300+ posters!
Image 2. More visual appreciation here: virtual sessions felt like you were really in a large, collective meeting of enthusiastic, like-minded laboratory professionals all learning, collaborating, and networking together!
Image 3. I was fortunate enough to to speak on this amazing panel regarding direct patient-and-pathologist interactions, making laboratory medicine and the overal healthcare experience, safer, more accessible, more interdisciplinary, and better equiped at dealing with the forefront of medical diagnostics!
Image 4. So, the session went well! Just look at that social media data: 36 million impressions over 3.5 days! That’s 1 million people engaging ASCP topics a day, or 12 people per second! All actively discussing and collaborating topics in pathology and laboratory medicine.
Image 5. How could I (of all people) ignore the fact that #ASCP2020 featured an amazing social (media) lounge where people from all over could connect, chat, network, and relax! There were interactive, virtual sessions covering all kinds of non-lab med stuff: yoga, meditation, mixology, and cooking! I hope this is a permanent addition to future (hopefully) hybrid in-person/virtual meetings.

What more could you ask for? The folks that run the logistics and planning for the ASCP Annual Meeting outdid themselves again. Sure this content would excite anyone in the field for 3 dedicated days of immersive learning and networking, but all this and more are still available online for virtual on-demand recorded viewing! Missed a session? No worries, it’s still waiting for you for about 6 months (through March of 2021). All the buzz aside from ASCP members having free access to all of this content, the excitement started months before the meeting went live. Estimates are still coming in, but membership grew by a couple hundred in the weeks leading up to the meeting—not surprising: free access for members? That was an excellent deal, so choice.

Image 6. The start of the #ASCPSoMeTeam’s amazing trajectory culminated at #ASCP2019 in Arizona, the more we work together the more we can accomplish for our profession and our patients, #StrongerTogether.
Image 7. ASCP’s Resident & Pathologist Councils are invaluable assets to promoting and advancing all of our professional development. #ASCP2020 was no different! From virtual fellowship fairs to online, interactive resident council sessions, there was a lot to take it—still available online!
Image 8. I’ve talked about previous ASCP Annual Meetings here and here, and while I can’t list every single aspect of what made this meeting (virtually) amazing, members can check in for about 6 months and see for themselves the quality and attention to detail that comes directly from our collective passion to make pathology and laboratory medicine better, for everyone. Kudos to the ASCP leadership and logistics teams that made this all possible!

Great to see you all at the meeting!

Thanks for reading! See you next time!


-Constantine E. Kanakis MD, MSc, MLS (ASCP)CM is a new first year resident physician in the Pathology and Laboratory Medicine Department at Loyola University Medical Center in Chicago with interests in hematopathology, transfusion medicine, bioethics, public health, and graphic medicine. His posts focus on the broader issues important to the practice of clinical laboratory medicine and their applications to global/public health, outreach/education, and advancing medical science. He is actively involved in public health and education, advocating for visibility and advancement of pathology and lab medicine. Watch his TEDx talk entitled “Unrecognizable Medicine” and follow him on Twitter @CEKanakisMD.

It’s Gettin’ Hot in Here: Cytology Case Study

In my previous post here on Lablogatory, I discussed the diagnosis and comparison of two mediastinal fine needle aspiration (FNA) cases – thymoma and thymic carcinoma. I tooted my own horn of how I instantly recognized the tumors on Rapid On-Site Evaluation (ROSE), as the characteristics were exactly how I remembered them from my cytology knowledge bank formulated in grad school. Here’s a case that completely threw me off my game. I had never seen this type of tumor nor heard of it, at least not to my memory, but that’s the beauty of lab medicine—we’re continuously learning.

A 43 year old female with hypertension and no cancer history presented to a vascular surgery clinic for treatment of varicose veins, and an ultrasound was performed, noting a mass in the left inguinal region. The patient subsequently had an MRI, which demonstrated a predominantly fatty mass in that area with enhancement and probable necrosis within the lesion. The differential diagnosis determined by imaging was fat necrosis versus liposarcoma. With this risk of malignancy, the patient came to our institution for biopsy and further guidance. The ultrasound department visualized the left inguinal mass of mixed echogenicity, measuring 3 centimeters with a focal area of central necrosis.

After receiving two FNA passes of the patient’s left inguinal mass from the radiologist, I made mirror-image smears of the samples, air-drying one slide for Rapid On-Site Evaluation (ROSE), fixing the other in 95% Ethanol, and rinsing the needles in Hanks Balanced Salt Solution to later make a FFPE-Cell Block.

