Christie, Deborah, and Sarah Glew. "A clinical review of communication training for haematologists and haemato‐oncologists: a case of art versus science." British Journal of Haematology (2017).

http://www.nejm.org/doi/full/10.1056/NEJMra043442

REVIEW ARTICLE. CURRENT CONCEPTS

Diagnosis from the Blood Smear

Barbara J. Bain, F.R.A.C.P., F.R.C.Path.

N Engl J Med 2005; 353:498-507August 4, 2005DOI: 10.1056/NEJMra043442

"CONCLUSIONS: Even in the age of molecular analysis, the blood smear remains an important diagnostic tool. Physicians should request a blood smear when there are clinical indications for it. Members of the laboratory staff should make and examine a blood smear whenever the results of the complete blood count indicate that a blood smear is essential for the validation or the further elucidation of a detected abnormality. If error is to be avoided, sophisticated modern investigations of hematologic disorders should be interpreted in the light of peripheral-blood features as well as the clinical context."

Dra Barbara J Bain. NEJM Review

Dear José Antonio

the B. Bain article "Diagnosis from the Blood Smear" is a beacon used by all morphologists for orientation in the daily blood smears review. However, experience teaches us that every haematological case could be source of new or peculiar morphological features.  The sharing of these can be a tool to increase the knowledge of all professionals.This is the meaning that I would like to give to this discussion

Caro Antonio

The Bain article is useful for the clinicians to understand our "job"

The "machine" are unuseful without the clinical suspiction and an experimental eye!

Best regards

José Antonio

While I agree with the above comments on the importance of blood/bone marrow smear observation, in the modern world proper evaluation must rely on objective procedures such as flow cytometry and genetic and molecular evaluation. With the explosion of targeted and directed therapies in many malignancies, these procedures are increasingly necessary.  I am old enough to recall the educated guessing of acute leukemias based on observation alone and the probable many errors made. 

Dear Jason

Morphological observation and "objective procedures" such as flow cytometry, genetic and molecular evaluation must be  alternative and opposite diagnostics tools? I don't think and I don't said this. These procedures are complementary and can (must) be used in different phases of the diagnostic process: the morphology when a haematological malignancy is supposed and when this hypothesis must strengthened. Instead, flow cytometry, genetic and molecular procedures are used in subsequent stages of confirming the diagnosis as well as in the classifiing and in the subsequent disease management. All these because a haematological malignancy does not begin in a haematological clinic but long before, when it is still asymptomatic. In this phase that usually occurs in the clinical laboratory, the morphology only can start the diagnostic pathway. In addition we must not forget that in the acute myeloid leukaemia not otherwise specified genetic and molecular are not useful. In this WHO group the morphology and the cytochemistry play the main role together the flow cytometry that nevertheless can't be used for quantification of blasts. Likely I'm older than you and I observed too often CML in transformed phase at the diagnosis or MDS with high number of blast in PB which could be diagnosed many months or years before if It was been reported  a morphological feature of an increase (even modest) of basophils or a granulocytic dysplasia. However I never thought that, for these reasons, the morphology should be abandoned. I thought instead that transferring our morphological knowledge and experience can be the strongest tool to make rigth these errors.

Because my purpose is the sharing of haematological images, I would like to propose some paradigmatic aspects of bone marrow in the MDS with isolated del (5q) that  even in the 2016 revision to WHO classification of  myeloid neoplasms, remain the unique MDS subtype  that is defined by a specific cytogenetic abnormality.

Lovely photo micrographs.

NICE PHOTOS (AND EXPLANATIONS)

GRACIAS

Great idea. I agree.

