This is a 7-year-old boy who was born at 31 weeks of gestation with severe intrauterine growth retardation.  There was evidence of short stature at birth and CBC performed prior to initiation of growth hormone at 3 years of age noted isolated macrocytosis (MCV 101.1 fL).  However, after 2 years of therapy, the boy was admitted with fevers at this time, there was absolute neutropenia.  Vitamin B6 and vitamin B12 levels were normal.  Bone marrow biopsy was performed at the time.  The patient was also noted to have undescended testis.

CBC data at 5 years of age:

WBC =3400/mcL
Absolute neutrophil count = 374/mcL
Hemoglobin = 12.4 g/dL
Mean corpuscular volume =101 fL
Platelet count =81,000/mcL

The bone marrow biopsy depicted below shows hypocellular marrow with dysplastic megakaryocytes and megaloblastoid erythroid precursors with <2% circulating blasts and <5% bone marrow blasts with evidence of clonal monosomy 7.  The findings are typical of Refractory Cytopenia of Childhood (RCC; childhood MDS).  

Additional next generation sequencing studies on the bone marrow aspirate demonstrated pathogenic RUNX1 and EZH2 mutations.  Additional germline testing identified variants of uncertain significancer (VOUS) in SAMD9, SLX4 and SRP72 genes.

Learning points:

1.  The presence of <2% circulating blasts and <5% bone marrow blasts coupled with dysplastic megakaryocytes and clusters of immature erythroid precursors in a hypocellular marrow support classification RCC

2.  In children, neutropenia and thrombocytopenia with hypocelllarity is common whereas adults present with isolated anemia and hypercellular biopsies. Cases with 5-19% marrow blasts in children do not exhibit prognostic differences between cases with <10% and 10-20% blasts, as in adults.

3.  In RCC, patients with monosomy 7 (as seen in this case) have a higher probability of progression.

4.  A small but significant proportion of patients have underlying germline mutations related to bone marrow failure disorders.