Hematopathology Case Study: A 66 Year Old Man with Abdominal Pain and Diarrhea

Case History

66 year old man with a past medical history of Sjogren syndrome, hypertension and hypothyroidism presented to an outside hospital with abdominal pain and diarrhea. CT imaging showed extensive lymphadenopathy, splenomegaly, mesenteric thickening and ureteral dilatation, all highly concerning for lymphoma or other malignancy. A needle core biopsy of “mesenteric mass” showed reactive lymphoplasmacytic infiltrate in a sclerotic background. A second needle core biopsy of a retroperitoneal lymph node was performed which showed reactive features and numerous plasma cells. An excisional biopsy of an inguinal lymph node was ultimately performed due to worsening lymphadenopathy with increased PET FDG avidity.

Excisional Biopsy

H&E 10x
H&E 20x
H&E 20x
H&E 40x
IgG
IgG4

Diagnosis

At low power view, there is intact follicular architecture with reactive appearing germinal centers that are polarized and show tingible body macrophages. The higher power view shows a feature that can be seen in Castleman disease called a “lollipop” which has a thickened vessel with hypertrophied endothelial cells penetrating the germinal center. In addition, there are areas with sclerotic remnants of germinal centers, a feature that can be seen in infection or other reactive conditions. Notably, the interfollicular space is expanded by numerous plasma cells and rare scattered eosinophils. Overall, the lymph node shows reactive follicular and paracortical hyperplasia. Stains for IgG and IgG4 showed an elevated IgG:IgG4 ratio with 54% of IgG plasma cells positive for IgG4. These findings raise the possibility of IgG4-related lymphadenopathy (IgG4LAD). In addition to histopathologic findings, the patient was tested for a serum IgG4 level, which is an important diagnostic criterion for the diagnosis of IgG4 disease. Seen above, serum testing on 10/25/18 showed a low/normal IgG subclass 4 of 17 mg/dl. After the excisional biopsy was performed, suspicion of involvement by IgG4-related disease increased. A sample was re-sent on 11/27/18 with instructions to perform serial dilutions in case of the prozone effect (see discussion below). The test came back with an elevated serum IgG subclass 4 of 1239 mg/dl, further supporting the diagnosis of IgG4-related disease.

Discussion

IgG4-related disease is a condition that was originally described in patients with autoimmune pancreatitis. These patients were found to have elevated serum IgG4 concentrations and have large numbers of IgG4-positive plasma cells. IgG4-related disease is now recognized as a fibroinflammatory condition and has been described in almost every organ system. Similar histopathological characteristics can be seen regardless of location and include tumefactive lesions, dense lymphoplasmacytic infiltrate, increased IgG4-positive plasma cells and storiform fibrosis.1

IgG4 normally accounts for less than 5% of the total IgG in healthy people and is the least abundant IgG subclass. IgG4 is also seen to be involved in other immune-mediated conditions such as pemphigus vulgaris, idiopathic membranous glomerulonephritis, and thrombotic thrombocytopenic purpura. The majority of patients with IgG4-related disease have elevated serum IgG4 concentrations, but 30% of patients may have normal IgG4 concentrations.1 When testing IgG4 serum levels, it is important to be aware of the prozone effect. This occurs when very high concentrations of the antibody that is being measured are present. This will prevent appropriate antibody-antigen binding and agglutination from occurring. This will result in a falsely low level of antibody being detected. In a report by Khosroshahi et. al., after identifying the prozone effect in one patient with IgG4-related disease, 38 patients who had previously been tested for serum IgG4 levels were re-tested. The prozone effect was found to affect 26% of patients with IgG4-related disease. The samples were re-tested with serial dilutions and the mean serum concentration rose from 26 mg/dl to 2,008 mg/dl. This could have a large impact on patient care, as elevated serum IgG4 concentrations are very important in making the diagnosis of IgG4-related disease. 2

IgG4-related lymphadenopathy (IgG4LAD) is somewhat distinct from tissue based IgG4-related disease and presents with solitary or multifocal lymph node enlargement. Lymph nodes are involved by a lymphoplasmacytic infiltrate with increased IgG4-positive plasma cells and tissue eosinophils and are not typically involved by storiform fibrosis. Five microscopic subtypes have been described and include multicentric Castleman disease-like changes, follicular hyperplasia, interfollicular lymphoplasmacytic proliferation, progressive transformation of germinal centers, and a variant with the formation of inflammatory pseudotumor-like lesions. The differential diagnosis of this entity is broad and purely reactive lymph nodes as well as multicentric Castleman disease (MCD), in particular needs to be ruled out. The presence of HHV8 infection and elevated IL-6 and CRP can favor MCD, while tissue eosinophilia favors IgG4LAD.3    

The diagnostic criteria for the diagnosis of IgG4LAD includes lymph node involvement,  a serum IgG4 level greater than 135 mg/dl, and histologic findings of lymphoplasmacytic infiltrates with either >10 IgG4-positive plasma cells per hpf or a ratio of IgG4-positive to IgG-positive plasma cells to be greater than 40%. As seen in this case, patients may undergo multiple biopsies, often with extensive work-ups before a diagnosis is made. Treatment depends on the organ involved and extent of damage/dysfunction. While some cases may only need clinical follow-up, others will require urgent aggressive treatment. Glucocorticoids are typically the first line of therapy and have been shown to be effective in a majority of patients with IgG4-related disease. 3

