Microbiology Case Study: How to “Pin” a Diagnosis

Case History

A 7 year old female presented to the emergency department with left sided abdominal pain and a temperature of 103 degrees Fahrenheit. Labs drawn showed mild leukocytosis with a CT scan suggestive of acute appendicitis. The patient underwent uncomplicated appendectomy with no complication. Gross examination of the appendix revealed an unremarkable, non-perforated serosa and a fecalith within the lumen. Representative tissue sections submitted for microscopic analysis per grossing policy. The findings below led to the submission of the entire appendix to be evaluated.

Figure 1. Low power image of an appendix demonstrating mild acute inflammation, lymphoid hyperplasia and congestion.

Figure 2. High power image, Cross-section of an adult female E. vermicularis from the same specimen shown in Figure 1. Adherent to the appendiceal surface. Note the presence of the alae (blue arrow), and the presence of almond shaped eggs (red arrow).

Discussion

The nematode Enterobius vermicularis, widely known as the human pinworm, is one of the most common parasitic worm infections today in the United States, infecting approximately 40 million people. The patient population is often children who are infected via fecal-oral transmission, with autoinfection being common. Humans are the only known host of this nematode. Once E. vermicularis embryonated oocytes are ingested, the larvae hatch and inhabit the gastrointestinal system. At night, the larvae migrate down to the anus, lay their eggs, and the cycle recurs.

The clinical presentation can be asymptomatic or can present with perianal pruritus at night, which can be explained via the life cycle of the parasite as stated above. The method of choice for diagnosing E. Vermicularis is microscopic examination of the eggs via cellulose tape slide test. A piece of scotch tape collects the eggs near the perianal area of the patient, which is then used for analysis and identification of the eggs. Microscopically, E. Vermicularis can be identified by the spines or ‘alas’ on the surface with oval shaped, thick capsuled oocytes within, seen in figure 2. To improve the sensitivity of the scotch tape test, it is best to do this test in the early morning, when there is an increased chance of sampling the eggs.

Rarely, is this worm associated with any severe symptoms but patients can present with abdominal pain, suggesting intestinal obstruction, extra intestinal manifestations like vulvovaginitis, or appendicitis. The relationship between E. Vermicularis and appendicitis is up for debate as to whether there is a causative relationship or if it is an incidental finding seen within appendicitis. Regardless of the relationship, once a diagnosis of Enterobius vermicularis is made, treatment with an anthelmintic needs to be given to the patient, such as Albendazole or Pyrantel Pamoate. In addition, treatment for everyone in the household needs to be considered in confirmed cases of infection.

Routine surgical specimens, such as appendices, can perhaps be overlooked once acute inflammation is noted. It is important to be able to identify organisms, such as pinworms, on such specimens to get the patient the appropriate treatment.

References

  1. https://www.cdc.gov/dpdx/enterobiasis/index.html.
  2. https://www.sciencedirect.com/science/article/pii/S204908012030412X
  3. https://www.uptodate.com/contents/enterobiasis-pinworm-and-trichuriasis-whipworm?search=enterobius%20vermicularis&source=search_result&selectedTitle=1~32&usage_type=default&display_rank=1#H12

-Alexandra Medeiros, MD, is a first year anatomic and clinical pathology resident at Medical College of Georgia at Augusta University. Her academic interests include Forensic pathology, and surgical pathology.

-Hasan Samra, MD, is the Director of Clinical Microbiology at Augusta University and an Assistant Professor at the Medical College of Georgia.

Microbiology Case Study: A 26 Year Old Female with Diarrhea

Case Description

A 26 year old female with a past medical history of Hemoglobin SC disease (Hb SC) and iron deficiency anemia presented to the emergency department with lower abdominal pain and diarrhea for three days. She began having multiple episodes of watery diarrhea, followed by bloody diarrhea after eating at a restaurant. During this time, she also had fever, chills, body aches, and headache. The patient had been on a course of ceftriaxone and metronidazole started three weeks prior for sore throat, ear infection, and bacterial vaginosis. She completed her metronidazole course prior to the current illness. Abdominal computed tomography revealed splenomegaly and a mildly dilated, fluid-filled appendix without evidence of infectious or inflammatory abnormalities. Hemoglobin on admission was 11.1 mg/dL (Reference Range: 11.2- 15.7 mg/dL) and MCV 62.9 fL (Reference Range: 79.4- 94.8 fL), which is similar to her baseline.

Laboratory Identification

The patient underwent work up for community-acquired diarrhea. Stool cultures grew non-typhoidal Salmonella (Image 1). Blood cultures performed at the time of admission flagged positive with gram negative rods which were also identified as Salmonella species by MALDI-TOF. The organism was susceptible to ampicillin, ceftriaxone, ciprofloxacin, and trimethoprim/sulfamethoxazole. The patient continued on intravenous ceftriaxone and responded to therapy. She was discharged home on oral ciprofloxacin.

Image 1. Salmonella Microbiologic Diagnosis using Xylose Lysine Deoxycholate agar and Triple Sugar Iron slant. A) Non-typhoidal strains of Salmonella are lactose non-fermenting, hydrogen sulfide producing (black colonies) enteric Gram-negative rods on Xylose Lysine Deoxycholate agar (XLD agar). B) Non-typhoidal strains of Salmonella are Alkaline (pink) over Acid (yellow) with the production of copious amounts of hydrogen sulfide on Triple Sugar Iron agar (TSI).

Discussion

Hemoglobin SC disease (Hb SC) is the second most common hemoglobinopathy after Sickle Cell Disease (SCD, Hb SS) globally.1 Hb SC disease occurs when a patient inherits both hemoglobin S and hemoglobin C alleles. Hemoglobin S and C variants are caused by point mutations in the hemoglobin beta- chain, and both variants lead to reduced affinity to the alpha-chain. While hemoglobin C is an abnormal form of hemoglobin that does not cause sickling on its own, when co-inherited with hemoglobin S, the beta chains polymerize, causing red cell sickling when oxygen tension is lowered in the blood.2 Patients develop anemia due to reduced red cell lifespan (27-29 days for Hb SC vs. 15-17 days for Hb SS) and subsequent destruction of red blood cells.3

Complications arise from vascular occlusion and destruction of red blood cells, leading to gallstones, pulmonary infarction, priapism, and/or cerebral infarction. Other complications include avascular necrosis of the femoral head, bone marrow necrosis, renal papillary necrosis, retinopathies, splenomegaly, and recurrent pregnancy loss. Although Hb SC patients often exhibit similar symptomology to sickle cell disease, symptoms are typically milder and present later in childhood.2,3 In comparison to patients with Hb SS, Hb SC patients have milder anemia, less frequent sickle cells, and less severe hemolysis. While Hb SC patients have fewer sickling episodes compared to Hb SS patients, Hb SC patients have more severe retinopathy and splenomegaly. It is also important to note that the enlargement of the spleen is often caused by red blood cell sequestration and the optimal function of the spleen is significantly reduced (functional hyposplenia), which can lead to increased risk of infection from encapsulated bacteria.

