The Three Biggest Safety Audit Blunders

There are several potential safety indicators that can be used to help someone assess the effectiveness of a laboratory safety program. The results of a properly performed safety audit can be one of those indicators, and it can provide useful information to a lab safety professional whether he or she is new to the role or has been there for years. You’ll note, however, that the term “properly performed” was inserted, and that was no mistake. Safety audits are performed in laboratories across the world, but in some of these locations the environment remains very unsafe, and performing the audits hasn’t made any difference. Mistakes can be made when performing a laboratory audit, and those errors can lead to dangerous situations. While all audit errors need attention, there are three that can cause the most damage to your lab.

Probably the most common safety audit gaffe is a practice known as “pencil whipping.” This happens when someone quickly marks “yes” on every single item of the safety checklist without really checking for compliance. Pencil whipping occurs for many different reasons. The person performing the audit may be in a hurry, they may feel like they have performed the audit often and just know the answers, or they may just not care about the audit results. Perhaps there is no lab leadership oversight as to how the audit is performed, or maybe the person performing the audit doesn’t understand what the checklist items mean. No matter the reason, this pencil whipping of answers is dangerous. It provides false results, and it masks real safety issues in the department that will likely not have resolution. In an environment where this occurs, a preventable lab injury or exposure is likely to occur, and it could have lasting or even career-altering repercussions for the victims.

Another safety inspection misstep occurs when the person performing the audit begins going down the checklist with pre-conceived assumptions or a specific focus in mind. Some auditors have their minds made up about a lab safety culture before they start, and their version of what they see while inspecting may be skewed. That may cause them to cite a lab falsely and without enough investigation into a particular issue. Some inspectors might be so focused on one thing- chemical labeling, for example – that they miss other obvious safety issues such as trip hazards on the floor. This narrow focus or mindset can limit the effectiveness of a safety audit as it can prevent the auditor from noticing other real hazards in the laboratory.

The third safety audit blunder (and probably the one with the worst consequences) is a failure to follow up on the audit results. In a larger laboratory, a complete lab safety audit can take several hours. It may involve a procedure review, an employee file review, and a look through lab drawers and cabinets as well as a walk-through. However, even if all of the findings from that work is well-documented, it won’t mean anything if there is no follow-up. A failure to review and act upon audit results negates the entire process, no matter how well it was performed. Make sure your lab inspection method includes that final step – someone should review all results and ensure that any safety issues are addressed or resolved as soon as possible. A healthy lab safety cycle will include that review as well as repeat audits to make sure safety compliance is maintained on an on-going basis.

A properly performed audit can speak volumes about the overall lab safety program. If your audit form remains constant, it can be a good idea to train multiple people to perform the audit so the lab can be viewed with fresh eyes each time. Regardless of who performs the safety audit, make sure they refrain from pencil whipping, that their focus is not narrow, and that the person responsible handles the follow up of any safety issues discovered. By avoiding common audit blunders, a positive improvement of the lab safety culture can be assured.

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.

Hematopathology Case Study: A 33 Year Old Man with a Mass Behind the Ear

Case History

A 33 year old man of Japanese ethnicity presents with a 2 month history of a mass behind the right ear. Examination reveals a non-tender local with no other local or generalized adenopathy or hepatosplenomegaly. Laboratory investigations reveal an elevated ESR, serum IgE and peripheral blood eosinophilia. The lesion is excised.

Biopsy Findings

H&E stained sections demonstrate a follicular hyperplasia. The germinal centers demonstrate polarity and tingible body macrophages (A). Focally, follicular centers reveal eosinophilic microabscesses (B, C). Immunohistochemical analysis with an IgE stain reveals deposition in germinal centers (D). A diagnosis of Kimura disease is rendered.

Discussion

Kimura disease, also known as eosinophilic lymphoid follicular hyperplasia is a rare, chronic inflammatory disorder of unknown etiology. While an infectious etiology has been suggested, no pathogen has been identified to be causal, to date. Historically, Kimura disease was considered to be the same as Angiolymphoid Hyperplasia with Eosinophilia (ALHE); however, these entities are not the same.

