pathology – Page 27 – Lablogatory

The Lonely Life of a Clinical Pathologist

Have you ever felt like no one knows exactly what you do for a job; friends, family, even your colleagues? As a clinical pathologist, if you are ever asked what your job entails, it might take you a full 10 minutes to just explain the surface of it and by that time your audiences’ s eyes have glazed over and they are wondering when their next coffee break is. It can get pretty lonely when very few people understand your daily life of work.

I currently hold a general clinical pathology position and oversee the microbiology, chemistry, and immunology sections of a community hospital laboratory that services two hospitals totaling a little over 500 beds. I also get consulted on point of care testing and consult at two critical access hospitals that have a general AP/CP pathologist directing their lab.

As a new clinical pathologist, I was asked to blog about my experiences during the first year of working in the real world. I thought it would be a great venue to talk about how I have combatted the “loneliness” I face when I feel like no one knows what I do. Over the next couple of months I will highlight some of the tasks I have undertaken in my current position and I’d also love to hear what other clinical pathologist’s careers look like and/or how they have evolved over the years.

The beauty of a career in clinical pathology was explained to me by an attending during my residency training –you make of it what you want to. He also told me to not venture into the lab because they will ask you to do things, and since I am not very good at following advice, that is exactly the first topic I would like to explore: getting into the lab on a daily basis.

When I was in training, one of the best ideas I took away for my job was microbiology rounds. The first attending I observed holding these was a medical microbiologist that would round through the micro lab every day asking the techs if they had any odd cultures, questions that needed to be answered or anything that required follow up. When I took this job, I knew I wanted to incorporate this type of rounding as part of my work. My office is conveniently located at the back of the microbiology laboratory, so as I walk through the lab, I make it a point to say hi and ask the technologists if they have any issues, or any interesting cultures. It is not a formal rounding, but issues come out of these interactions and give me items to follow up with on a daily basis. Having my office located in the lab also allows the techs to come to me throughout the day with any questions they may have and has established a great rapport between us.

I also round through the chemistry and immunology section of the lab, specifically hitting second shift, as they lack a lot of interaction with clinicians. This has been a harder task for me because my subspecialty training was microbiology. I feel comfortable interacting with the technologists and lab staff, but when I first started I had the fear that I would not know the answer to a question I might be asked. Lucky for me, there are not as many questions that come out of these rounds. But of the questions I have gotten and I did not know the answer, it has never been a problem by me saying “I don’t know off the top of my head, but let me get back to you”. It also helps that I drop off candy in the break room while they wait on me – it is truly amazing how chocolate helps you make friends (thanks for the tip, Mindy Kaling). In addition to troubleshooting, rounding through the lab has given me the opportunity to interact with other people who have a passion for laboratory medicine. The techs will get just as excited about an interesting organism that was isolated or a new instrument we might bring in, and it is great to be able to share that passion you feel for your job with others.

Next month I will discuss a little more about the “formal” interactions I have set in the lab, but for now, let’s hear from you: how do you get involved in the lab and the technologists you work with?

racsa_small

-Lori Racsa, DO, is the director of microbiology, immunology, and chemistry at Unity Point Health Methodist, and a Clinical Assistant Professor at the University Of Illinois College Of Medicine at Peoria. While microbiology is her passion, has a keen interest in getting the laboratory involved as a key component of an interdisciplinary patient care team.

Collaboration is King

In the April issue of Transfusion journal, Joseph et al report their 1½ -year experience with the use of 4 Factor Prothrombin Complex Concentrate (4F-PCC) for urgent reversal of Vitamin K antagonists (Transfus 2016;l 56: 799-807).

As the authors mention, their “…study supports the safety of 4F-PCC for urgent vitamin K antagonist reversal even in unselected patients.”

I highlight this article for several reasons. It is incumbent upon those of us in the clinical laboratory, and especially the Blood Bank/Transfusion Service, to be aware of these new pharmaceutical agents that help provide rapid reversal of anticoagulants and allow for the potential elimination of unnecessary transfusions. I have found that often our clinical colleagues are unfamiliar with these strategies and we must take the lead in helping to establish protocols for their appropriate use. This article speaks, as well, to the need for ongoing evaluation of these drugs in, as they state in their title, the “real-world” of medical practice. Knowing how specific drugs affect outcomes outside of select studies with exclusions of particular patient populations (in this case, those with TE risk) is so valuable to our everyday work.