Diagnosis of Hb SC disease is typically made by performing hemoglobin electrophoresis (Image 2). Hemoglobin electrophoresis separates the differing varieties of hemoglobin by size and electrical charge. Capillary electrophoresis separates hemoglobin variants based on the “zone” of detection where each variant hemoglobin appears based on a reference pattern. Normal hemoglobin (A, F, A2) is easily discriminated from variant hemoglobins (S, C, E, D), and quantification allows for detection of beta-thalassemia (increased A2 fraction). While useful as a screening tool, the hemoglobin variants identified in the “zones” are not specific. For example, Hb C and Hb Constant Spring share a zone, and Hb A2 shares a zone with Hb O- Arab. Variants detected by capillary electrophoresis are confirmed by a second method, and in this case Hb SC was confirmed by acid agarose gel (Sebia Hydrogel). When subjected to acid gel electrophoresis, Hb C and Hb S migrate in separate bands, while Hb A, A2, D, and E comigrate in the “A” band, and the “F” band may contain F in addition to the glycated fraction of normal adult Hb A. Patients with Hb SC disease will have variants detected in the S and C zones in capillary electrophoresis and lack signal in the A zone.4

Image 2. Laboratory Diagnosis of Hb SC disease includes hemoglobin electrophoresis and peripheral blood smear review. A) Hemoglobin capillary electrophoresis (pH 9.4) separates F, S, C, A2, A (Sebia, Capillarys 2 Flex Piercing). B) Acid agarose gel (pH 6.0-6.2) separates hemoglobins F, A, S, and C (Sebia, Hydragel Acid QC lane).  C) Peripheral blood smear morphology showing characteristic Hb SC forms including target cells, boat shaped cells (single arrow), red cell with crystals (double arrow), and hemighost cells (triple arrow).

Examination of the peripheral blood smear from a patient with Hb SC disease (Image 2C) reveals frequent target cells, boat-shaped cells (taco shaped), and only rarely contains classic sickle cells. Hemoglobin C crystals can be seen, both free floating and inside red cells, a feature of CC and SC disease but not seen in SS disease. Hemi-ghost cells and cells with irregular membrane contractions are also more frequent in Hb SC disease. In contrast, sickle cells are rarely observed in peripheral smears from Hb SC patients.

Salmonellaeare flagellated gram negative bacilli that are members of the Enterobacterales. Salmonellosis is typically foodborne in nature and presents as a self-limiting acute gastroenteritis.5,6 However, these organisms can invade beyond the gastrointestinal tract resulting in bacteremia.6 This case presents Salmonella as a cause of bacteremia in a patient with Hb SC disease following a bout of gastroenteritis. Although there is a well-known association between SCD and invasive infections with Salmonella, the incidence of Salmonella infection in patients with Hb SC disease has not been well studied. Patients with SCD, particularly those in Africa, are at risk for developing invasive disease caused by non-typhoidal Salmonella, including osteomyelitis, meningitis, and bacteremia. It has been hypothesized that disruptions in the gut microbiome and increased permeability of enterocytes makes SCD patients more prone to invasive Salmonella infections.6 Furthermore, the compromised function of the spleen in both patients with SCD and Hb SC disease increases the risk of disseminated infection by encapsulated bacteria and Gram negative rods. The spleen plays an important housekeeping role removing old or damaged erythrocytes, but also has an important immunological function housing memory B cells, producing antibodies and macrophages that phagocytize circulating bacteria, particulates or other debris and then present the antigens to other immunological cells in the spleen.7 Although sepsis caused by Salmonella is an occasional progression of gastroenteritis, this patient’s Hb SC disease likely increased the likelihood of bacteremia because of her functional asplenia.

References

  1. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331–6.
  2. Tim R. Randolph,24 – Hemoglobinopathies (structural defects in hemoglobin),Editor(s): Elaine M. Keohane, Catherine N. Otto, Jeanine M. Walenga,Rodak’s Hematology (Sixth Edition), Elsevier, 2020, Pages 394-423, ISBN 9780323530453, https://doi.org/10.1016/B978-0-323-53045-3.00033-7.
  3. (https://www.sciencedirect.com/science/article/pii/B9780323530453000337)
  4. Nathan, D. G., Orkin, S. H., & Oski, F. A. (2015). Sickle Cell Disease. In Nathan and Oski’s hematology and oncology of infancy and childhood (8th ed., pp. 675-714). Philadelphia, PA: Elsevier. Retrieved from https://www.clinicalkey.com/#!/content/book/3-s2.0-B9781455754144000206y.com/#!/content/book/3-s2.0-B9781455754144000206. Accessed 2022
  5. Bain, BJ. (2020) Haemoglobinopathy Diagnosis, Third Edition. Hoboken: John Wiley and Sons, Ltd
  6. Kurtz, J. R., Goggins, J. A., & McLachlan, J. B. (2017). Salmonella infection: Interplay between the bacteria and host immune system. Immunology letters190, 42–50. https://doi.org/10.1016/j.imlet.2017.07.006
  7. Lim, S.H., Methé, B.A., Knoll, B.M. et al. Invasive non-typhoidal Salmonella in sickle cell disease in Africa: is increased gut permeability the missing link?. J Transl Med 16, 239 (2018). https://doi.org/10.1186/s12967-018-1622-4
  8. Leone G, Pizzigallo E. Bacterial Infections Following Splenectomy for Malignant and Nonmalignant Hematologic Diseases. Mediterr J Hematol

-John Stack is a first year AP/CP resident at UT Southwestern Medical Center.

-Marisa Juntilla is an Assistant Professor in the Department of Pathology at UT Southwestern Medical Center. Dr. Juntilla is a board certified Clinical Pathologist and is certified in the subspecialty of Hematopathology.

-Dominick Cavuoti is a Professor in the Department of Pathology at UT Southwestern Medical Center. Dr. Cavuoti is a board certified AP/CP who is a practicing Clinical Microbiologist, Infectious Disease pathologist and Cytopathologist.

-Andrew Clark, PhD, D(ABMM) is an Assistant Professor at UT Southwestern Medical Center in the Department of Pathology, and Associate Director of the Clements University Hospital microbiology laboratory. He completed a CPEP-accredited postdoctoral fellowship in Medical and Public Health Microbiology at National Institutes of Health, and is interested in antimicrobial susceptibility and anaerobe pathophysiology.

