Lablogatory

Proficiency Testing (PT) Part 2: Investigating Failures

Last month we discussed the rules and requirements for how to properly perform proficiency testing (PT) within your laboratory. In part 2 of this 3-part series we’ll review the rules associated with evaluating your results, and how to investigate any unsuccessful surveys. Still to come in part 3 we will look into how to utilize your PT results to monitor for trends and shifts in your values.

The rules:

Performance Review: Laboratories must initiate and document a review of their PT performance evaluations within 2 weeks of notification that results are available. This includes a review of both graded and non-graded/educational analytes and events as well.

Key things to note: Even though educational samples are not formally graded, you should still verify the accuracy of your results, with appropriate follow-up for any failures. CAP specifically requires you to evaluate these educational challenges as well. Whether the sample is graded or not does not change the fact that you had an incorrect result.

Unsatisfactory Performance: For any unsatisfactory results, you are required to perform a root cause analysis to determine why (see below for guidance). This also includes any clerical errors – you need to evaluate your process and find ways to prevent these simple errors from happening again. If they are happening with PT samples, it is possible they are happening with patient samples as well.

Cessation of Patient Testing: Unsatisfactory events indicate that there was a problem with that particular survey; whereas unsuccessful events indicate there has been a pattern of unsatisfactory events/samples and a larger problem exists. If a pattern of poor performance is detected, you may be asked by your local state department of health to cease all testing for a particular analyte.

Key things to note: This also applies to clerical errors. Even if there was no technical problem with the accuracy of your results, failure to submit results on time or clerical errors made while submitting can also have severe impacts on your ability to continue offering that test.

Remedial Action: If you’ve been notified by your PT provider or state DOH to cease testing, there are extensive steps that must be completed to prove that the problem was correctly identified and corrected. You must also identify where samples will be referred to for tests you are unable to perform in-house.

Key things to note: If testing has been removed from your laboratory, you will be required to demonstrate successful performance in 2 consecutive PT survey events for the analyte(s) in question before being granted permission to resume patient testing. This can cause significant delays and financial impact for your organization.

Root Cause Analysis: Investigate to determine who, what, why, when, and how the event occurred. Be sure to evaluate all phases of testing to ensure you identify all potential causes.

Pre-Examination:
- Human Resources – evaluate the training and competency records for staff involved in the handling and testing of samples.
- Facilities – reagent inventory control & storage temperatures, equipment maintenance and function checks
- Standard Operating Procedures (SOPs) – staff compliance with written policies, bench excerpts are current and valid, document version control up to date
- Specimen –test requisition/order entry (was the correct test code ordered/performed?), labeling (were aliquot/pour off tubes properly labeled?), transport (was appropriate temperature requirements maintained until testing performed), quality (was there visible deterioration with the sample prior to testing or cracked/damaged tubes received?), quantity (was the original sample spilled or leaking causing an incomplete aspiration of sample by your instrument?)

Examination:
- Method Validations – were instruments current with calibration requirements, any bias noted during instrument correlation studies, values being reported within the verified AMR
- Environmental Controls – temperatures/humidity within tolerance limits, for light sensitive studies (bilirubin) was there excessive exposure of the samples to light prior to testing, excessive vibrations occurring that may have affected results (nearby construction or a running centrifuge on a shared work bench)
- Quality Control – did QC pass on the day of testing, was QC trending or shifts noted that month
- Analytical Records (worksheets) – were sample results transcribed correctly between the analyzer and worksheet, between the worksheet and LIS
- Instrument Errors – were any corrective actions or problems noted for the days before, during, or immediately after testing of PT occurred
- Testing Delay, Testing Errors – were samples prepared and not tested immediately leaving them exposed to light or air which may affect results (blood gas samples), any errors or problems noted during testing that may have caused a delay or affected accuracy of results

Post-Examination:
- Data & Results Review – check for clerical errors, was data trasmitted correctly from the instrument into LIS, was data entered correctly on your PT provider entry submission forms
- Verification of Transmission – did your results correctly upload to the PT provider website, was there an error or failure with submission
- Review of LIS – are your autoverification rules set up correctly, is the autoverification validation current with no known issues
- Patient Impact – perhaps the most important step to take when reviewing PT failures, you need to determine what impact your failure had on your patient results. Depending upon the identified root cause and how different your values were from the intended response, this can potentially pose a severe impact on your patient values tested at the same time as the PT samples.

Involve your medical director to determine if the discrepancy in results is clinically significant. Perform a patient look-back to review patient values for the same analyte with the failure during the time period in question. Evaluate the bias that was present, and if deemed to be clinically significant then corrected patient reports will need to be issued with a letter from the medical director explaining why. If it was decided that the discrepancy is not clinically significant, document this in writing and keep on record with your complete investigation response.

