Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort

Abstract

SummarySporadic essential thrombocythaemia (ET) is rare in paediatrics, and the diagnostic and clinical approach to paediatric cases cannot be simply copied from experience with adults. Here, we assessed 89 children with a clinical diagnosis of ET and found that 23 patients (25Á8%) had a clonal disease. The JAK2 V617F mutation was identified in 14 children, 1 child had the MPL W515L mutation, and 6 had CALR mutations. The monoclonal X-chromosome inactivation pattern was seen in six patients (two with JAK2 V617F and two with CALR mutations). The other 66 patients (74Á2%) had persistent thrombocytosis with no clonality. There were no clinical or haematological differences between the clonal and non-clonal patients. The relative proportion of ET-specific mutations in the clonal children was much the same as in adults. The higher prevalence of nonclonal cases suggests that some patients may not have myeloproliferative neoplasms, with significant implications for their treatment.

Thrombopoietin Measurement as a Key Component in the Evaluation of Pediatric Thrombocytosis

“…Current algorithms for the diagnosis of ET include molecular genetic studies for a pathogenic variant in one of these genes . ET is a rare disorder in childhood and, in striking contrast to adults, only 25–30% of children diagnosed with ET will have an acquired JAK2, MPL , or CALR mutation . Thus, 70–75% of children are classified as having “triple negative” disease.…”

Bone marrow histology for the diagnosis of essential thrombocythemia in children: a multicenter Italian study

“…10 The differential diagnosis of pediatric thrombocytosis may be challenging in clinical practice, and, unlike in adults, molecular biology is of limited value. Children with suspected ET have indeed low rates of driver mutations 2,3,11,12 with a lower allele burden than adults. 13 Consequently, molecular studies cannot definitively identify the nature of several putative pediatric ET cases.…”

“…Although pediatric cases occur, they are rare, and their molecular features considerably differ from the adult counterparts: JAK2V617F mutation occurs in only 25% of cases, 1 CALR mutations are found in ,10% of patients, 2 and the MPLW515L mutation is anecdotal. 3 Overall, ,40% of children with unexplained, long-lasting thrombocytosis have a clonal marker of ET.…”

“…3 Overall, ,40% of children with unexplained, long-lasting thrombocytosis have a clonal marker of ET. 2 After the release of the 2001 World Health Organization (WHO) classification, 4 bone marrow (BM) evaluation has become a cornerstone of ET diagnosis. However, the majority of studies has focused on adults, and little is known about the role of BM biopsy in pediatric ET.…”

Chasing down the triple-negative myeloproliferative neoplasms: Implications for molecular diagnostics

“…[10][11][12] Whether these cases, analogous to a larger proportion of pediatric patients classified as MPN, truly have a clonal malignancy is questionable. 18 Re-consideration of the role of haematopoietic clonality assessment by X-chromosome inactivation patterns in triplenegative MPN may be necessary, however these approaches apply only to female patients, require considerable interpretation, and have been further confounded by the recent description of polyclonal hematopoiesis in some female MPN patients. 19 Furthermore, the pathogenesis of MPN may not be entirely explained by the detection of driver mutations: other complex processes, such as inflammation, are likely to play a key role in the development of these diseases.…”