-Clare McCormick-Baw, MD, PhD is an Assistant Professor of Clinical Microbiology at UT Southwestern in Dallas, Texas. She has a passion for teaching about laboratory medicine in general and the best uses of the microbiology lab in particular.

BOGO: Biopsy One, Get One Free

I’ve mentioned before how important it is to know clinical history before attending a biopsy, and I cannot stress this point enough. As the first line of screening, the intermediary between clinician and pathologist, the role of the cytologist is to prepare, assess, and convey. In a cancer center, we have three main populations: the patients with the unknown primary, the patients with the suspected primary, and the patients with the suspected metastasis. In the event of a suspected metastasis, we’ll review previous relevant pathology material if we have it onsite. Unless the clinician is requesting additional prognostic markers, the review process helps us eliminate the unnecessary repetition of immunostains (IHC) by confirming that the current material is morphologically consistent with the prior material. Sometimes we still perform old-school cytology without a plethora of ancillary studies. HA!

Most of the endobronchial ultrasound (EBUS) procedures performed at our institution are for lung cancer staging or differentiation between a lung cancer metastasis and an extra-pulmonary metastasis. Not that we don’t see the occasional sarcoid- or anthracosis-related process from time to time, but our most common indication is cancer. For an 88-year-old male patient with multiple lung nodules and both mediastinal and hilar lymphadenopathy, confirmation of metastasis was the main objective of the EBUS procedure. The patient’s pertinent medical history includes former tobacco use, squamous cell carcinoma of the lung (diagnosed percutaneously in 2022), clear cell renal cell carcinoma (s/p partial nephrectomy in 2020), prostate cancer (radiated in 2007), melanoma (excised in 2001), and cutaneous squamous cell and basal cell carcinoma (also previously excised in 2002 and 2008). With an extensive cancer history, the lung nodules and thoracic nodes could be any of them, although metastatic squamous cell carcinoma of the lung was clinically favored. My awesome cytologist colleague, Kelly, attended the EBUS procedure. The Rapid Onsite Evaluation (ROSE) was a clear-cut “adequate for diagnostic material,” and the attending pathologist added “tumor cells present.” The following morning, Kelly stopped by my desk to ask my opinion of the 12R (right hilar) lymph node she was screening. She said, “look at my dots. Do these look like the same cells to you? Or are they different? Because I feel like they’re different.” Before putting the slide on my scope, I asked, “so… like a combined adenosquamous? Or a small cell component?” She replied, “not small cell. Something… I don’t know, but they look different. The patient was recently diagnosed with lung cancer and has a history of renal cell.” I fixated on the H&E cell block slides (Images 1-3) before perusing the Diff-Quik and Papanicolaou-stained slides (Images 4-5). “Uhm… Why are there two different types of tumor cells here?! The cytoplasm here is so… vacuolated, but it’s not quite like lung adeno, and the other group… even the n/c (nuclear-to-cytoplasmic) ratio is different. What is this?” Kelly replied, “okay, so there are definitely two different types of tumor here.” I looked up, “It has to be. Absolutely, yes.”

Images 1-4. Lymph node, 12R, EBUS-guided FNA. 1-3: H&E cell block sections 1, 100x; 2, 400x; 3, 100x. 4: Diff-Quik stained smear.
Image 5. Lymph Node, 12R, EBUS-guided FNA. Pap-stained smear.

Kelly entered her diagnosis into our laboratory information system and brought the case over to the pathologist on cytology service for the day. She explained her thought process, and the pathologist also questioned if it was a combined process, such as a lung adenosquamous and maybe the original lung biopsy only sampled the squamous component. With the most recent clinical history of both lung squamous cell carcinoma and clear cell renal cell carcinoma, an IHC panel was appropriately selected. Later that afternoon, the pathologist exclaimed, “IT’S BOTH! IT’S SQUAMOUS AND RCC!” The clusters of squamous cell carcinoma did not stain for PAX8 (a renal cell carcinoma marker) (Image 6), and the same cluster stained positive for p40 (a squamous cell carcinoma marker) (Image 7). Within the same level of the cell block, the cluster of cells that appeared morphologically different than squamous cluster stained positive for PAX8 (Image 8) and negative for p40 (Image 9), confirming a renal cell carcinoma component. A small focus of p40-positive cells was present next to the p40-negative renal cell carcinoma (Image 9), further demonstrating mixed histology. This finding was shared with other pathologists, and the results were immediately called to the pulmonologist as this was a critical finding. Sometimes we encounter a partially involved node where the tumor cells are intermixed with lymphocytes, sometimes the lymph node yields more tumor than the primary site, and sometimes, albeit rarely, we encounter a lymph node infiltrated by two different carcinomas.

Images 6-9. Lymph Node, 12R, EBUS-guided FNA. Cell block section immunocytochemistry. Squamous cell carcinoma cluster – 6: PAX8-negative; 7: p40-positive. Renal cell carcinoma cluster – 8: PAX8-positive, 9: p40-negative (with small focus of p40-positive squamous cell carcinoma).

Due to the patient’s bulky disease and PD-L1 expression of 30%, the medical oncologists primary aim was to treat the squamous cell carcinoma first and follow up renal cell carcinoma therapy second. After the first few cycles of treatment, the lung nodules have decreased in size, but the thoracic nodes remain unchanged. Once the squamous cell carcinoma is controlled or demonstrates a more significant response, immunotherapy may be added to target both, with a tyrosine kinase inhibitor directed at renal cell carcinoma metastases in the event of progression.

-Taryn Waraksa-Deutsch, 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.

“Being a Doctor” Vs. “Doing Your Job”

I awoke to a text recently that simply said, “Can I ask you a question?” Having finished medical school 22 years ago, I get this very frequently and know from personal anecdotal statistics that it’s either a medical issue (high probability) or someone needs money (much less common). This is not a text from work nor is it from a channel that will result in additional funds deposited on my behalf. This is from an acquaintance, by which I mean it could be any of the following: family member, friend, colleague, ex-girlfriend of an ex-boyfriend, co-worker, random person I met somewhere, etc. I spent some time on the phone in response to this text, recommended a course of action, and solved the problem. The details of this discussion (or the hundreds of others I had over the years) are privileged and irrelevant. The point is that I was “being a doctor’. A problem was presented by a person in need with real concerns about their health (or a loved one’s), I assessed the information they provided, and suggested a next step. My advice is usually spot on and appreciated which stems from my being cautious but concerned. Another important feature of my advice derives from one of my mantras: “Don’t scare the straights!” (which I learned from the comic genius, Bill Murray, in Ghostbusters).

