Why Polycythemia Vera Rarely Develops in Children
Polycythemia vera (PV) is extremely rare in children due to its pathophysiology as a clonal stem cell disease that typically requires time to develop genetic alterations, with the median age of diagnosis being approximately 60 years. 1
Epidemiological Evidence
The Mayo Clinic comprehensive review on PV provides clear epidemiological data showing that:
- The median age at diagnosis is approximately 60 years
- Only about 7% of patients are diagnosed before age 40 years
- Children are rarely diagnosed with PV 1
This age distribution pattern is consistently observed across multiple studies, highlighting the strong correlation between advancing age and PV development.
Pathophysiological Reasons for PV Rarity in Children
1. Genetic Mutation Accumulation
PV is a clonal stem cell disease with trilineage myeloid involvement 1. The development of the disease requires:
- Acquisition of specific genetic mutations
- Time for these mutations to accumulate and express clinically
- Most commonly, the JAK2V617F mutation, present in >95% of PV patients 2
These genetic alterations typically take decades to develop and manifest clinically, explaining why the disease is predominantly seen in older adults.
2. Molecular Pathogenesis
The pathogenesis of PV involves complex molecular alterations:
- Clonal erythrocytosis is a hallmark feature 1
- Growth factor independence and hypersensitivity of erythroid progenitor cells
- Alterations in signal transduction pathways including EPO receptor signaling
- Abnormalities in TPO receptor (c-mpl) expression 1
These molecular changes typically develop over time and are less likely to have occurred in children's hematopoietic stem cells.
3. Distinctive Features in Pediatric Cases
When PV does rarely occur in children, it may have different characteristics:
- A Japanese nationwide survey identified only 5 children with PV among 50 pediatric myeloproliferative neoplasm cases 3
- Interestingly, none of the 5 pediatric PV cases in this study had the JAK2 V617F mutation 3, suggesting potentially different pathophysiological mechanisms
- Male predominance was observed in pediatric PV (4:1 ratio) 3, contrasting with the slight male preponderance (1.2:1) in adults 1
Clinical Implications
The rarity of PV in children has important clinical implications:
- Erythrocytosis in children should prompt consideration of other causes before PV
- Different diagnostic approaches may be needed for suspected pediatric PV
- Complications like thrombosis and leukemic transformation appear less frequent in pediatric cases 3
- However, leukemic transformation has been reported in pediatric cases and can be fatal 3
Conclusion
The rarity of PV in children is primarily explained by its nature as an acquired clonal stem cell disorder that typically requires decades for the necessary genetic and molecular alterations to accumulate. When PV does occur in children, it may have distinct genetic and clinical features compared to adult PV, suggesting potentially different underlying mechanisms.