A Pathologists’ Assistant Abroad

Jennison Hartong, MLS(ASCP)CM, PA(ASCP)CM, is a Pathologists’ Assistant who recently went to Ethiopia to teach grossing techniques. The editors of Lablogatory asked her a few questions about her experiences.

Lablogatory: How’d you get involved with ASCP’s Center for Global Health?

Jennison: Dr. Milner, Chief Medical Officer of ASCP, initially reached out to one of the pathologists at M.D. Anderson to inquire if any Pathologists’ Assistants (PAs) would be interested in attending a workshop in Nigeria. I reached out and expressed my interest in teaching grossing techniques rather than public speaking (not one of my strengths). Dr. Milner then told me about this opportunity in Ethiopia where pathologists were requesting advanced, gross training in lymph node dissections on breast and colon specimens. I immediately jumped at the opportunity to help in this way.

L: What were your motivations for going?

J: Whether with basic health needs or more complex areas like cancer treatments, I’ve always wanted to use my education and experience to help others and impact lives in areas around the world where certain aspects of healthcare may not be accessible. Before becoming a PA, I was a medical technologist and was always interested in working with Doctors Without Borders, however, I did not have the years of experience to apply. I decided to go to PA school and was disappointed to learn that Doctors Without Borders does not utilize PAs. I figured that dream would have to be accomplished another way, which was why I was so eager to work with the ASCP and their global health initiatives.

Another motivation for going on this trip was experiencing the work and organizational skills required for making a trip like this successful. I am currently finishing my second master’s degree in public health with a focus in health policy and management. I was very interested in learning everything I could about planning programs to help developing countries as well as being able to network with like-minded health professionals.

L: What did you hope to accomplish while you were there?

J: My main goal of this trip was to help advance Ethiopian residents and pathologists in certain grossing techniques. More specifically, I aimed to assist with lymph node dissections and, as it turned out, how to locate and sample the radial margin in colon cancer cases.  I also wanted to experience a different culture than my own, step out of my comfort zone and challenge myself as a PA by teaching others. At the end of this experience, I can say that this trip was definitely a life changing experience and one I am extremely grateful for.

Image 1. Jennison (black scrubs) training residents from St. Paul Hospital to locate radial margins on colorectal cancer cases.

L: What did you learn about lab medicine in Ethiopia?

J: During my week in Addis Ababa, I quickly realized that it was up to me to make this trip as successful as possible. Never before in my professional career were all the decisions up to me, and at first, it was slightly uncomfortable. I was worried I would come across as too bossy or even condescending. However, after meeting Eshetu Lemma, the ASCP local representative, along with the other participants and experiencing their kindness and eagerness to learn, I was newly determined to make this trip an absolutely positive experience for everyone. I made some changes to the training sessions and after the first day, the rest of the week ran smoothly. I learned a lot about how lab medicine is practiced in Ethiopia. I learned that, in the case of a power outage, you carefully set your blade down and wait it out. I learned that resources like aprons and sleeves are not thrown away unless completely used up. I learned that due to cassette shortages, tissue submission is done quite thoughtfully- more so than in the United States. I learned that the overwhelming majority of cancer cases are presented at stage 4 due to issues surrounding resources, fear, myths, and lack of cancer education. But most importantly, I learned that the labs in Addis Ababa, Ethiopia, are doing an amazing job with the resources they are given and are eager for opportunities to positively impact patient care.

L: Is what you learned there applicable to your work in the States?

J: I’ll take what I learned there and incorporate it into my work here in the States. I’ve gained confidence in my ability as a health professional and reignited my passion to help others.

To put it simply, this trip has been life changing. It has allowed me to experience and accomplish a lifelong dream for which I am forever grateful. I’m hopeful that my future holds more opportunities to serve other communities and help strengthen cancer programs in developing countries.

Image 2. View from St. Paul Hospital.

-Jennison Hartong, MLS(ASCP)CM, PA(ASCP)CM is a board certified Pathologists’ Assistant, specializing in surgical and gross pathology working mainly in oncology cases. Before attending graduate school, she worked as a Medical Laboratory Scientist (MLS) at Lurie Children’s Hospital of Chicago, Illinois. Upon graduating, Jennison started working at Memorial Sloan Kettering Cancer Center. In 2018, she relocated to Houston and currently works at M. D. Anderson Cancer Center in Houston, Texas. In May of 2019, Jennison will graduate with a second Master’s in public health with a focus in health policy and management from New York Medical College. She plans to use her extensive lab experience and newfound knowledge of public health to help bring basic healthcare to communities that would otherwise not have access to these necessities.

