Hematology Case Study: The Race to Save a 48 Year Old Man from a Rare Disease

A 48-year-old Caucasian male presented to a Baltimore Emergency Room complaining of fever, chills, and aches. He stated he had not been feeling well for the past week. His symptoms had progressed rapidly over the last 3 days to include night sweats, nausea and excessive somnolence. History taken in the ER revealed the patient had returned 10 days prior from a Safari in Botswana and Zambia. The patient was admitted to the ICU, in shock, with a BP of 75/50. Even though the patient had taken anti-malarial medication, the doctors suspected malaria. Blood was sent to the lab for a blood parasite exam and treatment for malaria was started while the doctors waited for the confirmation.

In the Hematology laboratory, technologists perform microscopy of thick and thin blood smears to look for malarial parasites. The thin smear is a typical Wright Giemsa stained wedge smear, and the thick smears are prepared and stained so that the red blood cells are lysed, and the sample is concentrated, making examination easier. Thorough, careful examination of the thick smear is aimed to identify whether a particular parasite is present, but they require a long drying period and take several hours to prepare and read. Thin smears can detect the parasites but also permit identification of particular species of malaria. While the thick smears were drying the technologist examined the thin smear.

The technologist who examined this patient’s thin smears saw parasites (image 1) under her microscope. She consulted with a supervisor and pathologist to confirm, and the patient’s doctor was notified that the patient did not have malaria, but instead, had Trypanosoma! This was an exciting find in the laboratory, as there have been only 40 cases seen in the US in the past 50 years.

Image 1. This slide shows the parasite, in dark blue. The parasite causes
African trypanosomiasis, also known as sleeping sickness
(Courtesy of Greater Baltimore Medical Center).

The race for diagnosis and treatment did not stop there, as there are 2 types of African trypanosomiasis, or African sleeping sickness, and effective and appropriate treatment must be started in a timely fashion. Both types look identical on a blood smear and both are considered universally fatal, if not treated. West African trypanosomiasis and East African trypanosomiasis are caused by the tsetse fly, which only lives in rural Africa. The patient stated he did remember being bitten by tsetse flies, and because there had been such a short span of time between being bitten and the onset of symptoms, doctors concluded that the patient had the rarer and fast-acting East African trypanosomiasis, which can kill within months.

Epidemiologists at CDC were contacted, who then consulted other infectious disease specialists at CDC. There are 2 treatments depending the stage of the disease. Surinam is the first line of defense, but melarsoprol, which is arsenic-like and very toxic, must be used if the parasites have reached the central nervous system. Because of the urgent need to start treatment, emergency shipments of both drugs were flown to Baltimore. The patient was started on Surinam to reduce the number of parasites in his blood to a level low enough to allow a spinal tap to be performed. After confirming that the CSF showed no signs of the parasite, treatment with surinam was continued and the patient was discharged a week later and has made a full recovery.

Because of the excellent work done by the medical technologists who made the first discovery, the speed with which the critical calls were made, the actions of the doctors involved, and the cooperation of the CDC, this patient received his first dose of Surinam a little over 24 hours after his blood was sent to the lab. This case shows the importance of a thorough medical and travel history in differential diagnosis. It also illustrates the importance of the competency evaluations and surveys in which all laboratory professionals are required to participate. None of the technologists, doctors or scientists involved had ever actually seen a case of African Trypanosomiasis, they had only read about it in books and seen it on competency assessments.

This case is based on an actual case from 2016. My coworker, Gail Wilson, was the technologist who first saw the Trypanosoma on the slides. Many thanks to Gail for her keen eye and attention to detail!

Image 2: L&R: Trypanosoma brucei in thin blood smears stained with Giemsa. Center: A close up of a tsetse fly. Credit: DPDx



