Langerhans cells, often referred to as the \"macrophages of the skin\", are dendritic cells that normally reside in the epidermis and papillary dermis. Just like macrophages, they function as antigenpresenting cells that activate naive T cells. Certain mutations such as those involving the BRAF gene can cause unopposed production of Langerhans cells, which is known as Langerhans cell histiocytosis (LCH). LCH triggers an inflammatory immune response that causes systemic manifestations such as fever and fatigue, as well as other manifestations depending on the affected organs. The pathogenesis behind LCH remains poorly understood. It is still unknown whether it is a neoplastic process or a reactive cancer-mimicking illness. Diagnosis of LCH is confirmed by biopsy, and treatment is largely dependent on the extent and severity of the disease. Common treatments include corticosteroids, excision, radiation, and chemotherapy. We present a case of a 1-year-old Saudi male with LCH.

Blueberry muffin is a descriptive term for a neonate with multiple purpuric skin lesions. Many causes are known, amongst them life-threatening diseases like congenital infections or leukemia. Indeterminate cell histiocytosis (ICH) is an exceptionally rare cause of blueberry muffin rash. ICH is a histiocytic disorder which can be limited to the skin or can present with systemic involvement. A mutation that has been described in histiocytic disorders is a MAP2K1 mutation. In ICH, this mutation has previously been described in merely one case.
A term male neonate was admitted to the neonatology ward directly after birth because of a blueberry muffin rash. ICH was diagnosed on skin biopsy. The lesions resolved spontaneously. The patient is currently 3 years old and has had no cutaneous lesions or systemic involvement so far. This disease course is similar to that of the Hashimoto-Pritzker variant of LCH.
ICH can manifest in neonates as resolving skin lesions. It is limited to the skin in most cases, but systemic development is possible. Therefore, it is essential to confirm the diagnosis with a biopsy before the lesions resolve and to monitor these patients closely with routine follow-up.

Juvenile xanthogranuloma (JXG) is a benign proliferative histiocytic disorder of the dendritic cell phenotype. It mostly presents in the pediatric age group as a solitary skin lesion. We describe a rare case of an infant born with disseminated JXG who presented with a blueberry muffin rash at birth. A term infant was noted to have multiple petechiae, purple nodules, and macules (1 mm-2 cm in diameter) and hepatosplenomegaly, at the time of birth. Further investigations revealed thrombocytopenia and direct hyperbilirubinemia and a magnetic resonance imaging showed scattered tiny foci of restricted diffusion in multiple areas of the brain. Patient received multiple platelet transfusions in the first few weeks with gradual improvement in thrombocytopenia. Ultimately, a biopsy of one of the lesions revealed the diagnosis of disseminated JXG with notable atypical features. Somatic mutation analysis showed a novel MYH9-FLT3 fusion, but a bone marrow biopsy was negative. The lesions faded over time, relative to patient\'s growth and normal neurodevelopment was noted at 18 months of age. JXG should be considered in the differentials of blueberry muffin rash in an infant. Although, JXG is mostly a self-limited condition, congenital disseminated JXG may be associated with significant morbidity and mortality.

Multiple papulonodular skin lesions at birth can indicate the presence of various benign and malignant disorders. Although the lesions\' clinical aspect (color and consistency, in particular) may steer the clinician towards one disorder or another (infantile myofibromatosis, xanthogranuloma, or metastatic neuroblastoma), the diagnosis can only be confirmed by the histopathologic assessment of a biopsy. In neonates, a rapid but accurate diagnosis is critical because skin lesions may be the first manifestation of a malignant disorder like leukemia cutis or metastatic neuroblastoma. Here, we review the various disorders that may manifest themselves as multiple skin lesions at birth.

BACKGROUND: Ganglioneuroblastoma is a tumor of peripheral neuroblastic tissue which occurs predominantly in the pediatric age group; it is a rare occurrence in the newborn period with only one case reported at birth to date.
METHODS: We report the case of a newborn male baby of Brahmin ethnicity from Nepal who presented with respiratory distress and blueberry muffin skin lesions after birth. A computed tomography scan showed a mass lesion in the posterior mediastinum, which was diagnosed as ganglioneuroblastoma on fine-needle aspiration cytology. He also had metastases to multiple sites including heart, lungs, skin and brain.
CONCLUSIONS: Ganglioneuroblastoma is a rare tumor in newborns. Any newborn presenting with respiratory distress associated with blueberry muffin skin lesions should be evaluated for neuroblastic tumor.