References

  1. Stone, J, Zen, Y, Deshpande, V. IgG4-Related Disease. N Engl J Med 2012; 366:359-551.
  2. Khoroshahi, A, Cheryk, LA, Carruthers, MN, et. al. Brief Report: spuriously low serum IgG4 concentrations caused by the prozone phenomenon in patients with IgG4-related disease. Arthritis Rheumatol 2014; 66(1):213-7.
  3. Wick, M, O’Malley, D. Lymphadenopathy associated with IgG4-related disease: Diagnosis and differential diagnosis. Seminars in Diagnostic Pathology 2018; 35(1)61-66.

Chelsea Marcus, MD is a third year resident in anatomic and clinical pathology at Beth Israel Deaconess Medical Center in Boston, MA and will be starting her fellowship in Hematopathology at BIDMC in July. She has a particular interest in High-grade B-Cell lymphomas and the genetic alterations of these lymphomas.

Opposites Attract

Welcome back! Thank you for the messages and shares for last month’s post about how medical professionals like us should be leading the charge to address gun violence as a public health issue. It’s a hot-button topic, but I was really glad to engage in some great conversations. I want to stick with the theme of using data to improve patient outcomes, but this time I’d like to shift focus just a little bit.

This is a longer one but, to me, there’s a lot of interesting stuff I wanted to share with all of you!

(TL;DR Path and Psych aren’t too different, but they are. There are interesting overlaps, and doing research right is really critical.)

The last month of 2018 has me rotating through my psychiatry clerkship in medical school. With that, I’ve had an interesting opportunity to look at pathology from a very distant lens. (Very distant; think diminutive picture of Earth from Mars far…) During one grand rounds session, Dr. Owen Muir, the medical director of Brooklyn Minds said something to the effect of, “[people say] Psychiatry is different, so much so that we’re the most removed from our tissue of concern.” That was pretty poignant. He was talking about the brain; in testing, treatment, and practice, it’s virtually inaccessible without a major neurologic undertaking and almost unreachable between pharmaceutical and external therapeutic interventions. Here’s the same thought another way: a neuropathologist can show you what parts of the brain do what in a particular pathologic process grossly and microscopically, while psychiatry focuses on pharmacologic, cognitive, and comprehensive behavioral therapies. A microscope versus a telescope—but both a way to focus on a problem. When I compared that to some things I heard during my orientations, it became clear that Psychiatry and Pathology might be very different animals.

I’ll get back to Dr. Muir and the Brooklyn Minds’ work with cutting-edge deep Transcranial Magnetic Stimulation (dTMS)—yes magnets—in just a minute. First I want to show you that, despite being light-years apart in distance, these two specialties overlap more than people realize. No, not with regard to behavioral stereotypes; read my previous post on stereotypes in lab medicine, and let’s get that out of the way right off the bat. The foundational concept which continues to bring every specialty closer together is translational research. Consider the following, if the field of Medicine was a tree, specialties would be complex branches and basic scientific principles would be the roots of knowledge. And what connects the roots to the branches? All the years of scientific research that translates data gathered from experimentation in fields like physiology, microbiology, or chemistry into specialties like nephrology, infectious disease, or endocrinology. Wait! That’s pretty much our job—duh. Cool, so since we translate the data, we’re all the junk in the trunk! So within the realm of research in medicine, I want to show you examples of cutting edge limitations, intersectional data sharing, and shortcomings in translational research.

Cutting edge or the bleeding edge?

So, I mentioned Brooklyn Minds. Sounds dramatic, like a movie title; but you won’t find any groundbreaking 90’s soundtrack by Coolio or a Michelle Pfeiffer-driven story about inner city youth. Instead, what their webpage outlines very nicely is the important and impactful work they do in psychiatry which includes repetitive or deep therapeutic magnetic stimulation (rTMS/dTMS). I promised I would explain the magnets thing, okay so here goes. Essentially, dTMS is a pulsatile magnet-driven energy wave directed at specific regions of a patient’s head. The energy works like a magnetic field to activate or inhibit (think “polarize” or “depolarize”) small patches of neurons within the brain, penetrating beyond the bony cranial vault and centimeters into the parenchyma of brain tissue. Using a premise which is basically similar to an MRI, patient’s brains are “mapped” for functional region analysis—a new, subtler way of looking into focal deficits. Two major mental illness that dTMS has literature supporting treatment include Major Depressive Disorder (MDD) and Obsessive Compulsive Disorder (OCD). So first, you have to understand one thing: neurons are basically our electrical circuitry, conducting energy potentials as signals back and forth translating and calculating motion, sensory input, and position. If nerves are electrical wires, think of myelin as a conductive insulator for higher signaling strength. The conduction potentials of certain mapped regions of the brain demonstrate decreased activity in particular areas with corresponding anatomical locations where we know disease processes can occur. For example, we understand the changes in brain chemistry to treat it pharmacologically, but depression has visible impacts on the hippocampus and prefrontal cortex. Why not treat this directly, like the way a surgeon would treat a hernia?