  1. Jon E. Rosenblatt Barth Reller Melvin P. Weinstein.pages 1103-1108, Laboratory Diagnosis of Infections Due to Blood and Tissue Parasites Clinical Infectious Diseases, Volume 49, Issue 7, 1 October 2009; retrieved March 2018 from https://academic.oup.com/cid/article/49/7/1103/316703
  1. Ivo Elliott, Trupti PatelJagrit Shah, and Pradhib Venkatesan. West-African trypanosomiasis in a returned traveller from Ghana: an unusual cause of progressive neurological decline BMJ Case Rep. 2014; 2014: bcr2014204451. Published online 2014 Aug 14.doi: 1136/bcr-2014-204451; retrieved March 2018 from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139564/
  1. Lena H. Sun. Medical Detectives raced to save a man from a rare, ‘universally lethal’ disease; retrieved March 2018 from https://www.washingtonpost.com/news/to-your-health/wp/2016/12/22/medical-detectives-raced-to-save-a-man-from-a-rare-universally-lethal-disease/?utm_term=.16d7b136bc47
  1. Parasites – African Trypanosomiasis (also known as Sleeping Sickness). Retrieved March 2018 from https://www.cdc.gov/parasites/sleepingsickness/
  1. DPDx- Laboratory Identification of parasites of Public Health Concern; retrieved March 2018 from https://www.cdc.gov/dpdx/



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


Microbiology Case Study: A 52 Year Old Man with End Stage Renal Disease

Case History

A 52-year-old man with multiple medical issues including a history of end stage renal disease on hemodialysis, chronic pancreatitis status post distal pancreatectomy, intravenous drug use through dialysis catheter, and multiple types of bacteremia presented with chills and abdominal pain. Labs on admission included a white blood cell count of 28.64 k/cmm, hemoglobin 8.8 g/dL, and platelets 581 K. He was diagnosed with a pancreatitis flare and admitted for pain management, with further labs drawn. After one day, he felt much better and was discharged with a pending blood culture to follow up on. At 61 hours, one bottle flagged positive with yeast seen on gram stain.

Laboratory findings

Image 1: potato flake agar with creamy tan-white colonies.
Image 2: calcofluor white fluorescent stain showing round yeast forms.

The organism was identified as Cryptococcus laurentii via MALDI-ToF MS. A follow-up fungal culture was negative, however, repeat blood culture grew Stenotrophomonas maltophilia. His tunneled catheter was removed, and two days later the patient required urgent interventional radiology access for dialysis. He completed a two-week course of ceftazidime and was discharged. 


Cryptococcus laurentii is a very rare fungal pathogen. It is a psychrophilic organism, growing ideally at 15 °C, and is the most common yeast found in tundra.1 Major reservoirs include soil, food, and pigeon excrement.2 C. laurentii usually causes infection in immunocompromised hosts, although rare incidents of infection in immunocompetent patients have been reported. Reported manifestations have included fungemia, meningitis, peritonitis, pneumonia, pyelonephritis, keratitis, and skin infection.3

Cryptococcus laurentii is a urease-positive organism. Gram stain shows large budding yeasts without hyphae. The yeast grows on routine agar as whitish-yellow creamy colonies and on birdseed agar as whitish or greenish colonies. Staining with calcofluor highlights encapsulated yeast forms. Molecular diagnosis can be accomplished by ribosomal RNA sequencing of the internal transcribed spacer and D1/D2 regions. Treatment in most cases has been with fluconazole, although in one case of peritoneal dialysis catheter-related peritonitis, voriconazole was used due to low fluconazole susceptibility.4


  1. Molina-Leyva A, Ruiz-Carrascosa JC, Leyva-Garcia A, Husein-Elahmed H. Cutaneous Cryptococcus laurentii infection in an immunocompetent child. International Journal of Infectious Diseases. 2013;17(12). doi:10.1016/j.ijid.2013.04.017.
  2. Johnson, L. B., Bradley, S. F. and Kauffman, C. A. Fungaemia due to Cryptococcus laurentii and a review of non-neoformans cryptococcaemia. Mycoses. 1998;41: 277–280. doi:10.1111/j.1439-0507.1998.tb00338.x
  3. Furman-Kuklińska K, Naumnik B, Myśliwiec M. Fungaemia due to Cryptococcus laurentii as a complication of immunosuppressive therapy – a case report. Advances in Medical Sciences. 2009;54(1). doi:10.2478/v10039-009-0014-7.
  4. Asano M, Mizutani M, Nagahara Y, et al. Successful Treatment of Cryptococcus laurentii Peritonitis in a Patient on Peritoneal Dialysis. Internal Medicine. 2015;54(8):941-944. doi:10.2169/internalmedicine.54.3586.


-Prajesh Adhikari, MD is a 3rd year anatomic and clinical pathology resident at the University of Vermont Medical Center.


-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.

Is It Possible to Have Coexistence of Hepatitis B Surface Antigen and Antibody?