This is one of the hardest aspects of being a doctor (especially when you are a student). It’s really great that you recognize (sometimes immediately) that someone has a life-threatening illness… but they don’t need to know that unless they are within a safe, secure medical environment where action can be taken. Moreover, medical issues are private for the same reason. It’s pretty clear to all of us that we shouldn’t yell “Fire!” in a crowded theatre or even jokingly say words that sound like “bomb,” at an airport. But here’s a true story of what I mean with medicine. Many years ago, I happen to be on an airplane (at cruising altitude) coming back from Africa, where my friend, Paul Farmer (RIP), was also a passenger. Another colleague of ours (a surgeon) was also on the plane. Paul was having an eye issue which looked mild but irritating. Our colleague said, loudly in her confident tone, “Do you think it could he Ebola?” Paul and I exchanged a quick glance, both thinking, “Don’t scare the straights!” I think you see my point. But, for clarity, a personal example. One winter, my husband and I were returning from the city to our suburb, which required a brisk, long walk from the train. The sidewalks were icy and, in places, uneven. He stepped off and fell full force on his shoulder. The next morning he couldn’t move it and it was painful. My immediate thought was, “He broke his shoulder.” Did I say, “Dude, you totally broke your shoulder!” No. We were having an open house to sell our place and he was all stressed about it. So, I said, “Be careful with your arm and we will go to urgent care afterward.” This made him calm. I even made him drive to urgent care (it was not his dominant shoulder) to reassure him he was okay. In urgent care, the ortho surgeon (who happened to be that day’s coverage) walked in after the x-ray and said, “Dude, you broke your shoulder!” And my husband promptly passed completely out onto the examination table. It’s all about understanding the acuity of the situation and striving to not make it worse.

Have I ever been wrong? Of course! Because the only way to truly care for a medical concern is to evaluate it yourself in person with appropriate tools. And almost all of the times I have been wrong (which is only a few), there was some crucial aspect that was not shared because either it wasn’t known or there was discomfort with sharing.

But what I am describing is not unique to me. I’m quite sure every doctor gets these calls with frequency. It’s the purest form of practice because there is no financial transaction presumed, assumed, or demanded.

But what about “doing my job?” Let’s break that down. I work for a non-profit and have a private consultation practice (non-overlapping, non-conflicting). Currently, I am financially compensated (at about $175/hour (pre-tax)) for any/all of the following: health system implementation, grant writing/administration, education, research management, social media production/communication, expert scientific/business consultations, committee participation, abnormal laboratory case review, daily laboratory management, intra-operative consultation, market insights/research, etc. Not much of that sounds like I’m fighting death and stamping out disease at the individual patient level, the life task I as trained for in medical school. Importantly, I’m also hard salaried across all my work so I don’t do individual billing except for a few things like abnormal slide review. Many of my physician colleagues do have to engage in individual billing. But I think much of what I do still sounds very familiar to many of my physician colleagues who see patients every day. When (in my opinion) my physician colleagues should be spending every hour of every day “being a doctor,” as I described above, I fear they spend a lot of time instead documenting, managing, and administrating to ensure they are compensated. I am of the very unpopular opinion that healthcare should be free but I also believe healthcare workers should be compensated aligned to their impact on patients. The medical profit insistence paradigm continues to widen inequity while decreasing the care time for patients in lieu of format/template/documentation to justify billing. I have to spend time doing this non-patient care but, fortunately, they are limited because of the narrow slice of medical billing to which my services are privy.

Here is a specific example to demonstrate the difference I’m discussing. I received an abnormal smear to review from the laboratory. The white blood cell count was over 400,000 cells (ref 10 – 30), the smear was a “medical student”-level diagnosis, the patient was on a supposedly effective treatment, but they had left against medical advice. There are many ways to respond to this case. My question was, “Is this patient okay, right now?” and my immediate action reflex said, “This patient needs to see an oncologist right now.” But she left AMA. How you as a patient or doctor respond to this says a lot about you as a person but also about the fiscal constraints in which you work. What did I do? I called the patient who had, thankfully, been admitted elsewhere, and asked them to please have their doctor call me back. The doctor did, I told them the information, and my suggestion that oncology see them immediately. Oncology saw them a few hours later. Let’s summarize. I spent about 20 minutes reviewing all of the clinical and laboratory information, about 1 hour on the phone over 2 days, and about 10 minutes documenting all of this in the patient’s medical record. I was subsequently paid an additional $25 two months later for that documentation by the patient’s insurance company. So, I “did my job” for $16.67/hour over my base but I was also “being a doctor,” which likely was best for the patient. Which is most important at the end of the day? I certainly didn’t need the extra $25 but the patient definitely needed my input. Importantly, note that the insurance company valued my time at a 10-fold lower rate than did my hospital.

A recent study demonstrated that when nurse practitioners are used instead of physicians, healthcare costs were higher.1 This study follows other studies which have shown the opposite. I don’t have an opinion about quality of care, appropriateness, or territorial pissings in the current debate between MDs and NPs about scope of practice; in fact, I see NP’s quite frequently for my healthcare. But we are all being asked to always be conscious of costs in healthcare when all we should be focusing on is, “How is the patient doing right now?” Grand efforts, like task shifting domestically and internationally, are assumed to save money but they simply don’t do so universally. Where costs could be easily cut (i.e., administration) or outsourced (i.e., finance, HR, IT), they aren’t because C-suites are in charge of cost cutting. But doctors (and NPs and all front line medical workers) are the ones being told to be cost conscious and find cost savings—when their job should only be asking the question, “How is the patient doing right now?”

I love “being a doctor,” especially when I can help someone reach a positive outcome. I love “doing my job” because it’s variable, ever-changing, challenging, rewarding, and I feel my compensation is appropriate. I really love when “doing my job” and “being a doctor” align around the same task. Finding this alignment as frequently as possible produces the happiest healthcare workers and the best care for patients, in my opinion.

Note: As an employee of a 501(c)(3), my salary information is public knowledge.

Reference

  1. https://www.ama-assn.org/practice-management/scope-practice/amid-doctor-shortage-nps-and-pas-seemed-fix-data-s-nope
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.

Omicron: Variant of High Significance?

Omicron is now the dominant variant in the United States and gained that title faster than any variant before it. I have been tracking variants in the North Texas region since February of this year and detected the first Alpha variant (B.1.1.7). During this time, there were multiple substrains circulating. Some like Epsilon (origin California) rose in prominence then declined to extinction. Rise in Alpha (origin U.K.) and Delta variants (B.1.617.2, origin India) were tracked over the course of weeks, but Omicron has been tracked on a daily basis, since it is rising so quickly.

Many places are using S-Gene Target Failure (SGTF) as a surrogate for Omicron variant (Yale, University of Washington below).