Generally occurring in Asian males, Kimura disease is most common in the 3rd decade of life and in a head/neck site. It presents as painless, slow-growing adenopathy. An association with nephrotic syndrome has been reported. Peripheral blood eosinophilia, elevated ESR, and serum IgE are common findings. Histologically, nodes reveal hyperplastic follicles with well-formed germinal centers and mantle zones with deposition of IgE and eosinophilic microabscesses, as seen in this case. Perinodal soft tissue may be involved. Necrosis may be present, but is not extensive. Cytologically, FNA material may reveal polymorphous cell population with many eosinophils.

Prognosis is indolent; however, most cases recur after excision and radiation therapy usually yields best outcome.

References:

  1. Zhou P. et al. Kimura disease. Dermatol Online J. 2017 Oct 15;23(10).
  2. García Carretero R et al. Eosinophilia and multiple lymphadenopathy: Kimura disease, a rare, but benign condition. BMJ Case Rep. 2016 Aug 31;2016. pii: bcr2015214211. doi: 10.1136/bcr-2015-214211.
  3. Sun QF et al. Kimura disease: review of the literature. Intern Med J 2008;38:668–72.  

Kamran M. Mirza, MD, PhD, MLS(ASCP)CM is an Assistant Professor of Pathology and Medical Education at Loyola University Health System. A past top 5 honoree in ASCP’s Forty Under 40, Dr. Mirza was named to The Pathologist’s Power List of 2018. Follow him on twitter @kmirza

Potassium Levels in Transgender Women

For transgender women, taking pills of estradiol is insufficient to counteract the endogenous levels of testosterone produced by their bodies. To counteract the undesired testosterone, anti-androgens are employed. These include cyproterone acetate (approved only in Europe) or spironolactone. Spironolactone is a potassium sparing diuretic that could have unintended consequences like gynecomastia.1 This effect comes from off-target binding of spironolactone to the androgen receptor. Like the intended spironolactone target (mineralocorticoid receptor), the androgen receptor localizes to the nucleus when activated and acts as a transcription factor. Taking daily high doses of spironolactone (100mg- 300mg daily) has been shown to be safe,1 but can increase Potassium levels. In a cohort of 55 transgender women, potassium was actually not higher (Figure 1).2 This was the first time a study had rigorously measured electrolytes like potassium in transgender patients. Current guidelines recommended checking electrolyte levels in transgender women taking spironolactone.3 Full electrolytes were included for 126 TW in our study and what we found was not what we were expecting.4

Figure 1.

We found no increased potassium levels in TW who had taken hormone therapy for at least 6 months (p>0.05). However, we did see a decrease in sodium which is consistent with the diuretic effect (p<0.0001, Figure 2).

Figure 2.

We wondered if variability in spironolactone dosing could explain why no significant potassium change was found. Luckily, we had a large number of patients who were taking various doses of spironolactone for comparison. One-way ANOVA with Tukey post-hoc tests revealed no difference in potassium levels (p>0.05)- even between the lowest (0mg daily) and highest dose (200-300 mg daily) (Figure 3). While the sodium level trended to decrease with higher spironolactone, it was not statistically significant.

Figure 3.

One reason that potassium levels did not increase is a difference in study populations. The original population studied for spironolactone involved patients with heart failure and hypertension whereas our study’s population was mostly in their 20’s and 30’s with very few co-morbid conditions.

Although sodium levels are decreased, they did not fall below the lower limit of normal (135 mmol/L). Low sodium would put transgender women at risk of dizziness and syncope (passing out) from low blood pressure. Thus, the takeaway is: sodium should be clinically monitored as it can decrease in transgender women.