Excelent images! Thanks for shearing! Very useful. I like the idea

I want to share an interesting case. A 24 years old male with syntomatic anemia and recently diagnosis of Chronic Hepatitis B. Hb 7.5 VCM 92 L 3070 Ne 53% Li 37% Mo 7% Eo 2% Ba 1% Platelets 332000. Directly Coombs Negative, HPN and Iron study negative, B12 and Folate normal, DHL normal, Reticulociyte low. Creatinine, Protein, Bilirubin, TGO, TGP, Ca and Uric acid Normal, B2 Microglobuline normal. Abdominal Ultrasound Splenomegaly 13 cm. IF Monoclonal Gammapathy IgG Lambda. IgG 1940. FCL ratio < 100. First Bone Marrow aspirate presents dyseritropoyesis, halting of maturation. Blastos 1%. Plasma cells 6%. Hemosiderin 4 +. Flow cytometry alteration in the maturational patterns of CD13 / CD11b and MGUS. Bone marrow Biopsy negative for neoplasic infiltration. karyotype normal. CT scan not bone lesions. He started antiviral treatment and EPO. However, He persist wiht Anemia and transfusional requirement. The new Bone Marrow aspirate present increment of plasmatic cell.

Hi Maribel. Very nice and interesting case. It's difficult to decide if IF pattern as well as plamocytosis in bone marrow are primitive or part of.chronic hepatitis. Nice photo!

Dear Maribel, I observed carefully your image. With respect to the description of first bone marrow aspiration (dyseritropoiesis), in this image we must observe:

1. a severe reduction of eritroblasts

2. a dysgranulopoiesis

These features must be considered with clinical and other haematological information

Thank you very much for your suggestions. Anemia was considered secondary to Multiple Myeloma. It has a monoclonal peak, increased the percentage of plasma cells (> 10%) and the IgG dosage. The viral load for Hepatitis B was always very low. The findings of dysplasia will be monitored, it is likely that coexist SMD. However, at this time, it does not meet criteria for high-risk MDS, with the tests available at our institution.

Very nice photo! We can observe pleomprphic plasma cells sometime with nuclear immaturity that rarely occurs in reactive plasmocytosis. So I agree with the multiple myeloma diagnosis. I agree with the difficulties to diagnose a concurrent MDS unless this hadn't been diagnosed previously (before the multiple myelomaMDS diagnosis).

Great, first step of a laboratory approach for diagnosis of a haematological malignancy is certainly morphology, which determines how should we proceed with next steps. For example the Morphology result tell us which one of CD  markers should be selected on flow cytometry analysis ....thus I suggest it may be helpful if we discuss about morphology  at  first but continue with the selection of a proper molecular approach to confirm or ...

Thanks for your contribute that I share complitely. I'd like to think that all laboratories were able to follow this diagnostic patway driven by morphology first.

Dear Maribel,

I envied the quality of your last photo of an entire microscopic field. I think you have  used a smartphone. Can you send me additional informations?

Dear Antonio,

To take pictures with the smartphone, you only need to use the maximum light and focus the shot as best as possible.

Thanks Maribel

I would want to know if you use a base or a support to put the smartphone on the eyepieces

The 2016 revision of WHO classification changed some diagnostics criteria for MDS. So Refractory anaemia with ring sideroblasts (RARS) was divided into MDS-RS with single lineage dysplasia (MDS-RS-SLD)  plus MDS-RS with multi lineage dyplasia (MDS-RS-MLD). The percentage of ring sideroblasts must be >15% of erythroid elements in the bone marrow instead of >15% of all nucleated cells (WHO 2008). 

I propose some images of an "old" RARS that had relevant erythroid dysplasia as well as megakaryocitic dysplasia which for these reasons  should be re-classified as MDS-RS-MLD.  

The aspects of dis-haemoglobinization in NRBC are more evocative for these forms of MDS than other features of dysplasia and are cause of the double RBCs population (normo- and hypochromic) in PB (Dacie JV et al. Refractory normoblastic anaemia: a clinical and haematological study of seven cases.Br J haematol (1959); 5:56-63)

Haemophagocytic lymphohistiocytosis is a hyper-inflammatory syndrome which can occurs in a primary familiar (fHLH) form in the paediatric age and in a secondary form prevalently in adult age (sHLH). Both fHLH and sHLH are characterized by a severe clinical onset with fever, hepato-splenomegaly, bi-, three-cytopenia in PB, hemophagocytosis in the BM as well as BM and multi-organ failure. sHLH is more commonly associated with other pathological condition including malignancies, immunodeficiency, infections, rheumatic diseases and autoimmune diseases. In the majority of cases a “trigger” event such as infections (by Epstein-Barr virus in primis) or drugs (anti-inflammatory, methotrexate, sulfosalazina, other) can be singled out.