Corrective Actions/Preventative Actions – use the following set of questions to help guide you in ensuring that the problem identified during your root cause analysis will not occur again:

What changes to policies, procedures, and/or processes will you implement to ensure there will not be a repeat of this problem?
Do any processes need to be simplified or standardized?
Is additional training or competency assessment needed? If so, identify specific team members to be trained, and who will be accountable for performing and documenting this training.
Is additional supervisory oversight needed for a particular area or step?
Are current staffing levels adequate to handle testing volumes?
Would revision or additional verification of the LIS rules address or prevent this problem?
How can the communication between laboratory, nursing, and medical staff be improved to reduce errors in the future?

Continuous Process Improvement – after identifying the true root cause(s) for the failure and implementing corrective/preventative actions, you need to evaluate the effectiveness of those improvements. Have they been sustained? Are they working to correct the original problem? Have you created new problems by changing the previous process?

Quality Management Meetings – if necessary, increase the frequency of these meetings during the evaluation period for timely feedback to management and staff
Implement internal audits and quality indicators to check for potential issues
Access the specimen transport conditions to ensure they meet test requirements
Evaluate and monitor your turnaround time metrics to track problem specimens and impact of testing delays
If necessary, increase the frequency when QC is performed or calibration frequency if stability issues are identified

Performing a thorough root cause analysis for any failures will allow you to implement appropriate corrective actions that will address the true issues. Having a robust quality management program will help ensure these issues are identified and corrected in a timely manner, and reduce the potential for the dreaded Cessation of Patient Testing letter from your local DOH.

Coming up in the final installment of this series on PT testing, we’ll review all of the quality indicators and data that can be found in your PT evaluation reports to help ensure you’re on track for accurate patient values.

-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.

Microbiology Case Study: A 54 Year Old Male with Right Upper Quadrant Pain

Case History

A 54 year old male with a past medical history of Type II diabetes mellitus and obesity was admitted for a few days history of severe pain over right upper quadrant accompanied by fevers, chills, nausea, vomiting and diarrhea. Physical exam revealed a palpable gallbladder. Ultrasound imaging showed a distended gallbladder with a thickened, edematous and hyperemic wall that was interpreted as acalculus cholecystitis. The patient underwent percutaneous drainage of the gallbladder with plans to undergo a cholecystectomy once the acute phase of his illness stopped. The gallbladder fluid was sent to microbiology for analysis.

Laboratory Findings

Anaerobic plates obtained from organisms growing in thioglycollate broth grew low, convex opaque white colonies. The organisms did not produce the classic double zone of beta hemolysis (Image 1). Gram stain of the culture showed gram positive bacilli that were “boxcar” shaped (Image 2). Aerobic plates had no growth. The organisms were catalase negative and non-motile. MALDI-TOF identified the organism as Clostridium perfringens.

Image 1. Growth on CNA plate in anaerobic environment

Image 2. Gram stain from the anaerobic culture shows boxcar-shaped gram positive bacilli.

The patient was also placed on piperacillin-tazobactam while in the hospital. His condition improved and he was discharged home with a seven day course of cefpodoxime and metronidazole with a general surgery follow up appointment.

Discussion

Clostridium perfringens is a gram positive bacilli with blunt ends (boxcar shaped). These obligate anaerobes are spore formers, however these are rarely seen. When seen, they produce subterminal spores. These organisms cause of crepitant myonecrosis (gas gangrene), gangrenous cholecystitis, septicemia, and food poisoning. They are present in large numbers as normal microbiota in the gastro-intestinal tract of humans and animals, the female genital tract and oral mucosa. Typically, infections are caused by endogenous strains gaining access to normal sterile sites due to a predisposing factor that compromise normal anatomy: surgery, trauma, or altered host defense mechanisms (diabetes, burns, immunosuppression, and aspiration).

Penicillin is recommended in most infections, however resistance has been reported. Optimal management of intra-abdominal infection is to achieve appropriate source control and drainage is important.

References

Tille P. Bailey & Scott’s Diagnostic Microbiology. Fourteenth Edition. Elsevier; 2017.
Murray P. Medical Microbiology. Seventh Edition. Elsevier; 2013.

-Angela Theiss, MD is a 3^rd year anatomic and clinical pathology resident at the University of Vermont Medical Center.

-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.

