Not only a chicken and egg problem in children with pancytopenia

Excerpt

Making the correct diagnosis and defining the appropriate treatment in a case of persistent pancytopenia in a child can be enigmatic. The major choices are whether pathogenesis is more neoplastic, more immunologic, or more germline based. In other words, whether it is myelodysplastic syndrome (MDS), severe aplastic anemia (SAA), or inherited bone marrow failure (IBMF). Or a mixture of all of those potential causes (which cause is primary, and which is secondary may not always be obvious). The newest confusion of wording between the two international reference nomenclature systems, i.e., the one by the World Health Organization (WHO) as opposed to the other proposed by the new International Consensus Classification (ICC) group does not add much to solving the problem [1, 2]. Description of pediatric MDS by both remains mostly descriptive and morphologic in many cases, although both standards of reference otherwise introduce revolutionary aspects into making a diagnosis of hematolymphoid tumors by putting much more weight on cause (genetics) over appearance (morphology, e.g., blast counts). Already in parallel to the inclusion of what is the most frequent form of pediatric MDS, i.e., refractory cytopenia of childhood (RCC), into the MDS category (a clonal hematopoietic stem cell neoplasm) by WHO in 2008 there were reports that RCC can be cured solely by immunotherapy [3, 4]. This is why ICC correctly states that RCC cannot always be considered a bona fide MDS (although it was included in the MDS category). So what is it: neoplastic, immunologic, germline-based? As shown in this edition of memo by Novak et al., it can be all of this: SAA by morphology, IBMF by genetics, therapeutic response still as a classical SAA; or RCC by morphology and IBMF by genomics [5]. What do we learn from this: pathogenesis of pancytopenia in a child frequently is not unimodal and sharp classification may rather obscure our understanding (and treatment choice). We need to consider that there is still a conundrum around pediatric pancytopenia and use all diagnostic methodologies available to choose best available treatment for this enigmatic disease. …