References

  1. Clark E. Spironolactone Therapy and Gynecomastia. JAMA. 1965;193(2):163-164.
  2. Roberts TK et al.  Interpreting Laboratory Results in Transgender Patients on Hormone Therapy. The American Journal of Medicine. 2014; 127(2): 159-162.
  3. Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, et al. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2017
  4. SoRelle JA, Jiao R, Gao E et al. Impact of Hormone Therapy on Laboratory Values in Transgender Patients. Clin Chem. 2019; 65(1): 170-179.

-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.

Whether or Not to Report Cytoplasmic Pattern of ANA IFA

Anti-nuclear antibody (ANA) test is commonly used to screen for systemic rheumatic disease. Indirect immunofluorescence assay using HEp-2 cells as substrate, containing approximately 100-150 autoantigens, is still the gold standard for ANA testing (1). Although the test name refers to only anti-nuclear antibody, there are often cytoplasmic staining patterns overserved in this assay. Cytoplasmic patterns result from antibodies against cytoplasmic components, like Jo-1 or Ribosomal P, and have clinical association with various systemic autoimmune disease, like polymyositis, systemic lupus erythematosus or primary biliary cirrhosis.    

There is no standardized recommendation regarding how to report cytoplasmic pattern on ANA IFA, and laboratories independently decides whether to indicate cytoplasmic pattern in their result.  The International Consensus on ANA Patterns (ICAP) workshop discussed this topic in 2015 and proposed two approaches for reporting ANA cytoplasmic patterns (2). Either to regard cytoplasmic pattern as positive or negative, both approaches recommended to include a statement of cytoplasmic staining.

We encountered cases in our laboratory in which reporting cytoplasmic staining had significant clinical values, and our laboratory started to report cytoplasmic staining as an additional comment in the test result a few years ago. Here is one of these cases:

Case: 35 year old woman with a history of hypertension complained about increasing muscle pain, weakness, and swelling. She had difficulties to raise her arms and had multiple falls, and was admitted to hospital three time for rhabdomyolysis. Her initial laboratory assessment were, CK >11,196 U/L, lactic acid 2.5 mmol/L, ALT 152 U/L, AST 416 U/L, and ALKP 42 U/L. Her ANA IFA test didn’t shown any nuclear staining, but there is very strong cytoplasmic staining observed. The clinician was suspecting inflammatory myositis and ordered myositis autoantibody panel to follow up. This panel detects numerous antibodies that are either specific or associated with inflammatory mycosis.

Her myositis autoantibody test result was positive for antibodies against signal recognition particle (SRP). SRP is an abundant, cytosolic, universally conserved ribonucleoprotein that targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes. Antibodies against SRP have been found in 5-8% of adult idiopathic inflammatory myopathies and <1% juvenile myopathies. It is closely associated with necrotizing myositis. Clinically it presents with acute onset, rapidly progressive, severe weakness, with high CK levels and commonly has cardiac and lung involvement. 

Clinically significant antibodies can be present in patients with connective tissue disease that may appear as strong cytoplasmic staining on screening ANA test. It would be helpful to add a comment in these cases to aid the clinician in pursuing further work-up with a strong clinical suspicious of connective tissue disease.

References:

1. Position Statement: Methodology of Testing for Antinuclear. Antibodies American College of Rheumatology. 2009.

2. Damoiseaux J, et al. International consensus on ANA patterns (ICAP): the bumpy road towards a consensus on reporting ANA results. Auto Immun Highlights. 2016 Dec;7(1):1. doi: 10.1007/s13317-016-0075-0. Epub 2016 Jan 30.

Xin-small

-Xin Yi, PhD, DABCC, FACB, is a board-certified clinical chemist, currently serving as the Co-director of Clinical Chemistry at Houston Methodist Hospital in Houston, TX and an Assistant Professor of Clinical Pathology and Laboratory Medicine at Weill Cornell Medical College.

Just Culture: Growing Trend or Lab Requisition?

Hello again everyone!

Last month, I discussed some really interesting topics at the intersection between psychiatry and pathology—two fields that aren’t exactly the closest; more so “diverged” in the hospital milieu as if in a poem by Robert Frost. This month I’d like to bring the conversation back to a topic I’ve addressed before: improving multidisciplinary medicine and creating a Just Culture in medicine.

