The Utility of Flow Cytometry in Establishing the Correct Diagnosis of a Rare Aggressive Lymphoma

Case history

A 73 year old woman presented with shortness of breath and was found to have bilateral pleural effusions. She had a history of marginal zone B-Cell lymphoma involving the bone marrow, which was diagnosed 3 months before this presentation and was treated with Rituximab.

Thoracentesis revealed an atypical lymphoid population comprised of intermediate and large sized cells with eccentrically placed nuclei, multiple prominent nucleoli and scant to moderate amounts of basophilic cytoplasm (Image 1). Initial evaluation of the cytology material was concerning for large-cell transformation of the patient’s previously diagnosed marginal zone B cell lymphoma. A representative portion of the fine needle aspirate sample was sent for flow cytometric immunophenotyping.

Image 1. Cytology (Diff Quik, 400X). The atypical lymphoid population is comprised of intermediate and large sized cells with eccentrically placed nuclei, multiple prominent nucleoli and scant to moderate amounts of basophilic cytoplasm.

Flow cytometric immunophenotyping showed a distinct population of atypical cells with moderate CD45 expression and increased side scatter in keeping with cytoplasmic complexity (Figure 1, black arrows). On an initial screening B cell lymphoma panel these cells were negative for CD19 and positive for CD30 (partial), and CD44 (Figure 2).

Figure 1. The neoplastic population shows expression of CD30 and CD44.

The population of interest lacked expression of CD10, CD20, CD22 and surface immunoglobulin light chains and CD138 (Figure 2 and 3).

Figure 2. The neoplastic population lacks expression of CD10, CD19, CD20, and CD22.
Figure 3. The neoplastic population of cells are negative for surface immunoglobulin light chains and CD138.

CD30 expression prompted the investigation of additional T-cell markers to rule out a T cell lymphoma (Figure 4). This population showed dim expression of CD7 but was otherwise negative for pan T cell markers (CD2, CD3, CD5) as well as CD4 and CD8 (Figure 4).

Figure 4. The neoplastic population of cells are positive for CD7 (dim) and CD30 and negative for CD3, CD4, CD8, and CD26.

Given the unusual immunophenotype of the neoplasms, a diagnosis of diffuse large B cell lymphoma (transformation of the known marginal zone lymphoma) seemed less likely and other possibilities were considered.

The presence of CD30 expression and the plasmablastic morphologic features together with the clinical presentation with effusions raised the possibility of primary effusion lymphoma. IHC for anti-HHV8 was performed on the cell block sample (Image 2).

Image 2. Cytology (cell block 400X) A. Hematoxylin and eosin stain of the cell block reveals large, atypical lymphoid cells; Small and large atypical lymphoid cells are highlighted by CD30 (B), HHV8 (LANA-1) (C), and CD138 (focally) (D).

Final diagnosis  

Primary effusion lymphoma (HHV8 positive).

Discussion

Primary effusion lymphoma (PEL) is a large B-cell neoplasm usually presenting as serous effusions without a detectable tumor mass [1]. It is universally associated with the human herpesvirus 8 (HHV8). It usually occurs in the setting of immunodeficiency [2]. Some patients with PEL secondarily develop solid tumors in adjacent structures such as the pleura [3-5].

Immunophenotype of PEL:

POSITIVE: CD45, HLA-DR, CD30, CD38, VS38c, CD138, EMA, HHV8 (LANA1).

NEGATIVE: pan- B-cell markers (CD19, CD20, and CD79a), surface and cytoplasmic Ig, and BCL6.

PEL is usually negative for T/NK-cell antigens, although aberrant expression of T-cell markers may occur. PEL is usually positive for EBV-encoded small RNA (EBER) by in situ hybridization but negative for EBV latent membrane protein 1 (LMP1) by IHC.  This could be explained by EBV virus latency. It is ability of a pathogenic virus to lie dormant (latent) within a cell, denoted as the lysogenic part of the viral life cycle. EBV expresses its genes in one of three patterns, known as latency programs. EBV can exhibit one of three latency programs: Latency I, Latency II, or Latency III. Each latency program leads to the production of a limited, distinct set of viral proteins and viral RNAs. The Epstein-Barr virus encoded RNAs (EBERs): EBER1 and EBER2 are expressed during all latency forms [6], whereas LMP1 is expressed only in latency 2 and 3 rendering it a less sensitive marker for detection of EBV infection. EBV-negative PEL is common in elderly, HIV-negative patients from HHV8-endemic regions (Mediterranean) [7].

Differential Diagnosis

Most common cavities involved by PEL: pleural, pericardial, and peritoneal [8-10].

It was thought that PEL can involve an artificial cavity related to the capsule of a breast implant [11] although it was described only in one case report without appropriate HHV8 staining and before recognition of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), which this case probably was presenting [12].

Primary effusion lymphoma (PEL) Prognosis

The prognosis is very unfavorable. Median survival is < 6 months. Rare cases have been reported that responded to chemotherapy and/or immune modulation [13].

Flow Cytometry Utility

The importance of utility of flow cytometry in establishing a diagnosis of PEL has been previously shown by others [14]. In the series by Galan et al. the authors described a case of PEL in an 88-year-old HIV-negative female with right-sided pleural effusion without significant lymphadenopathies or other effusions. The cytological study of the pleural fluid revealed a dense proliferation of large plasmablastic cells. A six-color multiparametric flow cytometry immunophenotyping study revealed 45% of large in size and high cellular complexity cells positive for CD45 (dim), CD38, CD138, CD30 and HLA-DR; and negative for CD19, CD20, cytoplasmatic CD79a, surface and cytoplasmic light chains Kappa and Lambda, CD3, CD4, CD5, CD7, CD8, CD28, CD56, CD81, and CD117. In situ hybridization for EBV-encoded small RNA was negative and immunohistochemistry for Kaposi sarcoma herpesvirus (HHV8) confirmed the diagnosis of PEL. These results in addition to the current case highlight the utility of flow cytometry in the diagnosis of lymphomas involving body cavities.

In Summary

PEL is associated with a proliferation of large B-cells which are positive for HHV8, CD45 (dim), CD30, CD38, and CD138 and negative for lineage defining B cell markers (CD19, CD20, and CD79a). Although PEL is a very rare lymphoma, it is important to consider it in patients with pleural, pericardial, and peritoneal effusions by sending a sample for cytological examination and flow cytometric immunophenotyping. Due to the absence of a mass lesion, cytology and flow cytometry are essential for establishing the diagnosis of PEL.