Image 1. Left inguinal FNA, DQ-stained smear.
Image 2. Left inguinal FNA, Pap stained smear.
Image 3. Left inguinal FNA. H&E cell block section.

I remember my differentials – Lipomatous tumor of unknown etiology versus clear cell renal cell carcinoma versus adrenal cortical carcinoma. I knew it was a neoplasm of sorts and that we had adequate material for a diagnosis. But I could not make a definitive diagnosis, and it mind-boggled me. That’s when my cytopathology director reviewed the case with me, and I went straight to the cytology encyclopedias.

The FNA specimen was signed out as a “Benign-appearing adipose tissue neoplasm, consistent with hibernoma.

Image 4. Left inguinal core biopsy, H&E section 100X.
Image 5. Left inguinal core biopsy, H&E section 400x.

Hibernoma was also diagnosed on the concurrent core biopsy specimen by the surgical pathologist on service.

Hibernomas are rare brown fat tumors that typically develop where brown fat is normally distributed throughout the body, such as the upper back, thigh, and retroperitoneum.2 Brown fat, or brown adipose tissue is responsible for non-shivering, mitochondria-rich thermogenesis.3 From the cytology images, one can appreciate the small, eccentric nuclei and capillaries, featuring three cell types: mature adipocytes (think lipoma), lipoblast-like cells (think liposarcoma), and hibernoma cells, which appear to be highly, but uniformly vacuolated adipocytes with granular cytoplasm.

Two months after the initial biopsy, the patient underwent a radical resection of her left thigh hibernoma en bloc with a portion of the iliopsoas muscle and femoral nerve neurolysis. The intraoperative findings showed a 5.2 centimeter well-circumscribed mass directly beneath the femoral vessels, beginning at the common femoral artery and extending to the level of bifurcation of the superficial femoral artery and profunda. The mass was adherent to the posterior wall of the vessel, but fortunately did not involve the adventitial layer. The mass, however, was more adherent to the pectineus muscle and inseparable from the middle portion of the iliopsoas muscle. The mass was also adherent to the hip, and in order to clear the mass from that space, an arthrotomy was made.

Image 6. Left inguinal resection, H&E section 100 x.
Image 7. Left inguinal mass resection, H&E section 400x.

The surgical pathologist signed out the case as follows:

– Hibernoma with focal myxoid changes, 5.3. cm. The inked margins showed no tumor.

 In the middle of the hibernoma, there was a nodular myxoid lesion with spindle cells. Due to a question of liposarcoma, cytogenomic microarray analysis (CMA) was performed which was negative for genomic imbalances. Immunostain performed on a frozen section of tissue showed that the atypical cells were positive for Desmin, confirming that they are skeletal muscle.

If this case was diagnosed as a liposarcoma rather than hibernoma, one would see atypical lipoblasts with more prominent capillaries, like a well-differentiated liposarcoma. Depending on the type of liposarcoma, one might also identify a myxoid stroma or round cells.2

Hibernomas are a unique kind of tumor where the consensus on how to manage them remains split – some favor observation, while others suggest surgical intervention. From the literature, there are no reports to suggest metastasis or malignant degeneration/transformation, but many do favor a resection if feasible.1

References

  1. AlQattan, A. S., Al Abdrabalnabi, A. A., Al Duhileb, M. A., Ewies, T., Mashhour, M., & Abbas, A. (2020). A Diagnostic Dilemma of a Subcutaneous Hibernoma: Case Report. American Journal of Case Reports, 21, 1–5. https://doi.org/10.12659/ajcr.921447
  2. Cibas, E. S., & Ducatman, B. S. (2009). Cytology: Diagnostic Principles and Clinical Correlates, Expert Consult – Online and Print (3rd ed.). Saunders.
  3. Cypress, A., & Khan, C. (2010). The Role and Importance of Brown Adipose Tissue in Energy Homeostasis. Curr Opin Pediatr, 22(4), 478–484. https://doi.org/10.1097/MOP.0b013e32833a8d6e

Taryn Waraksa, MS, SCT(ASCP)CM, CT(IAC), has worked as a cytotechnologist at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, since earning her master’s degree from Thomas Jefferson University in 2014. She is an ASCP board-certified Specialist in Cytotechnology with an additional certification by the International Academy of Cytology (IAC). She is also a 2020 ASCP 40 Under Forty Honoree.