Hepatitis B surface antigen (HBsAg) is the serologic hallmark of acute Hepatitis B virus (HBV) infection. It can be detected in serum using immunoassays a few weeks after HBV infection, and normally disappears after 4-6 months in recovered patients (1). Antibodies against HBsAg (anti-HBs) appears as a response from the host immune system, and these antibodies neutralize HBV infectivity and clear circulating HBsAg (2). Anti-HBs generally persist in life, indicating recovery and immunity from HBV infection.

Some of us may simply assume that the presence of anti-HBs should always associated with the loss of HBsAg. However, it is possible to see concurrent anti-HBs and HBsAg in patients. In fact, coexistence of HBsAg and anti-HBs is not rare, and has been reported in 10 to 25 percent of HBV chronic carriers in previous studies (3-4).  The underlying mechanism is not fully understood but several reports explained it as HBsAg mutants escaping the immune system (2-4). HBsAg mutants are believed to arise under the selective pressure from the host immune system, or from vaccinations (4-6).

“a” determinant in HBsAg is one of the main target of anti-HBs. It has been reported that mutations in the “a” determinant of the surface gene (S-gene) result in amino acid substitutions in HBsAg, and reduce the binding of anti-HBs to HBsAg, leading to immune escape (4). The first HBV mutant was reported by Zanetti et al in 1988 as G145R mutation. In their report, infants born to HBsAg carrier mothers developed breakthrough infections despite receiving HBIG and HBV vaccine at birth (5). Since this report, several other HBsAg mutations have been reported (4, 6).

Currently, there is no easily available assay to diagnose individuals who are suspected of harboring HBsAg escape mutants. Moreover, mutated HBsAg may leads to false negativity in some serologic assays, leading to a missed diagnosis of chronic HBV infection (6). Another concern is the potential risk of transmission to others, as vaccination does not provide protection from these mutated viruses (8); this is especially important in liver transplant recipient and newborns from HBsAg positive mothers.


  1. Lok A, Esteban R, Mitty J. Hepatitis B virus: Screening and diagnosis. UpToDate. Retrieved Feb 2018 from https://www.uptodate.com/contents/hepatitis-b-virus-screening-and-diagnosis#H3
  2. Liu W, Hu T, Wang X, Chen Y, Huang M, Yuan C, Guan M. Coexistence of hepatitis B surface antigen and anti-HBs in Chinese chronic hepatitis B virus patients relating to genotype C and mutations in the S and P gene reverse transcriptase region. Arch Virol 2012;157:627–34.
  3. Colson P, Borentain P, Motte A, Henry M, Moal V, Botta-Fridlund D, Tamalet C, Gérolami R. Clinical and virological significance of the co-existence of HBsAg and anti-HBs antibodies in hepatitis B chronic carriers. Virology 2007;367:30–40.
  4. Lada O, Benhamou Y, Poynard T, Thibault V. Coexistence of hepatitis B surface antigen (HBs Ag) and anti-HBs antibodies in chronic hepatitis B virus carriers: influence of “a” determinant variants. J Virol. 2006 Mar;80(6):2968-75.
  5. Zanetti AR, Tanzi E, Manzillo G, Maio G, Sbreglia C, Caporaso N, Thomas H, Zuckerman AJ. Hepatitis B variant in Europe. 1988 Nov 12; 2(8620):1132-3.
  6. Leong J, Lin D, Nguyen M. Hepatitis B surface antigen escape mutations: Indications for initiation of antiviral therapy revisited. World J Clin Cases 2016;4:71.
  7. Colson P, Borentain P, Motte A, Henry M, Moal V, Botta-Fridlund D, Tamalet C, Gérolami R. Clinical and virological significance of the co-existence of HBsAg and anti-HBs antibodies in hepatitis B chronic carriers. 2007;367:30–40.
  8. Thakur V, Kazim S, Guptan R, Hasnain S, Bartholomeusz A, Malhotra V, Sarin S. Transmission of G145R mutant of HBV to an unrelated contact. J Med Virol 2005;76:40–6.



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

Critical Care, Critical Labs

Sepsis is a medical emergency and a global public health concern. The Surviving Sepsis Campaign started in 2012 and has since issued International Guidelines for Management of Sepsis and Septic Shock. These Guidelines have been updated several times, and the 4th edition of the 2016 guideline have been issued. The Guidelines are written from the perspective of developed (“resource-rich”) countries, where critical care settings are equipped with tools for managing these patients. Yet, the developing world carries the greatest burden of sepsis-related mortality. Unfortunately, the developing world lacks access to many of the necessary tools for managing the critically ill patient – including basic laboratory testing.

