A Trainee Abroad: One Cytopathology Fellow’s Experience at a Teaching Hospital in Rwanda

The University Teaching Hospital of Kigali (CHUK) is the largest hospital in its District of Nyarugenge and the biggest national referral hospital in the country of Rwanda, with a 565 hospital bed capacity and 6 operating theaters. It is located in the heart of the capital of the country, Kigali, contributing to its easy accessibility by patients. Rwanda is a country of over 12.5 million people, with an estimated 70.2% of the population living in a rural setting. Per the World Bank, there is an estimated 1 physician per 10,000 people in-country. The government of Rwanda is focused on elevating the country from a low-income developing nation to a middle-income country with a robust health sector capable of ensuring a healthy people with adequate healthcare access. It provides universal healthcare, at a small cost, to all Rwandan citizens who aren’t provided health insurance through employment. In Rwanda there are a total of 14 practicing pathologists, which equates to approximately 1.1 pathologists per million people in the country. In contrast, within the United States there are an estimated 60 pathologists per million people. CHUK offers an array of outpatient, inpatient, surgical, and diagnostic medical services. Inpatient and outpatient services include surgery, accident & emergency, internal medicine, mental health, anesthesiology & critical care, gynecology, pediatrics, maternal & neonatology, ear/nose/throat, ophthalmology, neurosurgery, pediatric surgery, urology, nephrology, dialysis, oncology, and dermatology. Surgical services include general surgery, general pediatric surgery, neurosurgery, orthopaedics, ophthalmology, ear/nose/throat, and obstetrics/gynecology. Diagnostic services include ultrasound, digital x-ray, CT scan, and anatomic and clinical pathology services. In its current state, the hospital has a total of 18 divisions.

There are two facets to the pathology laboratory at CHUK: the Anatomic Pathology (AP) and the Clinical Pathology (CP) laboratories. Within the AP laboratory, also known as the histopathology laboratory, all surgical specimens are grossly examined by a pathology resident and/or pathologist, prepared by a pathology resident for processing, and processed by laboratory technicians into formalin-fixed paraffin-embedded tissue placed onto glass slides. These glass slides are then reviewed by both the pathology residents and the pathologists in order to render a diagnosis, which is communicated to the clinician in order to help direct appropriate patient management. Specimens reviewed at CHUK are predominantly “in-house” specimens generated by the surgeons and clinicians functioning within the walls of the institution. “Referral” specimens are a rarity and generally consist of small biopsies. Cytopathology specimens are also processed within the AP laboratory and include a mixture of fine needle aspiration (FNA) specimens, obtained by pathology residents via superficial FNA, as well as exfoliative cytology specimens such as effusions and urines collected by “in-house” clinicians. Cervical screening conventional pap smears are a rarity. Within the AP laboratory, Diff-Quik, Papanicolaou, and hematoxylin & eosin (H&E) staining was available for slides, as well as a limited panel of special stains: PAS-D, auramine, and a modified acid-fast stain. No immunohistochemistry was available on-site, though cases could be sent for free to nearby Butaro Hospital for IHC or consultation via digital slide scanning.

Regarding my experience at CHUK, I departed the United States on a Saturday evening and reached Kigali, Rwanda by 1AM the following Monday morning. On my first day at CHUK, I was introduced to the 5 anatomic pathology staff, 9 anatomic pathology residents, and the single visiting pathologist serving as a laboratory inspector conducting a mock inspection/assessment. I was given a tour of the pathology facilities as well as the entire hospital system.

There were two aspects to my primary job at CHUK: teaching the residents cytopathology and microscopic review of all live cytopathology cases received in the laboratory. Regarding resident education, there were four ways in which I interacted with the residents during my time to facilitate cytopathology education: lectures, multi-headed microscope unknown slide sessions (unknown case conference where I provided the residents with cases they had never seen before), multi-headed microscope “stump the chump” unknown slide sessions (where the residents presented me with unknown cases I had never seen before), and interactive practicals where we performed various hands-on aspects of cytopathology and general pathology practice.

In respect to lectures, I delivered a total of eight 1.5 hour powerpoint-based lectures covering the following topics: breast cytology, thyroid cytology, lymph node cytology, salivary gland cytology, urine cytology, effusion cytology, peritoneal washing cytology, and frozen section pathology (frozen section lecture presented as a combined effort with Dr. Raina Flores). For unknown slide sessions in which I presented cases to the residents, we had 6 sessions covering the following topics: breast, thyroid, salivary gland, urine, conventional pap, and cerebrospinal fluid. We completed a total of 5 “stump the chump” sessions, where residents gave me slides that I had never seen before and we discussed each case and its work-up as well as its associated differential diagnosis or final pathologic diagnosis at the multi-headed microscope. Topics covered included: breast, thyroid, salivary gland, lymph node, and effusions. Finally, with the assistance of “in-house” pathologists, I helped conduct 2 hands-on practicals with the residents: the first regarding fine needle aspiration technique and slide smearing technique (with Dr. Claire Nadyisaba) and the second regarding performance of frozen section intraoperative consultations using Leica CM1850 cryostats and cow liver (with Dr. Raina Flores).

The second of my duties, live cytopathology case review, was also performed at the multi-headed microscope with the residents each afternoon. On a given day, we would typically receive somewhere between 1 and 4 FNA consultations for which the residents would go to FNA clinic and perform the procedure. The laboratory also received various aspirated and exfoliative cytology specimens, such as pleural effusion and ascites fluids, from clinicians within the hospital system. In total, we reviewed 51 cytopathology cases together at the microscope. 27.5% were neoplastic, with 7.8% being malignant and 2% being lymphoma. 56.8% of cases were negative for malignancy, with 21.5% being inflammatory/infectious. In total, 9.8% of cases were interpreted as “atypical” and 5.9% of cases were non-diagnostic. Of the 51 cases, 21 (41.2%) were FNA consultations that I attended and the resident performed.

