Malignancy-associated hypercalcemia in children: A Systematic Review

Abstract Purpose Malignancy-associated hypercalcemia (MAH) is a rare but potentially life-threatening oncologic emergency in pediatric patients. Although extensively described in adults, evidence regarding the epidemiology, pathophysiology, clinical presentation, management, and outcomes in children remains limited. This systematic review aimed to summarize the current evidence on pediatric MAH. Methods A systematic literature search was conducted in PubMed/MEDLINE, Embase, and the Cochrane Library following PRISMA guidelines. Studies reporting hypercalcemia in patients aged 0–18 years with an underlying malignancy were eligible for inclusion. Data regarding incidence, malignancy subtype, clinical presentation, pathophysiology, treatment, and outcomes were extracted. Risk of bias was assessed using the Joanna Briggs Institute tool. Results A total of 123 studies were included, comprising 16 cohort studies and 107 case reports. The reported prevalence of MAH was generally below 1%. MAH occurred in hematological malignancies (49%), predominantly acute lymphoblastic leukemia (ALL, 75%), and solid tumors (51%). Hypercalcemia was reported at initial diagnosis (44%) and disease relapse (36%). The most reported underlying mechanisms were parathyroid hormone-related peptide (PTHrP)-mediated hypercalcemia (11.6%) and osteolytic bone destruction (9.9%). Management strategies were relatively consistent and typically included intravenous hydration, bisphosphonate therapy, and treatment of the underlying malignancy. Conclusion MAH is an uncommon yet clinically significant complication in pediatric oncology, occurring across hematologic and solid malignancies. The principal underlying mechanisms are PTHrP-mediated hypercalcemia and osteolytic bone destruction. Current treatment approaches primarily consist of supportive care, antiresorptive therapy, and malignancy-directed treatment. These findings may contribute to standardized international guidelines for the diagnosis and management of pediatric MAH.