Curious Image from bone marrow

Dear Antonio,

Your initiative is very welcome.

As a hematopathologist, while I'm not dealling with cytology in our institution but work closely with the hematologists, I understand what you want to do. My experience is that their morphologic skills are more and more lost, they mainly rely on flow cytometry, genetics and...biopsies for diagnosis. Many time it would have been very useful to get their findings from smears to allow a more targeted diagnostic workflow for bone marrow biopsies, for example. Many time I get a biopsy with a LPD, like CLL/SLL, not previousely diagnosed, and when looking for the peripheral blood CBC I find in the patient files it appears that there is a borderline lymphocytosis since months or even years, that was overlooked and not investigated till the disease evolved to a more advanced stage. Could it be that an experienced hematologist was able to suspect then the disease if he was looking at the PB smear?

To my opinion, it would be good to establish a website/blog dedicated to what you are doing here, sharing and building progressively an archive of cases, accesible by everyone who's searching for images to learn online or solve a difficult case not always fitting what is describe in textbooks, aslo dedicated to ask and/or answer questions from other professionals in the world dealing with unusual cases that are not always easy to find in the literrature (if ever described...). I don't know if it does already exist, do you?

As a pathologist I'll be very happy if we can have the same for histology. There are some website I know, but still did not find a real efficient professional site where you can bring a difficult case and ask the community's opinion about it. Not only (but also if possible) top specialists. Sometime someone saw the same and resolve the problem, but you not always publish everything weird you see in your practice, especially if you work in a non-academic institution.

Thanks a lot for your initiative. I'd like to know what others think about this topic.

Philippe

Thanks for your "entusiastic" comment!

You was able to recognize my aim and you described this exactly. I worked (inter alia) on haematological morphology for 40 years observing more than 10,000 bone marrow aspiration as well as several tens of tausand peripheral blood smears. In parallel I observed a progressive decrease of skill in my younger Collegues. I'm retired now, so the aim to transfer part of my experience have the double result to helping a preserving of high interest for the haematological morphology as as well to ....stay young.

I halways tought that the capability of  understanding small signs in their diagnostic significance is one of opportunities for clinical laboratory to shortening diagnostic timing of a disease until then not known in a-, pauci-symptomatic patients.So, agree with you that, probably the diagnosis of  your LPD case might be delayed by the inattention of laboratory. Look for a similar discussion  regarding a mantle cell lymphoma, that I started on RG, if you like

Antonio

this is good idea , i have many blood smears of camels

I will share it with others

Hi Dr Antonio La Gioia

It is interesting to discuss some difficult cases and it is good chance to learn from your experience.

Child 7 years old with Hepatosplenomegally. CBC showed cytopenia: Bone marrow smear

Attempting a diagnosis based on a photo alone can be a serious gamble. In this beautiful image, a macrophage is completely padded by formations that, although the kinetoplasts are not visible clearly, evoke amastigotes forms of Leishmania. Periferal cytopenia and hepatosplenomegally could be in agreement with a visceral leishmaniasis.

Apart from this, I would emphasise the not usual aspect of this image caused by the very high number of parasites that fill the cytoplasm. Usually, a lowest number of leishmanias (10-20 only) is present.

Thank you. Of course the clinical manifestations, pancytopenia and presence of phagocytosis and other specific features in the presence of LD bodies. Some times there is difficulty to find LD bodies but the morphology of bone marrow give us the impression of diagnosis to follow it by other methods.

Article Clinical and hematological manifestations of visceral leishm...

Thanks for these interesting images as well as for the article