References

  1. Said, J.a.C.E., Primary effusion lymphoma, in WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition), C.E. Swerdlow SH, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Editor. 2017: Lyion. p. 323–324.
  2. Song, J.Y. and E.S. Jaffe, HHV-8-positive but EBV-negative primary effusion lymphoma. Blood, 2013. 122(23): p. 3712.
  3. Dotti, G., et al., Primary effusion lymphoma after heart transplantation: a new entity associated with human herpesvirus-8. Leukemia, 1999. 13(5): p. 664-70.
  4. Jones, D., et al., Primary-effusion lymphoma and Kaposi’s sarcoma in a cardiac-transplant recipient. N Engl J Med, 1998. 339(7): p. 444-9.
  5. Luppi, M., et al., Molecular evidence of organ-related transmission of Kaposi sarcoma-associated herpesvirus or human herpesvirus-8 in transplant patients. Blood, 2000. 96(9): p. 3279-81.
  6. Khan, G., et al., Epstein Barr virus (EBV) encoded small RNAs: targets for detection by in situ hybridisation with oligonucleotide probes. J Clin Pathol, 1992. 45(7): p. 616-20.
  7. Dupin, N., et al., Distribution of human herpesvirus-8 latently infected cells in Kaposi’s sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma. Proc Natl Acad Sci U S A, 1999. 96(8): p. 4546-51.
  8. Otsuki, T., et al., Detection of HHV-8/KSHV DNA sequences in AIDS-associated extranodal lymphoid malignancies. Leukemia, 1996. 10(8): p. 1358-62.
  9. DePond, W., et al., Kaposi’s sarcoma-associated herpesvirus and human herpesvirus 8 (KSHV/HHV8)-associated lymphoma of the bowel. Report of two cases in HIV-positive men with secondary effusion lymphomas. Am J Surg Pathol, 1997. 21(6): p. 719-24.
  10. Beaty, M.W., et al., A biophenotypic human herpesvirus 8–associated primary bowel lymphoma. Am J Surg Pathol, 1999. 23(8): p. 992-4.
  11. Said, J.W., et al., Primary effusion lymphoma in women: report of two cases of Kaposi’s sarcoma herpes virus-associated effusion-based lymphoma in human immunodeficiency virus-negative women. Blood, 1996. 88(8): p. 3124-8.
  12. Lyapichev, K.A., et al., Reconsideration of the first recognition of breast implant-associated anaplastic large cell lymphoma: A critical review of the literature. Ann Diagn Pathol, 2020. 45: p. 151474.
  13. Ghosh, S.K., et al., Potentiation of TRAIL-induced apoptosis in primary effusion lymphoma through azidothymidine-mediated inhibition of NF-kappa B. Blood, 2003. 101(6): p. 2321-7.
  14. Galan, J., et al., The utility of multiparametric flow cytometry in the detection of primary effusion lymphoma (PEL). Cytometry B Clin Cytom, 2019. 96(5): p. 375-378.

This case was previously presented by authors as eCSI Case on International Clinical Cytometry Society website.  For more information please follow: https://www.cytometry.org/public/newsletters/eICCS-10-1/article7.php

-Dr. Loghavi is an Assistant Professor of hematopathology and molecular pathology MD Anderson Cancer Center in Houston, TX. She received her MD degree from the Azad University in Tehran, Iran. Shen then completed an Anatomic and Clinical Pathology residency training at Cedars Sinai Medical Center in Los Angeles, CA, followed by Surgical pathology, Hematopathology and Molecular pathology fellowship training at the University of Texas, MD Anderson Cancer Center. Dr. Loghavi is passionate about medical education. Her clinical and research interests are focused on hematologic malignancies, with particular focus on myeloid neoplasm and the applications of flow cytometric immunophenotyping and molecular methods in detection of minimal/measurable residual disease. She has authored 100 peer-reviewed articles, 5 book chapters, and numerous abstracts in the fields of hematopathology and molecular pathology. 

-Kirill Lyapichev, MD, FASCP, is a board-certified anatomical and clinical pathologist who completed 2 years of hematopathology fellowship at MD Anderson Cancer Center. He is currently a molecular genetic pathology fellow at MD Anderson Cancer Center. Additionally, he is interested and involved in other research projects including neoplastic as well as non-neoplastic entities: MALT lymphoma, Castleman Disease, Kikuchi-Fujimoto Disease, and others. In 2020 he was selected as one of ASCP’s 2020 Top 40 Under Forty. Follow him on Twitter: @KirillLyapichev.

Dr. Who?

Welcome back everyone!

Thanks for reading my piece last month on liquid biopsies. And, as a side note, there is a growing number of awesome quality content and posts from pandemic response, to inclusion, alongside COVID and case-studies so subscribe, share, and add this page to your bookmarks—STAT! Lablogatory has been a fantastic platform to share and learn so much in this past year, I could barely keep up!

Or super-STAT if you’re one of those people…but hey, that language belongs to all of us! Lab professionals, nurses, scientists, and doctors alike. And this month, I just want to take a quick moment to celebrate a milestone.

I’m officially a resident physician/trainee, medical post-graduate! (There was confetti falling just now on my end, not sure about yours, but work with me here.) It’s just one of those life-goals that feels great when you get there. But there’s a lot more to it than it seems…if I told you being a pathology resident means sacrificing early adulthood, amassing soul-crushing debt, and explaining to your peers and colleagues what it is exactly you do and why you also bear the moniker of “physician,” you’d delete that bookmarked webpage faster than I can make you scroll through this thing.

(oh good you’re still here!)

All that said, I’ve got to say: it’s worth every single bit of it. Times a million. But I really did mention some red flags that, were we discussing any other work environment, would make you definitely think twice before committing 5-10 years of your life. Furthermore, as a PGY-1 in pathology, I could stand next to any other patient-facing PGY-1 colleague (read: intern) and they wouldn’t have the faintest about what I actually do. Listen, the “lifestyle” specialty, generally 9-5er, no weekend, no 24hr call isn’t something I’m shy to celebrate, but it’s not the whole story. I’ve matched and started learning and working at a great institution with great faculty, mentors, and other residents/fellows. Bottom line: I’m more than a little happy about where I’m at professionally.

Image 1. Most path & lab med residents get cubicle-style desks to spend time reading, prepping, writing, learning, and previewing cases between responsibilities in sign-outs, tumor boards, or OR/gross room work. Most of my non-path friends don’t like this. It makes me very happy.

So, to my non-pathology friends, what is it exactly that I do during my residency training while you might be busy rounding, managing glucose levels, triaging cases, putting orders in—you know, regular intern stuff *shudders* … (pathology trainees don’t have an intern year, we jump right into the specialty and go for 3-4 straight on through). Like most of you I have a transition period where I get acclimated to the workload and patterns of my specific residency, but sans-anno-interna, I’ve got lots of work ahead to climb the steep learning curve that med school pathology merely skims.

What does non-patient-facing mean, exactly?

Well, without an intern year you jump right into what most path residents go into which is a 4-year combined anatomic and clinical pathology (AP/CP) track. You immediately begin training in all the fields in pathology. They include surgical pathology (of various sub specialties like head-and-neck, gynecologic, gastrointestinal, thoracic, neuro, etc.—think surgery, then add pathology), autopsy training, dermatopathology, cytopathology, hematopathology, transfusion medicine, clinical chemistry, microbiology, hemostasis and coagulopathy, pediatric pathology, forensic pathology, molecular, training as a laboratory director, and much, much more. Each of these services has a workload which is usually comprised of cases from biopsies and grossed specimens for histologic analysis (anatomic pathology) or the ongoing maintenance and advancement of clinical diagnostic testing through laboratory methods and management of staff/resources (clinical pathology).

Image 2. August 2019 Issue of The Pathologist magazine. Pathologists, medical students, microscopes, you get it…Specifically, that’s one of my mentors (and now faculty) Dr. Kamran Mirza and (then) medical student Austin McHenry discussing the critical role pathology plays in every circle of medical care.

