To Be (MDS) or Not To Be? The Conundrum of Cytoplasmic Vacuolation in Hematopoietic Precursors

Every hematopathologist and pathology trainee knows to be wary of the myriad of causes that could mimic the dysplastic changes seen in marrows involved by MDS. Many times morphology alone, without genetic or cytogenetic evidence of clonality can be tricky. The list of things that can recapitulate changes seen in MDS seems to grow longer every day – and with it the length of our ‘canned comments’ on ruling out reactive causes of dysplasia. Within the recent past, two bone marrow biopsies crossed my microscope, both sent to ‘rule out’ MDS. Both had almost identical morphologic findings, but very different diagnoses. Here are some representative images from the marrow aspirates and iron stains:

Figure 1. Representative Wright-Giemsa stained cells from Case 1 (A and B) with accompanying iron stain (C) showing numerous ring sideroblasts.  Representative Wright-Giemsa stained cells from Case 2 (D) with accompanying iron stain (E) showing some ring sideroblasts. 


Images A through C come from case 1, a 67-year-old woman with a past medical history of non-alcoholic steatohepatitis (NASH) complicated by hepatic encephalopathy and recurrent ascites who underwent bone marrow biopsy for new onset pancytopenia with transfusion-dependent anemia. The marrow was slightly hypercellular for age and showed progressive trilineage maturation. Granulocytic and erythroid progenitors did not reveal quantitatively significant dysplasia. The one dysplastic megakaryocyte identified is pictured here (panel A). Interestingly many erythroid and granulocytic precursors showed cytoplasmic vacuolation (panel B showing granulocytic vacuolation). An iron stain (panel C) revealed 44% ring sideroblasts. Case 2 is represented in images D and E and was from a 64-year-old man with no significant past medical history who presented with lethargy and anemia. This marrow was also slightly hypercellular for his age and showed borderline-significant dysplasia in megakaryocytic maturation. Granulopoiesis and erythropoiesis were unremarkable except for cytoplasmic vacuolations in many cells (panel D). An iron stain showed 8% ring sideroblasts (panel E).

Both cases were signed out descriptively, urging the clinician that we needed to rule out reactive causes of dysplasia before a definitive diagnosis of MDS could be rendered. In both cases we suggested waiting for the cytogenetics results for a more comprehensive analysis. Additionally, we recommended testing for serum copper since copper deficiency can be the cause of dysplastic morphology, cytoplasmic vacuolation, and ring sideroblasts.

Case 1 revealed markedly diminished copper and normal cytogenetics. Copper replenishment was curative. Case 2 revealed normal copper levels and a complex karyotype that contained numerous MDS-associated abnormalities confirming the clonal, and therefore malignant nature of these changes. Despite being almost identical morphologically, these case were diagnostically and prognostically poles apart.

Copper is an element that serves as a micronutrient required for hematopoiesis. It’s presence in many readily available foods including meat, fish, nuts, and seeds renders diet-related copper deficiency a rare phenomenon. Zinc-supplementation is one of the causes of copper deficiency in published reports. Copper deficiency has been well documented to mimic dysplastic changes seen in MDS; but these morphologic findings and cytopenia are reversible. Characteristically, cytoplasmic vacuolation is an important morphologic clue that there could be an underlying paucity of serum copper.  Another aspect of copper deficiency is the presence of ring sideroblasts which also can mean MDS. It is very important to consider this differential diagnosis when dealing with marrow specimens sent to rule out MDS. This Lablogatory post highlights the significant overlap between presentation and morphologic findings between MDS and copper deficiency supporting the notion that a high index of suspicion, good communication, stat copper levels, and cytogenetics or MDS FISH studies are very helpful in delineating benign from malignant.


  1. Dalal N. et al. Copper deficiency mimicking myelodysplastic syndrome. Clin Case Rep. 2015 May; 3(5): 325–327.
  2. Willis M.S. Zinc-Induced Copper Deficiency: A Report of Three Cases Initially Recognized on Bone Marrow Examination. AJCP. 2005 Jan; 123(1): 125–131
  3. D’Angelo G. Copper deficiency mimicking myelodysplastic syndrome. Blood Res. 2016 Dec; 51(4): 217–219.
  4. Karris S and Doshi V. Hematological Abnormalities in Copper Deficiency. Blood 2007 110:2677



-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.

Hematopathology Case Study: A 45 Year Old Male with Mediastinal Mass

Case History

A 45 year old male underwent a chest MRA for aortic dilation due to his history of an aneurysmal aortic root. Upon imaging, an incidental anterior mediastinal mass was seen that measured 4.0 cm. In preparation for an upcoming cardiac surgery, the patient underwent a thymectomy with resection of the mass. The sample is a section from the mediastinal mass.