Image 4: Let’s take depression, for example. In the PET scan on the right, you can see what a “normal” brain functional status is mid-scan. On the left, however, would be a “depressed” brain. With cortisol in surge-mode and a poverty of available serotonin and norepinephrine in the brain, you can see widespread variable activity from the amygdala, hippocampus, prefrontal cortex, and beyond. (Source: Mayo Clinic)

This seems like some next-level Doctor Who science, right? So, the biggest question here would be: does this work? Since TMS (of which there are multiple types, with special equipment—not important for this discussion) is a medication-free treatment, doesn’t this sound almost perfect? Combine that with the fact that dTMS treatments often potentiate positive response for follow up treatment since the “rewiring” promotes future effectiveness and this might sound too good to be true. Studies are being published by the pound hailing this type of therapy as a potential life-saver for psychiatry which has been struggling to contribute longitudinal positive outcomes for patients. Evidence is strong for the use of dTMS in a variety of mental health issues, but it’s still early—you might find studies with large number of subjects, but you might not find ones with long-term analyses. So the research today is overwhelmingly positive and there are multiple studies in published literature about the effectiveness of this therapy in depression resistant to medication, or the utility as a maintenance therapy in an outpatient setting, or even potential use for substance use disorders. But, there are skeptics just as vocal as supporters. (Side note: If Dr. Oz does a story on a treatment like TMS, do we have to abandon it and move on completely?) As an emerging therapy, Psychology Today published a consumer report of sorts which discussed issues like access, refractory response, and more proven standard therapy like ECT (electroconvulsive therapy). Although it is FDA approved and non-invasive (minus some potential headaches), questions about TMS address things like how to get insurance to cover it, should it be reserved as a last resort after things like medications/ECT, and since it’s a relatively new treatment should we pursue more longitudinal studies first?

Image 5: Have a seat! This instrument has the potential to treat a myriad of psychiatric illnesses by using magnetic fields aimed at “adjusting” improperly firing neurons in the brain. Research still remains outstanding as to whether dTMS can affect someone’s …magnetic personality. (Source, except for my pun: Cognitive Psychiatry of Chapel Hill)

Taking it back to the source

Way back in the beginning of 2018—if you can remember such a time—an article was quietly published in the journal Science. This was a large collaboration funded by the National Institute of Mental Health (NIMH) among many other supporters, with a team that spanned from UCLA, to Denmark, to Chicago (woot!). Printed in the section header “Psychiatric Genomics,” it was called “Shared Molecular Neuropathology Cross Major Psychiatric Disorders Parallels Polygenic Overlap”—wait, what? Yes, among some major psychiatric disorders we all know, love, and read about in the DSM-5, some of them share specific genetic mutations. Full stop. Pivot. Let’s leave our Freudian couch and walk over to the lab…

Image 6: Experimental rationale and design where section (A) illustrates the model of proposed psychiatric disease pathogenesis and the authors’ (B) experimental process which they concluded was “highly suggestive of a causative genetic component” (Source: Gandal et al. 2018, Science 359, 693–697)

What these authors suggest is that five major psychiatric disorders—autism spectrum disorders (ASD), schizophrenia (SCZ), bipolar disorder (BD), major depressive disorder (MDD), and alcohol abuse disorder (ADD)—all share specific gene-expression changes which indicate transcriptional dysregulation (i.e. mutations) at single nucleotide polymorphism (SNP) locations which is very consistent with inheritable genetic variants. In short, small, specific mutations seem to be identifying features for those five disorders, which might reveal genetic risk and potential future treatment targets. Even more than this, what we see commonly as overlapping features in patients’ clinical presentations may actually be explained by overlapping genetic expression and penetrance. We’ve long had historical evidence supporting the hypothesis of mental illness as an inheritable disorder. Twin studies have shown the increased probability of expressed diseases like bipolar disorder or schizophrenia in monozygotic twins compared to dizygotic ones—but the twins’ clinical presentations don’t always yield 100% confidence there. Clinicians are acutely aware of the genetic component present in diseases like these, but targetability has proven difficult. According to the National Institute(s) of Health and Mental Health (NIH/NIMH), “strong evidence may exist for genetic susceptibility, but no specific gene has been unambiguously identified for common forms of mental disorders,” and “the estimate of the influence of environmental factors on the disorder provides an index of how difficult the search will be.” (Source: NIH/NIMH Genetics and Mental Disorders: Report of the National Institute of Mental Health’s Genetics Workgroup – Mental Disorders and Genetics: What We Know Today) That was in 1997! A similar paper to this one published in The Lancet in 2013 addressed these same five psychiatric disorders correlating some genetic components to a region on Chromosome 3 against almost 30,000 normal/wild-type patients. The NIH responded then saying that though there were significant correlations presented therein, there isn’t enough evidence to show the risk associated with the mutation and further research is necessary. Fast forward to some further research and we now see evidence of overlap between particular mental illnesses as well as cell-to-cell signaling as a specific neuropathological mechanism of disease. Is it enough for a Nobel Prize? No. But think of it somewhere between a paper titled “We’ve Discovered Insulin!” and “Patients with Diabetes Often Have Elevated Blood Glucose.”