When I say “non-patient facing” this means that the majority of that work is not done in 1-on-1 settings with patients in a clinic or hospital floor. It is done ancillary to their clinical experience whereby pathology attendings manage the simultaneous training of residents and processing of case sign outs for rapid and accurate diagnostic output for our patient-facing colleagues. For example, while a patient, their family, and doctor are discussing and managing symptoms related to a possible cancer diagnosis. The pathologists are examining microscopic behavior of the cancer-in-question’s cells and adding immunohistochemical testing and molecular analyses to identify, stage, and prognosticate that cancer. Returning information about what it is and what can be done back to the patient-facing clinician, who can then best-translate a tailored approach for their patient. Old-timey medical texts would often refer to the pathologist as the “doctors’ doctor,” and I’m not here to hate on that haha. My clinical friends and readers might feel forlorn now at the prospect of 4 years of medical school training to “just look into a microscope all day?” Well, for some folks in path it means a lot more than that, every slide is a patient. So we care just as much as if they were right opposite our desk. But that’s not all we do…

(More on that in a minute.)

So What Do You Do?

Okay, there are lot of words in path that might act as a barrier to understanding the common ground between me and …let’s say a colleague and friend in Family Medicine. So for the purposes of transparency here’s my friend from medical school Dr. Danash Raja and how a small part of his schedule and my schedule aren’t so different…

Image 3. Dr. Raja is from Alaska, and now works as a resident physician in Family Medicine in Eu Claire, Wisconsin! Alaska! Look at this graduation photo!

On both sides of this table are clinicians managing their patients and ensuring the best possible outcomes. Both sides are deeply vested in intensive hours of training, procedural experience, evidence-based best-practices from the literature, and ongoing continuing education.

Image 4. They see me grossin’, they hatin’…A lot of surgical pathology and microscopy in general revolves around understanding the gross layout of a specimen and its orientation before it becomes a thin microscope slide. As a junior pathology resident, we spend a lot of time up near the OR. Critical skill for a crucial foundation of knowledge.

Literally the biggest differences:

  • In pathology, I get my own desk space and I need it! I’ve got to start amassing a physical and digital library to supplement the next 4-6 years of subspecialty training for the eventual day when a colleague will see me in an elevator and expect concise, thorough, and actionable material to inform their clinical management from the pathologic diagnosis.
  • Pathology residents and clinical residents both take “call” except Dr. Raja has to pull grueling 24-hour+ shifts and stay in the hospital for the duration, and I answered a page about a transfusion reaction from a grocery store once.
  • When a patient thinks about the person who helped them find out what kind of cancer they had and what treatment to begin, they’ll probably think of Dr. Raja or someone patient-facing in Heme/Onc—but I’m working on this, every day!

Bottom line: I’m as important as he is, and he is as important as I am. Our work is what really matters, and what really connects us as clinical colleagues. It’s all about patients, remember? But I’m more than happy to be the pathologist to his patient-facing, diabetes-managing, vaccine-giving, life-improving super hero doctor!

You Never See Patients?

We’re back on this. Remember how I said looking into microscopes isn’t all we do? Okay, well it’s not. And if you’re lucky enough to have matched to as awesome of a place as I did, then you know what I’m talking about. If you’ve read some of my pieces, you know full well my passion in pathology lies in Hematopathology and Transfusion Medicine. I like to sit right on the fence between AP and CP, and mostly look at the green grass on the CP yard. This month, I’ve been on service for Transfusion Medicine and let me tell you about the few weeks…

Image 5. Dr. Kimberly Sanford, ASCP leadership and Director of Transfusion Medicine at VCU was highlighted in The Pathologist magazine for her work outside the laboratory seeing patients every day, and encouraging residents to do the same and do what pathologists do best: enrich and improve the channels of communication so patients better understand their conditions and the medical process.

I, a pathologist trainee, resident physician, under the supervision of two attending physician pathologists have been seeing and following up on patients nearly every day. Gasp! No, I’m not part of some backwards resident exchange program (because OMG how dangerous haha), no I’m not lost, no I’m not being overly gunnery, that’s it, that’s the Tweet. Seriously, it’s just part of the service. Larger academic hospitals with robust clinical blood bank services often have apheresis clinics and I find myself working exactly there. Blood bank/Transfusion Medicine is one of those subspecialties where patient contact is part of the routine. At some institutions, I’ve been a part of some pathology-led teams that procure the bone marrow aspirates from their patients in Hemepath service, or conducted their own fine needle aspirations for cytology service, or dermpath services that operate in clinics alongside their dermatology colleagues—I’ve even been working on frozen sections and surgical path grossing when called into an operating room to discuss methods and approach for biopsy! There were patients at every turn, all with pathologists on the front line! Dr. Syed T. Hoda (@01sth02 on Twitter) from NYU Langone often says, “Person FIRST, doctor SECOND, specialist THIRD.” And trust him, he’s a bone and soft tissue pathologist that left the lab and went to the floors to help clinical staff when overwhelmed during the peak of the COVID crisis in NYC. So for my dual-interests, I would say I’d expect to see quite a bit of patients in my future practice.

Image 6. My awesome co-residents! (Left-to-right): me, Dr. Elnaz Panah, Dr. Aayushma Regmi, and Dr. Sandra Haddad—you’re going to hear more about them, don’t worry.

So, would I pick pathology again? Uh, yeah! Without a single hesitation. Every day at work I am reminded that I am at the right place, with the right co-residents, the right faculty and mentorship, and the right environment to train and hone my future skills for a career that lines up exactly with what I want to do.If you’re interested about the intersections between clinical medicine and pathology, and want to learn more about “patient-facing pathology” keep an eye out during the 2020 ASCP Annual Meeting for a talk by yours truly as part of a panel discussion on communicating directly with patients! Register now! Free for members.

See you next time!

BONUS: did you notice that I referenced The Pathologist magazine a bit in this post, well it’s because they named me to their Pathology Power List for 2020! An exclusive, international list of 80 professionals in the field of pathology and laboratory medicine who contribute and advance the profession every day! I was highlighted for my active social media work and my response to the early COVID pandemic in Manhattan, NY.


-Constantine E. Kanakis MD, MSc, MLS (ASCP)CM is a new first year resident physician in the Pathology and Laboratory Medicine Department at Loyola University Medical Center in Chicago with interests in hematopathology, transfusion medicine, bioethics, public health, and graphic medicine. His posts focus on the broader issues important to the practice of clinical laboratory medicine and their applications to global/public health, outreach/education, and advancing medical science. He is actively involved in public health and education, advocating for visibility and advancement of pathology and lab medicine. Watch his TEDx talk entitled “Unrecognizable Medicine” and follow him on Twitter @CEKanakisMD.

Microbiology Case Study: 40 Year Old Male with A Diabetic Foot Ulcer

Clinical Presentation and History

The patient is a 40 year old male with a past medical history of type 2 diabetes mellitus with significant neuropathy and hypertension with a past surgical history of right metatarsal osteomyelitis. He presents to hospital with fever, right ear pain, headache, two episodes of diarrhea and redness and blistering to the right 3rd metatarsal. Upon examination he was noted to have a 1 cm ulceration on the right 3rd toe on the dorsal aspect associated with redness and edema. He was therefore assessed as having diabetic foot ulcer with possible osteomyelitis for which blood cultures were performed.