Not exactly culture with a swab or agar dish, a Just Culture is an all-encompassing term for system-based thinking and process improvement not at the expense of individuals. In a post I made last July, the topic of high reliability organizations (or HROs) is one that addresses communication and accountability in high stakes environments—like healthcare!

Just Culture isn’t a stranger to lab medicine. The American Society of Clinical Laboratory Science (ASCLS) published a position paper in 2015 utilizing this trending healthcare buzzword. On the subject of patient safety, ASCLS believes “Medical Laboratory Professionals must adopt a ‘fair and just culture’ philosophy, recognizing that humans make errors, and understanding the science of safety and error prevention.” (Source: ASCLS 2015, https://www.ascls.org/position-papers/185-patient-safety-clinical-laboratory-science) We all know how we maintain patient safety in the lab, right? We do that through quality control, QA measures, competencies (both internal and from accrediting bodies like CAP), and continuing education. Raise your hand if your lab is getting inspected, just finished getting inspected, will be inspected soon, or if you’ve recently done competency/proficiency testing yourself, CE courses for credentialing, or are reading this blog right now! We’re all “continuing” our education in health care ad infinitum because that’s how it works—we keep learning, adjusting, and ensuring best practices concurrent with the latest knowledge. And, instead of punishing lab professionals when we make errors, we try to be transparent so that each error is a learning opportunity moving forward.

Image 1. I’d panic too if my lab was being inspected by 007. What, you wouldn’t?

I’m currently in my OB/GYN rotation at Bronx-Care and during the most recent Grand Rounds we had someone talk about “Just Culture”—a sort of continuation on the themes of the same lecture series that inspired my article on HROs. Essentially, the theme is that disciplining employees for violating rules or causing error(s) in their work is less effective than counseling, educating, and system-oriented and best-practice-informed care. In this talk, we watched a short video (embedded below) which walked us through approaching faults or errors in medicine in a way that empowers and educates. A story from MedStar Health, a Maryland-based health system, demonstrates how systems-based thinking can be the best way to solve problems in healthcare.

Video 1. “Annie’s Story” has become a widespread example of Just Culture for nearly twenty years. Being serious about high reliability and just culture means adopting a system’s approach to analyzing near misses and harm events—shame and discipline are becoming antiques. Learn more about Quality and Patient Safety (http://ow.ly/M1aZk) and Human Factors Engineering in Healthcare (http://MedicalHumanFactors.net)

Annie, a nurse in the MedStar Hospital system, is the spotlight story in this video. She came across an error message on a glucometer after checking someone who was acutely symptomatic. She double checked it and made clinical decisions, with her providing team, to give insulin. This sent the patient into a hypoglycemic event which required ICU support. In the story, she was actually suspended and reprimanded for her “neglect”—other nurses made the same error just days later. This prompted some action, inciting nursing managers and other administrators to investigate further, ultimately involving the biomedical engineers from the company to weigh in on this systemic fault in glucose POCT. Annie returned to work, and the problem was recognized as not user-error, but system error; she went on to talk about how she felt unsure of her clinical competency after being reprimanded. Imagine if you accidentally reported the presence of blast cells in a manual differential in a pediatric CBC while you were alone on a night shift only to find out from the manager on days that you made a pretty big mistake with clinical implications. Then imagine you were suspended for a few weeks instead of simply asked to explain and identify opportunities to increase your knowledge. Pretty harsh, right? I’m glad the MLS who did that didn’t lose his job and only had to do a few more competency trainings…yep.

Fine. It was me. I mentioned mistakes in my discussion on HROs and discussed that particular mistake in part of a podcast series called EA Shorts with a clinical colleague of mine. Everyone makes mistakes, especially in training, and that’s okay! It’s how we deal with them that matters.