Image 7: Evidence to suggest that certain gene expression patterns overlap which demonstrates transcriptosome similarity between various two-disease combinations/overlaps (A) and that there seems to be a spectrum or progression of disease intensity relating to a gene’s mutability (B). However, gene expression can both show that normal biologic function can be associated with these variants (C) and that, even though disease overlap implies correlation, ASD seems to mutate independent from the rest (D). (Source: Gandal et al. 2018, Science 359, 693–697)
Image 8: Hub genes are targets of research because of they are modeled as functionally significant markers of genetic variation and/or mutability. In this abbreviated data infographic, the top 20 gene hubs were collected for their association with gene activity in each of the five diseases. The functional aspects represent mutations (colored circles) in various aspects of neuronal cells including receptor activity (dark blue), mitochondrial structure (green), immune response/regulation (yellow-green), mitochondrial metabolism (purple), neuronal activity (pink and light blue), cellular architecture and growth (tan), and other neuronal metabolism (yellow). The lines connecting these mutations are a representation of Eigengene networking, which illustrate gene co-expression and functional relationships. (Source: Gandal et al. 2018, Science 359, 693–697)
Image 9: What’s the take-home message here? Basically, the final conclusion is this: take all these demonstrated mutations as functional pieces of mental health and down-regulated neuronal expressions of genes highlight potential risk stratification. Genome-wide association studies (GWAS) shows high concentrations for SCZ, ASD, and BD variants (A) and those variants presence in the neuronal model for various nerve cell types is shown (B). The main lesson here is the projected diagnostic liability and risk assessments for patients who have these specific mutations (C & D) which may be correlated to this research’s co-expression models. (Source: Gandal et al. 2018, Science 359, 693–697)

Correlation does NOT imply causation, but isn’t it so tempting!

While promising articles like these offer amazing potential insights into a deeper understanding of clinical diagnostics for psychiatry, articles are as numerous and complex as patients. An article published this month from the Journal of the American Medical Association (JAMA) Psychiatry correlated an association between hospitalization and subsequent mental disorders in children. Anything that purports to associate new causality between disease entities and trends is always worth a read. And, like any other experienced clinician, you go straight to the title and design methods to determine your gut feeling about this paper before continuing. The title: “A Nationwide Study in Denmark of the Association between Treated Infections and the Subsequent Risk of Treated Mental Disorders in Children and Adolescents;” the number of patients studied: over 1 million. What? That’s amazing! 1 million cases, what amazing data, what amazing insights, what …a statistical nightmare. Finding results in a million is both exhaustively comprehensive and statistically problematic. Black holes are rare. But if you search the entire universe you’ll find millions. “With a large enough sample size, rare things become common…” this was said with a pregnant pause and the normal gravity delivered by astrophysicist Neil DeGrasse Tyson, PhD, during a live taping of Star Talk my wife and I attended a month ago.

Image 10: From Star Talk, November 14th at the Beacon Theatre in NYC, left to right: co-host and comedian Eugene Mirman, actress Ellie Kemper, comedian John Mulaney, scientist Julie Huber from Woods Hole Oceanic Institution, scientist Kevin Hand from the NASA Jet Propulsion Lab, and co-host and astrophysicist Neil DeGrasse Tyson. The show discussed life on other worlds, and the realistic expectations of research and what to look for when you’re looking for life in space. The most poignant point of the night came during Dr. Tyson’s conclusion where he talked about different specialties growing apart and coming together over the last few hundreds of years—we used to have an isolated biologist and astronomer, where today astro-biology is a new exciting front!

What came up during that show was the same theme I’m discussing today: it’s very important to do research, collect data, and translate that data appropriately. Especially in medicine, where conclusions and results from research can affect patient outcomes, lab professionals like us need to be leaders.

Back to this paper, the authors report a strong significant correlation between hospitalization events requiring antibiotics and the prevalence of mental illness later in life. Analyzing the hazard risk ratio (HRR) for these patients reveals values usually over 1.0 which show that they are above the regular risk when compared to patients not under these conditions. The authors associate treated infections with childhood/adolescent mental disorders, but include a very important remark at the very end which is ever-present in most good research. They address the fact that results and conclusions from their data may be explained by other, non-studied causes directly because of otherwise not understood pathophysiology. And, like 99% of pathology reports I’ve seen end with a dogmatic “suggest clinical correlation,” this paper closes with something similar to “further research is needed.”

Image 11: Hazard risk ratios (HRRs) here demonstrate that individuals requiring hospitalization for infection were increased (with high confidence analysis) for having a hospitalization for any mental disorder and for redeeming a prescription for any psychotropic medication. (Source: JAMA Psychiatry 2018. doi:10.1001/jamapsychiatry.2018.3428)
Image 12: You can find tons of funny causation-correlation infographs on the internet. They prove a great point: we have to be careful how we translate our data. Without arguing that because higher global temperatures melt the icecaps pushing more sailors to a life of pillage and plunder, these two findings are assuredly non-related.