H&E, 2x
H&E, 4x
H&E, 10x. Green Arrows: “lollipop” germinal centers
H&E, 10x. Red arrow: focal “twinning” of germinal centers

Sections show an enlarged lymph node with several follicles demonstrating atrophic-appearing germinal centers which are primarily composed of follicular dendritic cells. These areas are surrounded by expanded concentrically arranged mantle zones. Focal “twinning” of germinal centers is present. Additionally, prominent centrally placed hyalinized vessels are seen within the atrophic germinal centers giving rise to the “lollipop” appearance.

By immunohistochemistry, CD20 highlights B-cell rich follicles while CD3 and CD5 highlight abundant T-cells in the paracortical areas. CD10 is positive in the germinal centers while BCL2 is negative. CD21 highlights expanded follicular dendritic meshwork. CD138 is positive in a small population of plasma cells and are polytypic by kappa and lambda immunostaining. HHV8 is negative. MIB1 proliferation index is low while appropriately high in the reactive germinal centers.

Overall, taking the histologic and immunophenotypic findings together, the findings are in keeping with Castleman’s disease, hyaline vascular type. The reported clinical and radiographic reports suggest a unicentric variant.


Castleman’s disease comes primarily in two varieties: localized or multicentric. The localized type is often classified as the hyaline vascular type (HVCD). Demographically, it’s a disease of young adults but can be found in many ages. The most common sites for involvement are the mediastinal and cervical lymph nodes.

The classic histologic findings of HVCD involve numerous regressed germinal centers with expanded mantle zones and a hypervascular interfollicular region. The germinal centers are predominantly follicular dendritic cells and endothelial cells. The mantle zone gives a concentric appearance, often being likened to an “onion skin” pattern. Blood vessels from the interfollicular area penetrate into the germinal center at right angles, giving rise to another food related identifier, “lollipop” follicles. A useful diagnostic tool is the presence of more than one germinal center within a single mantle zone.

The differential diagnosis of HVCD includes late stage HIV-associated lymphadenopathy, early stages AITL, follicular lymphoma, mantle cell lymphoma, and a nonspecific reactive lymphadenopathy. A history of HIV or diagnostic laboratory testing for HIV would exclude the first diagnosis. AITL usually presents histologically as a diffuse process but atypia in T-cells with clear cytoplasm that co-express CD10 and PD-1 outside of the germinal center are invariably present. EBER staining may reveal EBV positive B immunoblasts in early AITL, which would be absent in HVCD. The most challenging differential would include the mantle zone pattern of mantle cell lymphoma. Flow cytometry revealing a monotypic process with co-expression of cyclin D1 on IHC would further clarify the diagnosis.1

Overall, unicentric Castleman’s disease is usually of the hyaline vascular type. Surgical resection is usually curative in these cases with an excellent prognosis.2



  1. Jaffe, ES, Harris, NL, Vardiman, J, Campo, E, Arber, D. Hematopathology. Philadelphia: Elsevier Saunders, 2011. 1st ed.
  2. Ye, B, Gao, SG, Li, W et al. A retrospective study of unicentric and multicentric Castleman’s disease: a report of 52 patients. Med Oncol (2010) 27: 1171.



-Phillip Michaels, MD is a board certified anatomic and clinical pathologist who is a current hematopathology fellow at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. His research interests include molecular profiling of diffuse large B-cell lymphoma as well as pathology resident education, especially in hematopathology and molecular genetic pathology.

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:
  3. Wible, Pamela L. “Doctors and Depression: Suffering in Silence.” Medscape. May, 2017. Link:



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.

The “C” in HCV Stands for “Curable”

Hi everyone! It has felt so good to find myself back in the throes of hospital life. My time in the classroom during the first half of medical school was great—but this new chapter is what makes medical school very worth it. As with any new hospital, orientation was pretty run-of-the-mill: administrative paperwork, employee/student health clearance, and yet another Mantoux PPD (despite having a current QuantiFERON—lab family, you get me).