Image 2 (a, b). Take a look at that glucometer. Would you have caught the error? Did you catch the “LO” value in the background vs. the out-of-range foreground prompt? Or was the screen prompt as distracting for you as it was for Annie? Who was responsible for this error: nurse, lab, or engineer?

Anyone else notice a stark absence of professional laboratory input in the video? I assume many of you sharp-sighted lab automation veterans didn’t miss the glaring “LO” behind the dialogue box on the glucometer. And, to me, that begs the question: was there any lab input on this instrument, its training, or its users? Nurse Annie made a mistake—but she’s not alone, according to a Joint Commission study from November last year, close to 11% of users make mistakes when prompted with error messages compared to 0% of users misinterpreting normal values on screens of a particular model of glucometer. And that’s just one type of instrument. Imagine 1 in 10 nurses, medical assistants, or patients misinterpreting their glucose readings. (Source: The Joint Commission Journal on Quality and Patient Safety 2018; 44:683–694 Reducing Treatment Errors Through Point-of-Care Glucometer Configuration) This should also be a good opportunity to remind us all of CLIA subpart M, the law that outlines who can accredit, use, and report point-of-care results. Herein lies another problem, stated well by the American Association for Clinical Chemistry (AACC) in 2016, “… another criteria for defining POCT—and possibly the most satisfactory definition from a regulatory perspective—is who performs the test. If laboratory personnel perform a test, then this test typically falls under the laboratory license, certificate, and accreditation, even if it is performed outside of the physical laboratory space, and regardless of whether the test is waived or nonwaived. On the other hand, waived or nonwaived laboratory tests performed by non-laboratory personnel are nearly always subject to a different set of regulatory and accreditation standards, and these can neatly be grouped under the POCT umbrella,” and that can mean trouble when we’re all trying to be on the same clinical page.

In previous posts, I’ve mentioned the excellent knowledge contained within the Lab Management University (LMU) program. One of the modules I went through discussed this topic exactly: Empowerment as a Function of Leadership and Peak Performance. In short, if we want to be good leaders in the lab, we have to set expectations for positive patient outcomes, including safety. Good leadership should empower their staff with education, support, and resources. Poor management can create toxic environments with staff that can be prone to mistakes. If we can be dynamic leaders, who adapt to ever-improving best practices and respond with understanding and compassion to mistakes, then our colleagues become just as reliable as your favorite analyzer during that CAP inspection I mentioned.

Image 3. LMU class module for promoting Just Culture and inciting positive behavior in your department.

I often get clinician input about how the processes between the bedside and the lab can be improved. Often, they include comments about the need to share relevant clinical data for improving diagnostic reporting or improving a process between specimen collection and processing. But what often gets left out is the human element: the scientist behind the microscope, the manager behind the protocol, and the pathologist behind the official sign out report. Let’s continue to incorporate all of the feedback our colleagues provide while maintaining a safe and empowered culture for ourselves, our staff, and our patients.

What do you think? How does your lab, hospital, clinic, etc. address POCT safety or patient safety at large? Do you operate within a Just Culture? Share and comment!

Thanks and see you next time!

–Constantine E. Kanakis MSc, MLS (ASCP)CM graduated from Loyola University Chicago with a BS in Molecular Biology and Bioethics and then Rush University with an MS in Medical Laboratory Science. He is currently a medical student actively involved in public health and laboratory medicine, conducting clinicals at Bronx-Care Hospital Center in New York City.

Working With Baby Boomers: How Other Generations Can Adapt

Baby Boomers were for a long time to largest working generation in the workplace. They are slowly retiring and the next largest generation, Generation Y, is becoming the largest. However, Baby Boomers’ impact on the workplace is still profound and most organizations, if not all, are currently employing many Boomers. They are likely to be working in leadership roles and exert influence on many policies, procedures, systems, and organizational cultures.

Similar to Traditionalists, Baby boomers also appreciate face-to-face meetings. However, their preference for leaving and receiving voicemails is a lot higher than Traditionalists. They also appreciate social media more, especially as their children and grandchildren are using it. Baby Boomers utilize the internet more than Traditionalists and send text messages, even if they still prefer to talk over the phone instead of texting.

