Pathophysiological insights and diagnostic challenges associated with blueberry muffin baby

Blueberry muffin baby (BMB) is a clinical manifestation characterized by bluish‑purple macules, papules, or nodules resulting from dermal extramedullary hematopoiesis (EMH) or malignant infiltration. The present review discusses this condition by presenting data from 32 case reports, including 7 cases of infectious etiology (TORCH and other infections, such as COVID‑19), 20 cases of neoplastic origin congenital leukemia (acute myeloid leukemia and aAcute lymphoblastic leukemia), neuroblastoma, rhabdomyosarcoma, Langerhans cell histiocytosis and juvenile xanthogranuloma, and 5 cases of hematological disorders (severe anemia, hemolytic diseases, Gaucher disease, hemophagocytic lymphohistiocytosis and εγδβ‑thalassemia). The present review focuses on the pathophysiology and diagnostic approaches for each etiology, suggesting the role of histopathological and immunohistochemistry markers in differentiating reactive EMH from malignant processes. Early recognition and precise diagnosis are crucial for appropriate management, ranging from supportive care to targeted therapy in malignant conditions. The present review underscores the importance of integrating clinical evaluation, histopathological findings and molecular analysis to optimize the outcomes of neonates with BMB.