On my final day of work, I provided the residents with a 41-page cytology knowledge assessment (in PDF format) to complete at their leisure. This test covered the following topics: cervical and vaginal cytology (19 questions), urine and bladder cytology (11 questions), effusion cytology and peritoneal washings (13 questions), cerebrospinal fluid cytology (12 questions), breast cytology (8 questions), thyroid cytology (17 questions), salivary gland cytology (13 questions), and lymph node cytology (11 questions). Within the document, an answer key with associated detailed explanations was provided so it could serve as a learning aid/study guide for the trainees.  On my last workday, the residents were asked to evaluate their experience with the Cytopathology Module/Course. A total of 7 of 9 residents completed the evaluation. Regarding preparation and organization of different topics, all residents found the quality of the powerpoints to be “very good” or “excellent”. The quality of the practical sessions was rated as “good,” “very good” or “excellent by all residents and the entire module was given an overall rating of “very good” or “excellent” by all of the residents. The majority of residents felt their time was used effectively during this module and that the venues for theoretical and practical learning were appropriate. In the free-text areas for additional comments, suggestions for improvement included a longer duration (at least 4 weeks) of the module, more hands-on practical time, the opportunity for residents to present information, and more microscopy sessions. For additional topics to be covered, respiratory cytology was suggested. In overarching comments regarding their module experience, the residents felt the module was well-prepared, the teaching sessions were well-organized, and that the course was interesting and helpful.

Finally, though not within the confines of my assigned “duties”, I also spent a portion of each day acting as “consultant” to the on-site pathologists for challenging surgical pathology cases, offering opinions as able for various lesions that were challenging to classify on H&E morphology alone. I also served as a “second reviewer” for new malignant diagnoses being rendered in the laboratory, offering my name to be included in the report as a board certified pathologist who has laid eyes on the case and agrees with the interpretation. Examples of some interesting surgical pathology cases I saw in “consultation” included Wilms tumor (nephroblastoma), cystic partially differentiated nephroblastoma (CPDN), pleomorphic xanthoastrocytoma (PXA), sinonasal undifferentiated carcinoma, basaloid moderately-differentiated carcinoma of the uterine cervix, high-grade large cell lymphoma of the cervical lymph node, high-grade squamous intraepithelial lesion of the vulva arising within a condyloma acuminatum, and low-grade papillary urothelial carcinoma of the bladder. I also attend a single Tumor Board Multidisciplinary Conference with two residents and 1 staff pathologist in which a resident presented a case of mucinous moderately-differentiated adenocarcinoma of the colon transmurally invading adjacent ileum. It was interesting to hear the clinicians, pathologists, and radiologists interact in addressing quality of care, efficiency of care, and clinical decision-making. The time of initial presentation to the time of surgery was greater than 1 year for this patient.

My time spent at CHUK in Kigali, Rwanda was an invaluable experience. The work setting granted me the opportunity to expand my role as an academic educator. I was offered the opportunity to present as many lectures as possible to the resident trainees, participate as the leader of multi-headed microscope slide sessions, serve as a spearheading physician in laboratory services expansion efforts, and work as an ‘attending’ physician overseeing trainees’ performance of FNAs. It was an experience that demanded personal growth, via the assumption of roles that I am not privy to as a post-graduate medical education trainee in the United States. Additionally, I was exposed to a cytopathology and surgical pathology workload for a patient population quite dissimilar from the community I am used to serving. With limited ancillary testing capabilities, I returned to a more “pure” form of rendering pathologic diagnoses, based on H&E morphology alone rather than on the synthesis of cyto- and/or histomorphologic appearance coupled with various ancillary diagnostic testing data points. In conclusion, this was an experience that expanded my understanding of the ways in which I can be useful as a board certified anatomic and clinical pathologist interested in incorporating medical mission work into my clinical practice. Beyond arriving in countries without expansive pathology laboratory systems and simply doing the work, I can also pursue opportunities where I can help educate and shape burgeoning in-country pathologists who will then go on to have productive, hopefully decades-long careers in their country, serving their countrymen. This trip certainly expanded my understanding of the role of a “visiting” pathologist. This experience was made possible by the ASCP Trainee Global Health Fellowship Award. Thank you so much to the ASCP, Dr. Dan Milner, Alpa Pandya, and the CHUK pathology department for helping to facilitate this opportunity!

Image 1. Dinner with CHUK pathologists and pathology residents
Image 2. Frozen section training with CHUK pathology residents
Image 3. CHUK laboratory medicine building
Image 4. CHUK hospital
Image 5. CHUK hospital entrance
Image 6. Small “downtown” area near CHUK hosptial–Kwibuka (“to remember”) memorial in remembrance of the 25th anniversary of the Rwandan genocide.
Image 7. Overlooking Kigali.
Image 8. Ferry ride to various neighborhoods in Kigali

-Kelsey McHugh, MD is a board certified anatomic and clinical pathologist, with cytopathology subspecialty certification, who is currently completing gastrointestinal, hepatic, and pancreatobiliary pathology subspecialty training. She anticipates graduating from the Cleveland Clinic Gastrointestinal, Hepatic, and Pancreatobiliary Pathology Fellowship in June 2020, after which she will remain at the Cleveland Clinic as a staff pathologist beginning July 2020.

Respiratory Protection in the Days of the Novel Coronavirus

In the peak of the flu season we might see many people wearing masks in physician offices and hospitals. In the news today, as the 2019 Novel Coronavirus (SARS-CoV-2) continues to spread, we see many images of people wearing different types of respirators, some are N95 respirators and others are surgical masks. Not all experts agree on the efficacy of these pieces of personal protective equipment in the face of viruses, but if you’re going to use them, it is important to know how, when and why.

OSHA’s Respiratory Protection standard (1910.134) provides information about requirements for staff who may potentially be exposed to airborne pathogens. These requirements include specific instructions for choosing the proper respirator, for providing fit-testing, and for user training. The College of American Pathologists (CAP) also expects labs to determine the risk of airborne pathogen exposure for each employee, and they require labs to have a plan which outlines engineering and work practice controls that reduce exposure potential.

The purpose of a respirator is to protect the employee from contaminated or oxygen-deficient air. Therefore, two classes of respirators are common; air-purifying respirators which use filters to remove contaminants from the air you breathe, and atmosphere-supplying respirators which provide clean air from an uncontaminated source. These types of respirators can also be classified further as tight-fitting or loose-fitting.  Tight-fitting respirators need a tight seal between the respirator and the face and/or neck of the user in order to work properly. For now, let’s focus on the air-purifying respirators which are in high demand these days as a potential 2019-nCoV pandemic looms.

