Developmental Differences in Megakaryocyte (MK) Size in Infants and Children.
Deborah A Fuchs, Sarah G McGinn, Carlos L Cantu, Robert R Klein, Martha C Sola-Visner, Lisa M Rimsza. University of Arizona College of Medicine, Tucson; Children's Hospital Boston and Harvard Medical School, MA
Background: Developmental differences in MK size and ploidy between neonatal (<1 month) and adult bone marrows have been previously described (M Sola-Visner et al Pediatr Res 2007). However, the age at which MKs transition from a neonatal to an adult phenotype is unknown. Small MKs are often described as “dysplastic” in the pathology literature. Thus, recognizing the normal features of MKs at different ages has implications for the diagnosis of MK disorders. We hypothesized that the shift from a neonatal to an adult MK phenotype would occur in the first 5 years of life.
Design: We searched the hospital records for patients aged 0 to 5 years who had undergone bone marrow biopsies for staging of solid tumors between 1991 and 2008, were free of disease, and had normal cellularity. All specimens meeting these criteria were immunohistochemically stained with anti-CD61 antibody. Each sample was evaluated by one of the investigators (SM or CC), who measured the largest diameter of each MK using the measurement tool (at 400X) of the Arcturus XT Laser Capture Microdissection System. Five cases were analyzed by 2 investigators, and inter-observer variability was examined using equivalence testing.
Results: This study identified 47 cases with clot sections and/or core biopsies from 28 patients, aged 0.5-53 months (14 neuroblastomas, 3 Wilms, 2 PNET, 2 sarcomas, 7 other). There were no significant differences in MK measurements between observers or between clot and core preparations. A scatterplot of MK size by age revealed a relatively normal distribution of sizes at the youngest ages, with a shift to multiple distinct peaks starting at 24 months, suggesting the appearance of MK subpopulations with different sizes. Logistic regression analysis also demonstrated a significant decrease in the percentage of intermediate-sized MKs over time, from 72% at 1 month to 54% at 53 months (p < 0.001). This was accompanied by a commensurate age-related increase in the proportions of both small and large MKs.
Conclusions: In the current study, we extended our previous observations of MK size in neonates to include young children. Our findings demonstrated that neonates have more uniform MK sizes, which diverge into separate clusters of larger and smaller MKs during childhood, starting at approximately 24 months of age. These observations have direct implications for the evaluation of bone marrow MKs in infants and children.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 161, Tuesday Afternoon