Gastric Cancer: A Multidisciplinary Approach

Maryam Zenali1*, Dmitriy Akselrod2, Eric Ganguly3, Eswar Tipirneni4 and Christopher J. Anker5*

1 Department of Pathology, 2 Department of Radiology, 3 Division of Gastroenterology, and 5 Division of Radiation Oncology, The University of Vermont Medical Center (UVMMC), Burlington, VT and 4 Department of Hematology Oncology, Central Vermont Medical Center (CVMC), The University Of Vermont Health Network, Adult Primary Care, Berlin, VT

*corresponding authors

A 57 year old woman with a personal and family history of breast cancer presented with early satiety and dysphagia for 5 months. Her abdominal computed tomography (CT) scan (Image 1 A) showed marked thickening of an apparently featureless gastric wall (A, blue arrows indicating the mucosal [rightward pointing] and serosal [leftward pointing] aspects of the gastric wall). Prominent gastrohepatic lymph nodes were noted as well. Her fluoroscopic upper GI study (Image1 B), following administration of barium and effervescent crystals (a double contrast effect to allow for mucosal evaluation), showed thickened rugal folds (B red arrow) and pooling of barium within an antral ulcer (B blue arrow). A subsequent CT scan (Image 1 C) after administration of intravenous and enteric contrast, confirmed marked diffuse gastric wall thickening (C blue arrows again indicating the mucosal [rightward pointing] and serosal [leftward pointing] aspects of the gastric wall) (Image 1, composite radiographs A-C).

The gastric body distended poorly with insufflation and demonstrated thickened, erythematous, edematous folds with erosions (Image 2, endoscopy image). On endoscopic ultrasound, the total thickness of the stomach was 12 mm with expanded wall layers in the proximal stomach to the antrum and a thickness of 3.5 mm in spared areas. Biopsies were obtained; the corresponding H&E and keratin stains are provided (Image 3, composite photomicrographs A-B).

Image 1. Composite radiographs.
Image 2. Endoscopy image.
Image 3. Composite photomicrographs.

Based on the original radiographic imaging that led to the biopsy, what are the differential diagnoses?

Working with Generation Y: How Other Generations Can Adapt

Generation Y is coming and they are coming in strong! It is fast becoming the world’s largest working generation and their impact on the workforce will become even clearer in the next few years. These digital natives find communication natural, in any shape or forms it comes. They prefer texting and instant messaging, but also appreciate face-to-face meetings and hand-written notes. They use social media for both personal and professional use and consider it essential to know how and where to access information. Instant gratification has become one of this generation’s key values, because they grew up with the world of information at their fingertips. They value professional development and feedback and they are at work to learn and grow.

When working with a Millennial the first step is to show them that you respect them and what they bring to the table. This generation has received more negative attention than other generations, but they have a tremendous amount to offer to the workplace (as do all the other generations). They value collaboration and learning opportunities, so they are typically quick to adjust when giving constructive feedback. Because of their collaborative approach, they value inclusion and Social Media to bring people together. They are well versed in finding information and can typically solve smaller technological issues without any help.

This generation is focused on having their work mean something, to have a purpose that is larger than simply getting a paycheck. They dislike long email and voicemails and anything that is a waste of paper. They appreciate flexibility and sending documents electronically. They experiences high academic pressures, so they are comfortable working in a fast-paced environment. They are comfortable multitasking and handling multiple projects simultaneously.

Millennials who work in larger organizations are on the brink of entering leadership positions. However, there are many self-starters who have had to learn leadership skills along the way. Because this generation values collaboration, leaders tend to encourage group work and giving people an acknowledgement for trying. They dislike people who are afraid or do not want to learn new technology and cynicism as they are a generally very positive generation.

When working with Millennials, note that they respond well to a participation work environment so ask for their input and suggestions. Be open about any processes, systems, and share information freely. Provide them with lots of feedback to help them learn and grow. Millennials respond well to a faster pace work environment, so do not try to slow them down. They dislike formality and stiffness, so allow flexibility whenever possible. For example, invite them to provide input for their own goals and do not hover over them. Give them multiple things to work on simultaneously so that they can go from project to project when their energy shifts. This generation is crucial to bring your organization to the next level, so mentor them, help them grow and develop and you get their dedication, passion, collaboration, and positivity in return.

