The diagnostic utility of eosinophil morphology.

Abstract

Despite continued advances in our understanding of the genetic basis of inherited and acquired haematological diseases the role of blood and bone marrow morphology remains paramount. This skill takes time to acquire, as every trainee is well aware, but continues to develop throughout many years of practice. There are many areas of Haematology where a morphological assessment alongside appropriate other laboratory data, can rapidly narrow a differential diagnosis and inform specific targeted confirmatory tests. In some clinical situations the morphology assessment alone can yield a rapid diagnosis. There are many excellent texts that describe the various nuances of blood cell morphology and their likely diagnostic implications. The characteristics of all cell lineages at various stages of maturation have been well described both in conditions of health and disease. The eosinophil, however, has continued to elude our grasp. We are all familiar with the importance of this cell and there are specific guidelines on how patients with eosinophilia should be investigated. What has been missing is a formal assessment of how abnormalities of eosinophil morphology can inform diagnosis and help differentiate between clonal and reactive conditions. As eosinophilia can have diverse aetiologies varying from reactive states seen in connective tissue disorders, helminth infections and solid tumours to the clonal proliferations seen in acute and chronic leukaemias this is actually quite important. Anecdotally, it has long been felt that changes in eosinophil morphology were unreliable in informing the differential diagnosis, but this topic has never been formally addressed. In this issue of the British Journal of Haematology, Goasguen et al.1 (The International Working Group on the Morphology of MDS) have addressed this very question. The group examined blood films from healthy controls and from patients with known reactive and clonal eosinophilias. The planning group categorised abnormalities in terms of nuclear shape and segmentation together with the degree of cytoplasmic granulation and vacuolation that could represent eosinophil dysplasia (DysEo). Representative images of each type of abnormality were collected for reference. Digitised images of 5594 eosinophils taken from normal controls and patients with reactive and clonal disorders, together with idiopathic hypereosinophilic syndrome, were collated and circulated to the wider group for their assessment. Each assessor independently graded any abnormalities and was asked to comment on whether they felt a primary haematological abnormality was likely. There was excellent consensus on morphological features at 91·8% between the group. Importantly, the images were of eosinophils only: other cells in each blood film were carefully excluded as this would bias the interpretation. The study concluded that morphological abnormalities of eosinophils, assessed in isolation had poor specificity for the diagnosis of a myeloid neoplasm. Abnormalities were seen in a significant proportion of reactive cases, with 43% of cases being graded moderate or severe. There was a trend for a higher frequency of changes in nuclear form (non-lobated, hyperlobated, binuclearity or ring nucleus) to be seen in myeloid neoplasms, but even so these were also noted in reactive cases. This study has therefore answered an important question. It does not suggest however that morphological assessment of eosinophilia should be abandoned. In every case it is still necessary to scrutinise the film, not only noting the characteristics of eosinophils, but more importantly to assess the company that they keep. The presence of blasts, monocytes and their precursors, dysplastic neutrophils, basophils, mast cells, abnormal lymphoid cells, leucoerythroblastosis and parasites should all be noted, as this will guide the differential diagnosis. Careful consideration of the multiple potential aetiologies with targeted subsequent investigation will yield a definitive diagnosis in the majority of cases.