In the laboratory, N95 respirators are probably the most commonly-used respirators, often used for protection against tuberculosis and other airborne pathogens. These respirators filter out 95% of airborne pathogens that are 0.3 microns or larger. While the exact size of the 2019-nCoV is not yet known, most coronaviruses are slightly larger than 0.1 microns. Does that mean a N95 respirator (recommended by the CDC) will not offer protection from the coronavirus? Not necessarily.

According to biosafety expert Sean Kaufman (www.saferbehaviors.com), the filter in the N95 respirator works three ways- through interception, impaction, and diffusion. Interception collects larger particles which are blocked by mask fibers, and impaction collects larger particles which have too much inertia to be moved around the filter fibers. Diffusion occurs as smaller particles are bombarded with larger air molecules and are pushed against filter fibers. Most of the bacteria or virus particles are removed from the airstream making the respirator quite useful and protective (HEPA filters on a Biological Safety Cabinet work in much the same way).

Employees who may need to wear a tight-fitting respirator as part of their job are required to have fit-testing every year. This is required by OSHA, and contracted employees (such as pathologists) should be fit-tested as well. Employees who may need such respirators would be those who work in microbiology labs, cytology techs who participate in patient procedures, and others. Labs should perform a risk assessment for each job category to determine the type and level of potential harmful airborne exposure.

Procedure masks, such as those handed out when people suspect they have the flu, are not technically considered respirators. Often, the person who is sick will wear these masks in order to prevent the spread of droplets when coughing or sneezing. They can protect others in the area, but they do not protect the user from harmful airborne pathogens or vapors.

Can these surgical masks be useful for the healthy public when a coronavirus is present? Sean Kaufman says “yes. If you wear a surgical mask in a potentially contaminated environment (on a commuter bus, for example),” Kaufman says, “it can keep you from touching your nose or mouth- two major routes of entry for viruses. Behaviorally speaking, these masks do offer some protection.”

Knowing when and why you use a respirator is vital, but knowing how to use it is important as well. Tight-fitting respirators should never be used without fit-testing to make sure the correct size is being used. Otherwise, the protection offered will be limited. Make sure your staff is properly trained and protected to work in environments where the air is not safe to breathe, and teach others about the usefulness of respirators when the flu and other viruses are lurking!

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.

EUA for 2019-nCoV Test

On February 4th, the FDA announced an Emergency Use Authorization for the CDC’s 2019 Novel Coronavirus real-time RT-PCR Diagnostic Panel. Here’s the press release:

Audience: Clinical Laboratory Professionals

Subject: Laboratory Update: Information about Emergency Use Authorization for  2019 Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel

Level: Laboratory Update

This message is to ensure that clinical laboratories are aware that CDC has developed a new laboratory test kit called the CDC’s 2019 Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel, for use in testing patient respiratory specimens for 2019-nCoV. On February 4, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) to enable emergency use of the test kit in the United States. All EUA documents are available on the FDA website.

The test kit will be available for ordering today from the International Reagent Resource (IRR). Formerly, U.S. diagnostic testing for 2019-nCoV was only being conducted at CDC; however, the FDA EUA and distribution of the tests will allow 2019-nCoV testing to take place at laboratories designated by CDC.  This includes U.S. state and local public health laboratories and Department of Defense (DoD) laboratories.

Clinical laboratories should NOT attempt viral isolation from specimens collected from 2019-nCoV persons under investigation (PUIs). For interim guidelines for collecting, handling, and testing clinical specimens from PUIs for 2019-nCoV, please see the CDC 2019 Novel Coronavirus website

The FDA website lists current EUA assays, and also includes a link to terminated EUA assays. Each pathogen-specific EUA includes the device-specific Letter of Authorization, fact sheets, and manufacturer instructions/package inserts. These documents are updated when amendments are made (e.g., additional specimen types, extraction methods, procedural clarifications), so check the website routinely to ensure your laboratory staff members have the most up-to-date information.

Additional Resources

If you have any questions, please contact LOCS@cdc.gov.

Patient Interaction

Medical school councilors have good intentions in mind when they steer medical students who realize that direct patient care isn’t their strong suit into pathology. But I am different kind of pathologist – the one who sees (or talks to) patients every day. I am a member of unique subspecialty – Transfusion Medicine – which is the most patient-centric subspecialty of all pathology subspecialties. And, contrary to the popular wisdom, I like seeing patients.

Don’t get me wrong though, my heart and soul still live in the lab, deeply rooted in understanding test performance, troubleshooting and quality control. But direct patient care helps to put all the work I have done in the lab into a perspective.

One program that became especially dear to my heart is our chronic RBC exchange program for the kids and adults with sickle cell anemia who have high risk of developing serious complications from the disease, such as stroke, acute chest syndrome, and severe iron overload. As an apheresis physician I see these patients quite frequently due to the nature of the program – chronic RBC exchanges every 4 to 6 weeks. This also means that I quickly had to learn quite a lot not only about managing the exchanges, but also about patients’ success and failures, spend time explaining to parents the benefits of the program and engaging them to maintain compliance with rigorous schedule. The work is not immediately rewarding. All the adjustments I do to the plan of care show changes in lab values in a month or two at best. But it is not entirely about numbers. Another aspect that makes this program special is when you notice that the kids you treat are doing better at school, have less ED visits and overall live a more fulfilling life.

Sometimes the patient interaction is not as direct as in the case of the sickle cell RBC exchange program. For example, being part of the obstetric team that cares for the patient with severe hemolytic disease of fetus and newborn is also extremely rewarding. And the more challenging clinical question is the more rewarding it is in the end. Just this summer we had a patient who developed an antibody to very high frequency antigen that is present in 99.7% of the population and finding the right donor for intrauterine transfusion involved quite a few people in at least 3 cities.  When all the pages, phone calls, emails, and personal conversations between me and residents, obstetricians, anesthesiologists, pediatricians, and blood suppliers result in a positive outcome for mom and baby – I feel elated. And who wouldn’t?! That is why I enjoy what I do!