Microbiology Case Study: 83 Year Old Male with Bladder Cancer

Case History An 83 year old male with bladder cancer was treated with Mycobacterium bovis Bacillus Calmette-Guérin (BCG), his last treatment occurring 1.5 months prior to presentation. He has a past medical history of chronic obstructive pulmonary disease, hypertension, obstructive sleep apnea, obesity, and diabetes. The patient has been hospitalized four times over the last two months and his symptoms include generalized weakness, malaise, shortness of breath and recurrent fever. He was found to have patchy lung infiltrates and he was diagnosed with pneumonia, COPD exacerbation and symptoms of heart filature. He was treated previously with antibiotics, steroids and fluid management which would temporarily relieve his symptoms. He presents to the hospital again, four days after his last hospital discharge, with generalized weakness, malaise, shortness of breath and recurrent fever. On initial evaluation he was found to be pancytopenic.  

Laboratory Identification

Blood cultures were negative. A bone marrow biopsy was performed for fever of unknown origin and pancytopenia. The biopsy showed non-caseating granulomas which were negative for acid-fast bacilli (AFB) by Ziehl-Neelsen stain and fungal elements by Gomori Methenamine Silver Stain (GMS). A laboratory-develped PCR test for Mycobacterium tuberculosis complex (MTBC) was performed on the bone marrow and was negative. AFB culture of bone marrow was positive for after 30 days of incubation and the organism was confirmed to be acid-fast bacilli by auramine-rhodamine fluorescent dye and Kinyoun stain. A second laboratory-developed test that uses heat shock protein (HSP) 2 and HSP3 to determine species level identification of Mycobacteria identified the organism as M. tuberculosis complex. Due to the patient’s history, further identification was performed at a reference lab using specific oligonucleotides targeting the gyrb DNA sequence polymorphisms which is able to separate different members of the MTBC. The patient’s isolate contained a RD1 deletion which is specific for Mycobacterium bovis bacillus Calmette-Guérin (BCG).

Discussion

Mycobacterium bovis is a slow growing mycobacterium which produces rough, dry colonies on growth solid media. It is one of the species in the MTBC with a natural host of domestic and wild animals. Routine molecular tests will not accurately differentiate between members of the MTBC. For definitive identification of M. bovis, 16S rRNA and gyrB gene sequencing is necessary. Safe handling procedures should be followed prior to molecular testing of MTBC.

Mycobacterium bovis BCG is a live, attenuated strain of Mycobacterium bovis that was created for vaccine and is used in the treatment of superficial bladder cancer. The treatment may cause localized symptoms including hematuria, fever, nausea, and dysuria which are marker of anti-tumor effect. Serious complications occur in <5% of patients with complications including sepsis, pneumonitis, hepatitis, lymphocytic meningitis, bone marrow involvement, and mycotic aneurysms. The cardinal sign of BCG infection is a relapsing fever with drenching night sweats persisting beyond 48 hours. Disseminated infection can occur days to years after the therapy. Clinical suspicion should be high for M. bovis BCG dissemination if there are symptoms and a high grade fever ≥72 hours. Treatment includes a regiment of isoniazid, rifampin and ethambutol. Most isolates of M. bovis are resistant to pyrazinamide.

References

  1. Lamm DL. Efficacy and safety of bacille Calmette-Guérin immunotherapy in superficial bladder cancer. Clin Infect Dis 2000; 31 Suppl 3:S86.
  2. Shelley MD, Court JB, Kynaston H, et al. Intravesical Bacillus Calmette-Guerin in Ta and T1 Bladder Cancer. Cochrane Database Syst Rev 2000; :CD001986.
  3. Richter E, Weizenegger M, Rusch-Gerdes S, Niemann S. Evaluation of Genotype MTBC Assay for Differentiation of Clinical Mycobacterium tuberculosis Complex Isolates. Journal of Clinical Microbiology 2003; 41(6): 2672-2675
  4. UpToDate

-Crystal Bockoven, MD is a 4th year anatomic pathology resident at University of Chicago (NorthShore). Crystal has an interest in and will be doing a fellowship in pediatric and perinatal pathology. In her spare time, she enjoys reading, hiking and biking. 

-Erin McElvania, PhD, D(ABMM), is the Director of Clinical Microbiology NorthShore University Health System in Evanston, Illinois. Follow Dr. McElvania on twitter @E-McElvania.