Musculoskeletal symptoms and misdiagnoses among children with neuroblastoma.
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BACKGROUND: Neuroblastoma often presents with non-specific signs and symptoms, including musculoskeletal (MS) symptoms, potentially leading to misdiagnoses. This study aimed to identify, characterise, and compare children with neuroblastoma who had prior MS misdiagnoses to those without, analysing clinical presentation, diagnostic interval, and outcome. METHODS: We performed a nationwide, historic cohort including all children under 15 years of age diagnosed with neuroblastoma in Denmark from 1996 to 2018. The patients were identified using the Danish Childhood Cancer Registry, and data were collected through a medical chart review. RESULTS: Out of 143 children diagnosed with neuroblastoma included in this study, MS symptoms occurred in 30% and misdiagnoses in 12%, mainly as reactive arthritis. The group with MS misdiagnosis more commonly presented with back pain, arthralgia, and more advanced disease with a higher rate of stage 4 at diagnosis, bone metastases, relapse, and increased mortality. The group with MS misdiagnosis had an increased diagnostic interval, primarily due to hospital delays. After adjusting for age and disease stage, no significant difference in survival was observed between the children with or without MS misdiagnosis. CONCLUSION: MS misdiagnoses occur in 12% of childhood neuroblastoma with back pain and arthralgia as potential red flags. IMPACT: This study is the first nationwide, population-based cohort to quantify musculoskeletal misdiagnoses in children with neuroblastoma. We show that 12% of patients were initially misdiagnosed, most often with reactive arthritis, leading to longer diagnostic delays and more advanced disease at presentation. The findings add to existing literature by identifying specific clinical red flags-back pain and arthralgia-that should prompt consideration of malignancy. Early use of abdominal ultrasound in children with unexplained musculoskeletal symptoms may help reduce diagnostic delay and improve care.