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-Lotte Mulder earned her Master’s of Education from the Harvard Graduate School of Education in 2013, where she focused on Leadership and Group Development. She’s currently working toward a PhD in Organizational Leadership. At ASCP, Lotte designs and facilitates the ASCP Leadership Institute, an online leadership certificate program. She has also built ASCP’s first patient ambassador program, called Patient Champions, which leverages patient stories as they relate to the value of the lab.


What’s the purpose? That’s the question that most Gen Ys, or commonly known as Millennials, ask of their job. Why am I here? Can I make a difference in the world if I remain doing what I am doing?

The Baby Boomers worked because they felt an obligation to put in a hard day’s work whether they liked doing what they were doing or not. It was a job. The Generation Xers introduced a focus on work-life balance, which was not the case for the Baby Boomer. The Boomers never heard of the concept of “work-life balance” until their children, the Gen Xers, made it a job requirement and reality.

As for the Millennials, they need to really believe in their job and what they are doing. Millennials ask questions that the Boomers and Gen Xers wouldn’t think of asking. This is often misinterpreted as being lazy or looking for the easy way out. This is not the case. The Millennials took the best of their predecessors. Most Millennials have a good work ethic and they definitely look for balance. However, they’re also searching for a purpose.

My favorite story of a Millennial is centered on the importance of taking lunch at work. This topic surfaced from a Roundtable Discussion with laboratory professionals last October 2018, at the ASCP Annual Meeting in Baltimore. The actual topic for this Roundtable Discussion was “diversity.” However, that quickly changed when the nine people at the Roundtable focused on generational differences. This roundtable was rich in generational diversity. The table was comprised of Boomers, Gen Xers and Millennials. Boomers stated that they found it both necessary and easy to work through lunch. Why? It’s because they pride themselves in their incredible work ethic. The Boomers praised themselves for being better than “most Millennials” who often don’t and won’t work through lunch. Instead of that mindset, perhaps the better approach would be “What can we learn from Millennials in the work place?” That answer is “purpose and balance.”

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-Catherine Stakenas, MA, is the Senior Director of Organizational Leadership and Development and Performance Management at ASCP. She is certified in the use and interpretation of 28 self-assessment instruments and has designed and taught masters and doctoral level students.  

Global Health Narratives Interview Series: Meet Dr. Danny Milner

I had the pleasure of talking recently with Danny Milner, Jr., MD, MSc(Epi), who serves as the Chief Medical Officer of ASCP. He has worked to improve diagnostic access and improve laboratory medicine services in low- and middle-income countries [LMICs] his entire career. I recently read his book for which he served as editor for titled “Global Health and Pathology.” This highly informative compilation of articles written by the foremost experts in the field is a MUST READ for anyone interested in global health! You can order your copy here: https://www.elsevier.com/books/global-health-and-pathology-an-issue-of-the-clinics-in-laboratory-medicine/milner/978-0-323-58158-5.

After reading the book, I hoped to learn more about Dr. Milner and how he became a leader in global health and pathology. Below you will find his fascinating narrative of his career and his reflections on the importance of providing high quality pathology services worldwide.

Q: Dr. Milner, I’m curious to know where your service in global health began and how your career in pathology has intersected with that?

A: Truly, many events occurred that were serendipitous in shaping my career and life. I grew up very poor in a rural community in Alabama, in an area known as the “black-belt” of the southern states due to the rich black soil found there. This area was home to many of the relocated former slaves after the end of the civil war and is now home to a 50/50 mix of Caucasian and African-American members of the community.

Towards the end of high school, I was awarded a scholarship for high achievement and a scholarship geared to support healthcare careers.  At the award ceremony, a person giving me an unrelated award knew of my scholarship for pre-med and said to me and the crowd, “go become a doctor”. When I was in college, I worked as a nurse’s assistant for a physician and became interested initially in primary care . After some careful consideration, I decided to embark on a path that would take me to medical school, finishing my pre-med requisites and graduating in three years. I was accepted to the MD/PhD program at the University of Birmingham [UofB] wanting to do my PhD in Medicinal Chemistry. Unfortunately, this particular PhD wasn’t allowed, so I decided to pursue a MD only.