Photo credit @NathanGrubaugh (Yale, Left) and @pavitrarc (UW virology, right)

SGTF occurs when the TaqPath COVID-19 multiplex test has 2/3 targets successfully amplify when the S-gene target does not or “drops out.”  This phenomenon was first observed in the Alpha variant, because the probe for this target overlapped a characteristic mutation: S:Del69_70 (deletion of the 69th and 70th amino acids in the spike protein from a 6 base pair deletion). This mutation is absent in Delta, but present in Omicron, so has been used as an early tracker of Omicron prevalence.

Most of this discussion is speculative and we won’t ever really know, but given the rate of transmission of this variant, it seems unlikely that it would have acquired so many mutations and not been detected before now. The most recent common ancestor is from over a year ago suggesting it was incubating for a long time.

We’ve seen a case of a person severely immunocompromised with no antibody response to vaccination + booster who still has an unmutated wild type strain in their system. With no immune pressure, the virus has not evolved.

However, in HIV+ patients with variable/ low immunity, there could be enough pressure to drive the immune evasion properties seen in Omicron. Southern Africa has over 30% of their HIV+ patients not on therapy who would be likely candidates for this type of host.

Did we see this coming?

Yes. Other immune evasive variants have arisen in areas with high prevalence of previous infection (Brazil/ S. Africa). Organisms evolve just enough to overcome the challenges in their environment. Thus the level of immunity provided by various immune exposures are approximately:

 Previous infection < 2x Vaccine < 2x Vaccine+ previous infection ~ x3 Vaccine

Scientists theorized that either Delta would evolve more immune evasive mutations or a totally new variant would arise. However, I didn’t think it would spread this quickly.

What is the impact?

Therapies. Most antibody therapies are directed as the business end of the spike protein—the receptor binding domain (RBD). The rest of the protein is covered in glycosylation modifications that block much recognition. Thus with many mutations in Omicron compared to the wild type strain (white), most therapeutic antibodies no longer bind/ inactivate viral replication.

Source: https://biorxiv.org/content/10.1101/2021.12.12.472269v1.full.pdf

Only one monoclonal antibody—Sotrovimab from GSK—is effective, because it binds a pan-coronovirus epitope outside of the RBD. However, this antibody is in short supply.

  • Thus, knowing which variant someone has can direct therapy. Several hospitals in our area are out of Sotrovimab, and only people with the Delta variant can access other options. Thus, knowing the variant in a short time frame has clinical implications.
  • Whole genome sequencing takes too long, so the FDA has agreed to review PCR genotyping approaches for clinical use. I have described some previous approaches, but many of these methods are useful as a screening method and would not have sufficient specificity to determine whether an omicron variant is present. Next time, I will discuss variant genotyping, why it is important, how it can be done, and what clinical actions can be taken with the knowledge.

Severity. There are signs that it is less severe. Is this due to increase in immune tolerance? We now have been prepared by either previous infection or vaccination to be protected from hospitalization or severe disease.

@Jburnmurdoch https://twitter.com/jburnmurdoch/status/1478339769646166019/photo/1

Or is the decline in severity due to lower pathogenicity? A recent non-peer reviewed study indicates the virus replicates x70 faster than Delta in the upper airways (left), but infiltrates cells 10% as well as the original strain.

From: https://www.med.hku.hk/en/news/press/20211215-omicron-sars-cov-2-infection?utm_medium=social&utm_source=twitter&utm_campaign=press_release

We all hope this will continue to be better news about the severity of Omicron, but from the lab side, I’ve heard of positivity rates >50% at some places. So this can still have a broad impact.

-Jeff SoRelle, MD is Assistant Professor of Pathology at the University of Texas Southwestern Medical Center in Dallas, TX working in the Next Generation Sequencing lab. His research interests include the genetics of allergy, COVID-19 variant sequencing, and lab medicine of transgender healthcare. Follow him on Twitter @Jeff_SoRelle.

Peritoneal Problems

A 74 year old male patient with an extensive cardiac history initially presented to the ER with black stool, warranting a CT scan, upper endoscopy, and colonoscopy, identifying a large, obstructive mass in the colon, smaller, yet unresectable polyps, and subcentimeter liver lesions and lung nodules. The colonic mass was biopsied, consistent with adenocarcinoma; however, the liver lesions were too small to characterize. One month after the onset of symptoms, a right hemicolectomy was performed, and the pathology was signed out as moderately differentiated adenocarcinoma, microsatellite stable, with evidence of lymphovascular and perineural invasion, placing the patient’s stage at IIA (pT3, pN0, cM0). Through shared decision-making, the medical oncologist and patient elected for surveillance due to multiple comorbidities. Forgoing adjuvant therapy, the patient was discharged to physical therapy/rehabilitation. The patient returned for imaging 4 months after his hemicolectomy, demonstrating an enlargement in one of the liver lesions, but then, the patient was lost to follow-up for 20 months.


The patient reestablished care and surveillance imaging, which demonstrated a hypodense liver lesion (in a background of poorly visualized subcentimeter liver lesions), a nonocclusive thrombus in the right portal vein, a heterogenous enhancement of the left portal vein (suggestive of an underlying tumor thrombus), and an 8 cm heterogenous right adrenal mass. Based on the most recent CT scan, the differential diagnoses of the adrenal mass include metastatic disease or a primary adrenal lesion including adrenal cortical carcinoma or pheochromocytoma (for which biochemical analysis should be performed before attempting a biopsy). Extensive peritoneal lymphadenopathy was visualized as well. The area of the right hemicolectomy, however, did not show evidence of recurrence. After biochemical evaluation for metanephrines ruled out a pheochromocytoma, the patient underwent a CT scan-guided adrenal FNA and core biopsy.

The Diff-Quik smear assessed at the time of biopsy revealed a highly cellular specimen, some cells with bare nuclei, enlarged nuclei, and some pseudoglandular structures.

Images 1-2: Adrenal Gland, Right, Fine Needle Aspiration. 1-2: DQ-stained smears

Telepathology confirmed an adequate sample of tumor cells present, and core biopsies were obtained.

The following morning, the pap-stained smears and H&E cell block sections were screened. The cells appeared polygonal with a high N/C ratio and prominent macronucleoli. Cell arrangements formed thickened trabeculae. However, the cytoplasm is more granular than the lipid-rich cytoplasm seen in an adrenal cortical carcinoma. The H&E cell block sections depicted a beautiful trabecular pattern with endothelial cells wrapping the periphery.

Images 3-6: Adrenal Gland, Right, Fine Needle Aspiration. 3-4: Pap-stained smear; 5-6: H&E Cell Block sections.

The preliminary morphology was interpreted as carcinoma, and both cytotechnologist (or cytologist, as we now prefer to be called) and pathologist suggesting features of adrenal cortical carcinoma; however, the IHC markers proved otherwise!