Laboratory Identification

Gram stains performed on the positive blood culture broth showed gram negative rods (Image 1). In our institution initial positive blood cultures are tested by the Verigene System (Luminex Corp., Austin, TX), which allows for rapid identification of common bacterial pathogens causing blood stream infections (Escherichia coli, Klebsiella oxytoca, Klebsiella pneumonia, Pseudomonas aeruginosa, Acinetobacter spp., Citrobacter spp., Enterobacter spp., and Proteus spp.) along with detection of several resistance genes (CTX-M, IMP, KPC, NDM, OXA, VIM) within ~ 3 hours. In this case, no targets on the Verigene panel were detected. Simultaneously, the specimen was plated onto blood, chocolate and MacConkey agars where the organism grew robustly on all three plates (Image 2). The MacConkey agar showed the organism to be a non-lactose fermenter. Once the organism adequately grew on these agar plates, final species identification was performed on the automated MALDI-TOF instrument which showed Salmonella species. To appropriately type the organism, Salmonella latex agglutination testing was performed which identified Salmonella species Group B (Non-typhoidal). Of note, multiple blood cultures from this patient were positive for Salmonella species, Group B.

Image 1. Gram stain of blood culture broth containing gram negative rods.
Image 2. Growth of the organism on chocolate, 5% sheep blood, and MacConkey agars.

Discussion

Salmonella is a gram negative, flagellated facultative anaerobic, non-lactose fermenting bacilli. The taxonomy and nomenclature of salmonella organisms are quite complex however the most widely used classification scheme is the Kauffman-White which is updated yearly by the WHO. Currently, members of the 7 Salmonella subspecies can be serotyped into one of more than 2500 serotypes (serovars) according to antigenically diverse surface structures: somatic O antigens (the carbohydrate component of lipopolysaccharide [LPS]) and flagellar (H) antigens.

Nontyphoidal salmonellae are a major cause of diarrhea worldwide. In the United States, non-typhoidal salmonellosis is one of the leading causes of foodborne disease. Salmonella enteritidis and Salmonella typhimurium are among the most frequently isolated organisms. Salmonella is most commonly associated with ingestion of contaminated poultry, eggs, and milk products. Salmonella gastroenteritis typically occur within 8 to 72 hours following exposure, however lower bacterial doses can prolong the incubation period. Although Salmonella typically causes diarrheal diseases including gastroenteritis and enteric fever, however there are rare instances where hematogenous involvement leads to bacteremia, osteomyelitis or endovascular infections.

In this case the source of Salmonella-related bacteremia is still a mystery. The presumed source was osteomyelitis, but the patient’s subsequent toe amputation revealed minimal osteomyelitis and rare fungal organisms.

References

  1. Procop, Gary W. et al (2017). Koneman’s Color Atlas and Textbook of Diagnostic Microbiology. 7th edition. Philadelphia, PA.
  2. Hohmann, Elizabeth L. (2018). Nontyphoidal salmonella: Gastrointestinal infection and carriage. Uptodate.com. Retrieved on November 14, 2019. https://www-uptodate.com/contents/nontyphoidal-salmonella-gastrointestinal-infection-and-carriage

-Anna-Lee Clarke-Brodber, MD is a 3rd year AP/CP resident at University of Chicago (NorthShore). Academically, Anna-Lee has a particular interest in Cytopathology. In her spare time she enjoys hanging out with her family.

-Erin McElvania, PhD, D(ABMM), is the Director of Clinical Microbiology NorthShore University Health System in Evanston, Illinois. Follow Dr. McElvania on twitter @E-McElvania. 

It’s Personal: A Case Study Close to Home

I’ve always been fascinated with medicine and the human body, knowing that I wanted to make a career of it since childhood. I was taking an elective summer course in Histology when a close relative was diagnosed with breast cancer over a decade ago, and that’s when I recognized pathology/laboratory medicine was my specialty. My questions began when her sentinel lymph node had both a different morphological picture and immunohistochemical signature than the primary tumor, and I wanted to know why. Why did her initial core biopsy only show ductal carcinoma, yet post-lumpectomy, her sentinel node was diagnosed as metastatic lobular carcinoma? Where was the second primary tumor? I needed answers, my family needed answers, and that quest propelled me to apply to Jefferson’s Master of Science in Cytotechnology program, fueling my career in Cytotechnology.

A year after I started my career at Fox Chase Cancer Center, my relative received a call – her mammogram showed two abnormal areas. Eight years after her first lumpectomy and completion of a chemotherapy and radiation regimen… eight years in remission, we both knew what this meant. I drove her to the physician’s office, and her surgeon called me into the room after he procured the core biopsies of both lesions. I saw the white “worms” of tissue in the formalin containers and felt confident of a successful procedure. I looked up to see the image of the localization wires within the tumors and heard him say, “if this does come back as cancer, which I’m fairly certain it will, we can either proceed with another lumpectomy or mastectomy.” My relative was silent the entire ride home; she needed time to process. After the not-so-surprising path report came back as ductal carcinoma in both lesions, I called her from work and said, “you’re coming to Fox Chase for a second opinion. You’re having a double mastectomy. We are NOT messing around. Not everyone gets a second chance, and I’ve seen what this care team is capable of – they know your cancer better than anyone.” She calls me her “tough cookie” both out of affection and annoyance. Little did she know my tough cookie exterior was shielding a crumbling interior. After much hesitation due to her fear of the unknown, she scheduled her second opinion.

Images 1-6: My relative’s ductal carcinoma: H&E, ER+, PR+, HER2 1+ (negative FISH), E-cadherin+, sentinel node micromatastasis.

In the meantime, she had an MRI which demonstrated the two known lesions in the right breast, but also a large “enhancement” in the right breast. The MRI identified an area of enhancement in the left breast as well. And with those results, my relative felt comfortable withdrawing the lumpectomy plan from the table and played the card of double mastectomy with possible right-sided axillary lymph node dissection. A diagnosis of grade II invasive ductal carcinoma was made in the 1.5 cm right breast lesions, and the 6 cm right breast mass was diagnosed as invasive lobular carcinoma. The right axillary sentinel node demonstrated micrometastasis. On the left side, the pathology revealed a 3.5 cm grade II residual in-situ and invasive lobular carcinoma. She had a TRAM flap reconstruction at the time of her double mastectomy with radiation to the right breast after she recovered. She is tolerating and responding well to the daily dose of her aromatase inhibitor and now knows far too much about breast cancer and hormone receptor status thanks to my harping on the subject.

We both went through clinical genetics screenings, and despite our strong family history of breast cancer, no known germline mutations or variants of undetermined significance were detected in either of our peripheral blood samples. I’m already on board with the “increased lifetime risk of breast cancer” screening guidelines, and if so much as atypical ductal hyperplasia is diagnosed, I am more than willing to have a semi-prophylactic double mastectomy, just to reduce my overall risk of both carcinoma AND recurrence. My relative’s breast cancer experience set the precedence for my approach in the field of cytotechnology. From the beginning, I craved definitive answers for her, and I will do whatever I can as a cytotechnologist to provide definitive answers for all of my patients.