So that’s it! Using data is great! It’s the best. Translating direct and clinically relevant findings from the bench to the bedside is what we do best. Consulting with our clinical colleagues, those of us in laboratory medicine have a responsibility to make sure of four main things. First, we have to make sure that the results we obtain are clear. Pre-to-post analytical analysis is paramount to testing efficacy and we’re the experts on standard procedures and accountability. Second, the interpretation of results whether it comes from a research lab or hematology bench must be valid. Protocols and metrics are great, and using them to ensure effective use of information is critical. Third, the conclusions we reach should be meaningful. If it’s a cancer staging diagnosis biopsy report or a groundbreaking publication on shared genetic variants, the implications must provide the best information for patients. Because finally, we do what we do for them. Our work and efforts always go back to improving patient outcomes, and giving each person the best chance at maximum health and quality of life. Pathology and psychiatry might be worlds apart, but only in vocabulary at best. We’re on the same team. And, despite finding each other as great neighbors in most Medscape physician job reports, we both work very hard to lead the charge in protecting, healing, and advocating for our patients.

Wishing you good mental health! Even outside the Seattle area, fictional Dr. Frasier Crane’s “I’m listening” catch phrase is great advice toward patients, colleagues, and generally everyone. Leadership is a great responsibility, but it’s worth nothing if you don’t pay attention to what needs to get done.

Thank you, and happy holidays!

Microbiology Case Study: A 14 Year Old Female with 3 Day History of Abdominal Pain

Case History

A 14 year old Caucasian female was transferred to the pediatric emergency department from an outside hospital due to a 3 day history of abdominal pain. The pain was concentrated in the right lower quadrant and was accompanied by nausea and two episodes of vomiting. Her vital signs were normal and physical exam demonstrated tenderness and guarding upon palpation of the right lower quadrant of the abdomen. Her white blood cell count was elevated at 21.1 TH/cm2 and showed 91% neutrophils. Abdominal ultrasound was unremarkable and CT scan was inconclusive for appendicitis. The patient was taken to surgery for an exploratory laparotomy and her appendix was removed.

Laboratory Identification

Image 1. Microscopic review revealed a female nematode with characteristic cephalic inflations, numerous eggs in the uterine cavity, and an intestinal cavity at the posterior end (H&E, 20x).
Image 2. Numerous oval shaped eggs with a thick shell that are slightly flattened on one side were observed (H&E, 200x). The eggs measured 55 x 25 um in dimension.

Gross examination of the appendectomy specimen showed an unremarkable appendix that measured 5.7 cm in length by 0.7 cm in diameter. There was no evidence of perforation. On sectioning, a small, white, “worm-like” structure (0.6 x 0.1 cm) was identified at the tip of the appendix and submitted for histologic examination. Microscopic review identified a female nematode with many eggs characteristic of Enterobius vermicularis. There was no acute inflammatory process identified upon microscopic review of the appendix.

Discussion

Enterobius vermicularis, commonly referred to as pinworm, is a nematode infection that frequently presents as perianal itching in young children or those living in crowded settings, with symptoms most prominent in the evening and night time. Adult female worms reside in the cecum of the large intestine and migrate to the perianal area during the night to lay eggs, resulting in irritation. Often, infections can be asymptomatic as well. E. vermicularis is one of the most common helminthic infections in the United States.  

Humans are the only known host of E. vermicularis and become infected by ingesting embryonated eggs from feces or handling contaminated materials such as clothing, bed linens or from bathroom surfaces. Pinworm has a direct lifecycle and the larvae hatch in the small intestines and develop into adult worms that occupy the colon. It takes about one month from ingestion of infective eggs for E. vermicularis eggs then to be shed on the perianal folds.

Laboratory identification of E. vermicularis is usually made by using a piece of scotch tape or an adhesive paddle applied to the perianal skin in the morning and then visualizing the eggs microscopically. The eggs of pinworm are oval in shape & are flattened on one side with a thick capsule and measure between 50-60 x 20-30 um in size.On occasion, the eggs can be seen on pap smears as well. E. vermicularis worms can sometimes be visualized during colonoscopy, gastrointestinal & pelvic surgeries, and are capable of being identified by histology. Histologic sections of adult E. vermicularis worms usually show prominent lateral alae on the outer surface, testis or ovaries depending on the sex of the worm, and the intestinal tract. In gravid female worms, the characteristic eggs are numerous and can be helpful in the identification. 

Treatment options of an E. vermicularis infection include an initial dose of albendazole, mebendazole,or pyrantel pamoate followed by a second dose two weeks later to prevent possible reinfection. Family members and other close contacts may be treated as well ensure eradication. In the case of our patient, her post-surgical course was uneventful and her white blood cell count trended down to 7.0 TH/cm2 after surgery. She was discharged home the following day. 

-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.

Contextual Factors of Work

Work is central to the human experience, even though the actual practice of work has continuously changed through the decades. These changes impact personal life as well, since there is a strong correlation between work life and life outside of formalized productivity. There are certain factors that influence how work is practiced that impact people’s approach to work.