Working with Baby Boomers is all about the relationship. Establishing interpersonal connection should therefore be one of your main priorities when collaborating with someone from this generation. Because of the personal nature of their working style, it can sometimes take a few weeks (or longer) for decisions to be made. Calculate that in when working on a proposal or project. Baby Boomers appreciate formal presentations and a consensus-based process.

A Baby Boomers’ approach to leadership centers on incentives, data-driven decisions, and a democratic process. They typically are open to input from peers and their leadership style is friendly. They value receiving recognition, so any award or reward is appreciated and they will often display them publically. Because of their focus on interpersonal relationships, they do not respond to people who are not friendly and who indicate their hierarchy. Instead, make sure that they feel you are listening to them and including them. One way to do this is by taking notes and asking follow up questions.

Baby Boomers’ professional dream is continuing to be useful and productive in the workplace while feeling they are wanted and rewarded. If you want to increase your working relationship with Baby Boomers, connect with them on an interpersonal level by inviting them out to lunch and get to know who they are outside of the workplace. Provide them with positive affirmations, recognitions, and awards to make them feel they are a valued members of the organization and that they input and work is essential to producing results. Baby Boomers bring a lot of patients, experience, and knowledge and they help create and foster a team environment when they feel they are contributing members of the organization. Do not show impatience and question their ways of doing things openly. If you do need them to change something, include them in the process to make it a consensual and democratic process. Adding a Baby Boomer to a team can greatly improve the outcomes and success of that team.

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.


I’d like to tell you a story that happened at the ASCP Annual Meeting last October, 2018 in Baltimore.

Lotte Mulder and I presented a course on “Discovering Your Diversity Strengths” to about fifty people. Lotte is a Millennial and I am a Baby Boomer, and we’ve been working closely together for over three years on a daily basis. The presentation went really well and the audience was very participative and interactive. We talked about how different we were, how we complimented each other, and the value of human diversity in the workplace. 

At noon that day, we both participated in a Lunch Roundtable where the topic was Diversity in the laboratory. We quickly learned that those at our table had a strong interest and frustration about working with people from different generations. The focus was primarily on Millennials and Boomers. There were eight other people at our table and they each shared their frustration about working in the lab with either older or younger people.

This was a real opportunity for us to share the generational strengths and differences with each of these people. The Boomers seemed to think that the Millennials didn’t have a good work ethic. The more I asked questions of those in both generational groups, the more I was able to help them to share their opinions and/or frustrations. Most importantly, I made a point of asking each person what was important to them in the workplace.

The Millennials learned that the Boomers were “bred” to work beyond the expectations of their job. Most importantly, they found their identity in their work. This is one reason the “Boomer co-worker” delayed their retirement because of the fear of losing their identity.

The Boomers learned that the Millennials had a very good work ethic, they just valued work-life balance. It was actually Generation X that introduced work life balance to the workplace and the Millennials bought into the concept. The other strength of the Millennial is their passion for finding a purpose in their job.

By the time our hour was up, you could see the difference in how they related to each other. It’s amazing what education and awareness can do for people.

As a final note, the next day we co-taught a course on Stress Management. Wouldn’t you know it, we experienced the same situation at our “Stress Management Roundtable” lunch! It was fun to see how people began to see their co-workers through a different lens.

Stakenas-small

-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.  

Hematopathology Case Study: A 60 Year Old Man with Recurrent Bronchitis

Case History

60 year old man with recurrent bronchitis and extensive smoking history underwent CT scan. The CT scan showed an incidental finding of a 2.2 x 1.4 cm anterior mediastinal mass.