I still remember attending my first ultrasound-guided FNA (Fine Needle Aspiration) after my relative’s mastectomy. The patient was 42, a mother to a 3 year old and 6 year old, and presented with triple negative, grade III, poorly differentiated breast cancer and cervical, occipital, hilar, and mediastinal lymphadenopathy.

Image 7,8: US-guided FNA of right cervical lymph node, Diff-Quik and Papanicolau stains. Metastatic PD Breast Carcinoma.

I assisted the radiologist in obtaining cellular material from the patient’s targeted right cervical lymph node, and when the radiologist prepared the core biopsy needle, the patient started to tear up, knowing well what the lymphadenopathy indicated. She told us she knows how aggressive her cancer is, how her young children are going to lose their mom, and I remember doing everything I could to hold it together and provide my adequacy statement to the radiologist. Like a child on the playground trying not to cry in front of her friends after skinning her knee, I gathered all my paperwork and the specimen containers, cleaned up my cytology cart, and walked back upstairs to our cytoprep lab. I assigned the specimen an accession number, handed the prep tech my cell block tube so she could spin down the residual material in formalin and ensure the cold ischemic time was less than one hour, and I bee-lined for a private space. I found our cytology file room, closed the door behind me, sank against the wall, and cried. I, too, knew the likelihood of her children losing their mom without medical intervention, and that the intent to cure would be the most difficult journey of this young woman’s life. This is why I’m here. This is why I fight for more material, why I fight for answers, and why I will always put the patient first.

Taryn Waraksa, MS, SCT(ASCP)CM, CT(IAC), has worked as a cytotechnologist at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, since earning her master’s degree from Thomas Jefferson University in 2014. She is an ASCP board-certified Specialist in Cytotechnology with an additional certification by the International Academy of Cytology (IAC). She is also a 2020 ASCP 40 Under Forty Honoree.

Beggars CAN Be Choosers

There is a fine line between obtaining enough cellular material for every ancillary study in the book and risking harm to the patient. So how do we ensure that the patient remains safe, but doesn’t need to come back for a second biopsy due to insufficient material?

Hi! I’m Taryn, a Specialist in Cytotechnology at Fox Chase Cancer Center and a medical laboratory professional who thrives on patient advocacy. Welcome to my first post for Lablogatory! Each month, I’d like to share a story of how the middleman/woman cytotechnologist becomes the biggest campaigner for the patient. Typically, I’ll be posting case studies of rare tumors and how we arrived at the diagnosis, but I’ll start with how to guarantee that we have ample material to provide a comprehensive result for both the patient and clinicians.

 It’s a fight, to say the least. With personalized medicine at the forefront of our cancer center’s mission, we need ALL of the material for any and every ancillary test one can think of, from immunohistochemistry to flow cytometry to molecular diagnostics. That sounds like a lot because it is. From my experience, many clinicians feel that just because cytotechnologists can make a satisfactory adequacy statement on a Rapid On-Site Assessment (ROSE) of a Fine Needle Aspiration Biopsy (FNA), and the pathologists can make a definitive diagnosis based on cytomorphology alone, that means they have obtained sufficient material. For years, that was a valid thought. But now that we have taken various leaps from diagnostic to prognostic and now theranostic approaches, “enough” for cytomorphology is nowhere near “enough” for the patient’s clinical outlook.

As a cytotechnologist present on FNA’s, I have been called “greedy” and a “beggar” by clinicians on more than one occasion. No hard feelings, I promise. As long as the anatomical location of the biopsy does not pose more risk than reward, rest assured, I’m going for the gold medal. Starting out, I obtain one or two fine needle aspiration passes from the radiologist, pulmonologist, gastroenterologist, etc., and from each pass, I prepare one smear to be stained on-site via Diff-Quik (Modified Wright-Giemsa stain) and the mirror image smear fixed in 95% ethanol to be Papanicolaou stained later in the lab. The residual material in the needle is rinsed in Hank’s Balanced Salt Solution (A.K.A. Gatorade for cells) and later spun down into a pellet for a Formalin-Fixed Paraffin-Embedded (FFPE) Cell Block. I look at the Diff-Quik stained smears under the microscope and tell the clinician if the material I have is adequate, scant, or inadequate. This is where it gets interesting.

Clinician: “Adequate. So, we’re done? Okay.”
Cytotechnologist: “The smears are adequate, but I need more material for the Cell Block. Can I have two more passes? And a core biopsy, as requested on the presentation state.”
Clinician: “But you have enough. We already know the patient has lung cancer. You don’t need anymore. I’ll give you a core biopsy, but no more fine needles.”
Cytotechnologist: “I need at least two more needles. The core biopsy material will be saved for molecular. The ordering physician wants to know if the patient’s EGFR-mutated tumor also carries a T790M mutation to see if they are eligible for this therapy. But I also need additional needle passes for the Cell Block to prove that the immunohistochemical profile is the same as the original material. If there is a small cell carcinoma component in the metastasis, that changes things.”
Clinician: “Fine. Pathology is so greedy.”

Okay, so we have definitely progressed into a new era. Many newly trained clinicians understand the need for ample material, but this conversation still occurs on a daily basis. Don’t get me wrong, the veteran clinicians (from my snippet) are remarkable. They can find a needle in a haystack, hit a moving target time and time again, and provide me with a perfect tumor-rich sample. But alas, in trying to educate and advocate, I admit- I do come off as a beggar. The key in our ROSE role is to not back down though. Cytotechnologists remain strong in their convictions, fighting for the patient, so that not only do we have enough cellular material for all of the necessary ancillary studies the first time around, but that hopefully the first time around is the ONLY time around.

We’ll chat soon!


Taryn Waraksa, MS, SCT(ASCP)CM, CT(IAC), has worked as a cytotechnologist at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, since earning her master’s degree from Thomas Jefferson University in 2014. She is an ASCP board-certified Specialist in Cytotechnology with an additional certification by the International Academy of Cytology (IAC). She is also a 2020 ASCP 40 Under Forty Honoree.

False Negatives in COVID-19 Testing

I left for vacation at the beginning of June thinking “once I get back, all of this COVID stuff will be quieted down.” …Well that wasn’t quite the case and testing for novel Coronavirus has continued to be very important. In fact, this last weekend I was tested by occupational health. It came back negative, but I’m am very enthusiastic to get alternative specimen types validated; those Nasopharyngeal swabs are quite…uncomfortable. Luckily, my test was processed at our institution which gets results back in 24-48 hours. However, with the resurgence around the country, turnaround times are backing up to 7-8 days. One solution has been the widely used IDNOW point of care platform. However, there has been significant concern over false negatives produced by this platform. One reason the sensitivity is different is because this platform performs isothermal amplification of nucleic acid. This method amplifies RNA at a stable temperature instead of cycling the temperature as in real-time PCR.

Colleagues at my institution reflexed any negative IDNOW samples to the m2000 Real-Time PCR assay for SARS-CoV-2 for one month. Within that time, over 500 samples were tested and the IDNOW was found to have missed 21% of positive cases (prevalence rate of 5%)2. One the positive side, it had a 98% negative predictive value, which helped rule out COVID19 infection. However, as prevalence rates are increasing, a high negative predictive value isn’t as important as sensitivity.