The first factor is technology. Technology has significantly altered the practice and implications or work. For example, try to compare what office work was like 50 years ago compared to now, or how laboratory diagnostics were different back then. In today’s age, the majority work tasks are conducted on the computer or through technological advances: emailing, writing, analyzing, diagnosing. Fifty years ago, such tasks were conducted via phone, typewriters, or by hand. Technology has also increased the amount of information available to workers. This information allows organizations to prepare to lead in a VUCA world, namely one that is volatile, uncertain, complex, and ambiguous.

The second factor that influences work is globalization. Through the increase in technology and information as mentioned above, cultural, linguistic, and national boundaries do not impact the work environment as much as they did. Such lack of confines pushes both organizations and individual workers to be more competitive due to reduced market and job security, respectively. On the other hand, it also increases collaborations and opportunities to help others. For example, through telepathology, we are now able to provide diagnostics to people in places that do not have access to local laboratory services.

The third factor that has an impact on work is the psychological contract between worker and employer. During the industrial age, this contract was mostly stable and predictable and was based on the assumption that if workers performed well, had integrity, and were responsible their work created a sense of connection. In today’s work culture, this contract has shifted towards a focus on self-development, experience, and personal long-term goals instead of a long-term relationship between worker and employer.

Lastly, a factor that influences work is the knowledge gap. Since many of the unskilled jobs are now conducted by computerized machines, employers will rely more on workers with specific skills and knowledge. However, educational opportunities are not equally distributed and the lower classes are at a clear disadvantage.

It is important to understand these factors when working with people from different educational, technological, and cultural backgrounds. All these factors influence people and how they perform their jobs.

lotte-small

-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.

Training and Competency: They’re the Same Thing, Right?

As a fitting end to my previous 3-part series on how to prepare for and survive your regulatory inspections, one of the hospitals we provide consulting services to was just visited by The CAP. Overall we did great and I’m proud of everyone there, but the inspectors found a weak area for us to improve upon that others may be struggling with as well: documentation of training and competency.

It is a common misnomer that training and competency are equivalent and essentially the same thing. Whether you’re subject to CLIA, CAP or your local state DOH requirements, you will be required to provide proof (documentation) of both training AND competency for each employee, for each task that they perform. This is not just limited to your technical staff, but also includes non-technical personnel (phlebotomists, lab assistants, LIS personnel,transport couriers, etc.), as well as staff outside of the immediate laboratory testing area (respiratory clinics with blood gas analyzers, Point of Care testing, etc.).

Simply put, training is coaching, mentoring, and teaching someone step-by-step how to perform a specific task. Proper documentation of this training includes:

  • Objectives for the training (i.e., “After completing training, staff will understand howto successfully perform maintenance tasks on the hematology CBC analyzer.”)
  • Identification of the methods to be used during the training (direct observation, monitoring recording & reporting of results, review of worksheets & preventive maintenance records, evaluation of problem solving skills)
  • Identification of the materials to be used during the training (cleaning agents, QC samples, previously tested & scored proficiency testing material)
  • Criteria used to assess the effectiveness of the training (minimum score of 90% on critical thinking quiz, ±10% correlation with previously tested sample)
  • Signature of both the trainee and trainer confirming that training was completed, and when

In addition to the obvious routine tasks a lab professional will need to perform (running QC, instrument maintenance, running patients), don’t forget to document their training for the low frequency tasks performed as well. Based on an employee’s job description, they may be involved in additional tasks such as specimen handling, safety precautions, packing and shipping of samples to reference labs, computer system training, telepathology training, and supervisory functions. These tasks too will require documentation of training.

Documentation of all of these tasks can be organized through the use of a departmental orientation checklist. This will help you keep track of what each staff members’ specific job junctions will include that they need to be trained on, and which tasks have been completed by each trainer. Depending on the task, training can be completed quickly after several minutes of demonstration (waived urine hCG testing), or may take several weeks for staff to fully understand and master the task (flow cytometry leukemia work-up). Keep in mind that until a staff member has documented training followed by successful assessment of competency of that task, they should not be permitted to perform or result patient testing independently of their trainer.

Once training has been completed and documented, you must then assess each staff member’s ability to successfully perform these tasks. This is their competency, where you assess if the training was successful and staff are able to perform each assigned task correctly. To fully demonstrate successful competency of non-waived tests, all 6 of the following elements must be documented for each employee, for each task:

  1. Direct observation of patient test performance, including patient identification, specimen collection, handling, processing and testing.
  2. Monitoring the recording & reporting of test results, including when appropriate the handling of critical results.
  3. Review of testing worksheets, QC records, proficiency testing results, and preventive maintenance records.
  4. Direct observation of performance of instrument maintenance and function checks.
  5. Assessment of test performance through testing previously analyzed specimens, internal blind testing samples or external proficiency testing samples.
  6. Evaluation of problem-solving skills.
  7. Observation of compliance with safety protocols (based upon your specific local state DOH regulations).

The documentation of your competency elements should include the date each item was evaluated, as well as a way to identify and recreate the test performance if asked by an inspector. This is most easily accomplished with the specimen ID number, or PT survey name so records can be located or reprinted.