-Aleh Bobr MD is currently the medical director of blood bank and tissue services at University of Nebraska Medical Center in Omaha, NE. He did his residency in Anatomic and Clinical pathology and Fellowship in Transfusion Medicine at Mayo Clinic Rochester, MN. Prior to that he did his post-doctoral research fellowship in Immunology with focus on dendritic cell biology at University of Minnesota and Yale University. He received his medical degree from Vitebsk State Medical University in Vitebsk, Belarus. Current interests include application of apheresis, platelet refractoriness.

Hyping Technology with Opinions rather than Facts

I often have an argument or discussion with my spouse about facts versus opinions. Although both concepts represent information, my brain is mostly concerned with facts as a scientist and a problem solver. My spouse, having spent years in the hospitality, banking, and real estate business, is “all about the customer,” with success rooted largely in recognition of and alignment to their opinions. In my current role as CMO at ASCP where we have “concierge customer service” as one of our principles, I have adapted to listening, understanding, and operationalizing the opinions of a diverse group of individuals. However, when it comes to science, I feel that it is important to remain with facts until the point where science runs out of answers, and we have to guess about something. Where I run into trouble is that I have the opinion that people who do not understand the facts should not necessarily espouse their opinions. Someone once said an expert is someone who knows everything about a topic as well as everything that is wrong about a topic—referring to common misunderstandings that flow through our common knowledge. Opinions are like belly buttons—everyone has one, but some are cleaner than others.

When it comes to journalism, I am unfortunately a purest. I just want the facts. I was, therefore, a bit taken aback by a New York Times article discussing an innovative technology in neurosurgery for intraoperative consultations for brain tumors. My visceral negative response emerged from the surgeon discussed in the article owning part of the company that built the device for the study. My secondary  concerns stem from the article discussing intraoperative consultations done by pathologists and, yet, not a single pathologist was interviewed for the article. But the biggest concern I had which made me delve deeper into the topic  was the enormous number of inaccurate facts or complete untruths presented in the article. It is hard to say it wasn’t poor journalism but, as a scientist, I had to go to the source.

The scientific article in question was “Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks” published on Jan 6, 2020. The New York Times article, “A.I. Comes to the Operating Room” was published the same day. I read the article myself, and when it didn’t quite pass my sniff test, asked three of my colleagues who are experts in this area to also read the paper and the news report. Jane Brock, a breast pathologist who is truly an innovative thinker and dreams of the day when pathologists can study tissue immediately with confocal laser imaging and rapid molecular testing—part of her research—said of the technology, “this is a great paper and a great microscope.” She further mentioned how brain is ideal because it is homogenous, easily flattened, and amenable to artificial intelligence (AI) review because of the limited parameters needed to be evaluated for clinical decision making intraoperatively. “This is definitely the future of pathology—getting rid of frozen sections in favor of fresh tissue imaging,” Dr. Brock said. “It also means you can take tissue for research/molecular diagnostics, image it, and not waste it just by imagining it [on frozen section]. The time savings are huge.” It was exciting to hear Dr. Brock’s enthusiasm for the technology conceptually and how it could be a boon for pathologists’ ability to consult during surgery.

Dr. Rebecca Folkerth,  a surgical neuropathologist for more than 20 years before she became the neuropathologist for the Office of the Medical Examiner of New York, had some concerns about the science in the paper and the maturity of the technology to replace a consultation with a pathologist today. “The questions asked [in the paper] were of necessity extremely basic, and hardly represent the real world as encountered in the operating room and neuropathology laboratory,” said Dr. Folkerth. She was concerned in the news article with the statement “Final pathologic diagnosis is increasingly driven by molecular rather than morphologic criteria.” “That is actually true for a minority of nervous system lesions, such that the ‘gold standard’ for diagnosis remains ‘macroscopic (gross) pathology’ [essentially imaging] and ‘cytologic and histoarchitectural features’ as well as clinical and laboratory findings. In other words,” concluded Dr. Folkerth, “the training and experience of a physician [pathologist] is what allows the synthesis of all data points to arrive at a comprehensive interpretation.” With regard to the immediate application to real world practice, Dr. Folkerth said, “It is telling that no ‘gliosis/treatment effect’ cases were analyzed [because] distinction of post-treatment changes from a neoplastic process in the brain is one of the most difficult encountered in clinical neuropathology.” Other cellular processes that occur in the brain were also not in the study. “A glaring omission of this paper,” Dr. Folkerth concluded, “were the consequences of the errors in ‘predicting diagnosis’. Were these ‘class A’ [leading to radical changes]?” In the article, the surgeon states that neuropathologists “hate frozen sections” which Dr. Folkerth says is simply not true. Perhaps the author should have interviewed an actual neuropathologist for this piece. Both Dr. Brock and Dr. Folkerth had concerns about the practicality of the technology where Dr. Brock felt it was currently “too expensive” (relative to current practice which provides more information across the spectrum of neuropathology) while Dr Folkerth was not clear who this process could work in smaller or decentralizes or underserved surgical settings (as the new article suggests) without a lower cost. Dr. Folkerth agreed with Dr. Brock, however, that this technology “may well represent a revolution in intraoperative decision-making and outcome.”

Lastly, I spoke with Dr. Jason Hornick, who in addition to be an internationally renowned surgical pathologist, has been in charge of quality of intraoperative consultations at one of the premiere hospitals in the US. The “frozen section [procedure] does not often take longer than 30 minutes, and is not often ‘far less accurate’ than in the study,” Dr. Hornick began. “The rates of significant discordance between intraoperative diagnosis and the final diagnosis in published surveys (for all of surgical pathology) are generally less that 1.5%.” Dr. Hornick (and I) agree that the surgeon quoted in the article is bashing the practice of pathology without any accuracy to his statements. He is not quoting facts and he is not quoting opinions. He is simply saying things that are wrong and not supported by data or years of experience. Dr. Hornick also mentioned that the cost of frozen sections are trivial compared with the cost of this technology and, as pointed out by Dr. Folkerth, the pathologists’ intraoperative consultation is much broader than just reviewing a slide for signs of tumor. Dr. Hornick said it best: “The expert consultation provided intraoperatively by the pathologist to the surgeon is not restricted to making an accurate diagnosis; pathologists are uniquely suited to integrating the patient’s clinical history, imaging, prior pathology, and surgical findings to assist the surgeon in making surgical decisions.” He concluded, “The intraoperative consultation is not a laboratory test; it is a consultative opinion by an expert physician who often understands the patient’s disease better than the surgeon.”