Another reason that this article is important is it underscores the importance of collaboration. The authors are representatives of departments of Pathology, the School of Medicine and Pharmacy. It is vital that we, as laboratory professionals, push to participate alongside our clinical colleagues in the assessment and implementation of new therapies and adjuvant treatments.

It is obvious from the Transfusion Medicine perspective, that our Pharmacy “friends” play a huge role in patient care, often spearheading and specializing in areas such as anticoagulant reversal strategies, release of factor concentrates, antifibrinolytics, IVIg and albumin. All of these pharmaceuticals can ultimately affect our laboratory testing and our potential interventions. Be certain you have representative from Pharmacy as a member of your Transfusion Committee.

It always pleases me to see, not only excellent literature, but also ongoing collaboration with laboratory professional often at the helm!

Burns

-Dr. Burns was a private practice pathologist, and Medical Director for the Jewish Hospital Healthcare System in Louisville, KY. for 20 years. She has practiced both surgical and clinical pathology and has been an Assistant Clinical Professor at the University of Louisville. She is currently available for consulting in Patient Blood Management and Transfusion Medicine. You can reach her at cburnspbm@gmail.com.

Microbiology Case Study: 47 Year Old Woman with History of Systemic Lupus Erythematosus

Case history

A 47-year old woman with a past medical history of Systemic Lupus Erythematosus (SLE) and liver cirrhosis of unknown etiology was admitted to the hospital for back pain and new onset neurological symptoms. She soon developed pancytopenia and study of her peripheral blood smear showed evidence of thrombotic microangiopathy. ADAMTS-13 inhibitor was negative ruling out thrombotic thrombocytopenic purpura (TTP). She then developed multiple thrombi, including a nonocclusive thrombus in the superior mesenteric vein with extension to the splenic vein as well as a femoral deep vein thrombosis. Her hospital course then became complicated by lupus cerebritis, a small ischemic focus in the left corona radiata and the left medial midbrain, and decompensated liver failure with hepatic encephalopathy. Despite intensive medical treatment, she became hypoxic and hypotensive requiring pressors, and expired in the ICU after several months of hospitalization. The autopsy was performed based on the relative’s request to better understand pathological processes that lead to patient’s demise. The flowing images were obtained from the brain at autopsy (Image 1).

toxo1 — Light microscopy of H&E-stained sections of the hippocampus reveal encysted *Toxoplasma* bradyzoites as well as extracellular *Toxoplasma* tachyzoites in the CA1 region, suggestive of a subacute focal infection.

Discussion

Toxoplasmosis is considered to be a leading cause of death attributed to foodborne illness in the United States. More than 60 million men, women, and children in the U.S. carry the Toxoplasma parasite, but very few have symptoms because the immune system usually keeps the parasite from causing illness.

People typically become infected with Toxoplasma by contaminated food or animal-to human routes of transmission. Toxoplasmosis is not passed from person-to-person, except in instances of mother-to-child (congenital) transmission and blood transfusion or organ transplantation.

Persons with compromised immune systems may experience severe symptoms if they are infected with Toxoplasma while immune suppressed. Persons who acquire HIV infection and were not infected previously with Toxoplasma are more likely to develop a severe primary infection. The diagnosis of toxoplasmosis is typically made by serologic testing. A test that measures immunoglobulin G (IgG) is used to determine if a person has been infected. If it is necessary to try to estimate the time of infection, which is of particular importance for pregnant women, a test which measures immunoglobulin M (IgM) is also used along with other tests such as an avidity test. Due to the high rate of falsely positive Toxoplasma IgM testing, the FDA advises physicians testing pregnant women not to rely on the results of any one positive IgM test as the sole determinant for diagnosis of acute Toxoplasma infection.

Diagnosis can be made by direct observation of the parasite in stained tissue sections, cerebrospinal fluid (CSF), or other biopsy material. These techniques are used less frequently because of the difficulty of obtaining these specimens. Molecular techniques that can detect the parasite’s DNA in the amniotic fluid can be useful in cases of possible congenital transmission.

Clinical correlation

The case patient was at risk for developing toxoplasmosis due to SLE disease, and chronic immunosuppressive therapy that she was receiving for the aggressive course of her illness. However, most likely Toxoplasma gondii organisms seen in the brain parenchyma were in a dormant state due to lack of associated inflammation or architectural distortion. Her neurological decline is most likely related to thrombotic microangiopathy. Opportunistic infection is common in patients with SLE. In some patients, it is difficult to distinguish between the effect of infection and exacerbation of SLE because both can produce similar symptoms. There have been many reports of toxoplasmosis in SLE patients, with conditions such as cerebritis and pericarditis mimicking SLE manifestations.