Be mindful of your local state regulations regarding the specific requirements for who can perform a competency assessment. In many cases, assessors will need an additional supervisor competency for themselves to confirm they are able to successfully assess the performance of their peers. If weaknesses are identified during the competency assessment, additional training should be performed with appropriate corrective actions documented. Competency should be reassessed to ensure staff are correctly performing all duties, prior to them resuming patient testing.

So to summarize:

During training, I am showing you how to do something. I will document all aspects of the training steps that I reviewed with you. When I assess your competency, you are showing me that you know how to do the task correctly. You will document your results as you were trained how to do, and I will validate the accuracy of your work.

-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.

A Year in the Life of a Hematology Laboratory

As this year comes to a close and we look forward to celebrating holidays with family and friends, we can also celebrate our accomplishments over the year. Our jobs in the clinical laboratory are vital in helping physicians make clinical decisions and we should celebrate the role we play in healthcare. In hematology, techs are busy doing daily tasks; QC,maintenance, and analyzing all the samples that come into the lab, 24 hours a day, 7 days a week. We work constantly to provide physicians with accurate and precise results in a timely fashion. But, what else goes on in hematology?

This past year has seen many changes and challenges in our hematology lab. In February, we switched our hematology analyzer to a new Sysmex system,and went to autoverification at the same time. This was a process that had begun months before with meetings with the Sysmex team, building rules for WAM,validations, training key operators, as well as site surveys and actual planning for the location of the instrument and water and electrical connections. Before we went live, new procedures had to be written and all techs had to be trained on the new system. Every tech in the department had to do competencies, everything had to be documented and the new procedures had to be signed. This doesn’t stop once the instrument is in use. There has been a continual learning process since then as techs become more familiar with the system.

During all the excitement and work involved with a new instrument, we, as have many labs, have had turnover in staff which has led to its own challenges. Techs have retired, moved out of state, been on maternity leave and have left us for other opportunities both in other areas of our lab and elsewhere. New staff needs to be hired and trained. Students need mentors during their rotations. It’s a cycle we go through every year, a never ending process. And, no sooner had we seemed to have everyone trained, then it was time for 6 month validations and competencies.

In September we moved to new Coagulation instruments, which, fortunately, was not as big a change as our Sysmex analyzers, because the coag instruments are newer versions of instruments we already used. Yet, there were validations to be done, training to be done on the new software, and procedures to write, all at a time when we were about to go live with a new LIS!

Perhaps our biggest project of the year came to fruition in September when we moved to Epic for a hospital wide software system. This was an undertaking which was well over a year in the making. Again, this transition involved many months of meetings, working with Epic and our IT department to create test codes and profiles and to build the system to our needs. We worked with Sysmex and WAM support to verify that there would be a smooth transition from the old system to the new. The month before go live, we did wet and dry testing of every possible scenario and tested every rule in WAM. And then we tested every rule in Epic. Many hours and late nights were spent entering test orders, creating spreadsheets, taking screen shots, and going back and forth to IT for changes and updates. An integral part of this Epic journey was more training for employees. Superusers were trained, training sessions were held for all, and then superusers helped to support other users at Go Live. And, of course, all of this this meant more procedures had to be written. The epic day arrived, and though things didn’t seem too smooth at first, the support teams were and continue to be available to help and make changes as necessary.

These are just a few of our particular challenges this year in the department. Even without these added projects, though, there is a lot that goes into operating a hematology laboratory. Every week, every month and every year, there are ‘extra’ or ongoing projects to be completed in every laboratory department. While we had some major changes this year, there were also many smaller ones. There are always new pieces of equipment that need to be validated, and new procedures or job aids to be written. Quality control has to be monitored, calibrations have to be performed, new lots need to be entered and tested, linearities have to be done. CAP surveys need to be assigned,reviewed and submitted. Inventory needs to be taken, vendors need to be met with or contacted and supplies need to be ordered. Equipment repairs ,troubleshooting and maintenance all need to be addressed. Training doesn’t stop at new hires and students. All techs have to complete annual competencies. Every year instruments have to be validated, new lot crossovers have to be done, and all procedures must be reviewed and updated. We need to get ready for inspections, or perform self-inspections. I’m sure I am leaving out a list of things, but this is a brief overview of all that goes into laboratory operations. It’s certainly more than just analyzing samples!

Who does all these ‘behind the scenes’ tasks? The department supervisor or technical specialist may be designated to make sure these are all completed, but often senior techs or career ladder techs can play an important role in meeting all these requirements. Many hospitals now have career ladders that allow techs to use the designation MLS II or III or MLT II or III. Our laboratory started such a program this year. For anyone interested in moving up the career ladder in their laboratory, there are many opportunities to be involved in lab operations and management. All the tasks that are required to run a lab cannot be done by one person alone. Tier program requirements differ from hospital to hospital but may ask candidates to submit a tier application and complete a list of achievements to show their commitment to the laboratory and their community before being designated a tier II or III.

Tier techs are generally required to meet education and certification requirements. They should be pro-active performers who are seen as leaders with excellent customer service skills. A tier level tech is a proficient performer with strong critical thinking and problem solving skills. They are mentors to coworkers and can train staff and perform competencies. Hospitals often look to these techs to contribute to the growth of the profession outside of the lab, as well. Being laboratory science community ambassadors, performing community service and upholding the mission and values of your facility all constitute qualities a hospital looks for in a tier tech.