With these three experts’ views including their clarification of the facts and their opinions, it seems pretty clear, in my opinion, that this news article is presenting an inappropriate picture of the practice of pathology and making claims about this technology which are not, in fact, accurate or fair. What struck me, however, was the comment by the surgeon that when he was working with pathologists, he may only ask two questions because of the very long time for the frozen section but with this technology he can ask six or seven questions and get the answers really quickly. If this surgeon needed to know the answers to those question, that is, if they were mission critical to patient care, why didn’t the surgeon work with the pathology team and demand higher quality and faster turnaround time rather than investing time and money in a novel, expensive technology (from which he profits) which can only provide a fraction of the answers that a pathologist can provide? Unless the technology completely replaces a pathologist—which it doesn’t seem to be able to do—the pathologists and frozen section labs still have to be available. Thus, costs are increased, not decreased. The only parameter for increased value for the patient would appear to be time savings; however, most clinicians and pathologists would agree that the value to a patient of a two-minute AI read versus less than 20-minute intraoperative consultation is minimal compared with the cost difference.

But outside of all of this, as the entire field of pathology faces pressure from technologies—largely driven by non-pathologists—we have to realize that pathologists’ consultations, whether intraoperative or on permanents, are a tool of quality directly for the patient. If a surgeon is able to perform a surgery and discard tissue, use a system from which he/she profits, or depends solely on a computer algorithm informed by a couple of hundred cases, where is the quality check for the patient? How do we know that was tumor that was removed? Pathologists are paid to perform intraoperative consultations and ASCP works very hard to ensure that pathologists are not only fairly paid for their work but that their involvement occurs whenever it can improve quality and care for the patient. Dr. Folkerth alone has seen thousands of cases on intraoperative consultation for neuropathology and the collective knowledge of currently living neuropathologists would be millions of cases. If such knowledge were captured by an AI across the full spectrum of neuropathology, the technology would truly be remarkable. But you can’t have such integration of knowledge without involving pathologists.

milner-small

-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.

Prozone Effect in the Fecal Immunochemical Test (FIT)

Case History

An 80 year old female had a history of chronic iron deficiency anemia with unknown cause and comorbidities included hypothyroidism, congestive heart failure (CHF), severe aortic stenosis and COPD. The patient presented at the ED with initial presentation with increasing shortness of breast, NYHA class 3-4. She was admitted to the hospital for further treatment for CHF, as well hyperventilation, sleep apnea and COPD. Her serum iron and iron saturation were tested and results were 2 umol/L (reference range for iron: 10-29 umol/L) and 7% (reference range: 14-51%), respectively. Part of her investigations included a qualitative fecal test to screen for gastrointestinal bleeding. The immunochemical fecal occult blood test was performed using a CLIA waived Hema Screen SpecificTM POCT test (Immunostics, Inc, USA) in the hospital lab. Hema Screen Specific test is a qualitative, sandwich dye conjugated immunoassay that uses a combination of monoclonal and polyclonal antibodies to detect the globin component of hemoglobin in the fecal samples. The manufacture recommended using Hema Screen Specific test in routine physical examines, hospital monitoring of bleeding in patients and for screening for colorectal cancer or gastrointestinal bleeding for any source (statement from the product package insert).

 The specimen submitted to the lab was markedly red (Image 1), yet Hema screen test returned a negative result. Since this device is designed to detect occult blood in fecal samples, a prozone effect was suspected, as the stool appeared to contain overt hemorrhage. The specimen was reanalyzed with serial dilutions by a factor of 5, 10, and at 100 × dilution. The FIT result became clearly positive for blood (Image 2). The patient received a colonoscopy, which revealed internal hemorrhoids, severe diverticulosis in the left colon, as well as multiple angiodysplastic lesions. One such lesion was in the ascending colon and was actively bleeding at the time of colonoscopy. The others, which were not bleeding, were distributed in the proximal ascending colon, hepatic flexure, and proximal transverse colon. All angiodysplastic lesions were treated with argon plasma coagulation.

Image 1. Fecal specimen demonstrating overt hemorrhage.
Image 2. Fecal immunochemical test performed on the patient sample submitted. Serial dilutions of fecal specimen were performed. At the dilution factor of 1:100, the result showed positive. Saline was used to dilute the fecal sample.

Moreover, we have tested the device with another bloody fecal sample during the initial evaluation. When an appropriate dilution factor was used, the prozone effect begins to lose its interference as show in Image 3.

Image 3. Fecal immunochemical test (FIT), showing control (C) and test (T) lines, applied to serial dilutions of fecal specimen (B ─ undiluted, C ─ 10 ×, D ─ 100 ×, E ─ 1 000 ×, F ─ 10 000 ×, G ─ 100 000 ×). At 10 × dilution, the prozone effect begins to lose its interference, and at 100 × the test is clearly positive. At dilutions higher than 1 000 ×, the concentration of blood becomes too low to return a positive result. (Image 3 provided by Dr. Andrew Lyon, PhD, DABCC, FCACB, Lab Medicine & Pathology, Saskatchewan Health Authority)

Discussion

The prozone effect (or Hook effect) has long been appreciated as a source of interference in immunoassays.1 It typically occurs in sandwich assays, of which the FIT test is an example.2 When the concentration of the analyte is excessively high, it oversaturates the capture and detection antibodies in favor of forming single antibody:analyte complexes, rather than sandwiches. This results in a false negative result where the assay is unable to detect the analyte. The solution to the prozone effect is serial dilution to lower the concentration of the analyte.

The FIT test is designed to detect microscopic amounts of blood, hence its function in screening for fecal occult blood. A number of hospital labs use this test in an acute care setting to screening bleeding in patients. However, its capacity is oversaturated in specimens containing overt hemorrhage, as in our patient. In these cases it is nevertheless important to prove that the red color of the specimen is truly due to blood, as bright red stool can be caused by a wide range of dietary factors. Some examples are red food coloring, beets, cranberries, and tomato juice.3 If these possibilities are not ruled out, the patient may become subject to the risks of unnecessary endoscopy. Serial dilution of the specimen is extremely useful in this type of situation.

