Essential thrombocythemia vs. pre-fibrotic/early primary myelofibrosis: discrimination by laboratory and clinical data

Among several groups of clinicians and hematopathologists a conflict of opinion has been repeatedly expressed concerning the validity of bone marrow (BM) features characterizing myeloproliferative neoplasms (MPNs) 1 , 2 . In this regard, controversy is mainly focused on the distinction between essential thrombocythemia (ET) and pre-fibrotic/early primary myelofibrosis (pre-PMF) 3 , 4 , 5 . Although other groups confirmed the characteristic BM features and emphasized the clinical impact to discriminate both MPN subtypes 3 , 6 , 7 , 8 , 9 , 10 , the existence of pre-PMF has been questioned, including clinical usefulness and particularly reproducibility of the corresponding diagnostic guidelines 11 . In this context, it has been criticized that the MPN classification proposed by the World Health Organization (WHO), updated in 2008 12 and revised in 2016, 13 was focused on BM morphology as the gold standard of diagnosis. As has been highlighted until now, none of the various mutations identified so far have proven to be specific and therefore cannot be applied for a molecular classification of MPNs and especially not for the distinction between ET and pre-PMF 14 . Given the very different outcome and treatment options in clinical practice, there is an active interest to evaluate whether laboratory or clinical parameters could help to distinguish WHO-defined ET and pre-PMF in patients presenting with thrombocytosis. A first step to elucidate if blood tests could exert a predictive power in patients presenting clinically with an ET-like phenotype was initiated by Carobbio et al 15 . To identify pre-PMF cases mimicking ET, the laboratory parameters for hemoglobin (Hb), white blood cell (WBC) count, and serum lactate dehydrogenase (LDH) level were used in a dichotomized manner, resulting in a step-by-step algorithm. The cutoff values at each step in this algorithm were optimized to produce the desired specificity and sensitivity. The result was that nearly 50% of all patients mimicking an ET-like phenotype could correctly be attributed to the pre-PMF group 15 .