Images 7-9: Adrenal Gland, Right, Fine Needle Aspiration, IHC Cell Block Sections. 7:HepPar1+; 8: Arginase+; 9: pCEA (canalicular pattern)+.

Other differential diagnoses considered renal cell carcinoma and pheochromocytoma (to be safe). The IHC profile ruled out adrenal cortical carcinoma as the cells of interest were negative for inhibin, calretinin, and Melan A. Negative PAX-8, EMA, AE1/AE3, and vimentin staining ruled out renal cell carcinoma, and negative chromogranin, synaptophysin, GATA-3, vimentin, and S100 staining enabled us to safely say that a pheochromocytoma was out of the equation as well. Positive staining for HepPar1, arginase, pCEA (canalicular pattern), and CAM5.2 supported the unlikely diagnosis of metastatic hepatocellular carcinoma (HCC).

This diagnosis placed the patient at Stage IV HCC. It came to light that the patient has a remote history of hepatitis and a high-risk history of drinking, contributing to a poor prognosis. Due to the patient’s condition, they held off on HCV antiviral therapy and decided to observing viral load through regular blood work. The patient and clinician discussed the risks and benefits along with alternatives of systemic therapy, as his multiple comorbidities still pose a significant risk. Immunotherapy was determined to be the best option to delay the progression of his cancer and maintain quality of life.

-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.

Validations/Verifications of Alternative Anticoagulants for Platelet Clumping

Platelet clumping can cause a falsely lowered platelet count on hematology instruments and can be difficult to resolve. With thrombocytopenia, physicians need an accurate count to diagnose, treat, or monitor patients. Clumping can be due to pre-analytic issues with specimen handling, can be caused by medications, or may be an in vitro phenomenon caused by anticoagulants. The clumping makes precise counting impossible and even estimates can be very tricky. If there are clumps, and recollection of the sample still yields platelet clumping, then many labs will have an alternate tube drawn or an alternative method to help resolve clumping.

Many of us have heard of using sodium citrate tubes for patients who have clumped platelets in EDTA. So, if you are having platelet clumping headaches, you can just order some sodium citrate tubes and start using those on your hematology analyzers, right? Not so fast. There are many published references of the use of sodium citrate tubes to resolve EDTA induced thrombocytopenia but we still see samples in which the clumping is not resolved with the sodium citrate tube. Published studies have shown that several other alternate methods have been helpful in resolving platelet clumping issues. These include drawing specimens in CTAD, ACD, or ‘ThromboExact’1 tubes, or adding amikacin or kanamycin to the EDTA after the specimen is drawn.

So, why can’t we just order one of these other tubes and start reporting results? Hematology analyzers are only FDA approved for EDTA tubes. Before you can use any modified method, and before you can report any patient results, your laboratory must do validation or verification studies to prove that the method produces valid results.

A validation provides objective evidence that a test performs as intended. A validation uses a defined process and is used when setting up and implementing a new test. One example is a laboratory developed test (LDT), which is a test performed by the clinical laboratory in which the test was developed. A LDT can be one that is neither FDA-cleared nor FDA-approved or can be one that is FDA cleared/approved but has been modified by the performing laboratory. The use of sample types or the use of collection devices not listed in manufacturer instructions constitute modifications, by this definition. In a validation, accuracy should be tested with at least 40 samples across the analytical measurement range (AMR). Correlations are then performed. Precision should be tested over approximately 20 days. A verification, on the other hand, uses an abbreviated process and is used when setting up and implementing new tests that are cleared or approved by FDA. Before reporting patient results, the laboratory must demonstrate that a test performs in agreement with prior claims and must demonstrate performance specifications are comparable to the manufacturer’s specifications. Verification therefore is a confirmation that a test method meets specified requirements and would be applied to a method which has already been validated. For a verification, a smaller sample size may be used, and precisions tested over 5 or more days.

Table 1. Validations vs. Verifications

So, which would you do if you wanted to use an alternate method for reporting platelet counts? Hematology analyzers are only FDA approved for platelet counts on EDTA, but the by which the sample is analyzed does not change with an alternate tube, so it may be possible to do a limited validation or verification with a smaller sample size. A laboratory needs to prove correlation, accuracy, and precision. Follow your laboratory SOPs for validation/verification and consult with your accrediting agencies, if necessary. A plan needs to be written and signed off by laboratory director. Choose the alternative method you wish to investigate and run correlations for platelet counts on EDTA and the alternate anticoagulant. If your instrument has more than one platelet mode, it is important to run samples in the mode which you would normally use for thrombocytopenia or flagged platelet counts. Apply any dilutional factors and calculate correlations. This data will be Included in your report, which, along with a procedure needs to be signed by the laboratory director.

The most important thing is to write a plan and a follow-up report according to your SOPs and to make sure any requirements of accrediting agencies are included. There can be some differences in interpretation of standards, so it is the laboratory’s responsibility to make sure what you have done meets the standards that apply to your lab.

The use of alternate tubes for platelet counts has been well reviewed in literature. Sodium citrate tubes are the most common, likely because they are the easiest to use and the most cost effective. Remember though that sodium citrate and other methods cannot resolve all case s of pseudothrombocytopenia. There are several special notes to consider. Counts from sodium citrate tubes are known to be stable for approximately 3 hours, after which counts decrease. As well, it has been shown in literature that sodium citrate tubes do show a negative bias. It has been reported that the 10% dilutional factor may be too low. Some studies have been done to determine dilution factors that correlate more closely with EDTA tubes, and researchers have suggested factor of 17%-25%. If your laboratory wishes to determine its own dilutional factor for sodium citrate or other tubes, this will also have to be included in your platelet studies. Lastly, CBCs are calibrated for EDTA, so only the platelet count should be reported from an alternative anticoagulant.

The end of another busy and challenging year is upon us, and at this time of year we can find ourselves rushed to finish ‘end of year’ tasks such as competencies and continuing education requirements. and a response to Sysmex’s recent webinar “Those Sticky, Tricky Platelets – Solving the Puzzle of Platelet Clumping” (Oct.20,2021). After the webinar I had many questions from techs asking, “Do we need to validate our alternative method?” and “How do we go about doing that?” The webinar discusses pseudothrombocytopenia and its causes in more detail than my earlier blog from Oct 2019, “Hematology Case Study: The Story of the Platelet Clump: EDTA-Induced Thrombocytopenia”. The webinar can be found at https://webinars.sysmex.com/webinars/11ae743e-ac99-47e7-acb7-2b24cedc1a1a and is available for CEU, free of charge.