References

  1. Dasgupta A, Wahed A. Clinical Chemistry, Immunology and Laboratory Quality Control: A Comprehensive Review for Board Preparation, Certification and Clinical Practice. Amsterdam: Elsevier; 2014. 2.11.
  2. Allison JE, Fraser CG, Halloran SP, Young GP. Population Screening for Colorectal Cancer Means Getting FIT: The Past, Present, and Future of Colorectal Cancer Screening Using the Fecal Immunochemical Test for Hemoglobin (FIT). Gut and Liver. 2014 Mar;8(2):117-30. https://doi.org/10.5009/gnl.2014.8.2.117
  3. Picco MF. Stool color: When to worry [Internet]. Mayo Clinic; 2019 Feb 19 [cited 2019 Feb 23]. Available from: https://www.mayoclinic.org/stool-color/expert-answers/faq-20058080

-Hao Li, MD is a currently a first year anatomical pathological resident at Western University, London ON, Canada. Prior to be a pathology resident, he was a neurosurgery resident at the University of Saskatchewan, Saskatoon SK, Canada. When he was at the University of Saskatchewan, he spent his third year primarily in neuropathology, with also some general anatomical pathology and clinical pathology. Through these experiences, he has come to realize that his passion and calling lay more in pathology than in surgery. He has successfully transferred into pathology, and started a new residency in anatomical pathology in July 2019. Having a background in the clinical neurosciences, he hopes to eventually pursue a fellowship in neuropathology, and possess the skill set to practice both anatomical pathology and neuropathology.

2020 Vision

Welcome back everybody! Thank you for all the engagement on my last post, Up In Smoke¸ where I discussed the plenary publications surrounding the vaping crisis and EVALI as new pulmonary pathology entity. This month, let’s start 2020 off right. After the holiday break and going on some of my last pathology residency interviews, I’d like to reflect on this new year by taking a look at 20 exciting things on the horizon for those of us in pathology and laboratory medicine!

So, let’s take a look at 2020 with some 20/20 vision… (sorry, not sorry)

20. Big, big, big, big data

Image 1. Can’t mention databases without this invaluable website that has made me look somewhat semi-competent in many instances! Thanks Pathology Outlines (Source: um, pathologyoutlines.com)

Last year, Elsevier’s Clinical Solutions Director in China discussed three topics that would impact our profession in 2019—so let’s start there. These first three go hand-in-hand in prepping the stage for 2020. Up first: the never-ending explosion of biomedical information and the continuing tidal wave of health data we don’t even know what to do with just yet! It’s a very interesting estimate that, by 2020 (aka now!) the whole sum of medical knowledge will double every 73 days. How on earth are we to manage, when compared to 1950 it would have taken 50 years to double? Well, the argument in the linked Elsevier blogpost discusses how evidence-based inquiry databases will store and organize this knowledge for us: think UpToDate, or ExpertPath, or ImmunoQuery…some of you are nodding your heads in relief, great, I’ll move on.

19. Precision Medicine

Image 2. PD-L1, or programmed death ligand 1, is one of several new targets for cancer therapy that utilized cellular checkpoints in cell cycles alongside T cell and NK cell functional immunity to fight cancer a little more precisely than classic chemotherapy regimens. Look at you, all up to date, and stuff. (Source: AstraZeneca graphic, azimmuno-oncology.com, content)

The second topic last year’s Elsevier’s blogpost discussed was the growth and rapid development of highly specific, targeted, individualized treatment plans. The mainstay example is of course how oncology treatments are moving away from one-size-fits-all chemotherapies to individualized mutation-specific immunomodulating therapy. (We’re moving like melting glaciers but moving nonetheless.) I was definitely well equipped with my ASCP online CE credits as I found myself discussing testing patients during my heme/onc training for PDL-1 and other tailored targets. We’re just starting to ride this wave and it’s definitely growing fast.

18. AI in healthcare (part 1)

Image 3. Artificial Intelligence is getting really good at pattern recognition. Why did I choose this picture? Oh, because it’s a study of how China-based JF Healthcare, a Siemens off shoot start up AI group, designed an algorithm that beat radiologist at Stanford on precision, delivery, and accuracy. Woah. (Source: hitconsultant.net)

Yep. I went there—it’s exciting! But notice I’ll come around after some other topics to really get into the heart of AI in path. Basically, the last point in the blogpost discussed the way smart software has been growing in medicine; particularly with radiology and surgery, using advancements in robotics and detection software to predict and stratify clinical information for patient care. Within this context let me quote them directly for you, “…there remains some uncertainty around the role of AI and its true impact on pathology, it is important to recognize that AI-based technologies or machines will never replace pathologists. Instead, such innovations will play an assistive role, augmenting the decision-making capabilities of pathologists and helping them perform better and faster…” All my pathologist friends may now exhale. It’s going to be okay. We’ll talk more about this at #10.

17. New Tech, New Toys

Image 4. You don’t have to go far to read about new tools and new tech. How’s this: a saliva-based rapid Malaria detection assay, courtesy of our friends at ThePathologist.com. New, rapid, accurate and deliverable diagnostics…now within spitting distance. Nailed it.

Pathologists are like the 007’s of the clinical team…at least when it comes to developing tech. There are so many new gadgets and tools we clinicians have available to us today. I delivered a recent TEDx talk where I discussed the “unrecognizable future” of medicine—and obviously now look for new and exciting ways to tell people I gave a TEDx talk. The important thing is that 73 days of doubling medical knowledge is happening so fast we don’t even know what we have available to us! Finger-print drug tests, smartphone facial capillary blood pressures, liquid biopsies, virtual MS-based immunohistochemical stains that never actually stain a single cell, cytology AI, deep data mining of free text pathology reports…it’s not a short list. It’s exciting, and we should all be sharing and collaborating to use these exciting tools together in creative ways for positive outcomes!

16. No More Silos

Image 5. Business and management have long discussed the importance of tearing down silos of knowledge in order to improve workflow and outcomes. It’s a growing conversation in healthcare and we’ve got our own isolated pockets of data that need to come out to the forefront, too. (Source: ERP Consulting, Estes Group Image, estesgrp.com)

Last year, I wrote a few pieces here on Lablogatory that mentioned High-Reliability Organizations (HROs) which require absolutely full sharing of responsibility as well as knowledge in order to solve problems and improve patient-care outcomes. There are many ways siloed thinking can harm the progress of any institution. It takes leadership, creative problem-solving, transparency, and teamwork. In the coming months of 2020, keep an eye out for pockets within your organizational environment that act as black holes or veils to keep pieces of critical data from the rest of the team. Encourage discussions between you and your peers, check biases about what you think might be important for one team vs. another, and try to share successes and failures as a group.