One study drew much attention when it claimed the IDNOW had a sensitivity of 52% in a New York City academic institution (Basu)4. However, this seems to be an outlier compared to other studies of this platform: one large multi-center study found positive percent agreement (equivalent of sensitivity when a gold standard test hasn’t been established) of 74%1. The highest PPA of 88%3 for the IDNOW was found in a study that indicated it can be completed in 17 minutes, whereas another quick instrument (but not point of care instrument: Xpert Xpress, 45min) had a PPA of 98%2.

Myself and other colleagues looked more closely at the clinical characteristics of false negative test results on the IDNOW. Overall, we found 82% PPA, and 8 patients with false negative tests. Interestingly, a majority of these patients were tested over 2 weeks after their initial onset of symptoms. The virus is known to be at its highest levels at the beginning of symptom onset. So the test may not be limited, but it should be used in the correct clinical context (< 2weeks from symptom onset). After that time, other RT-PCR based tests are more appropriate.

As clinical laboratorians, we often hear: “the right test for the right patient at the right time.” Now with so many platforms available for use in different contexts, we should help guide clinicians to Choose Wisely.

References

  1. Harrington A et al. Comparison of Abbott ID Now and Abbott m2000 methods for the detection of SARS-CoV-2 from nasopharyngeal and nasal swabs from symptomatic patients. JCM 2020. PMID: PMID: 32327448
  2. McDonald et al. Diagnostic Performance of a Rapid Point of Care Test for SARS-CoV-2 in an Urban ED Setting. Academ. Emerg. Med. 2020. PMID: 32492760
  3. Zhen W et al. Clinical Evaluation of Three Sample-To-Answer Platforms for the Detection of SARS-CoV-2. JCM 2020. PMID: 32332061
  4. Basu A et al. Performance of the rapid Nucleic Acid Amplification by Abbott ID NOW COVID-19 in nasopharyngeal swabs transported in viral media and dry nasal swabs, in a New York City academic institution. BioRxiv 2020.

-Jeff SoRelle, MD is a Chief Resident of Pathology 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 improving genetic variant interpretation.

The Laboratory’s Role in Inclusion

“Where do we go from here…chaos or community?” is the question Dr. Martin Luther King, Jr. asked in 1967 before the civil rights riots in the hot summer of 1968.  The query was directed to the nation as it sought to address the racism and pain deeply felt in the daily lives of its African-American citizens.  Over 50 years later, that very same question is asked again as the nation is roiled with civil demonstrations, daily videos of racist behavior, and the seemingly senseless killings of African-American men and women. 

As American culture and the nation evolves, uncomfortable conversations are beginning to occur in healthcare and across the country.  Laboratory administrators and managers may want to reflect on the culture of their laboratory to ensure all voices are heard and that they are creating and supporting an inclusive work environment.

Diversity, inclusivity, and equity are goals healthcare organizations seek to incorporate into their culture to foster a healthy workplace environment and be reflective of the communities they serve.  As with most industries, the laboratory has found itself challenged to improve cross-cultural intelligence and eliminate implicit and unconscious bias.  The scientific community would like to believe it operates and makes decisions based solely on objectivity and facts.  However, everyone is human and prone to perceptions influenced by preconceived beliefs and life experiences. 

In the laboratory, questions involving race relations are pondered and discussed by workers of all creeds and colors.  Historically, laboratorians have viewed themselves as scientists focused strictly on the pursuit of facts, hard data, and helping patients.  However, one would err in thinking the lives of minority lab workers were encased in impenetrable bubbles of logic and reason. Instead, early on in their career (correction—their lives), many minority workers learned to compartmentalize and hide feelings of unfairness and helplessness in their effort to “fit in” and not make others feel uncomfortable.

Laboratory administrators should let employees know that their office is a “safe place” if an employee feels he or she needs to discuss issues affecting how they feel about their work environment. Many employees of color working in predominately white environments may avoid conversations involving race out of fear as being labeled as “one of those.”  However, avoiding difficult conversations does not make the problems go away; in fact, the lack of addressing an issue often creates a more significant problem later on, or the employee simply quits.  One thing managers should be prepared to hear if they are successful in creating a safe space and the employee chooses to talk, harsh truths.

Lab managers can be proactive and ask if the employee has encountered any barriers or obstacles to their success in the healthcare organization.  Minority employees frequently experience microaggressions, favoritism, and racial discrimination.  Discussing feelings may provide a release for the employee, allow the manager to begin to understand, and offer the opportunity for the manager to reflect on their behavior. 

 The diversity of today’s protest marchers provides evidence of the progress America has made toward vanquishing the problems of racism and discrimination.  All colors, creeds, and ethnicities are together expressing their desire to defeat the scourge of racial injustice.  Laboratories are a part of the social community, and minority employees are often reluctant to share anxiety and experiences they feel are race-based.  Lab managers should be reflective and reach out to their employees to let them know their office is a “safe place” to discuss issues openly, including those with racial overtones.  It is only through open and honest dialogue that we can avoid chaos and become the community we seek.

Darryl Elzie, PsyD, MHA, MT(ASCP), CQA(ASQ), has been an ASCP Medical Technologist for over 30 years and has been performing CAP inspections for 15+ years. Dr. Elzie provides laboratory quality oversight for four hospitals, one ambulatory care center, and supports laboratory quality initiatives throughout the Sentara Healthcare system.

Microbiology Case Study: Skin and Soft Tissue Infection Caused by an Unusual Bacterium

Case History

A 20 year old female with no significant past medical history presented with a painful pruritic rash on the bilateral inner thighs that had been persistent for one month. Prior to presentation, she had been treated with oral and topical antihistamines, topical steroids, valacyclovir, and partial courses of doxycycline and cephalexin without improvement. Physical examination was notable for diffuse erythema and dermal edema of the bilateral medial thighs with superimposed exophytic papules with dark, necrotic cores, the largest of which measured 1 cm in diameter (Image 1). Punch biopsy of the lesions was taken and sent for histology. A sample from necrotic tissue was sent to microbiology laboratory for gram stain and cultures.

Laboratory diagnosis

Gram stain showed gram positive cocci in clusters. After 32 hours of incubation, tissue cultures grew white, β-hemolytic colonies which were catalase positive, coagulase negative, and pyrrolidonylarylamidase (PYR) positive. The organism was identified as Staphylococcus lugdunensis by MALDI-TOFmass spectrometry. Histology revealed eosinophilic inclusions consistent with molluscum bodies as well as inflammatory infiltrate (Image 2). Brown and Hopps stain on tissue showed Gram-positive cocci is small clusters (Image 3). A diagnosis of molluscum contagiosum superinfected with Staphylococcus lugdunensis was made based on laboratory and histologic findings.

