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Diseases of the monocyte, macrophage and dendritic cell system are referred to as histiocytoses. Based on improved understanding of their pathobiology and molecular background histiocytoses have been recently re-classified into five groups. Nevertheless, for practical reasons the histiocytoses are grouped into: Langerhans cell histiocytosis (the most common entity), hemophagocytic lymphohistiocytosis (encompassing primary and secondary hyperinflammatory syndromes), non-Langerhans cell histiocytoses (encompassing entities and syndromes not belonging to one of the first two categories), and true histiocytic malignancies. Proliferation of bone marrow-derived mature histiocytes with CD68+/CD163+/CD1a-/CD207- phenotype is the common denominator of the non-Langerhans cell histiocytoses (non-LCH). The clinical manifestations are extremely heterogeneous, though partially overlapping. There are some distinct disease forms (particularly those belonging to the juvenile xanthogranuloma family) confined to the skin. Some other entities may present as systemic diseases requiring differential diagnosis with hematopoietic malignancies and solid tumors. This paper provides a brief overview on key clinical features, diagnostic criteria, and management of the most common systemic non-LCH entities: Juvenile Xanthogranuloma (JXG), Rosai-Dorfman disease (RDD), and Erdheim-Chester disease (ECD). 
The non-LCH histiocytoses with systemic manifestation are uncommon diseases in the pediatric hematology/oncology praxis. Due to their broad spectrum of manifestations, keeping in mind their key features and an adequate index of suspicion are important for timely and correct diagnosis. Non-LCH histiocytoses have to be considered in the differential diagnosis of papulonodular cutaneous lesions with xanthomatous appearance, osteolytic and osteosclerotic lesions with benign morphology and histiocytic infiltration, orbital lesions with proptosis, suprasellar masses presenting with central diabetes insipidus, as well as leptomeningeal mass lesions.

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Juvenile xanthogranuloma (JXG), is the most common form of non-Langerhans cell histiocytosis. It is a rare and usually benign, monoclonal proliferative disorder of histiocytic cells. The occurrence of multiple brain lesions is extremely rare. Due to the rarity of CNS disease, the preferred treatment and overall prognosis of these patients remain unclear. In this case report, authors present their experience about a patient with isolated multiple cerebral JXG which yields considerable outcomes. The patient was an eleven-year-old boy with anorexia and recurrent vomiting. Brain MRI demonstrated multiple lesions involving right lateral ventricle wall and periventricular white matter, the right side of splenium, mammillary body and tuber cinereum, fourth ventricle floor and roof, and cerebellar tonsil. After initial response to chemotherapy, the lesions recurred and radiotherapy was done. Consequent to good response after radiotherapy and despite the occurrence of a seizure attack, long term follow-up showed the marked resolution of the lesions and a good general status.