References
1) http://www.cdc.gov/parasites/toxoplasmosis/

2) Seta N, Shimizu T, Nawata M et al. A possible novel mechanism of opportunistic infection in systemic lupus erythematosus, based on a case of toxoplasmic encephalopathy. Rheumatology (Oxford). 2002;41(9):1072-3.

3) Zamir D, Amar M et al. Toxoplasma infection in systemic lupus erythematosus mimicking lupus cerebritis. Mayo Clin Proc. 1999; 74(6):575-8.

Contributors

Written by Anastasia Drobysheva, MD, 2^nd year Anatomic and Clinical Pathology resident, UT Southwestern Medical Center

Image provided by Bret Evers, MD, PhD, Neuropathology fellow, UT Southwestern Medical Center

-Erin McElvania TeKippe, Ph.D., D(ABMM), is the Director of Clinical Microbiology at Children’s Medical Center in Dallas Texas and an Assistant Professor of Pathology and Pediatrics at University of Texas Southwestern Medical Center.

Show Us Some Skin

Which epidermal layer is indicated by the arrow?

A. Stratum corneum
B. Stratum germinativum
C. Stratum granulosum
D. Stratum lucidum
E. Stratum spinosum

Skin1

The answer is E, stratum spinosum. The stratum spinosum, also known as the prickle cell layer of the skin, is often several cell layers deep, and is located immediately above the stratum germinativum. Cells in this layer are polygonal, and are connected to each other by numerous desmosomes. During fixation, the cell membrane retracts around desmosomal contact points, giving the cells a prickly appearance. The cells contain many bundles of intermediate filaments as well as keratinosomes, which are membrane-bound granules thought to deposit a “toughening” layer on the surface of the cell membrane.

Skin2

The stratum germinativum (also known as the basal layer) is composed of a single layer of cells adjacent of the basal lamina. The cells are tall cuboidal or columnar, and are connected to the basement membrane by hemidesmosomes, and to other cells by desmosomes. Cells in the basal layer are mitotically active, and contain numerous polyribosomes and intermediate filaments.

Skin3

The stratum granulosum is 3 to 5 cell layers thick, and is composed of flattened, polygonal cells arranged with the long axis parallel to the basement membrane. The cytoplasm of these cells contains numerous basophilic granules, called keratohyalin granules, which are thought to be keratin precursors.

The stratum lucidum is not truly a distinct layer of skin, but rather a staining artifact. It is visible in some sections of thick skin as a glassy-appearing, eosinophilic artifact at the bottom of the stratum corneum. It is not present in this particular image of epidermis.

Skin4

The stratum corneum is the outermost layer of skin. The thickness of this layer varies considerably from region to region in the body. The cells of this layer are dead, flattened, and fused together, with completely keratinized cytoplasm.

Skin5

Krafts

-Kristine Krafts, MD, is an Assistant Professor of Pathology at the University of Minnesota School of Medicine and School of Dentistry and the founder of the educational website Pathology Student.

Chief Resident Advice to Junior Residents

I haven’t been able to blog as much of late. It’s been a busy year with more than its fair share above the usual crises that a chief resident is expected to handle – an “August year” for me as my program director put it. But I’ve learned a lot and have been lucky to have the support of my attendings, program coordinator, and program director to help. Even when we’ve not always agreed on what is best for our residents, I’ve always been allowed to speak up for our residents and felt as if our concerns were heard and acknowledged even if policies didn’t go our way. I think that’s the biggest strength of a smaller program–the ability to form strong relationships with mutual respect, whether it is with one’s mentors, peers, or hopefully, both–and I know we will cheer each other on when we hear of each other’s accomplishments in the future even if we won’t see each other daily as we do now because of those bonds we built during these past couple of years. The lessons I’ve learned regarding “soft skills” have been equally as important as the knowledge I’ve gained about my favorite lymphomas or molecular mutations. And four years is really shorter than one might think to fit in all we need to as AP/CP pathology residents, so see it for the gift it is–protected time to grow into the physician you want to be. I see the fruits of these lessons more clearly now as I prepare to graduate. Much of it was obtained through mentorship, formal and informal, from those more experienced and with my best interests at heart.