Does this sound like you? We are constantly in need of techs to aspire to working in supervisory positions and management. With an increase in age of supervisors, managers and administrators, we are seeing an increase in retirements. We need more techs doing routine bench work to take the initiative and the steps to become tier techs and lead techs. We need aspiring supervisors and managers. Why wait? I encourage you to make a New Year’s resolution to seek out your facility’s tier or career ladder program. If one doesn’t exists, make it a project to see if one can be introduced!

Laboratories are often hidden in the basement, out of sight of visitors and out of mind of the general public. When we mention we work in a hospital, people ask “Are you a nurse?” Even though we may not be a well-known profession, we are a very important group of dedicated scientists and can be very proud of our accomplishments and contributions. I thank my supervisor and mentor, Gene Galligan, for her encouragement and support of the tier program and for all the things she has taught me in this very busy year.

PS: As I wrote this, The Joint Commission team arrived to start their accreditation process. There is never a dull moment in the laboratory!

Happy New Year!

-Becky Socha, MS, MLS(ASCP)CM BB CM graduated from Merrimack College in N. Andover, Massachusetts with a BS in Medical Technology and completed her MS in Clinical Laboratory Sciences at the University of Massachusetts, Lowell. She has worked as a Medical Technologist for over 30 years. She’s worked in all areas of the clinical laboratory, but has a special interest in Hematology and Blood Banking. When she’s not busy being a mad scientist, she can be found outside riding her bicycle.

Microbiology Case Study: A 31 Year Old Man with History of IV Drug Use

Case History

The patient is a 31 year old man with a history of intravenous drug use with last reported use nine months previous, who reports low back pain. The patient’s symptoms started as a mild pain and progressively worsened over two weeks to the point that he was unable to stand or ambulate. He also developed intermittent radiation of pain to the bilateral lower extremities and associated symptoms of chills and diaphoresis. Blood cultures were sent. MRI showed an epidural abscess at the level of L5-S1. The patient underwent lumbar spinal decompression surgery, and intra-operative cultures were sent for evaluation.

Laboratory Identification

Gram smear of blood cultures showed gram negative bacilli (Image 1). Culture of the abscess specimen and blood cultures showed growth on chocolate, blood, and MacConkey agar; growth on MacConkey plates did not show lactose fermentation (Image 2,3). MALDI-TOF identified this organism as Serratia marcescens.

Image 1. Gram stain of blood culture showing gram negative rods.
Image 2. Blood agar showing large colonies without hemolysis.
Image 3. MacConkey agar showing non lactose fermenting colonies.

Discussion

Serratia marcescens is a motile, facultatively anaerobic, gram negative bacillus of the Enterobacteriaciae family. Some strains of Serratia produce a distinctive brick red pigment, prodigiosin (Image 4), although non pigmented strains are frequently isolated from human infection sites. Serratia marcescens is one of the few Enterobacteriacea that produces DNAse, lipase, and gelatinase. It does not usually ferment lactose. This species is widely present in the environment, including in animals, insects, plants, water, and soil, but unlike other Enterobacteriaciae species it is not a typical component of normal human fecal flora.

Image 4. Colonies of Serratia marcescens producing red pigment. Photo from the CDC Public Health Image Library (https://phil.cdc.gov/Details.aspx?pid=10544).

Eight species of Serratia have been found to cause infections in humans. Of these, >90% are caused by Serratia marcescens (1). This is a rare cause of infection in immunocompetent hosts but can cause opportunistic nosocomial infections, especially following invasive procedures such as such as intravenous catheterization, respiratory intubation, and urinary tract manipulations. The most common infections caused by Serratia marcescens are urinary tract infections, pneumonia,surgical wound infections, eye infections, and bacteremia. Multiple hospital outbreaks of Serratia have been reported, with sources of infection including tap water, soap, blood transfusion products, and injected medications (2). It has also been described as a cause of endocarditis in injection drug users (3).

Serratia is intrinsically resistant to ampicillin, ampicillin-sulbactam, and 1st and 2nd generation cephalosporins due to an inducible, chromosomal AmpC beta-lactamase. Resistance to later-generation cephalosporins may be induced through exposure to these antibiotics, despite not being detected on initial antibiotic susceptibility tests. Thus, susceptibility testing is misleading and thirdgeneration cephalosporins (such as ceftazidime, ceftriaxone, and cefpodoxime) should be avoided for the treatment of Serratia species regardless of in vitro susceptibility.

References

  1. Laupland KB, Parkins MD, Gregson DB, Church DL, Ross T, Pitout JD. Population-based laboratory surveillance for Serratia species isolates in a large Canadian health region. Eur J Clin Microbiol Infect Dis. 2008; 27: 89–95.
  2. Mahlen SD. Serratia infections: from military experiments to current practice. Clin Microbiol Rev. 2011; 24:755.
  3. Mills J., Drew D. Serratia marcescens endocarditis: a regional illness associated with intravenous drug abuse. Ann Intern Med. 1976; 84:29–35.

-Erica Worswick is a pathology student fellow 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.