Image 1. Lesions on left medial thigh (left) and right medial thigh (right).
Image 2. Molluscum bodies
Image 3. Brown and Hopps stain on tissue showing gram positive cocci

Discussion

S. lugdunensis is a coagulase-negative staphylococcus first isolated in 1988 that was initially thought to be a commensal skin organism but has been shown to cause skin and soft tissue infections (SSTIs), bacteremia, endocarditis, prosthetic joint infections, and osteomyelitis,2 with a virulence more similar to S. aureus than to that of other coagulase-negative staphylococci. SSTIs are one of the more common manifestations of S. lugdunensis infection; one analysis of 229 S. lugdunensis clinical isolates demonstrated that 55.4% were associated with SSTIs.3 The spectrum of S. lugdunensis-related SSTIs includes folliculitis, pustulosis, cellulitis, abscesses, and rarer secondary infection of molluscum contagiosum and hidradenitis suppurativa.5 Molluscum superinfection itself is a rare phenomenon, and when it occurs, the superinfecting agent is most often S. aureus.1 Our case suggests that S. lugdunensis should also be considered as a potential causative agent of molluscum superinfection. There is growing recognition that S. lugdunensis is a virulent pathogen that should not be disregarded as a contaminant if found on culture. Importantly, when compared with S. aureus, S. lugdunensis has a more limited resistance profile; methicillin resistance is still uncommon, and 74.6% of isolates in one recent study were penicillin susceptible.4 Awareness of this more favorable resistance profile can facilitate selection of narrower-spectrum antibiotic therapies for S. lugdunensis infections.

In our case, patient received one dose of vancomycin and metronidazole in the emergency department and was then started on cefazolin for cellulitis. After wound culture identified S. lugdunensis, the patient was discharged on cefadroxil 1g twice daily for 10 days. On follow up, the rash had resolved.

References

  1. Berger EM, Orlow SJ, Patel RR, Schaffer JV. Experience With Molluscum Contagiosum and Associated Inflammatory Reactions in a Pediatric Dermatology Practice: The Bump That Rashes. Arch Dermatol. 2012;148(11):1257–1264. doi:10.1001/archdermatol.2012.2414
  2. Douiri N, Hansmann Y, Lefebvre N, Riegel P, Martin M, Baldeyrou M, Christmann D, Prevost G, Argemi X. Staphylococcus lugdunensis: a virulent pathogen causing bone and joint infections. Clinical Microbiology and Infection, 2016;22(8):747-748. doi:10.1016/j.cmi.2016.05.031
  3. Herchline TE, Ayers LW. Occurrence of Staphylococcus lugdunensis in consecutive clinical cultures and relationship of isolation to infection. J Clin Microbiol. 1991;29(3):419–421.
  4. Taha L, Stegger M, Söderquist B. Staphylococcus lugdunensis: antimicrobial susceptibility and optimal treatment options. Eur J Clin Microbiol Infect Dis. 2019;38(8):1449–1455. doi:10.1007/s10096-019-03571-6
  5. Zaaroura H, Geffen Y, Bergman R, Avitan‐Hersh E. Clinical and microbiological properties of Staphylococcus lugdunensis skin infections. J Dermatol, 2018;45: 994-999. doi:10.1111/1346-8138.14496

-Ansa Mehreen, MD. 1st year AP/CP resident at University of Chicago hospital program based at Evanston Hospital. Her academic interests include gastrointestinal pathology.

-Erin McElvania, PhD, D(ABMM), is the Director of Clinical Microbiology NorthShore University Health System in Evanston, Illinois. Follow Dr. McElvania on twitter @E-McElvania. 

From Panic to Pandemic: Laboratory Emergency Response Plans

In 2018, Hurricane Florence ripped through the Carolinas causing an immense amount of destruction and taking a record amount of lives in the area. Superstorm Sandy had a devastating impact on New York and New Jersey in October 2012. In Joplin, Missouri, an EF-5 tornado cut a damaging path through town in May 2011, directly hitting the hospital. Severe storms, flooding, and even blizzards are regular events throughout large areas of the United States every year, disrupting normal life and the delivery of services, including healthcare services.

Natural disasters occur frequently, and labs must consider them in their Emergency Response plans. These disasters have consequences for hospitals and laboratories and their operations. Given the wide variety of possible disasters that can affect a laboratory, it may seem impossible to be prepared for every type of event that could occur. Some labs take a reactive approach and create individual plans for different disaster types. For example, a lab manager may decide to create a blizzard response plan after a major winter storm—a plan that is separate from any previously existing lab emergency response plan. That may not work well, and it many plans may become cumbersome for lab staff when the event occurs.

As 2020 has shown us, other types of disasters that are not normally considered can also affect laboratory operations. The COVID-19 pandemic situation has created issues like the reduction of the availability of staff, a need to quickly alter testing platforms, and even major supply acquisition issues. Clearly, pandemic issues need to be considered when looking at lab disaster responses.

The best type of laboratory emergency response plan is a single plan that will enable the laboratory to continue to provide services in a variety of disaster scenarios, including pandemics. The College of American Pathologists (CAP) requires labs to develop an emergency plan which is based on the overall facility’s Hazard Vulnerability Analysis (HVA). The HVA is a risk assessment tool that lists types of disasters that can affect the facility, and it ranks which disaster types are most likely. If you work in an independent lab, you must perform your own HVA and update it every year. In 2020, it would be prudent to quickly add “pandemic” to the list.

There is no need to panic, however. In your plan which has been designed to have an “all hazards” approach, you may find some aspects of pandemic response are already addressed. Fluctuating staffing levels should already be addressed. Be sure the plan discusses how to best utilize staff when fewer people are available. That process may include a reduction in testing or utilizing a reference lab if necessary. In some instances during the pandemic, labs were left with too many staff members once an overall reduction in lab volumes occurred. How can extra staff be used? Can they go to other departments or facilities where needs may exist? There should be a section in the response plan regarding how to handle supply issues. If it is known there is going to be a problem obtaining PPE, reagents, and other supplies, decide what procedures will occur. Stockpiling, finding alternative vendors, and changing the type of supplies purchased are some options.

Once all of the pieces of the updated lab emergency operations procedure is complete, it is important to test the plan for flaws or needed improvements. One thorough method of testing includes the use of a table-top drill or exercise. Present a step-wise disaster scenario to key lab stakeholders and discuss possible responses as the imagined situation unfolds. Be sure to discuss important aspects such as staffing, supplies, communications, and relocation of testing. If the COVID-19 pandemic has led your lab to utilize its emergency response plan, be sure to take the opportunity to review how it is working for your department. Ask lab leaders and staff members if the current plan works- what went well and what needs improvement? This current disaster can help us all to improve our current procedures and keep us ready for the next event.

Is your laboratory emergency operations plan up to date? Does your staff know how to use it or will they panic when a disaster occurs? Has the plan been tested? Now is the time to review what you have and make sure it works for pandemics as well as a wide variety of disaster scenarios.

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.