In medical school, I decided to slow down my fast track through school– so I applied to a post-sophomore fellowship in Pathology and at the same time applied for a summer program offered by UofB that entailed working in a clinic in The Gambia. This would be the first time that I had traveled outside the United States. I first went to Africa, with my fellowship to follow on my return.

In The Gambia, I lived in a compound with 12 people in an extremely rural area with no running water or electricity. I spent four weeks working in a clinic with a Gambian doctor, seeing patients without the use of diagnostics. I was traumatized by the extreme suffering of the patients we saw. My take away from the experience was the idea that it would have been so much easier to help had there been any sort of diagnostics available – a malaria smear, a microscope, anything that could have helped us do a better job than we were doing.

When I returned from Africa, I started my post-sophomore fellowship and my first rotation was autopsy. There was a neuropathologist there named Angelica Oviedo, and she had just gotten back from Malawi. Hearing about my recent trip to The Gambia, she encouraged me to pursue more work in global health. She put me in contact with Terrie Taylor – who is an internal medical physician who has been working in Africa since 1986. It was in the 1990’s and she had just started a cerebral malaria autopsy study which would become the largest study on this topic in the world.

This post-sophomore fellowship really inspired me to pursue pathology. I was thrilled to be offered a position at the Brigham and Women’s in Massachusetts for pathology residency.  I finished medical school by spending time in Germany and then under the supervision of Terrie Taylor in Malawi working on the cerebral malaria autopsy study. I continued to work with her for thirteen years following this.

In residency, it was a natural fit for me to gravitate towards all things related to global health which meant a focus on infectious diseases. I continued to work in Africa and traveled there 4-5 times during residency, scrounging together any time and any money that I could to try to help.  It was during my second time in Malawi, around 2001, that I was surprised to find that all the cases crossing the surgical pathology bench were cancer – there was nothing but cancer, and it was often very advanced. This was 15 years before the WHO resolution on cancer. I was suddenly very interested in this aspect of care. Up until this point, I was heavily focused in infectious disease, and how this related to oncology, but now I wanted to really focus on cancer. I was not encouraged by my elders to try and tackle this because they said, “they are all going to die anyway.”

Fast forward, I finish a fellowship in Microbiology and am joining the Brigham as faculty to work in infectious disease pathology. During this time, I continue to go to Malawi and I am continuously signing out cancer cases for Africa. This was tragic since there was no intervention at that time, and every case was essentially a death sentence. The first oncologist did not arrive in Malawi until somewhere around 2008-2009.  

During my time at the Brigham, Partners in Health [PIH] began sending tissue biopsy cases to us to diagnose. Every year, the cases increased more and more. Because cancer started to become the majority, PIH decided to strategize the best way to meet this need. Larry Shulman, the lead for PIH based at Dana-Farber in Boston, reached out to me to build a pathology laboratory in Haiti, but since that idea was quickly followed by an epidemic of cholera, it was decided to build a pathology lab in Rwanda instead – this was in 2011. After a massive effort entailing equipment installation, capacity building, infrastructure, and staff training, Butaro Cancer Center officially opened 6 months later. With the help of a few other volunteers, we continued to run the lab remotely using static image telepathology. In 2016, a full-time local pathologist took over the lab and ASCP brought in whole-slide telepathology services. In 2015, I met Blair Holladay in person for the first time. He shared his vision for ASCP to expand their global outreach and we had a healthy discussion about the details of making it happen. Blair asked me to volunteer to become part of the team, and I worked together with ASCP to launch the Partners for Cancer Diagnosis and Treatment in Africa Initiative. The project grew and ASCP reached out to recruit me to work as the Chief Medical Officer and lead the global health team. I was excited to have the opportunity to work in global health full time.

Dr. Milner (left center, front row) with members of the Partners Initiative local team at the 2017 ribbon cutting ceremony to celebrate the opening of the second telepathology lab in Rwanda.

Q: Why is pathology the essential cornerstone of global health?

A: First, you should consider how important the laboratory is in medicine. An often-quoted study says approximately 70% of the clinical decision making is based on laboratory results. In certain subspecialties of medicine, like surgery or oncology, these clinicians are nearly 100% dependent on the laboratory for delivering care. In fields like psychiatry, it is going to be much less dependent on the laboratory. Even so, it is reasonable to say that almost all medical decisions are best informed by high quality laboratory results.

