Primary histiocytosis of the central nervous system: a case report

Abstract

Case Presentation: A 17-year-old patient with a previous diagnosis of migraine and mood disorder presented with worsening headache in January 2025. A brain magnetic resonance imaging (MRI) performed at that time showed no significant abnormalities. Trigger-point injections were performed and treatment with fremanezumab was initiated, without improvement. In May 2025, due to refractory pain, the patient was hospitalized. On admission, the patient was somnolent and prostrated. A new brain MRI revealed bilateral and symmetrical signal abnormalities in the mid portions of the cerebellar hemispheres, characterized by T2/FLAIR hyperintensity with mass effect, compression of the fourth ventricle, downward herniation of the cerebellar tonsils through the foramen magnum, and anterior displacement of the brainstem. These findings were associated with supratentorial hydrocephalus and signs of intracranial hypertension. The patient underwent decompressive craniectomy and placement of an external ventricular drain, with tissue collection for biopsy. Cerebellar biopsy showed areas of nonspecific chronic inflammatory infiltrate with CD1a-positive histiocytic cells and interspersed eosinophils, establishing the diagnosis of histiocytosis. Considering the rarity of primary central nervous system involvement, a PET-CT scan was performed but did not reveal other disease sites. Discussion: Histiocytoses comprise a heterogeneous group of disorders derived from cells of the mononuclear phagocytic system, including dendritic cell disorders, macrophage-related disorders, and malignant histiocytic diseases. Langerhans cell histiocytosis (LCH) is currently considered a hematopoietic neoplasm. Its estimated incidence ranges from two to five cases per 1,000,000 individuals, most commonly affecting male children between one and three years of age. Although the central nervous system may be involved, cases in which it represents the primary site of disease are rare. The most frequently affected CNS structures include the hypothalamic–pituitary axis, infundibular stalk, choroid plexus, pineal gland, and white matter. Diabetes insipidus is the most common clinical manifestation of CNS involvement. The most specific immunohistochemical marker for LCH is the CD1a antibody, identified in the biopsy specimen of this case. Treatment depends on lesion location, number of lesions, and clinical manifestations, and may include surgery, chemotherapy, radiotherapy, or conservative management, often combined with high-dose corticosteroids to control the inflammatory component. In this case, the patient received cladribine at a dose of 0.14 mg/kg/day for five days. Final Comments: The prevalence of central nervous system involvement in histiocytosis ranges from 3.4% to 54%, depending on the subtype. However, Langerhans cell histiocytosis with the CNS as the primary site is extremely rare, and epidemiological estimates of its prevalence are scarce.