15. New Types of Colleagues

Image 6. We’re all different. And that’s ok. Each one of us is a brain, and an athlete, and a basket-case, a princess, and a criminal. Okay maybe not the last one, but we can all contribute in some important meaningful way. (Source: The Breakfast Club, 1985)

What I just mentioned about engaging in new conversations with folks you might not have worked with before—its not groundbreaking, its just good practice! In order to tear down #16’s silos, we’ve got to seek out and explore new ways to collaborate with colleagues outside our everyday scope. There will always be discussions about generational divides and differences that create culture strife in the workplace, or political/opinionated schisms that divide even the most cohesive of medical specialties. (I’m looking at you ACOG, ACP, ASCCP, and others: it’s Cervical Cancer Awareness Month, can we just agree on some guidelines already…) Soapbox over. But seriously, this isn’t a new concept. Feel like a lab half filled with boomers and millennials can’t make the cut? Well, the Harvard Business Review gave us great recommendations for this exact type of interpersonal growth exercise—in the NINETIES! The take home message: having an open culture and proactive leadership allows for fruitful exchange and growth!

14. Digital Pathology!

Image 7. Bigger, I want these screens bigger! The desk of tomorrow’s anatomic pathologist might have less glass and more pixels, screens, and queued data with high-output servers that are stocked with smart software to sift out normal results so they can focus on really tough morphologies. Maybe even with augmented reality software, or other crazy stuff I can’t think of yet! (Source: Inspirata, digital pathology)

It’s coming. You can’t stop it. It’s exciting. I don’t care what you think. Well I actually do care, but don’t knock digi-path till it grows into whatever it’s going to become. The desk of the (anatomic) pathologist-of-the-future will look a lot different from today and that’s really cool. Once upon a time, a very long, long time ago—in the eighties maybe—radiologists still had films where we actually used radiation to change the exposure of images to be read over a light box. Classic scene, right? Doctor, the x-ray is ready! *THWIP* *CLICK* *BUZZ* and cue the contemplative stare on the wall light. Then, they went digital and get to hang out in the dark with four computer screens and coffee, and really comfy chairs. I mean what a form of progress, can’t deny.

13. MS Methodologies

Image 8. Okay, MSI crash-course time. All you really need to know is that this method allows for great specimen preservation on tiny samples, high resolution, the ability to combine with molecular testing, and fascinating implications for margin detection, mutation analyses, and more! (Source: https://blog.waters.com/molecular-visualization-ms-imaging-delivers-insights-for-cancer-research)

In my mailbox this month, is another excellent edition of The Pathologist and in it there’s a great article on Mass Spec imaging transitioning from a research tool to a clinical one. Woah. We’ve all talked about and praised MALDI-Tof methods for microbiologic assays and detection, but the expanse of mass spectrometry has developed rather quickly. Now, it’s looking for a niche in routine laboratory diagnostics outside of the old chemistry analyzer… It’s a new, non-destructive way of examining tissue and gleaning data from the smallest pieces of gross specimens. We’re onto something here, keep an eye on MSI.

12. Molecular—Need I say More?

Image 9. Move over International Space Station, the folks at Thermo Fischer Scientific want to share their take on the Next Generation of molecular testing. (Source: The Pathologist)

Same edition of The Pathologist, about 25 pages back: a discussion on the value of molecular Next Generation Sequencing. I’ve already bored half of you, wait! Come back. I agree with you, you can only call it Next-Gen so many times before a whole generation of laboratorians get bored of talking about new tumor markers or mutations. But what’s happening with NGS testing that you should know? Simply put, there are NGS analyzers that are faster, with smaller footprints, combined with smarter software that is making molecular more feasible for laboratories that used to shy away from the notion of including NGS or LDTs in their lab testing menus. This means more labs, running more molecular, for more specific populations, in real time that can collaborate with that many more new colleagues while breaking silos—well just look up at #18, 17, 16, and 15!

11. Global Health

Image 10. From Dr. Razzano’s post on Lablogatory

Dr. Dana Razzano recently interviewed me for her global health series, and we got the chance to talk about the important intersection of laboratory medicine and global public health. Getting involved in a community—especially for those of us in healthcare—often includes a survey of what kind of health challenges you face. For some it’s access to clean resources like water, for others it’s a complex system of reimbursement and billing issues that complicate delivery of care, or even more basic assessments reveal high rates of local infections with preventable illness. But you can’t tackle infrastructure change, political reform, or vaccine education single-handedly. Global health is an increasing part of our global world and, if we stay true to our professional values, we should be at the forefront.

10. AI in Healthcare (part 2)

Image 11. Drawing to represent AI from my TEDx talk, Unrecognizable Medicine 2019, TEDxAUCMED

Oh I told you I’d come back to this. Some folks are still apprehensive about AI—that’s ok—I am too, but only because I want to make sure it’s done right. Don’t expect any Skynet stuff, we’re not going that deep. So let me tell you some of the things I got to see on the residency interview trail that piqued my interests. At one hospital system, I saw plans for their anatomic pathology department to go fully digital with augmented AI software to help score mitoses and other morphologic traits by 2025. At another institution, I saw plans for data mining historical free text pathology reports to predict and stratify future specimens before they even got signed out! At a third system, I saw the utilization of smart software to predict clinical lab values for a patient’s personalized reference range…pre-analytically! This stuff is coming in hot so watch for it! What AI-related advancements are you seeing in your neck of the lab?

9. Patient Consultation

Image 12. Courtesy of SUNY Upstate Pathology Department via Twitter, a newly renovated pathology residency review room and patient consultation suite for the dedicated purpose of this invaluable interaction.

Another thing noteworthy of my residency trail are institutions which are championing the face-to-face consultative role of the clinical pathologist in patient care. We, at the end of the day, are consultants to all; physicians and patients alike. And many in our field are celebrating this role by pushing the envelope toward a progressive and effective future for pathology and laboratory medicine at large.