However, after all the introductory logistics, I finally reported to my first rotation. It is an elective clerkship in primary care focused primarily on patients with HIV and/or Hepatitis. My familiarity with hospital life made the transition back easy enough as I made my way to the nurses’ station looking for my attending. Being forwarded in the direction I had to go, I knocked on the door and started to introduce myself—but was abruptly interrupted. There were already two fellow student colleagues in that room with my attending and a patient. I was enthusiastically included in the process right away, and it has been non-stop since then. I am told this is a “different” rotation where I’m going to feel lucky to have so much hands-on experience, and so far, I agree. While I reminisce on these past few weeks, it’s not a specific patient or case that has stuck with me, but an overall theme I’ve noticed in this rotation. With heavy utilization of the right test at the right time (I’m sure we’re all familiar with ASCP’s Choosing Wisely campaign) and proper interpretations of lab data, patients’ chronic illnesses are being managed well and even cured.

Essentially, pharmaceuticals have been advancing so well in the last 5-10 years that treatment regimens for chronic diseases like HIV and HCV are now being actively controlled and cured, respectively. Why does this pique my interest enough to share it with all of you? As I try my best each month to provide you a window into the life of a medical lab scientist/medical student, I do so while focusing on the lab details that seem to be present in every aspect of my journey. The cures and treatments I’m currently working with are tied to lab tests like CD4 counts, viral loads, liver and kidney function tests, and many other routine values. Diagnostic criteria for different patients’ stages of hepatic damage are classified using a Child-Pugh (CTP) score from clinical information such as ascites and encephalopathy along with lab data like INR, bilirubin, and albumin. Patients with chronic conditions come back for follow up week in and week out for lab tests that let us as care providers adjust therapy accordingly. The clinic I currently rotate in provides its patients with the most up to date treatment protocols based on current literature. For example, The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) regularly publish their recommendations for patients with Hepatitis C. It’s heavy reading, and anyone who goes through literature on standards of care knows it’s dense, so I’ll leave the link to the most recent guidelines on HCV testing, management, and treatment here ( Actively and accurately incorporating these treatment protocols into the patient care algorithms works and demonstrates great utilization of lab driven data with new available therapies.

Figure 1. AASLD and IDSA HCV Recommendations Standards, 2018.

As a baseline it is critical to understand that patients with positive HCV antibodies will always test positive; once exposed at any point patients will remain positive. While 20% of patients can clear the infection on their own, the remaining majority develop a chronic HCV infection. There is no vaccine for HCV currently; however, there is potential to cure patients—assuming the lab values are interpreted correctly. So, we’ve established that positive HCV antibodies don’t necessarily provide diagnostic data, so the next logical step is to examine a patient’s HCV viral load. Since 2015, the New York State Department of Health established a mandate and protocol for reflex testing HCV Ab positive patients with HCV RNA viral loads. Read the public letter here ( While it makes logical sense, it’s still taking some time to get off the ground as I have seen patient records of different clinics’ providers ordering repeat HCV Ab testing for in-house confirmation—not the best use of resources or lab data. A clear example here of Choosing Wisely for the appropriate lab test. However, so long as HCV viral load stays undetectable by a validated testing method, patients with chronic HCV are promoted to a status of “cured HCV” and need no further testing or follow-up unless new clinical reasons appear to add testing as needed.

Figure 2. HCV Infection testing and treatment algorithm seen in literature from the Centers for Disease Control and Prevention (CDC), the NYS Health Department, the AASLD, and the IDSA.

Protocols for treatment are based on things like genotype, cirrhosis, and naïve vs. previously failed treatment; treatment schedules last from 8 weeks up to 24 weeks. So, what does a patient’s first visit for HCV treatment therapy look like? Right away (assuming a positive HCV Ab has been obtained) a Hepatitis C RNA viral load is ordered, along with genotype (older treatments are dependent on genotype due to potential for resistance, while newer treatments are pangenotypic), hepatic fibrosis scans (because cirrhosis status determines length of treatment), PT/INR, CBC, CMP, HIV, RPR/CG and other STI screening, and urine drug testing. New generation therapies allow us to proceed despite any comorbid conditions, while maintaining upwards of 95% or greater cure rates. Coinfected patients with HIV or otherwise compromised immune systems are no longer contraindicated to receive HCV treatment. The only significant contraindication in the standards of care currently is that patients not be terminal (i.e. they must have a general prognosis of greater than 6 months).

Figure 3. Calculated FIB-4 and APRI scores are useful in prognostic and treatment decision-making, demonstrating how crucial laboratory-driven data is in managing chronic illness.