Laboratory values are a significant part of the management of the septic patient. Take a look at the sepsis screening tool. Analytes and lab tests included in screening patients for sepsis include: lactate, creatinine, bilirubin, INR, and blood gases. The Surviving Sepsis bundles require a lactate concentration within 3 hours of presentation, and a subsequent lactate within 6 hours. The care bundle also requires a blood culture within 3 hours of presentation and prior to administration of antibiotics. Early-goal directed therapy for sepsis requires administration of crystalloid based on lactate concentrations. Basics of laboratories in the US, lactate and blood cultures are both difficult to obtain and far from routine in the resource-poor care settings.

Blood gases and lactate are particularly difficult to find and to maintain in the developing world. While there are a number of point-of-care or small benchtop devices – like the iStat (Abbott), the Piccolo (Abaxis), and the Stat Profile pHOx (Nova), it is often cost-prohibitive to maintain these devices.  The iStat and the Piccolo are examples of cartridge-based devices. All of the chemistry takes place in single-use cartridges and the device itself is basically a timer. In my experience, cartridge based devices hold up in environmental extremes better than open reagent systems. However, they are not cheap and this can be prohibitive. Cost of a single cartridge can range from $3-10 USD. In countries where patients and their families are expected to pay upfront or as they go for even inpatient medical care, and the income for a family is $2USD/day, routine monitoring of blood gases and lactate by cartridge is just not feasible. Reagent based devices like the Stat Profile use cartons of reagent for many uses. This is much cheaper – if all the reagent is used before it expires! Some healthcare settings can accommodate only 1-3 critical patients, and might not be able to use a whole carton before the expiry, even when adhering to Surviving Sepsis guidelines.

Blood cultures and subsequent treatment with appropriate antibiotics is a large part of the surviving sepsis campaign. Microbiology in the developing world is often limited to a few reference laboratories in country. Also, the number of potential infectious agents is larger in the developing world where diseases like malaria and dengue fever are common. Multiplexed nucleic acid tests might fill the gap here. Again, the cost is a major factor. Just reagents alone for a single multiplexed NAT can be over $250 USD.

In short, if the surviving sepsis guidelines really do help decrease sepsis mortality, the developing world doesn’t have a chance unless it has a greater laboratory capacity. Basic labs that we don’t think twice about can be very hard to come by in resource-poor environments. The tests already exist in forms that can be used in resource-poor settings – they just need to be cheaper, at least for those in limited resource settings. Are you listening, Abbott?


Sarah Brown Headshot_small

Sarah Riley, PhD, DABCC, is an Assistant Professor of Pediatrics and Pathology and Immunology at Washington University in St. Louis School of Medicine. She is passionate about bringing the lab out of the basement and into the forefront of global health.  

Microbiology Case Study: A 21 Year Old Female with a Sore Throat

A 21 year-old female presented to the emergency department with a sore throat. Her symptoms started two weeks prior to presentation. She was seen at student health last week and given Tamiflu, but her sore throat has grown progressively worse. She now has pain with swallowing and cannot swallow liquids. Upon examination the patient has no rash, no fever, and is not in respiratory distress. She does have left tonsillar fullness causing her uvula to be slightly deviated to the right along with an enlarged left cervical lymph node. Her complete blood count (CBC) was elevated at 19.7 x103/ul (reference range 4-10 x103/ul) with 12% lymphocytes, 2% monocytes, and 83% neutrophils. A rapid antigen test for S. pyogenes or Group A Streptococcus was negative. A CT exam of the neck was performed and a peritonsillar abscess of 1 x 1.3 x 1.6 cm was identified. The abscess was drained resulting in 1 ml of yellow purulent fluid which was sent to the microbiology lab for culture. The following was Gram stain was prepared from the abscess material.

Fusobacterium necrophorum Gram stain


The Gram stain of this abscess showed 4+ PMNs and 4+ small, pleomorphic gram negative bacilli. Anaerobic culture grew Fusobacterium necrophorum, identified by MALDI-TOF MS with a confidence score of 2.2. F. necrophorum is a non-motile, non-pigment forming, pleomorphic gram negative bacilli. It is a strict anaerobe that tests catalase negative, indole positive, and lipase positive on egg yolk agar. Anaerobic antibiotic disk testing for this organism shows susceptibility to kanamycin and colistin with resistance to vancomycin.