8. Graphic Medicine

Image 13. My very first #pathdoodle – What do Pathologists do?

Graphic medicine is fantastic! I wish I could have discovered this years ago. Nevertheless, in the last two years I have sought out and read numerous pieces which bridge a significant gap between clinician and patient. And if we in laboratory medicine plan to reach patients more directly, we shouldn’t be afraid to come up with creative solutions to communicate with them. My (current) approach, #PathDoodles which I post occasionally on social media, attempts to explain concepts in pathology to the everyday lay person. What will you do to reach your patients?

7. Wellness Programs

Image 14. Anonymous survey responses to Dr. Saint Martin’s program from trainees at Loyola University Medical Center. (Source: The Pathologist)

Another interesting thing I encountered on the residency interview trail was the way in which different programs addressed the concept of wellness. Some did, some did not, but everyone discussed it. Because, after all, it is important; not just for residents and physicians, but medical lab scientists, support staff, and …yes… even administrators. Work and work-life stresses and balance take a psychological and emotional toll, and in order to be happy and healthy we need ways to strengthen our mental health along the way. Last year, Dr. Marissa Saint Martin won a 2018 award from the American Association for Physician Leadership for her work in preparing residency resilience and promoting wellness through structured curricula at Loyola Health System and Mount Sinai in Miami. She’s been featured with ASCP numerous times as well as in The Pathologist. It’s promising to see such strong support for residency trainees; keep an eye out for other praise-worthy programs this year!

6. Social Media

Image 15. It takes a new kind of clinician to serve a new kind of patient. How will you rise to meet the challenges on the horizon that we can’t predict yet?

You caught me. I can’t make any predictions about the future of health care delivery, education, or collaboration without touting the importance of social media. As a member of the official ASCP Social Media Team (Go #ASCPSoMeTeam!), I’m a proud contributor not only to the content that we publish online, but to the message that unifies and spreads our #StrongerTogether mantra. Social media is fantastic tool to reach new colleagues, spread new ideas, and make new advancements in both our field and in reaching people where they are.

5. Moving Out of the Basement

Image 16. Is this closer to a representative image of your lab than you’d wish? Don’t worry, you’re not alone. Basement labs are so last season. (Source: Seret Studios, Bridge Basement, Brooklyn NYC)

One of the most memorable interviews I had this season was with a transfusion specialist who recounted to me his memory of training in pathology during his early days of residency. Green and eager, he told me how he remembered being taken on a tour of the facilities to be shown his desk/work space and upon reaching an underground level of the hospital building a sign read ‘BASEMENT’ with an adjacent one ‘PATHOLOGY’ …he paused to say it out loud, “What’s a basement-pathologist?” We bonded over the stifled stereotypes in our work and shared stories of great and terrible lab spaces we’ve seen. Some programs are renovating, some (for better) are moving on up… How are your facilities?

4. The Pipeline Problem

Image 17. The …scope of a pathologist has changed over time (see what I did there?). Sure, lots of us push glass and diagnose entities on tissue samples with complex investigations and work up, but many more of us ensure quality laboratory efficacy, develop new cutting-edge tests, manage donor centers and transfusion protocol, address infectious or public health crises, and more! I think the more we celebrate our profession, the more will join and contribute to our #StrongerTogether culture!

Well I mentioned stereotypes. I’ve talked about it before.  You already know about shortages in pathology from physicians to lab scientists. And don’t get me started on pay—especially for lab workers and those in forensic path! But this is a topic I think we’re going to see a boon in media coverage in the coming years, starting now. Some of our awesome colleagues are talking about the “pipeline problem” from a myriad of angles: addressing medical student clerkships, exposure to laboratory workflow in school curriculum, advertising the infinite possibilities of careers within our profession…and more. CAP, ASCP, USCAP, and other professional societies have done amazing work in their due diligence to represent our field and advocate for the advancement of our work and image. A former CAP president once said, “Pathology is what a pathologist does,” and well, it’s a good start. Where do you see solutions to our pipeline problem?

3. PA’s and… CPA’s?

Image 18. Pathologist assistants work directly under the supervision of a pathologist in a similar way that physician assistants work with physicians. Clinical pathologist assistants help to determine the cause of disease through the examination of blood and other bodily fluids and tissues. (Source: UAB)

Now this, this is a cool concept and it’s the first time I’ve seen it. We all know and love our pathology assistants (PAs)—especially resident pathologists—as they make the training, education, and workload a better process for learning. They have awesome training and operate essentially as highly specialized clinicians in anatomic pathology. But what about the clinical, laboratory medicine side of things…? I recently saw a program advertised at the University of Alabama at Birmingham that trains clinical PAs for consultative and ancillary support roles to the clinical pathologist! Fantastic! Read more about it here! There are a growing number of DCLS (doctor of clinical laboratory science) professionals, now we’ve got a new pipeline to invite talented folks to work with us in a new way.

2. I’ll Have a Residency!

Image 19. Need I say more? What does the paper say?? Where am I going to end up? It’s a whirlwind of a season and a crazy system—once in a lifetime sort of adventure! Stay tuned, I’m sure I’ll have a post or ten about the next chapter of my career… (Image source: AAMC)

I have seen so many fantastic programs across the US these past few months, and so many decisions go into the way medical graduates rank programs to match into. To learn how the AAMC/NRMP matching system works, watch this video (maybe with some calming tea). We’ll see where I end up matching to, but I’m excited for the next chapter and to really dive into pathology even more!

1. You!

Obviously, the most important thing to keep an eye out for this year is you! Your goals, your ambition, your plans, your ideas and thoughts, and all the ways you contribute to our fantastic profession! I encourage you all to share, collaborate, and be creative with the ways in which we advance the future of laboratory medicine and continue to keep in mind that we do these things for our patients everywhere.

Thanks for reading, see you next time!

Constantine E. Kanakis MD, MSc, MLS (ASCP)CM completed his BS at Loyola University Chicago and his MS at Rush University. He writes about experiences through medical school through the lens of a medical lab scientist with interests in hematopathology, molecular, bioethics, transfusion medicine, and graphic medicine. He is currently a 2020 AP/CP Residency Applicant and actively involved in public health and education, advocating for visibility and advancement of pathology and lab medicine. Follow him on Twitter @CEKanakisMD