The System

Outside the city of New Bern, in Craven County, North Carolina, there is a particular system for residents to dispose of their garbage. Locals must go to the nearest participating gas station and purchase stickers which cost about $2.00 each. These stickers must be placed on each bag of garbage generated in the household, otherwise they will not be picked up during the weekly trash collection. In order to save money, a group of widows has formed a club in which members scout out the open dumpsters in town (usually behind stores or gas stations). Then they call and let group members know where they can covertly dump their trash for free that week.

This story may seem funny, but for the most part, it is true. I have no doubt this also occurs in other parts of the country where the system for trash collection is similar. Why do people behave this way? Are they purposely trying to circumvent the trash collection system in place or is the system just not easy for locals to utilize? If you’re having difficulty getting people to change safety behaviors (like PPE compliance) in your laboratory, you might need to determine that for the systems you have in place and ask similar questions.

In one laboratory the manager struggles with staff who work part of the day in a clean office and another part in the lab itself. When the employees go into the lab for brief periods, they often fail to don their PPE. Upon further investigation, you would learn that staff are not allowed to keep their lab coats on their chairs and that all PPE is kept in one lab store room located on the opposite side away from the offices. The system is set up to reinforce PPE non-compliance.

In another lab the manager placed a permanently-mounted counter face shield in the chemistry department so that staff would be forced to use it when popping specimen caps. Staff loaded instrument racks behind the shield, but when they carried the racks over to the analyzers, their faces were not protected from splashing. Exposures continued to occur. Here the system is at play again. A face shield was put in place to change behaviors, but it was only a partial solution. In order to protect staff fully here, they would need goggles or a face shield that can be worn. Offer light-weight reusable or disposable face protection that staff can use easily. Be sure to give them a say in whatever option is chosen.

Sometimes the system issues are not apparent until there is a safety event, and unfortunately, that can result in bigger problems. If your training program does not include regular fire safety training, a small fire situation may get out of hand quickly. Does your staff have experience handling a fire extinguisher? Would they easily be able to put out a fire? Do they know their evacuation routes and meeting places, and could they get there with ease? What about the lab emergency management plan? Have staff participated in a table-top drill so they have a basic understanding of how to respond during a chaotic disaster? These are examples of some safety systems that need to be in place to keep staff ready and safe at all times.

When people take shortcuts or find ways to circumvent the system, there is usually a pretty good reason, Often, it is the design of the system. In New Bern, elderly women can’t lift large heavy trash bags, so they use smaller bags. They don’t want to pay the same price for a garbage bag sticker that others are paying for big bags. There’s a problem with the system- and those ladies found a way around it. What problems do you see in your lab safety system? If you don’t know what they are, ask around. Staff will talk. It’s better to find out what the workarounds are now and to fix them before an injury or exposure occurs.

–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.

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.

-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.

Genetic Test Results Change Faces

As a part of my Molecular Genetic Pathology fellowship, we experience a clinical component to training in addition to all of the laboratory training we receive. This last month, I rotated through Cancer Genetics, where genetic counselors discuss genetic testing with patients with a personal or family history of cancer. The counselors describe the process of genetic testing and help chose genetic tests to look at the patient’s risk for an inherited cancer syndrome.

Patients are looking forward to the certainty that will come from a genetic test, because it is the wave of the future and they think you can learn so many things from your genetics. The truth, however, can be much less clear. Up to 30% of people receive a Variant of Uncertain Significance (VUS) as their genetic test result. This rate increases as larger panels are test more genes.

Figure 1. A set of genes and associated cancer types tested by a hereditary cancer genetic test. (Taken from Myriad MyRisk Gene Table.)

A VUS represents a variation in a person’s gene that doesn’t have enough information to say that it is benign or pathogenic. This gray zone is very uncomfortable and confusing for patients and providers alike. There are several cases where someone acted on a VUS as if it were a pathogenic variant and ended up having radical interventions like a bilateral mastectomy.

We know that as scientific and medical knowledge increases, our ability to reclassify these variants improves. For laboratories, this means periodic reanalysis of previously reported variants. If this process is not properly set up, it can be very laborious and extensive. Furthermore, not only was a timeline for variant reanalysis unknown, but also the likelihood of variants becoming upgraded or downgraded had not been described.

Two recent studies helped provide some answers to these questions. The first, published in JAMA, comes from the cancer genetic group I was working with, led by Dr. Theo Ross M.D. Ph.D., worked in conjunction with Myraid (Lab that first started testing the BRCA genes, and now tests many more) to determine how often variants were reclassified. Looking at 1.1 million individuals tested at Myriad, the average time to reclassification for a VUS was 1.2-1.9 years (Mersch J et al Jama 2018). Additionally, 90% of VUS were downgraded to benign/ likely benign representing 97% of patients with a VUS. This figure from the paper shows how the time to issuing a reclassification (amended report) has decreased (Figure 2).