Being able to watch these treatment protocols in action is great, but one patient in particular will stay with me beyond this clerkship. We received lab results back for a male in his 60s. It was his final HCV viral load based on his treatment schedule. His chart had a box at the end of his schedule labeled “test for cure” and it had remained non-detectable the whole time through treatment. The staff at this clinic does painstaking follow-up with their patients via telephone with impressive results in patient adherence and treatment success. My task one day was to call this patient and inform him that, unless he needed any medical treatment outside of his annual physical, he no longer needed to come in for therapy or testing—his Hep C was cured. He was extremely delighted to hear this news, and I was happy to give it to him. He had been on therapy for less than a few months but had lived with HCV for years. It was an excellent experience! And even more excellent—being part of the connection between lab tests, clinics, and patients. When I started I was just excited to wear that white coat and go visit the hospital’s lab, but I was pleasantly surprised to see the impact on patients’ treatments. Especially considering using the right test at the right time, and truly making a visible difference with excellent data.

See you next time!

Image 1. Me (center) and my medical student colleagues Ahmad M. Khan (right) and Emeka Ajufo (left).

 Post script: listen to a new podcast my colleagues and I are in where we discuss clinical stories and pearls of wisdom through medical school. As they relate to my posts here on Lablogatory I’ll include a link—this post will focus more in depth on what I presented here regarding HCV cures and lab data.



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 42 Year Old Female with Right Breast Mass

Case History

A 42-year-old female presented with a right breast mass at an outside hospital that was concerning for carcinoma. A core needle biopsy was performed of right breast mass and the case was sent for expert consultation.


H&E, 5x
H&E, 10x
H&E, 20x
H&E, 50x

Sections of core needle biopsy material are composed primarily of adipose tissue shows a dense lymphohistiocytic infiltrate with histiocytes being the dominant cell type. Admixed plasma cells are present within the infiltrate. The histiocytes have abundant granular cytoplasm with irregular nuclear contours and some nuclei containing inconspicuous nucleoli. Frequent lymphocytic emperipolesis is identified. Immunohistochemistry performed at the outside facility show positivity for S100 and CD163 within the histiocytes, further highlighting the lymphocytic emperipolesis. Cytokeratin immunostains are negative.

Overall, the morphologic and immunophenotypic findings are consistent with a diagnosis of extranodal sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease).


Sinus histiocytosis with massive lymphadenopathy (SHML) was first described by Rosai and Dorfman in 1969, however, similar findings may be present in extranodal sites thus earning the designation of Rosai-Dorfman disease (RDD). Although primarily present in lymph nodes, RDD may involve extranodal sites with sinuses and skin being the most frequently affected tissue types. Clinically, RDD often maintains a benign and self-limited course but may undergo exacerbations and recur, requiring surgical management. On histologic examination, RDD involves a rich inflammatory infiltrate with histiocytes, plasma cells, and lymphocytes. The histiocytes usually display a unique phenotype in which lymphocytes are phagocytosed, a process termed emperipolesis. By immunohistochemistry, these histiocytes are positive for S-100 and histiocytic markers (CD68 and CD163) and are negative for CD1a1.

The largest cohort studied involved 423 cases with 182 having extranodal manifestations2. Chest involvement was first reported by Govender et al. in 1997 in a 34-year-old female3. Overall, RDD is considered rare with a slight male predilection and young African-Americans being the most commonly affected. Sites involved ranging from most common to least common include lymph nodes, skin, upper respiratory tract, and bone4.

Extranodal sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease, is a rare pathologic entity that histologically shows a dense lymphohistiocytic infiltrate and emperipolesis, a hallmark of the disease. Although lymph nodes are the most common site of involvement, extranodal sites may be affected and RDD should remain in the differential for lesions that contain abundant histiocytes, plasma cells, and lymphocytes as well as the classic feature of emperipolesis.


  1. Komaragiri et al.: Extranodal Rosai–Dorfman disease: a rare soft tissue neoplasm masquerading as a sarcoma. World Journal of Surgical Oncology 2013 11:63.
  2. Penna Costa AL, Oliveira e Silva N, Motta MP, Athanazio RA, Athanazio DA, Athanazio PRF: Soft tissue Rosai–Dorfman disease of the posterior J Bras Pneumol 2009, 35:717–720.
  3. Govender D, Chetty R: Inflammatory pseudotumour and Rosai–Dorfman disease of soft tissue: a histological continuum? J Clin Pathol 1997, 50:79–
  4. Montgomery EA, Meis JM: Rosai–Dorfman disease of soft tissue. Am J Surg Pathol 1992, 16:122–129.



-Phillip Michaels, MD is a board certified anatomic and clinical pathologist who is a current hematopathology fellow at Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. His research interests include molecular profiling of diffuse large B-cell lymphoma as well as pathology resident education, especially in hematopathology and molecular genetic pathology.