References

  1. Baccini V, Geneviève F, Jacqmin H, et al. Platelet Counting: Ugly Traps and Good Advice. Proposals from the French-Speaking Cellular Hematology Group (GFHC). J Clin Med. 2020;9(3):808. Published 2020 Mar 16. doi:10.3390/jcm9030808
  2. Bizzaro N. (2013): Pseudothrombocytopenia. In: Platelets, Vol. 3, ed Bizzaro N, Elsevier, Amsterdam, pp. 989–997 
  3. Chae H, Kim M, Lim J, Oh EJ, Kim Y, Han K: Novel method to dissociate platelet clumps in EDTA-dependent pseudothrombocytopenia based on the pathophysiological mechanism. Clin Chem Lab Med 50, 1387–1391 (2012)
  4. Socha, Becky. Calibration and Calibration Verification: Who, What, Where, When, Why, How & Did I Pass or Fail?. AMT 81st Educational Program and annual meeting, 2019
  5. Zhou X, Wu X, Deng W, Li J, Luo W: Amikacin can be added to blood to reduce the fall in platelet count. Am J Clin Pathol 136, 646–652 (2011)
  6. https://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA/downloads/6065bk.pdf
  7. https://www.cap.org/laboratory-improvement/proficiency-testing/calibration-verification-linearity
  8. https://www.westgard.com/cal-verification-criteria.htm
  9. https://labmedicineblog.com/2019/10/29/ hematology-case-study-the-story-of-the-platelet- clump-edta-induced-thrombocytopenia/
Socha-small

-Becky Socha, MS, MLS(ASCP)CMBBCM graduated from Merrimack College in N. Andover, Massachusetts with a BS in Medical Technology and completed her MS in Clinical Laboratory Sciences at the University of Massachusetts, Lowell. She has worked as a Medical Technologist for over 40 years and has taught as an adjunct faculty member at Merrimack College, UMass Lowell and Stevenson University for over 20 years.  She has worked in all areas of the clinical laboratory, but has a special interest in Hematology and Blood Banking. She currently works at Mercy Medical Center in Baltimore, Md. When she’s not busy being a mad scientist, she can be found outside riding her bicycle.

Where have all the Techs Gone?

Electronic media is replete with articles and editorials of employers lamenting the shortage of workers. Signs offering hiring bonuses hang outside of restaurants, stores, and other retail outlets all across the country.

The inability to find workers has forced employers to take another look at their business model and reevaluate whether the model is still viable in its current form. The power balance in the employer/ employee dynamic has shifted. Employers accustomed to having their choice of applicants now find themselves scrambling to find workers.

No schools, No students

The healthcare industry, including the medical laboratory, is not exempt from the shortage despite healthcare experts and administrators knowing that the trending laboratory employee shortage was inevitable years ago.

Laboratory school administrators and managers have been sounding the alarm about the lack of community college and university medical technology program applications. Many academic medical technology programs are shuttered due to a lack of students.  The decrease in the number of students going into the laboratory field and the normal attrition rate of older workers retiring or moving on to higher-paying occupations has led to a high vacancy rate and a loss of expertise.

Burnout

The pandemic has added more pressure on a cohort of employees experiencing the stress of a new and unknown danger. These allied health professionals were (and are) the front-line response to a disease threatening everyone, regardless of economic or social demographics. Lab worker burnout has become a documented phenomenon

We call them heroes, but in reality, these are the same people working every day (pandemic or not), serving patients and delivering quality test results. Labs across the nation are filled with these everyday people. But just like everyone, laboratory workers have families, feelings, and needs they are trying to meet while being asked to give a little more. Many have little left to give and are now leaving the field to pursue other less stressful occupations or to simply enjoy the life they have worked so hard to build.

Start recruiting early

How can healthcare organizations stem the tide of those choosing to leave the lab and simultaneously attract young fresh minds to the unglamorous and less financially rewarding but necessary field of laboratory testing?

Presentations to elementary school children are a great way to introduce the next generation to the laboratory field. What child doesn’t like looking into a microscope to see their own red and white blood cells? Roadshows put on in junior high and high schools are a great way to kindle interest in healthcare just when students are beginning to ponder the question of what they want as a career.

Educational Aid

The cost of college continues to rise. Scholarships are often garnered by high-performing “A” students. But there is a pool of “B” students that could also benefit from financial assistance and would be just as welcomed into clinical laboratories. Broadening and diversifying the qualifications to receive a scholarship and financial aid could conceivably add to the pool of potential laboratory workers. Another unique idea is to allow laboratory workers’ dependents access to unused employee educational benefits.

Wellness in the Lab

Resources should also be dedicated to retaining technicians and technologists who are considering leaving the laboratory field.  The level of compensation is meaningful, but studies have shown that employees often leave the job for more esoteric reasons. Reducing stress, supporting a culture of wellness, inclusiveness, and belonging can differentiate one workplace from another. The theme of workplace wellness was extensively discussed at this year’s ASCP 2021 annual meeting in Boston.

The Need is Real

The pandemic has highlighted the importance of the laboratory to the health of the nation. The medical laboratory should use this moment in the spotlight to advocate for more resources and emphasize the necessity for more laboratory programs and students to meet the future testing needs of the nation.

Of course, many lab managers are wondering what to do today to stem the slow leak of personnel. Providing mental health support and financial incentives do work to keep these knowledgeable workers in the lab. Managers realize that laboratory science is a demanding high acuity job with little or no margin for error. To maintain quality, the healthcare industry will need to change its perceptions about the laboratory and address the lack of technicians and technologists with the same interest and retention resources given to nurses and doctors.

-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.

Disruption in Cancer Care: Good or Bad … What’s Next?

The concept of disruption often has negative connotations. Everyone on the planet can understand the phrase, “COVID-19 has disrupted our lives” without explanation. Although this disruption has been global, the disruption and ensuing impact this has had on non-COVID-19 related healthcare and, specifically, oncology, have been dramatic.

Surgeries, chemotherapy and other medical treatments were canceled or delayed by months, and volumes of testing across the cancer landscape dropped to minimums. Existing infrastructure furthered the deployment of telehealth consultations and, eventually, clinics were reopened; however, there is no question that many people with cancer face being diagnosed at a more advanced stage of disease, with worse outcomes.

On 25-26 October, the World Cancer Leaders’ Summit, organized by the Union for International Cancer Control and hosted by the American Society for Clinical Pathology, brought together more than 600 leaders from some 100 countries. One of the major topics of discussion was, “What do we do for oncology after COVID-19?”

In addition to examining heart-wrenching data on disruptions to cancer services, there were also positive discussions about what we have learned from this pandemic, how we have adapted, and what novel approaches we should keep that could create optimal, more efficient, or more impactful cancer care.

The positive side of disruption

When applied to innovative technologies or ways of thinking, “disruption” can be positive, particularly when we consider the many advancements happening so quickly with treatments, including immunotherapies like check-point inhibitors, mRNA cancer vaccines, CAR-T therapy, epigenetic therapies, that the different members of the cancer community are often running to catch up.