Figure 2. The time to sending an amended report is shown by the year the report was first issued. From Mersch et al. JAMA 2018.

I worked on the second study, which looked at variant reclassification in childhood epilepsy genetic testing (SoRelle et al JAMA Peds 2019). The results, published in JAMA Pediatrics, also found most patients had a VUS reclassified to benign/likely benign. However, several clinically significant changes (reclassified to or from pathogenic/ likely pathogenic) occurred as well (Figure 3).

Figure 3. Patients with reclassification of gene variants from each category. Arrows that cross the red line represent an instance where a change in diagnosis would result from variant reclassification. Seven patients had both a pathogenic or likely pathogenic variant and VUS reclassified and are only represented once.

Furthermore, there was a linear relationship between the time the test was reported and the rate of variant reclassification (Figure 4). We found that 25% of patients with a VUS would experience a reclassification within 2 years.

Figure 4. Reclassification rate is plotted as the fraction of reclassified variants for each year testing was performed (VUS= black line, pathogenic or likely pathogenic= red line). Solid lines represent patients with a reclassified result and dotted lines are extrapolated slopes.

Overall, the conclusions of the two studies are somewhat similar:

Most patients with a VUS experience a downgrade reclassification to likely benign or benign.
Variant reclassification should be performed at least every 2 years
Rates of reclassification may differ by disease type. Investigation by a similar study design should be performed in other genetic diseases.

References

Mersch J, Brown N, Pirzadeh-Miller S, Mundt E, Cox HC, Brown K, Aston M, Esterling L, Manley S, Ross T. Prevalence of variant reclassification following hereditary cancer genetic testing. JAMA. 2018;320:1266–1274.
SoRelle JA, Thodeson DM, Arnold S, Gotway G, Park JY. Clinical Utility of Reinterpreting Previously Reported Genomic Epilepsy Test Results for Pediatric Patients. JAMA Pediatr. 2018 Nov 5:e182302.

-Jeff SoRelle, MD is a Molecular Genetic Pathology fellow at the University of Texas Southwestern Medical Center in Dallas, TX. His clinical research interests include understanding how the lab intersects with transgender healthcare and advancing quality in molecular diagnostics.

Blue Chips – Troubleshooting Ion Torrent Data

Ah, the blue chip – not much fun to see after spending a day preparing the libraries and running clonal amp overnight. There are a couple possible explanations for a blue chip, and you can figure them out by looking at the metrics of the run.

Test Fragments

The test fragments serve as a control for the sequencing run. They are spiked into the mixture of library ISPs before they are loaded on the chip. These will allow you to figure out where the problem occurred if you encounter a blue chip. If the Test Fragments are detected and are of sufficient quality, then this means the sequencing run worked and the problem most likely occurred before sequencing, during library prep or clonal amplification. If the Test Fragments are not detected, then it could mean one of two things – one – the clonal amplification did not work for either the library or the Test Fragment ISPs, or – two – the sequencing run was somehow at fault. Let’s take a look at both examples.

Troubleshooting a Blue Chip

In the event you see a blue chip, first, check to see what kinds of ISPs showed up after the analysis. For the chip pictured above, there were ISPs that had product on them, as you can see in the Live category (6,475,553 ISPs or 95.3% of the ISPs, shown in the screenshot below). This means clonal amp was successful for a small number of the library ISPs. Next, there were also Test Fragments detected, at 433,392 ISPs or 6.7% of the total ISPs. Scroll down to the bottom of the page, and you will see how the Test Fragments sequenced. We like to see the Percent 50AQ17 and Percent 100AQ17 at least in the 80’s, but even still, you can see that these were detected and were sequenced. Because of this, the sequencing run looks to be fine, so most likely the problem occurred before sequencing. In this case, we believe the library prep did not yield the expected 100pM concentration, so the library pool was over-diluted prior to clonal amplification. The library prep was repeated, and clonal amplification was run on the new pool of libraries, and the sequencing was successful.

In this next example, we have the other possibility. This chip was blue as well (this is a 520 chip, instead of a 530, to explain the different sized pictures).

