Defining The morphological Appearance Of ETV6-Abl Diseases. Evaluation Of a Case

A 30 year old female presented@30 weeks pregnancy with a few circulating myeloid blasts in her blood but a normal full blood count. She had previously used an epipen for acute allergic reactions and had bone pain at presentation. There was splenomegaly on examination. Bone marrow aspirate was extremely difficult to obtain but trephine roll showed eosinophils, basophils, occasional mast cells and occasional blasts A population of 23% hypergranulated basophilic cells were seen on aspirate whose aetiology is not clear and are assigned to the basophil/mast cell series. For want of a better term these cells are called Finella’s cells. Histological examination of trephine biopsy showed extreme hypercellularity, Grade III/IV reticulin fibrosis large numbers of eosinophils and basophils with mast cells confirmed by CD 117 staining. The large hypergranulated basophilic cells (Finella’s cells) were not visible on trephine staining. An isodicentric X on cytogenetic analysis and a bcr-abl probe showed a split abl with 2 signals. An ETV6-ABL1 gene rearrangement was present. The c-kit D816V mutation was not identified nor was FIP1L1-PDGFRA present. Subsequently the morphologic features described above allowed the suspicion in a further case. Various appearances of the bone marrow and blood allow the suspicion of a particular disease which then leads to the performance of the diagnostic test to confirm the suspected genetic abnormality. This is epitomised in the diagnosis of chronic myeloid leukaemia based on a high white cell count, myelocyte peak and excess of myeloid cells with an increase in cells such as eosinophils and basophils. The diagnosis is then made by demonstrating the presence of the Philadelphia chromosome or bcr-abl gene rearrangement. In contrast in cases with an ETV6-abl, the patient has a white cell count that is not markedly increased with a leucoerythroblastic blood film and a bone marrow examination that shows a superficial resemblance to a chronic myeloproliferative disease with marked myelofibrosis and large numbers of eosinophils and basophils some of which are morphologically abnormal. Megakaryocytes when seen show discrete nuclear fragments and hypolobation and eosinophils and basophils are increased leading to the case being mistakenly diagnosed as an eosinophilic disorder rather than a specific disease entity i.e ETV6-abl. It cannot be classified with the mastocytic leukaemia’s as the number of masts cells is not greater than 5% and they are not clustered but loosely distributed. The aetiology of Finella’s cells are unclear. Mast cells in blood smears are easily identifiable by their large granules which disfigure the nuclear outline and a central area of pallor or by their “slipper” shape and granule content. In this case the cells are larger than mast cells circular, have no central area of pallor,the excessive granularity masking the nuclear outline and leading one to question whether a PML-RARA fusion is present which it is not. The presence of eosinophils, basophils and these cells should make the viewer suspect an ETV6-abl disorder which is normally a cryptic fusion which will not be identified without use of the appropriate FISH/ RT-PCR test. The disease appears to undergo blast transformation as seen with CML and early transplantation is recommended as happened successfully with our case. Although several other cases have been reported in the literature by various authors and called bcr-abl negative CML, myeloproliferative neoplasms, myeloproliferative disorders with eosinophilia etc peripheral blood eosinophilia is not present and FIP1L1-PDGFRA is not present. The morphologic features that lead one to suspect the presence of theETV6-abl have not been previously delineated. THE ETV6-ABL fusion protein has tyrosine kinase activity and responds to imatinib or second generation TKI’s and therefore demonstrating its presence when faced by the classic morphologic appearance is of clinical importance. Disclosures: No relevant conflicts of interest to declare.