The two most clinically relevant species of Fusobacterium are F. nucleatum and F. necrophorum. Because they are strict anaerobes which are often not recovered in culture, Fusobacterium spp. are an under-recognized cause of disease. F. necrophorum colonizes the oral cavity, and like other colonizing anaerobes, it tends to cause infections near the mucosal surface where it resides. F. necrophorum most commonly causes pharyngitis, recurrent tonsillitis, and other odontogenic infections. In adolescents, 10% of tonsillitis that is not caused by S. pyogenes can be attributed to F. necrophorum. These infections can progress to septic thrombophlebitis of the internal jugular vein (Lemierre’s syndrome), bacteremia, and rarely F. necrophorum can cause abscesses throughout the body. Because it is an anaerobic bacterium, susceptibility testing is rarely performed on isolates of F. necrophorum. They are highly susceptible to β-lactam–β-lactamase inhibitor combinations, carbapenems, and metronidazole.

Lemierre’s syndrome was of great concern in our patient since it is most commonly observed in adolescents and young adults that were previously healthy, like our patient. Fortunately, CT scan of the neck showed no indication of thrombophlebitis in our patient. After drainage of the abscess, she felt much better and was able to tolerate liquids. The patient was discharged from the ED with a course of amoxicillin/clavulanate (augmentin). Upon follow up in ENT clinic she gave a more through history of 4-5 episodes of sore throat over the past year.


  1. Manual of Clinical Microbiology, 11th edition
  2. Principles and Practices of Infectious Disease, 7th edition


-Erin McElvania, PhD, D(ABMM), is the Director of Clinical Microbiology NorthShore University Health System in Evanston, Illinois.

A Serious Aside

As an unscheduled post, I’d like to make a quick side note separate from public health, zika, and medical school. You may have seen a post I wrote last January about the potential stereotypes and stigmas we might face in laboratory medicine. But, just because we as laboratory professionals operate behind-the-scenes most of the time, we’re still healthcare professionals—and clinician burnout can affect any of us.

I recently watched a video of Dr. Zubin Damania, also known as “ZDoggMD,” a primary care physician and founder of Turntable Health in Las Vegas. He’s a brilliant and passionate doctor with great opinions and an even greater creative sense of humor. Among his many parodies, and “rounds” Q&A questions, ZDoggMD recently had a guest on one of his Facebook shows called “Against Medical Advice” to address the serious issue of suicide and depression in medicine. Janae Sharp was the guest on this episode speaking about her husband, John, a physician fresh into his residency who committed suicide. They go on to talk about her life after this tragedy and how if flipped her and their children’s’ lives upside down. Janae’s described John as a father, a writer, a musician, an idealist, who always wanted to become a doctor. My interest was definitely piqued by this—I tend not to miss most of Dr. Damania’s content—and this is something I’ve been hearing more and more about as my path through medical school continues. But, at one point in the interview my heart just stopped: John was a clinical pathologist. Too close to home, for me at least. I was admittedly surprised.

Pathologist’s don’t have that much stress to make depression and suicide part of that life, I thought. But that is a cold hard assumption. Depression affects so many people at large, and when you’re in healthcare it almost seems like a risk factor on top of issues one might be struggling with. Med school is touted as one of the hardest intellectually, physically, and emotionally grueling experiences you could go through—I will personally vouch for Dr. John and Dr. Damania’s statements about how much these experiences push you to your limits. No sleep, no recognition, no support, fear of failure, imposter syndrome, a wealth and breadth of knowledge that makes you feel like you’re drowning—not to mention that if you do ask for help you’re immediately “lesser” for doing so.

Video 1. ZDoggMD interviews Janae Sharp about her tragic loss, her husband John’s suicide, and the rampant problem of depression and burnout in medicine. Against Medical Advice, Dr. Damania.

Last month, I was fortunate enough to attend a grand rounds session at my current hospital about this very topic. Presented by Dr. Elisabeth Poorman, internal medicine attending physician, and clinical instructor at Harvard Medical School, who talked about how (because of stigmas) medical trainees don’t get the help they need. She demonstrated that prior to med school students are pretty much on-par with their peers with regard to depression. However, once medical school starts, those peers all plummet together as depression rates rise and fall dramatically throughout the various stages of their careers. (I’m just going to go ahead and vouch for this too.) Dr. Poorman shared several case studies that effectively conveyed just how hard it can be when it seems like you are a source of help for many, but no one is there to help you. Story and story recounted the same model of apparent—and often secretive—burnout which ultimately led to a decrease in the quality of care, and in some instances suicide. Dr. Poorman was also brave enough to share her own story. No stranger to depression, herself, it was something that she encountered first hand. She connected herself with this increasingly difficult picture of inadequate support for those of us spending our lives serving others.