So here are some pearls I’d like to hand down:

Know thyself as early as possible: Be honest with yourself about your strengths and weaknesses so that you can build on the one while working on the other. As we have now signed on to be life-long learners, identify what works for you early or adjust those learning habits which might have worked before but are no longer working. Designate a couple of hours on a weekend day every week to do learning above and beyond what is expected for your current rotation and consistently stick to it. If you can, designating an hour everyday would be even better and it doesn’t have to be hard core studying like our med school days—you can leisurely read a review article, watch TedMed videos, casually look over boards materials or qbanks from day 1, and so forth as long as you do set aside time consistently. Take advantage of experiential opportunities to help decide early where you see yourself as a physician (academics, private practice, commercial lab, subspecialty, etc) in the future so that you can plan as early as possible your rotations, electives, opportunities, and networking with that goal in mind. But most importantly, knowing who you are, what you believe in, how you work best, and what you want and knowing early, will help you plan and see opportunities earlier. But always, be true to yourself.

Time management is key: Learning to plan early and efficiently is a skill and it takes time to learn. Honestly, I’m not the best on a daily basis unless I take time ahead of time to plan my day, which I don’t always do, but plan to be better about during fellowship. But I do know how to plan effectively to juggle multiple long-term projects with deadlines at a time. You will constantly hear about time management – whether on rotation evaluations or during fellowship interviews. I find that those who are very good at time management, all have checklists and planners (whether hard copy or digital) so maybe they’re on to something there. Whatever works for you, being a deliberate planner ahead of time will serve you well.

Be proactive: In some way, we’ve all be conditioned in a passive learning style where those who are more experienced hand down information to us which we are expected to regurgitate or ruminate on and respond. During residency, we don’t have the strict structure we are used to from medical school as we may be only given loose guidelines but are expected to figure out how best to manage our time on our own. We no longer have every hour planned out for us and so the quicker you learn to plan ahead and effectively use your time while at work, the more time you’ll have for personal activities. Don’t just do the minimum but use gaps in your time during the day to study, to build relationships with mentors with whom to work on book chapters, abstract submissions (for posters/platform presentations at conferences), and publications, to attend conferences/tumor boards outside your rotation even in non-pathology departments, to work with others outside of pathology on interdisciplinary projects. In some ways, these activities are networking without our even realizing it. For the rest of our lives, we will constantly be judged and compared to others by our character and work ethic and that often will include tangible items on our CV whether this is fair or not. Challenge yourself on every rotation by trying to do as much as a junior attending would within the limits of what you are allowed to do and not just the minimum.

Get involved in advocacy: Participate in leadership positions at an organized level–within our professional organizations, with interdisciplinary teams within your hospital, or with volunteer organizations in your community. Bringing about change takes time but if done with a positive goal in mind, can have such a rewarding impact on those we wish to serve as well as yourself. You might discover a previously unknown passion or skill you possess that you can share. Before residency, I was heavily involved with on-the-ground, upstream-minded health equity efforts in immigrant and minority communities. And while I took a hiatus from my work due to residency training, I know that as a future public health pathologist-scientist with both public health and research training, I will return to working to change those systemic and institutionalized societal structures that maintain health inequity within those communities. So it’s now your time to find your passion and to give back. Pay it forward for every good gesture someone has shown you.

Build relationships with mentors: Since I’ve been involved with organized medicine, I’ve always heard the word “networking”. Too me, it always seemed somewhat a Machiavellian “ends justify the means” insincere word but I guess that’s all up to interpretation. What I prefer to say is focus on finding colleagues with whom you share values and passions, who you respect and would like to emulate, and with whom in the future, you might want to collaborate. If your premise is sincere, opportunities always unexpectedly follow has been my experience.

Step outside your comfort zone: As busy physicians-in-training who are used to structure and consistency, it’s good every once in a while to try something new. You never know what you may find–it may even turn out to be a new passion for you. Life is too short and you want to live it without regrets. You want to say when your time comes that you lived life to the fullest and maybe even tried some things that scared but surprisingly made you happy.

Recharge with some “me” time: All work and no play can make any of us dull and cranky. Set aside time to spend with friends (especially non-physician friends) and family and do non-work related activities. Especially when life is getting you down, some time away from thinking about work may be the recharge you need.

Chung

-Betty Chung, DO, MPH, MA is a fourth year resident physician at Rutgers – Robert Wood Johnson University Hospital in New Brunswick, NJ.

Zika Diagnositics in the Media

Today NPR featured a write up about how to test for the Zika virus. While It didn’t delve into the diagnostic testing side of things as much as Lab Medicine’s recent podcast, it does give readers a good overview. In addition, it highlights how critical laboratory professionals and pathologists are to public health and infectious disease prevention.

Listen: Zika Virus Podcast

Dr. Diamond from the Washington University School of Medicine talked with Lab Medicine about all things Zika Virus: a brief history of the virus, modes of transmission, and the implications for laboratory professionals and pathologists.