Starting with that statement, the laboratory is what allows clinicians in certain fields to function. In the field of cancer, which is a major problem in LMICs, you cannot treat the patient without a diagnosis – and the diagnosis must come from the laboratory.

Q: Historically, pathology hasn’t always been associated with creating global health solutions. Why do you think that is now that we know it is an essential component of building health systems?

A: It’s a general challenge in global health that pathologists haven’t been involved as much as they could be. This could be due to multiple reasons. The need for pathologists to serve in low- and middle-income countries hasn’t traditionally been recognized. This may be due to a disconnect in understanding our potential to make an impact. We, like surgeons and radiologists, require electricity, supplies, and resources in order to volunteer in very remote settings worldwide. This is unlike clinicians and emergency medical doctors for instance, that can see patients without extensive resources available – they are more readily available to serve in small, remote communities. An exception would be the use of cytology which can, with very limited resources, be extremely effective even in remote areas. However, as a specialty, pathologists are typically able to serve in larger cities in LMICs and, there, have an enormous impact. So, there are plenty of opportunities for pathologists to practice their specialty in improving global health and make an impact.

It may also be that people and their families have concerns about their safety, or they don’t have the support of their institution in terms of time, or they may not feel they have a connection to a potential site. The desire may be there but there are perceived obstacles.

ASCP works to create relationships and facilitate connections, as well as allay fears for safety concerns. We also offer institutional support, for example, we provide a letter of explanation and support for our Trainee Global Health Fellows.  We try to bridge the gaps for people to feel that they have the ability and are empowered to volunteer, remove the barriers to participation, and make it as easy as possible for people to do so.

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

Hematopathology Case Study: An 83 Year Old Man with an Elevated PTT

Case History

An 83 year old man with rapidly growing squamous cell carcinoma of the left temple and scalp underwent workup prior to surgery which showed an elevated PTT and a slightly elevated PT. The patient denied a history of abnormal coagulation tests or excessive bleeding or bruising. He also noted that he had previous surgeries including dental procedures without excessive bleeding. In addition, he did not have a history of clot formation.

Lab Values

Differential Diagnosis

At this point, the differential diagnosis for a prolonged PTT included the presence of an inhibitor (specific factor inhibiter vs. non-specific lupus anticoagulant) vs. reduced levels/activity of intrinsic pathway factors that would prolong the PTT, but would not significantly affect clot formation. This would include factors XI and XII. 

Additional Testing

An inhibitor screen/mixing study was performed and was positive. An inhibitor screen is performed by mixing the patient’s plasma with pooled normal plasma and running a PT or PTT.  If the PT/PTT corrects than the screen is negative. This means that a factor or factors were deficient in the patient’s plasma and were replaced with the pooled normal plasma resulting in a correction of the PT/PTT. In this case, a PTT at time 0 of 68 seconds and a PTT at 2 hours of 66 seconds was a failure to correct and indicated that an inhibitor was present, thus a positive result was entered.

The dilute Russell’s viper venom time (dRVVT) was used to test for a lupus anticoagulant. The screening test is performed by adding Russell viper venom, which directly activates coagulation factor X in the presence of calcium and a phospholipid poor reagent to the patient’s plasma and calculating time to clot. The confirmation test is the same assay with added excess phospholipid. In the presence of phospholipid dependent antibodies, the time to clot will be shorter for the confirmation test. The screen and confirmation ratios are normalized ratios (NR) of the patient sample result in seconds divided by the mean of the normal range in seconds. If the screen is <1.20, the confirmation test will not be run. If the screen is greater than 1.20 as seen here, the confirmation test will be run. The end result is reported as a normalized ratio of the screening test over the confirmation test. If the NR is greater than 1.20, than a lupus anticoagulant is reported as present.

Specific factor assays are performed by mixing the patient’s plasma with substrate plasma that is severely deficient in the factor being measured. Factor deficient plasma would be expected to give a prolonged clotting time. When patient plasma is mixed with factor deficient plasma, the clotting time will shorten and the degree of correction is proportional to the factor level in the patient’s plasma. The clotting times for the patient sample are compared to a reference curve. The reference curve is made with dilutions of normal plasma (containing 100% factor) added to factor deficient substrate plasma. All tests are run with 3 dilutions at 25%, 50% and 100% and curves are checked for parallelism errors, which might indicate the presence of an inhibitor. For this patient, factor XI was initially resulted as 1%, which would indicate a factor deficiency.

