Morphological differentiation of severe aplastic anaemia from hypocellular refractory cytopenia of childhood: reproducibility of histopathological diagnostic criteria

Abstract

Baumann I, Führer M, Behrendt S, Campr V, Csomor J, Furlan I, de Haas V, Kerndrup G, Leguit R J, De Paepe P, Noellke P, Niemeyer C & Schwarz S (2012) Histopathology 61, 10–17 Morphological differentiation of severe aplastic anaemia from hypocellular refractory cytopenia of childhood: reproducibility of histopathological diagnostic criteria Aims: To evaluate the reproducibility and reliability of the histomorphological criteria differentiating severe aplastic anaemia (SAA) and hypoplastic refractory cytopenia of childhood (RCC), the most frequently acquired hypocellular bone marrow conditions of childhood. Methods and results: We performed a double‐blind interobserver study of 100 different cases of SAA and RCC among seven haematopathologists of the European Working Group of MDS in Childhood (EWOG‐MDS) and the German SAA study. Cases with foci of typical myelodysplastic syndrome (MDS) morphology, such as patchy erythropoiesis with defective maturation, in an otherwise highly hypocellular or adipocytic bone marrow were classified as having RCC. Bone marrow samples without a patchy distribution, few scattered myeloid cells or haematopoietic aplasia were diagnosed as SAA. In only four of 100 cases did the reference pathologists not reach agreement regarding classification as SAA or RCC. The kappa index was 0.79. Conclusions: Our results show that the vast majority of SAA and RCC cases can be reliably differentiated by morphological means alone. A clear differentiation between SAA and RCC at presentation is mandatory for optimizing therapy strategies, and might be responsible for the fact that, in the German childhood SAA study, the probability of developing clonal disease after immunosuppressive therapy has dropped to 3%.

Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome

“…2 Aplastic anemia (AA) shares several clinical and laboratory features with RCC, and nowadays histopathological assessment is a key method to distinguish between the two diseases. 3 Advanced MDS in children can be separated into three categories: 1) refractory anemia with excess blasts (RAEB); 2) RAEB in transformation (RAEB-t); or 3) myelodysplasiarelated acute myeloid leukemia (MDR-AML). 4 In some children, MDS or hypoplastic bone marrow failure is associated with an underlying genetic predisposition (e.g.…”

Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood

“…Based on the 2008 WHO criteria, 4 a distinction is made between RCC and the immune-mediated bone marrow (BM) failure syndrome (very) severe aplastic anemia ((v)SAA), with presence or absence of patchy erythropoiesis, respectively, as main differentiating parameter. 5 Nonetheless, because the majority of children with RCC have a normal karyotype and 80% of patients have a hypocellular BM, differentiating RCC from (v)SAA can be challenging. 4,6 Similar challenges are encountered in distinguishing (v)SAA and other non-clonal cytopenias from low-grade MDS in adults, especially in cases without specific morphological or cytogenetic aberrations.…”

The current perspective of low-grade myelodysplastic syndrome in children

“…Patchy erythropoiesis with impaired maturation, accompanied by sparsely distributed granulopoiesis, in an otherwise adipocytic BM is characteristic of hypoplastic low-grade MDS (Fig. 2b) [2,7,8]. Megakaryocytes are markedly decreased or absent.…”

“…Since hematopoietic cells in hypocellular low-grade MDS are often distributed in a patchy pattern (Fig. 2a), information obtained from aspiration cytology is limited [7,8]. Therefore, BM biopsies, which mirror the topography and cellularity of the local hematopoiesis, should be performed at least twice to diagnose hypoplastic BM disorders in children [2,7,8].…”

“…2a), information obtained from aspiration cytology is limited [7,8]. Therefore, BM biopsies, which mirror the topography and cellularity of the local hematopoiesis, should be performed at least twice to diagnose hypoplastic BM disorders in children [2,7,8]. Patchy erythropoiesis with impaired maturation, accompanied by sparsely distributed granulopoiesis, in an otherwise adipocytic BM is characteristic of hypoplastic low-grade MDS (Fig.…”