Excision

H&E4x
H&E 4x
H&E10x
H&E 10x
H&E20x
H&E 20x
cytokeratin cocktail
Cytokeratin cocktail
CD3
CD3
CD20
CD20
TdT
TdT

Diagnosis

The tissue shows nodules of epithelial cells in a lymphocyte-rich background. The epithelial cells have round to somewhat spindle shaped nuclei, vesicular chromatin and small mostly inconspicuous nucleoli. There is no high grade cytologic atypia, mitotic figures or necrosis seen. The nodules contain very few interspersed lymphocytes, but are surrounded by abundant lymphocytes which are small and mature appearing. A cytokeratin cocktail highlights the epithelial nodules and shows an absence of epithelial cells in the lymphocyte-rich areas. CD20 highlights stromal B-lymphocytes around the epithelial nodules which are arranged in follicles. CD3 highlights stromal T-lymphocytes, which surround the B-cell follicles and the epithelial nodules. TdT highlights only a very small subset of immature T-cells which are found scattered around the rim of the epithelial cell nodules. Overall, the findings are consistent with a micronodular thymoma with lymphoid stroma.

Discussion

The differential diagnosis for an anterior mediastinal mass includes thymoma, lymphoma, germ cell tumors, neurogenic tumors and benign cysts among other less common entities. Patients usually present with cough, chest pain, fever/chills or dyspnea and localizing symptoms are generally secondary to local tumor invasion. Typically, CT scans are the best modality to evaluate the mediastinum. Thymomas are the most common primary neoplasm of the anterior mediastinum, but are less than 1% of all adult malignancies. Patients are generally over 40 years old and between 30-50% of patients with a thymoma have myasthenia gravis, which occurs more frequently in women.1

The WHO has classified thymomas into 5 categories based on the morphology of the neoplastic epithelial cells along with the lymphocyte to epithelial cell ratio. Type A thymomas are composed of bland spindle/oval tumor cells with few or no admixed immature lymphocytes. Type B1 thymoma resembles normal thymus and has scattered epithelial cells in a dense background of immature T-cells. Type B2 thymoma is composed of epithelial cells in small clusters with a lymphocyte-rich background. Type B3 thymoma is primarily composed of mild to moderately atypical epithelial tumor cells in a solid growth pattern with few intermingled immature T-cells. Type AB thymomas are composed of lymphocyte-poor spindle cell (Type A) components as well as lymphocyte-rich (Type B) components.2

Micronodular thymoma with lymphoid stroma (MTWLS) is a rare type of thymoma and accounts for only 1% of all cases. Patients tend to be asymptomatic and the finding is usually incidental. The tumor tends to be well circumscribed and encapsulated with a tan cut surface. The histopathology is characterized by solid nests or nodules of epithelial tumor cells in a background of abundant lymphoid stroma. The tumor cells are bland spindle or oval cells without significant atypia or mitotic activity. The epithelial tumor cells are positive for pancytokeratins. The lymphoid stroma typically lacks keratin positive cells and consists of predominantly CD20 positive mature B-cells in follicles with admixed CD3 positive and TdT negative mature T-cells. There is typically a population of rare TdT positive immature T-cells that surrounds the epithelial nodules, as seen in this case. 2

Due to the rarity of MTWLS with only 74 cases reported since the first case described in 1999, there is limited data on its pathophysiology and prognosis. However, most cases are diagnosed as stage I/II disease according to the Masaoka-Koga staging criteria, involving only micro or macroscopic invasion into thymic or surrounding fatty tissue without invasion into neighboring organs.  Patients tend to have a very favorable prognosis with most patients alive without recurrence or metastasis many years after diagnosis.3

References

  1. Juanpere S, Cañete N, Ortuño P, Martínez S, Sanchez G, Bernado L. A diagnostic approach to the mediastinal masses. Insights Imaging. 2012;4(1):29-52.
  2. Travis WD, Brambilla E, Burke AP, et al. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart (Revised 4th edition). IARC: Lyon 2015.
  3. Qu L, Xiong Y, Yao Q, Zhang B, Li T. Micronodular thymoma with lymphoid stroma: Two cases, one in a multilocular thymic cyst, and literature review. Thorac Cancer. 2017;8(6):734-740.

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