This is an example of a factor assay that shows parallelism. The reference plasma calibration curve and the patient plasma are parallel lines. 1

Analysis

From the results, it initially appeared that there was both a lupus anticoagulant and a factor XI deficiency. However, it would be odd for a patient with no reported coagulation abnormalities to suddenly have both a lupus anticoagulant and a factor XI deficiency. The raw data from the factor XI assay was obtained.

Upon review, the factor XI assay did show parallelism errors. Parallelism is tested by performing serial dilutions of a standard with known normal concentrations of factor and recording the time to clot. This line is shown with the red arrow. In contrast, the patient sample appears to be a flat line that is not parallel to the calibration curve. Parallelism errors were flagged because from the 50% to 25% dilution, the corrected results more than doubled. If there is a >20% change between dilutions, this indicates possible interference and additional dilutions should be run to dilute out the inhibitor. The 25% dilution had a corrected result of 2.9, which was greater than a 20% increase from the 50% dilution result of 1.3. Once more dilutions were performed; the Factor XI level was ultimately close to 100%.

Additional factors were checked to see if they also increased with dilutions. This would add support to the theory of a non-specific inhibitor (lupus anticoagulant) that was affecting all of the factor levels, rather than a specific factor XI inhibitor or a concurrent factor XI deficiency. The curve from factor IX (below) showed a similar phenomenon. As the sample underwent additional dilutions, the corrected result increased significantly (from 12.8 at 50% to 26.8 at 25%). Ultimately, the factor level was close to 82%.

The curve from factor VIII also showed low results to begin with and ultimately normal levels with additional dilutions. Altogether, this supported the presence of a strong lupus anticoagulant that was non-specifically interfering with all of the factor levels and prolonging the PTT.

Discussion

A prolonged PTT can be caused by many factors. In a patient without a bleeding history, lupus anticoagulant and certain factor deficiencies are high on the differential. The most common specific factor inhibitors are to FVIII and FIX. These generally arise in hemophilia patients treated with factor concentrates. It is very rare for a patient to develop an inhibitor to factor XI or XII.

Factor XI acts in the intrinsic pathway of the clotting cascade and is important for hemostasis. Deficiency of factor XI is rare and mainly occurs in Ashkenazi Jews. Generally, it does not cause spontaneous bleeding; however excessive blood loss can occur during surgical procedures.

Lupus anticoagulants are directed against proteins that complex with phospholipids. Although they prolong the PTT, they are associated with an increase in thrombosis rather than bleeding. In addition to interfering with the PTT assay, lupus anticoagulants may interfere with individual factor assays and result in non-parallelism (patient curve is not parallel to calibration curve) as seen in this patient. With increasing dilutions, the lupus activity will be disproportionately neutralized and the coagulation factor activity will increase in a non-parallel manner. 1

In a letter to the editor by Ruinemans-Koerts et al., they performed a set of experiments to investigate whether lupus anticoagulants vs. individual FVIII and FIX inhibitors can cause non-parallelism in the one-stage factor assay.  Non-parallelism was only detected using lupus sensitive reagents in plasma with high titers of lupus anticoagulants. The FVIII and FIX inhibitor containing samples both resulted in curves that were parallel to reference sample.

This curve shows that the factor IX inhibitor line is parallel to the reference plasma, while the lupus anticoagulant line is not. 1

Ultimately, this demonstrates the importance of running dilutions and being aware of parallelism errors when performing factor assays. This is especially important in patients with known or suspected lupus anticoagulants. In this case, the unlikely presence of a FXI deficiency with no previously reported coagulation testing abnormalities or bleeding history raised the suspicion of an inhibitor interfering with the factor assay. With a concurrent positive inhibitor screen and lupus anticoagulant test, as well as interference demonstrated with multiple factor assays, the best unified conclusion was a strong lupus anticoagulant. 1

References

  1. Ruinesman-Koerts, J., Peterse-Stienissen, I, and Verbruggen, B. ”Non-parallelism in the one-stage coagulation factor assay is a phenomenon of lupus anticoagulants and not of individual factor inhibitors. “ Letter. Thrombosis and Hemostasis, 2010, p.104.5.