Some of these advances are simply operational efficiency (i.e., getting more output from the system by improving the inputs and the usage) while many are transformative innovations (i.e., immunotherapy for lung cancer and melanoma). And some advances are considered “disruptive” because they are not just a new way of doing something better but allow an entirely new approach that previously wasn’t available and that radically improves prevention, diagnosis, treatment or supportive care.

A disruptive revolution in cancer detection

In oncology, a true disruptive innovation is taking place with universal cancer screening (UCS) or multi-cancer early detection (MCED). The earlier a cancer is detected and the patient can start treatment, the higher the chance of survival. The current paradigm for cancer care is suspicion of cancer leads to diagnosis, which leads to treatment. Suspicion rests in either the results of a screening test or when a person shows symptoms, and diagnosis involves a biopsy that must be analyzed.

Primary care doctors and not just oncologists will be able to use UCS and MCED testing platforms. Tests will be performed on a timescale (e.g. annually, every five years) relevant to the person’s age, medical and family history as well as the type of cancer being detected for, rather than wait for a patient to present with symptoms. Furthermore, these platforms will be able to detect 20 to 50 or more cancers from a single sample and for myriad cancer stages, including precursor or pre-invasive cancer, and there is no need for a separate diagnostics phase: the result itself would dictate a treatment because the UCS/MCED platforms not only detect the cancer but can, in theory, give an origin and medical response parameters.

Whereas the current paradigm involves primary care, oncology, surgery, radiology, pathology, nursing, etc., this new paradigm would only involve primary care and an insurance provider.

Innovating, Creating and Breaking Down Barriers

The transition from traditional oncology to such novel platforms – as with all disruptive technologies – will not be smooth as we are talking about entire businesses and careers connected to traditional oncology possibly become obsolete. People with cancer, however, are expected to have shorter, more efficient journeys, likely with better outcomes and at a lower cost.

In LMICs, where oncology care systems are not nearly as developed as in HICs and where governments, unlike the US, are generally assumed or expected to pay for cancer services, UCS/MCED will require fewer dollars and provide better results than investing in the infrastructure required to create traditional cancer care systems. If this theoretical framework (UCS/MCED for cancer) does demonstrate the value in promises, it would set the stage for similar paradigms in other non-communicable diseases for which infrastructure and resources in LMICs are often lacking.

UCS/MCED was a hot topic at the WCLS. The leaders that were involved in the meeting sit on either side of a fence with regards to this innovation. There are those that support this technology’s development as quickly as possible, anticipating better patient outcomes, more efficient systems, less healthcare spending and more revenue. There are also opponents to this innovation, who throw up barriers resulting from fear of losses (revenue, employment, testing volume, referral networks, etc.).

The barriers they present, however, are important only if they are true barriers and not just perceived barriers. Why? True barriers are likely to require the engagement of the traditional oncology system to overcome; yet the act of overcoming those barriers may herald the disruptive innovation they fear. When an existing system must participate in its own creative destruction, can such a disruptive innovation take place?

No doubt the participants of the WCLS will continue to ask this question and let’s hope they find some answers for the sake of our patients.

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.

E(cto)pic Metastasis

A 72 year old female originally presented with lung carcinoid and bilateral renal masses. The patient’s left kidney biopsy demonstrated ectopic thyroid parenchyma by an outside institution. Her thyroid function tests were unremarkable, she had no known previous head and neck radiation, and to the best of her knowledge, there was no family history of thyroid cancer. She underwent FDG PET imaging, which showed increased bilateral uptake in the neck (thyroid and lymph nodes), and an avid right posterior renal mass. Otherwise, her scan was relatively clear. Her left renal mass was resected and demonstrated thyroid parenchyma, but the differential diagnoses included thyroid heterotopia and metastatic well-differentiated thyroid carcinoma.

FNA and core biopsy were then obtained from the right upper quadrant of the kidney. The findings are depicted below.

Images 1-6: Kidney, Right, Fine Needle Aspiration. 1: Pap-stained smear; 2: DQ-stained smear; 3: H&E Cell Block section; 4: TTF-1+; 5: Thyroglobulin +; 6: CK7+.

The FNA was signed out as “Atypical thyroid tissue present.” Immunohistochemical stains demonstrated positive staining for CK7, vimentin (partial), TTF-1, thyroglobulin, and PAX-8 (partial), and negative staining for RCC, Napsin A, synaptophysin, and chromogranin. While these immunostains suggest thyroid-type tissue, morphology was most worrisome for metastatic thyroid carcinoma. The chromatin presented as hypochromatic and powdery, nuclear grooves and pseudoinclusions were present, and the nuclei were enlarged with irregular membranes. However, the scant material present precluded a definitive diagnosis.

Images 7-8: Kidney, Right, Core Biopsy. 7, H&E section 100X; 8, H&E section 400X.

The core biopsy suggested benign-appearing thyroid tissue similar to that seen in the left kidney, however, the surgical pathologist diagnosed the material as metastatic thyroid carcinoma.

A thyroid FNA was obtained from one of the patient’s multiple right-lobed thyroid nodules consistent with TI-RADS category 5 the next day. This was diagnosed as atypia of underdetermined significance due to scant cellularity.

Images 9-10: Thyroid, Right Lobe, Fine Needle Aspiration. 9: DQ-stained smear; 10: Pap-stained smear.

The right renal mass was resected after molecular profiling was performed on the left renal mass tissue. Mutation Detection by Next Generation Sequencing demonstrated a tumor mutation burden of 3.6Muts/Mb and identified mutations in the PRKDC, PTEN, and KRAS genes. Two kidney tumors were identified in the right kidney (one measuring 8.0 cm and the other 4.5 cm), both diagnosed as metastatic thyroid carcinoma with papillary features.

Images 11-12: Kidney, Right, Resection. 11, H&E section 40X; 12, H&E section 400X.

The thyroid was then resected, and pathologic findings were consistent with invasive follicular carcinoma with extensive angioinvasion to 4 or more vessels. While renal metastases are rare, the high affinity for angioinvasion makes the kidney a prime metastasis site due to its vascular-rich tissue. The patient was prescribed a low iodine diet and Thyrogen-stimulated radioiodine ablation to remove any remaining thyroid tissue or micrometastases and enhance the sensitivity of thyroglobulin as a tumor marker for surveillance purposes. While thyroid cancer (papillary and follicular types) is typically considered “the best cancer to have” due its slow growth and low-risk of widespread malignancy, it doesn’t mean that it won’t metastasize, even to a distant organ that you normally wouldn’t suspect. Great caution must be taken to ensure that lumps, bumps, and swallowing issues are addressed at annual physicals to catch a low-risk cancer before it has the opportunity to become an epic metastasis.

-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.