Give it a listen.

And They Thought it was a Metastatic Tumor

A 74 year old patient presented to the emergency room with a syncopal attack. He had an underlying history of untreated adenocarcinoma of the prostate and reported of a 10 to 15 pound weight loss in the recent months.

CBC revealed pancytopenia with white cell count of 0.4 K/uL, hemoglobin of 9.9 g/dl and platelets of 22 K/uL. The clinical suspicion was widespread metastatic adenocarcinoma.

Review of peripheral smear revealed mostly lymphocytes, one blast and a large cell with very granular cytoplasm and large eccentric nucleus.

aml1 — Peripheral blood, Wright-Giemsa stain. Blast with increased N/C ratio, enlarged nucleus and scant cytoplasm.

aml2 — Peripheral blood, Wright- Giemsa stain. Large cell with eccentric nucleus and hypergranular cytoloplasm, reminiscent of abnormal promyelocyte.

Having reviewed the peripheral smear acute leukemia, likely acute promyelocytic leukemia was considered in the differential diagnosis. As there were no dacrocytes or nucleated red blood cells that were seen on the peripheral smear, it seemed less likely that patient would have metastatic tumor. Bone marrow biopsy was recommended.

aml3 — Bone marrow aspirate, Wright Giemsa stain. Abnormal promyelocytes with lobulated nuclei, Auer rods and hypergranularity.

aml4 — Bone marrow aspirate: Hypergranular promyelocytes with folded nuclei.

Bone marrow apsirate revealed hypercellular particles with numerous abnormal promyelocytes which were lobulated and hypergranular. Both the karytotype and FISH confirmed the presence of t(15;17).

Acute promyelocytic leukemia with t(15;17)(q22;q12);PML-RARA is an AML in which abnormal promyelocytes predominate. Typical forms are hypergranular (like this patient), although hypogranular (microgranular) forms also exist. Morphological review of the smear is the key to ordering the FISH testing for t(15;17). Often patients with APL present are at increased risk of DIC and needed to be treated on a more emergent basis.

Presence of t(15;17) defines the disease and has a significant therapeutic impact. APL has a particular sensitivity to treatment with ATRA , which acts as a differentiating agent. Prognosis of APL treated with ATRA is much more favorable than other acute myeloid leukemias.

Vajpayee,Neerja2014_small

-Neerja Vajpayee, MD, is an Associate Professor of Pathology at the SUNY Upstate Medical University, Syracuse, NY. She enjoys teaching hematology to residents, fellows and laboratory technologists.

Mycobacterium chimaera Infections in Cardiac Surgery Patients

A group of physicians from the University of Iowa have started a dialogue about Mycobacterium chimaera infections in patients who have undergone cardiac surgery. It seems as though the bacteria finds its way to the patients via a heater-cooler device used during their procedure. If you’re a micro tech or a pathologist and you come across a cardiac patient who has a fever of unknown origin, night sweats, loss of energy, and failure to gain weight, M. chimaera is something to keep in mind.

You can read more about this issue in the original blog post from the Iowa infectious disease doctors, Maryn McKenna’s write up over at Nat Geo, and the CDC guidance paper.

Routine Pap Smear from a 33 Year Old Woman

You are reviewing a routine Papanicoloaou smear from a 33 year-old female. She has no complaints and appears healthy. A representative field from her Pap smear is shown here. What organism is the most likely cause of the morphologic changes seen here?

pap1

Chlamydia trachomatis
Human papillomavirus
Trichomonas vaginalis
Leptothrix
Gardnerella vaginalis

The diagnosis in this case is Chlamydial infection. Genital infection by Chlamydia trachomatis is the most common sexually transmitted disease in the world. In women, chlamydial infection of the cervix is frequently asymptomatic, as it was in this patient. If untreated, however, the infection can lead to pelvic inflammatory disease, infertility and ectopic pregnancy.

Chlamydia trachomatis is a tiny, gram-negative bacterium that exists in two different forms: the elementary body, which is the infectious form, and the reticulate body, which is the replicative form. While Chlamydial organisms are too small to be visible with a gram stain, large, glassy inclusions containing both reticulate bodies and elementary bodies are occasionally clearly visible within cells, as seen in the squamous epithelial cells in this image (see arrows).

pap2

Krafts

-Kristine Krafts, MD, is an Assistant Professor of Pathology at the University of Minnesota School of Medicine and School of Dentistry and the founder of the educational website Pathology Student.