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

Microbiology Case Study: A 55 Year Old Woman with Cough and Headache

Clinical History

A 55 year old female presented to the gastroenterology clinic with a chief complaint of cough and headache. She reported no recent fevers, abdominal pain, or diarrhea. On further questioning she revealed she was originally from the Philippines and had a past history of a parasitic infection that was treated twice with praziquantel. She did not remember the name of the parasite but was concerned for a recurrent infection. A stool specimen for ova & parasite exam and basic laboratory work, including an IgE level, were collected and the patient was scheduled for a screening colonoscopy. Findings from the colonoscopy revealed no gross evidence of neoplastic or infectious disease; however, random rectal biopsies were obtained. 

Laboratory Identification

Image 1. Rectal biopsy showing unremarkable colonic mucosa with many calcified structures deep in the epithelium (H&E, 40x).
Image 2. Rectal granuloma surrounding a calcified structure (H&E, 400x).
Image 3. Intact parasitic egg with a small, inconspicuous spine measuring approximately 90 um in greatest dimension (H&E, 1000x oil immersion).

Discussion

Schistosoma japonicum is a trematode that can infect humans through direct penetration of the skin by the cercariae when wading or swimming in infected waters in the Far East, such as China, the Philippines, Indonesia, and Thailand. Infection can initially present as swimmer’s itch and then develop into Katyama syndrome, which includes fever, eosinophilia, muscle aches, lymphadenopathy, abdominal pain, and diarrhea.

S. japonicum migrates through tissues and the adult male & female forms take up residence in the mesenteric veins that drain the small intestine. The female lays eggs which travel to the lumen of the intestines and can be shed in the stool. The host immune response to the eggs is the major cause of clinical disease which presents as inflammation & ulceration in the intestines, portal fibrosis in the liver & splenomegaly, and more rarely, lesions in the central nervous system. As with all trematodes, snails serve as the intermediate host. 

In the microbiology laboratory, diagnosis is usually made by identification of the eggs in stool specimens. The eggs of S. japonicum are ovoid in shape with a transparent shell and a small, inconspicuous spine. The eggs typically measure between 70-100 um in greatest dimension. These eggs can commonly be visualized in rectal biopsies as well. It is important to get an accurate measurement of the size of the egg and multiple sections to be able to detect the location and morphology of the spine. The eggs of S. japonicum must be distinguished from those of S. mekongi which is similar in appearance; however, the latter is found along the Mekong River in Southeast Asia and is smaller in size (50-70 um in greatest dimension). Serology is also a viable diagnostic test in those that have traveled to endemic regions, but sensitivity and specificity of the assays vary depending on how the antigen is prepared and the Schistosoma species of interest.

Treatment of choices for those infected with S. japonicum is praziquantel divided into three doses over the course of one day and it should be administered at least 6 to 8 weeks after the last exposure to contaminated freshwater. Since our patient admitted to a recent visit to the Philippines with potential exposure to infected waters, she received another course of praziquantel therapy.

-Anas Berneih, MD, is a fourth year Anatomic and Clinical Pathology chief resident at the University of Mississippi Medical Center. 

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

Proficiency Testing (PT)Part 1: Are You Doing it Right?

Every laboratory knows that they must participate in proficiency testing (PT) for all of the regulated analytes they report. But did you know that there is more to it than simply checking your overall score in each survey you participate in? Whether you utilize samples from the CAP, API, or have developed your own in-house blind sample testing algorithm, there is a lot of data available to help you assess the quality of your laboratory program. In the first of this 3-part series, we’ll review why PT testing is important and the rules that must be followed. In part 2 we’ll discuss how to properly perform an investigation when scores are <100%. Lastly, in part 3 we’ll look at how to review your results so that you get the most out of them for a successful quality laboratory.

Why participate? Well frankly, because you have to. It is a CLIA/CMS requirement, and if your lab has additional accreditations, those agencies will have their own rules and requirements as well (we’ll get to the rules in a little bit). But outside of the regulations stating you must participate; all labs should want to participate. It’s an opportunity to check your accuracy against peers who are using the same instrumentation as you. Similar to utilizing an affiliated QC report, this is a way to see what the “real” value is supposed to be (despite what a manufacturer may claim it to be), and how close/far off your lab is to that true value. It can help you identify potential problems before they become huge problems with patient values being affected, and it’s also a great way to satisfy competency requirements for your staff.