Practicing Productivity in the time of Pandemic

At this point, you are either somewhat adjusted to working from home (likely taking on new roles and responsibilities while juggling your kids, dog, and spouse), battling COVID on the front lines (caring for patients, providing us with food, or keeping the lights on), or unemployed (yet another victim among a whole host of victims during this extremely trying time). Regardless of where you fall, you have likely been on at least one video conference since January and you will likely be on many more over the next six months. As live, in person meetings of 2500 to 5000 people that we are so used to have come to a screeching halt, the world of associations such as ASCP are carefully and artfully creating virtual experiences that you can be assured will enhance and improve your life but will most definitely be in a virtual format. But the whole world is now experiencing online happy hours, teaching sessions, work meetings, telehealth visits, group therapy sessions, and kid’s birthday parties. Step back from your current situation and ask, “Have I seen MORE or LESS of my friends and peers in the last six months than in the prior year?” That answer is different for each person and carries different emotional baggage. For the constant extrovert who needs that human interaction fuel to spur them on, video conferences may not be hitting the mark. For the ever-quiet introvert who happily recharges among their books and cats and knitting, constantly being required to video chat with people for hours on end may be pushing them toward a steep cliff of insanity. For the “mover and shaker” that loves a problem a minute, thrives in crisis, and gets utter joy out of solving a problem and moving on, facing a day filled with 8 pre-scheduled video conferences or, worse, a day with an empty calendar can be demoralizing. For anyone who had a rhythm to their email usage which involved key time points to check during the day and an internal list of priorities of how to deal with emails on a rolling basis, the extreme uptick in volume of email because everyone is working remotely in the same office (“where is the water cooler chat?”) is dizzying.

It is now July 2020 and we face the uncertainly of what working from home will mean or be or even when it will end (or will we choose this as a permanent solution?). For those of us who have been and continue to report to our work place using social distancing, masks, shift rotations, and the inability to touch anything around us, how can we make this sustainable long-term, do we need to do so, and how do we know when we can end it? For the hundreds of millions of non-laboratorians who are asking, “When will there be a test so we can go back to work?”, the job of the laboratory has long been a mystery but is now suddenly thought to be a miraculous answer to a complex problem of politics, public health, and capitalism. Amidst all of the uncertainty of COVID-19 that we are facing on a continuous basis, the country was already immersed into a “fake news” war between rival political factions that already had the bulk of America either fed up with all new sources, only trusting one “news” source (the bulk of which was political agenda opinion), or simply burying heads in the sand in hopes that this was all just a bad dream. We are halfway through 2020 and the optimists are saying, “It can only get better” and the pessimists are sighing, “what comes next?”. The only people who aren’t complaining are the myriad of investors who didn’t even need a crystal ball to predict the March stock market crash, sold short, and raked in billions—which they then returned to the market buying blue chips at rock bottom (relative) prices to now be showing a 20% return. If only we could all be so lucky?

But there is a light at the end of the tunnel and the sun will come up tomorrow. Nothing lasts forever and this virus will run its course—whether we fight it tooth and nail or ignore it—to a natural conclusion which is harmony within our population. Over the next 6 months, enormous amounts of data on epidemiology, biology, virology, and treatment will emerge. We will learn from our colleagues in Africa what the impacts of early, sustained interventions can do to thwart the virus. Over the next year, vaccines will appear and be available for the population at large. The myriad of tests will have settled around a handful of reliable “winners” that have the sensitivity and specificity we need for each of the valued applications in our systems. The stock markets (and your retirement funds) will have recovered and exceeded pre-COVID-19 levels. However, one aspect of our lives will be permanently changed and that is our dependence and use of video conferencing for the special, the everyday, and the mundane. To that end, let me conclude with some of my (hard earned) lessons from both the last 6 months and the last 20 years of working in global health.

  1. Video conferencing etiquette is a “thing”. Seriously. Tools available to the host can get you so far but nothing says, “we are all in this together” like a team on a video call that is following the rules. Mute yourself when you are not talking. Turn off your computer’s sounds or software that makes frequent sounds. Do not leave your cellphone on your desk on vibrate (computers have great microphones!). If your internet connection is bad, switch off your video. When you are listening, look directly into your webcam (then others feel you are looking directly at them and they feel more connected). Use a virtual background if possible so we do not see your kids making breakfast in the background. Brush your hair (you can totally get away with no pants and not showering but “bed head” is a dead giveaway). Sit within 3 feet of your computer. Rename yourself on the screen if possible, with your full name and organization. Do not take a video call while walking outside.
  2. Your workstation is your productivity cockpit. Make sure it has what you need. In today’s world of multitasking and conferencing, two screens are almost a must. You can use a laptop while traveling but for a home office, having two screens creates a much cleaner canvas to spread out your work, keep resources at your fingertips, take notes while conferencing, etc. Treat your digital workspace like your physical desktop. Keep only what you need on the desktop. File your files in folders you understand and can follow. If your virtual desktop is covered in hundreds of files and icons, your brain is not mentally able to process or prioritize. Use a background picture that sends you to your happy place so that, when you need a break, all windows can be closed, and you can zip to your happy place immediately.
  3. Develop a personal system for communications. Maybe you are a texter, a snapchatter, an emailer, a phone-call-aholic, an instant messenger fiend… Whatever you are comfortable with, the other dozen people you interact with are comfortable with something else. Your team lead may say, “We are using Teams!” or “We are using Basecamp!” or “We are using Sharepoint!” but, let’s face it, it may not fit your style or your work flow. The important thing is to develop a system for whatever communication type you feel most comfortable and work that system to be productive. I have seen the inboxes of people who have 85,000 unopened emails (both personally and professionally) to which I reply, “Delete them!”. If something in those emails was so important, the person will have found another way to contact you. You are never going to read them and, honestly, email just does not work for you. Pick another channel. Texting can work for many people but the organization of texts on a phone and the archiving eventually becomes a challenge such that screen captures or lots of copy/pastes must occur. Whatsapp is a good solution with its archiving function but can still present a permanence problem. Your chosen communication channel is important because it will dictate your productivity style. For example, one of my colleagues takes extensive notes on paper (extensive!) but sometimes takes extensive notes on a tablet. Their work stack (i.e., the collection of items they work through daily) is a combination of pieces of paper and digital notes, but it is disconnected from a communication system. The time required for note translation into understanding and then moving those thoughts to an email, for example, for me would be wasted time. But they remain one of the most productive people I know so this system works for them! Each person must decide what makes them most productive and what keeps them informed and connected; however, a good approach if you are feeling overwhelmed is to use a single system (digital) that moves with you. Microsoft Outlook, Gmail (and calendar), and iCloud all have cross functionality that allow seamless notetaking, email and calendar creation, and file connectivity. Outlooks category function for email can be a massive time saver for the adept user where a preliminary read through of email can allow for classification (for example, I use “Urgent”, “To do – Non-Urgent”, and “Waiting on Reply”) and then priority follow up. At the writing of this blog, I have less than 30 emails in my inbox, all are categorized, and all are calendared for completion.
  4. Go outside and breath. The single most important thing that we can achieve as a society as we emerge from the COVID-19 pandemic is an appreciation for life, freedom, and health and that is difficult to do if you stay in front of your computer for 12 hours a day. More than half a million people have died of COVID-19 and we could have been one of them. Unemployment spike from a flat 4% to more than 14% with many companies, restaurants, and small businesses never planning to reopen. The unfortunate tragedies that continue to befall our black brothers and sisters led to peaceful protests which were then corrupted by riot and ruin across many major cities. Even now, racial and ethnic disparities, especially our Navajo neighbors in the Southwest along with our black communities, cause disproportionately suffering from COVID-19. It is not a time to think, “I’ve been lucky!”. It is a time to say, “What can I do to help today?”And where the help is needed is outside, in your community. Yes, you should wear a mask if you can’t social distance. Be sure to wash your hands frequently. But get out there and be part of the change for the better!
milner-small

-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.