Figure 1. Dr. Poorman’s data reveals that depression rates for medical school classmates in a cohort generally rise and fall as their duties and responsibilities change during their career trajectory. I’m currently on the slope downward between the first 1-3 years of school’s peak and the 4th year trough.

There are clear problems facing those of us in healthcare jobs. An ironic consequence, however, of modern scientific advancement is the “doubling time” of medical knowledge. While not necessarily a problem, this refers to the amount, depth, and scope of knowledge physicians and medical scientists are expected to master in order to effectively treat, make critical clinical decisions, and educate our patients. While in 1980 it took 7 years for all medical knowledge to double in volume, it only took 3.5 years in 2010, and in 2020 it’s expected to double every 73 days!1. The problems come as a result of this knowledge because more data means more to do. More time on the computer, higher critical responsibility, and less time to focus on your own mental health all lend themselves to a cyclic trap of burnout. Physicians commit suicide at a rate of 1.5 – 2.3 times higher than the average population.1

Physicians, nurses, clinical scientists, lab techs, administrators, phlebotomists, PCTs—we’re all over worked, under-supported, fall victim to emotional fatigue, and have some of the highest rates for depression, substance abuse, PTSD, and suicide.1 Sometimes, reports from Medscape or other entities will report that burnout is a phenomenon of specialty, hypothesizing that critical nature specialties have more depression than lesser ones2 (the assumption that a trauma surgeon might burn out before a hematopathologist). But truthfully, this is just part of the landscape for all providers. A May 2017 Medscape piece wrote “33% chose professional help, 27% self-care, 14% self-destructive behaviors, 10% nothing, 6% changed jobs, 5% self-prescribed medication, 4% other, 1% pray.”3

So I’m talking about this. To get your attention. So that people reading know they’re not alone. So that  people with friends going through something can lend a hand. I’m talking about this. ZDoggMD is talking about this. Jamie Katuna, another prolific medical student advocate, is talking about this. Dr. Elisabeth Poorman is talking about this. This is definitely something we should come together to address and ultimately solve.

What will you do to help?

This was a heavy topic. So in a lighter spirit, I have to share this with all of my laboratory family. If you haven’t heard or seen Dr. Damania’s videos yet, this is the one for you:

Thanks! See you next time!


  1. Poorman, Elisabeth. “The Stigma We Live In: Why medical trainees don’t get the mental health care they need.” Cambridge Health Alliance, Harvard Medical School. Grand rounds presentation, Feb 2018. Bronx-Lebanon Hospital Center, New York, NY.
  2. Larkin, Mailynn. “Physician burnout takes a toll on U.S. patients.” Reuters. January 2018. Link: https://www.reuters.com/article/us-health-physicians-burnout/physician-burnout-takes-a-toll-on-u-s-patients-idUSKBN1F621U
  3. Wible, Pamela L. “Doctors and Depression: Suffering in Silence.” Medscape. May, 2017. Link: https://www.medscape.com/viewarticle/879379



Constantine E. Kanakis MSc, MLS (ASCP)CM graduated from Loyola University Chicago with a BS in Molecular Biology and Bioethics and then Rush University with an MS in Medical Laboratory Science. He is currently a medical student at the American University of the Caribbean and actively involved with local public health.

Hematopathology Case Study: A 69-Year-Old Man Presenting with Marked Thrombocytopenia One Year after Bone Marrow Transplantation

Case history

The patient is a 69-year-old man with a history of high-risk MDS (MDS-MLD-RS) diagnosed 1 year prior to his current visit. He was successfully treated with chemotherapy and bone marrow transplantation. For the next year, several marrow examinations were normal and chimerism analysis revealed >98% donor cells. Currently, he presents with vague symptoms and a CBC demonstrates marked thrombocytopenia of 4K/μL.  The low platelet count is initially thought to be related to GVHD; however, a bone marrow examination is performed to assess the status of his disease.