The rules:

  • Participation: For every regulated analyte being tested under your laboratory permit1, you must participate in a CMS-approved PT program2.

Key things to note: This only applies to testing performed using non-waived methodologies. Waived testing is exempt from PT requirements; although it is still recommended that participation occur if an evaluation program is available. Additionally, this only applies to your primary instrumentation. For example, if you have an automated urinalysis reader and your backup methodology is to read dipsticks manually, you are only required to participate in PT for the primary methodology. (Your backup method would then be evaluated for accuracy through semi-annual correlation studies.)

  • Routine Analysis: Unless otherwise instructed by the provider of your PT samples, PT samples are to be treated the same as patient samples. Meaning they are handled, prepared, processed, examined, tested and reported the same way you would perform patient testing; AND by the same staff who would handle patient testing.

Key things to note: If nursing staff perform a particular test within their unit (for example, ACT testing in the cardiac cath lab), it is those nursing staff members who must run the PT samples. You cannot have the laboratory perform PT testing unless the laboratory also performs the patient testing. Additionally, PT samples should be rotated among all staff members who perform patient testing. Meaning all shifts, and all days of the week that the test is performed – don’t let the day shift get all the fun.

  • Repeated Analysis: Similar to rule #2, unless you routinely perform duplicate testing on your patient samples, you cannot perform duplicate or repeat testing on your PT samples. You cannot run a PT sample in duplicate “just to make sure.” Patient samples are just as important to be accurate as a PT sample, which is why we participate in a PT program in the first place.

Key things to note: After the date that laboratories are required to report results back to the PT provider, you are then allowed to use the samples for repeat testing. This can be used to check for uniformity in grading of reactions among staff members, and to assess annual competency. But only after the submission date has passed.

  • Interlaboratory Communication: You cannot discuss the results or samples from a PT survey with any other laboratory (or Facebook user group) until after the results submission deadline has passed. Doing so before that time would be considered cheating. The point of PT testing is not to see how good your networking skills are, but to ensure accuracy of your own results. Plus, the other lab may not be as good as you think they are.

Key things to note: If your laboratory is part of a larger integrated health system, be careful that you have separate designated staff assigned to enter results from each location. Entering results for more than one permit number by the same person would be considered a violation of the interlaboratory communication rule as they could compare results from Lab A to Lab B prior to submitting. Also, be mindful of what you put on social media. User groups are a great networking resource and learning tool, but you still need to follow the rules. Violating them in a public arena such as Facebook for all the world to see would put yourself and your organization in great jeopardy if you were caught. 

  • Referral of Samples: You are not permitted to forward or share your PT samples with any other laboratory until after the result submission deadline has passed. Similarly, if your laboratory has received PT samples from another lab, state regulations may require you to notify your local Department of Health to inform them of the violation.

Key things to note: The intended purpose of performing PT testing is to verify the accuracy of your own laboratory testing. If you would routinely send a positive sample to a reference lab for additional confirmation testing, you would not do so in this case. Simply report out the values for the tests that your laboratory performs only. The reference laboratory will have their own PT samples to check accuracy for the confirmation testing they perform for you. Ensure your testing menu is up to date and accurate so that your PT provider is not expecting values for a confirmatory test if you do not physically perform it in-house.

  • Records Retention: Ensure that all records and documents related to the testing of PT samples are saved for the amount of time required by your regulatory agencies (typically 2-5 years). This includes instrument print outs, LIS chart copies of the filed results, QC records for the day of testing, and any associated worksheets used to document your results.

Key things to note: Retaining a copy of the instrument maintenance logs and QC records along with the actual PT results will help you investigate any scores that are less than 100%.

  • Attestation: Both the laboratory director and all personnel performing testing must sign the included attestation statement. This is not just a way to track who performed the test, but is a legal binding document assuring that testing was carried out appropriately as per the rules defined above.

The penalties for labs that are caught violating the rules (whether intentionally or not) can be quite severe. These penalties can include the revocation of your CLIA permit; a ban for the laboratory owner and laboratory director; as well as possible financial penalties and fines.

Coming up in the next blog we’ll review the rest of the rules related to evaluation of your scored PT results, and how to perform a thorough investigation into any unsuccessful survey events.

1: https://www.cms.gov/regulations-and-guidance/legislation/clia/downloads/cliabrochure8.pdf

2: https://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA/Downloads/ptlist.pdf

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