First, there are only 2.7% Live ISPs, so even lower than the chip above. But the even stranger thing was that there were 0.0% Test Fragments, and at the end of the analysis, there were absolutely no ISPs left to be analyzed, library or Test Fragment. This was the only time we had ever seen a chip like this; generally, if we had blue chips, they were like the previous example. We looked at our library pool quant and it was in the expected range, so we did not believe it was a library prep issue. The sequencing initialization was successful and did not have any errors, so we did not believe it was a sequencing problem. We repeated clonal amplification with the same library pool and had successful sequencing. In speaking with our Field Application Scientist, it was decided it must have been a failure of one of the reagents of the clonal amplification – either a Taq was not present or something, so the clonal amplification never occurred, or something similar.

Hopefully you will not experience too many of these blue chips, but if you do, I hope you are a little more prepared to troubleshoot! Happy sequencing!

-Sharleen Rapp, BS, MB (ASCP)^CM is a Molecular Diagnostics Coordinator in the Molecular Diagnostics Laboratory at Nebraska Medicine.

Gastric Cancer: A Multidisciplinary Approach

Maryam Zenali^1*, Dmitriy Akselrod², Eric Ganguly³, Eswar Tipirneni⁴ and Christopher J. Anker^5*

¹Department of Pathology,² Department of Radiology, ³Division 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).

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

Pages: 123456789101112

Microbiology Case Study: A 19 Year Old Woman Passes a Worm in Her Stool

Case History

A 19 year old woman with no significant past medical history presented to an outside clinic with psychological distress after passing a worm per rectum. She had no other complaints or symptoms.

Image 1. Eggs are spherical, 31 to 43 μm in diameter, with a thick yellow-brown (bile-stained) shell having radial striations and contain a hexacanth oncosphere (Image courtesy of: Fred Patterson, Parasitologist).

Image 2. Adult proglottids are longer (up to 20 mm) than they are wide (up to 7 mm) and have a genital pore (*) at the lateral margin.

Image 3. Formalin-fixed paraffin-embedded H&E stained section of a proglottid’s lateral uterine branches on each side of a central uterine stem (20x).

Discussion

Adult cestodes (tapeworms) have long, ribbon-like bodies made up of proglottids (egg-producing segments) that develop at the posterior of a scolex (specialized structure for attachment to the small intestine of a host). Taenia has 32 species, 2 of which are medically important for causing taeniasis: Taenia saginata and Taenia solium (beef and pork tapeworm infection, respectively). These parasites are distributed worldwide, with T. saginata being more common than T. solium.

The lifecycle of Taenia involves adult, egg, and larval stages. Adults release gravid proglottids and eggs that are passed in feces. The eggs reach pasture land via soil or water and are ingested by an intermediate host. For T. saginata, the intermediate host is a herbivore (cow), as eggs of T. saginata do not infect humans, and for T. solium, the intermediate host is a pig, human, or other animal. Ingested eggs hatch and release the hexacanth oncosphere (6-hooked embryo) that can penetrate tissues. Over 2 to 3 months, infective cysticerci (0.5 to 2.0 mm in diameter larvae) develop in muscles. Of note, only T. solium can cause cysticercosis (extra-intestinal larval forms within human tissues, ie. the human becomes the intermediate host) and this can be life-threatening if cysticerci invade the brain. When humans consume raw or undercooked beef/pork meat that is infected, cysticerci will attach to the small intestinal mucosa and, over 3 to 5 months, mature into the adult form. The adult T. saginata can reach 4 to 12 meters in length and the adult T. solium can reach 1.5 to 8 meters in length. Adult tapeworms can live within intestines for over 25 years while gravid proglottids and eggs are passed in stool.

Infections are usually asymptomatic or cause mild indigestion, anorexia, and abdominal discomfort. The eggs can be identified by ova and parasite examination (Figure 1) or a cellulose tape preparation of perianal skin. The oncosphere must be visualized to avoid misidentifying a pollen grain. However, eggs of Taenia species and Echinococcus species are indistinguishable. Diagnosis is also made by recovering gravid proglottids from the anal opening or passed in feces (Figures 2 and 3). Distinguishing the two species can be done by examining gravid proglottids for the number of lateral uterine branches present on one side of a central uterine stem. T. saginata have 15 to 30 lateral uterine branches while T. solium have 7 to 13 branches. Both species have a small anterior scolex (measuring 1 to 2 mm in diameter for T. saginata and 1 mm in diameter for T. solium) with 4 suckers. Definitive identification is possible since T. solium’s scolex has a rostellum (crown) with 2 rows of hooks whereas T. saginata’s scolex bears no rostellum or hooks. Treatment is a single dose of praziquantel and successful treatment is defined as passing zero proglottids over 4 consecutive months.

-Adina Bodolan, MD is a 3^rd year anatomic and clinical pathology resident at the University of Vermont Medical Center.

-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.

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.

-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.”

-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.