Wright-Geimsa, 2X
Wright-Geimsa, 100X
E-Cadherin IHC, 4X

Microscopic Description

Examination of the bone marrow reveals a markedly hypercellular marrow for age with a proliferation of abnormal erythroid cells comprised of sheets of immature and maturing red cell precursors with basophilic cytoplasm. There is a marked increase in larger cells with deeply basophilic cytoplasm, prominent nucleoli, dispersed chromatin, perinuclear hoffs, and a high nuclear to cytoplasmic ratio consistent with pronormoblasts. These pronormoblasts comprised 31% of a 500-cell cell count. Additionally, the background marrow revealed a total of 81% erythroid precursors with marked morphologic atypia and dyspoiesis. Significant dysmegakaryopoiesis is noted. There is no significant increase in myeloid blasts.


Immunohistochemical staining for E-cadherin, CD61 and CD34 is performed. These stains confirm no increase in CD34 positive blasts. CD61 highlights numerous dyspoietic megakaryocytes with widely separated nuclear lobes. E-cadherin staining is impressive, with over 80% of marrow cellularity shown to be comprised of E-cadherin positive erythroid cells.


The patient’s history of MDS with current dyspoiesis, presence of >80% immature erythroid precursors with >30% proerythroblasts is diagnostic of Acute Myeloid Leukemia, NOS (Pure Erythroid Leukemia) per 2017 revision of the World Health Organization classification of myeloid neoplasms.

While successive chimerism reports thus far had shown >98% donor cells, the chimerism associated with this marrow biopsy reveals a decrease in the percentage of donor cells to 44% confirming the relapsed nature of his myeloid malignancy.


Di Guglielmo syndrome, known as M6 leukemia in the FAB classification, was named after Giovanni Di Guglielmo, an Italian hematologist who first characterized the disease in 1917. After a few iterations in different classification schemes, the 2008 WHO Classification characterized two types of ‘erythroleukemia’ the erythroid/myeloid type and the pure erythroid leukemia. The former category of erythroid/myeloid type was removed in the 2017 update of the WHO classification with cases meeting criteria for that diagnosis now falling under the category of MDS. ‘Pure Erythroid Leukemia’ remains, and comes under the AML, NOS category, requiring >80% erythroid progenitors with > 30% proerythroblasts.

An extremely rare leukemia, PEL usually occurs as a progression of previous MDS and very uncommonly as de novo disease. Morphologically, PEL reveals proerythroblasts with deeply basophilic, agranular cytoplasm which is usually vacuolated. Occasionally, smaller ‘blasts’ with scant cytoplasm may resemble lymphoblasts. PEL is an exception to the rule of needing 20% ‘myeloid blasts’ to make an acute leukemia, since often the true myeloblast count is low.

In trephine core biopsies erythroid progenitors may take up an intra sinusoidal growth pattern with a sheet-like arrangement and typically reveal some element of background dysmegakaryocytopoiesis. When PEL lacks specific erythroid differentiation, it may be difficult to differentiate from other types of AML such as Acute Megakaryoblastic Leukemia. Park and colleagues recently categorized some under reported morphologic features of PEL and recurrent cytogenetic abnormalities associated with this disease. These findings included (but were not limited to) a broad morphologic spectrum of erythroblast morphology from undifferentiated blasts to proerythroblasts. They reported bone marrow tumour necrosis in trephine biopsies in over 70%  of their cases. Of the cases wherein karyotyping was available, there was a highly complex and monosomal karyotype noted involving the TP53 gene locus.

PEL is associated with an aggressive course with a median survival of 3 months.


  1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood. 2016 Jan 1:blood-2016.
  2. Wang W, Wang SA, Jeffrey Medeiros L, Khoury JD. Pure erythroid leukemia. American journal of hematology. 2017 Mar 1;92(3):292-6.
  3. Park DC, Ozkaya N, Lovitch SB. Acute leukaemia with a pure erythroid phenotype: under-recognized morphological and cytogenetic signatures associated universally with primary refractory disease and a dismal clinical outcome. Histopathology. 2017 Aug;71(2):316-321. doi: 10.1111/his.13207. Epub 2017 May 5.



-Michael Moravek, MD is a 2nd year anatomic and clinical pathology resident at Loyola University Medical Center. Follow Dr. Moravek on twitter @MoravekMD.


-Kamran M. Mirza, MD PhD is an Assistant Professor of Pathology and Medical Director of Molecular Pathology at Loyola University Medical Center. He was a top 5 honoree in ASCP’s Forty Under 40 2017. Follow Dr. Mirza on twitter @kmirza.