Multiple Primary Intracranial and Spinal Juvenile Xanthogranuloma: A Case Report

Case Report

Austin Surg Case Rep. 2021; 6(1): 1043.

Multiple Primary Intracranial and Spinal Juvenile Xanthogranuloma: A Case Report

Almanea AK1*, Alqazlan MS2, Bardisi MM3, Alotaibi F4 and Alshakweer W5

1Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Saudi Arabia

2Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Saudi Arabia

3Department of Pathology and Laboratory Medicine, Riyadh Regional Lab and Blood Bank, Ministry of Health, Saudi Arabia.

4Neuroscience Center, King Fahad Medical City, Saudi Arabia

5Department of Pathology and Laboratory Medicine, King Fahad Medical City, Saudi Arabia

*Corresponding author: Abdullah Khaled Almanea, Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Saudi Arabia

Received: June 11, 2021; Accepted: July 31, 2021; Published: August 07, 2021


Juvenile Xanthogranuloma (JXG) is a rare histiocytic disorder that belongs to the non-Langerhans cell histiocytosis family. It commonly occurs in the skin of young children, particularly the head and neck region. Occasional cases with extracutaneous involvement have been described. However, involvement of the central nervous system without cutaneous lesions is extremely rare. We present a case of an 11-year-old male child with multiple intracranial and spinal JXGs. At 30 months follow up, after administration of chemotherapy, the patient had passed away. The broad clinical spectrum of JXG and the morphological resemblance to other histiocytic lesions prompt a cautious approach for the diagnosis. Immunohistochemically, those lesions were positive for CD68 and negative for S100 and CD1a. A revised classification for histiocytosis was recently proposed, based on the underlying molecular characteristics. The diagnosis of extracutaneous or disseminated JXG with MAPK-activating mutation or ALK translocations was considered as Erdheim-Chester disease. However, our study did not fit into the proposed classification due to the absence of BRAF-V600E gene mutation and ALK gene rearrangement. Chemotherapy with or without radiotherapy has been suggested as treatment options for unresectable central nervous system lesions.

Keywords: JXG; Juvenile Xanthogranuloma; Histiocytic; Primary intracranial; Central nervus system histocytosis


JXG: Juvenile Xanthogranuloma; CNS: Cntral Nervous System; MRI: Magnetic Resonance Imaging; PET/CT: Positron Emission Tomography Computed Tomography; GFAP: Glial Fibrillary Acidic Protein; AFP: Acid-Fast Bacilli; PAS: Periodic Acid-Schiff; GMS: Grocott’s Methenamine Silver Stain; RDD: Rosai-Dorfman Disease; LCH: Langerhans Cell Histiocytosis; ALK: Anaplastic Lymphoma Kinase; ECD: Erdheim-Chester Disease; MAPK/ERK: Mitogen- Activated Protein Kinase/Extracellular Signal-Regulated Kinases


Juvenile Xanthogranuloma (JXG) is a benign cutaneous disorder of non-Langerhans cell histiocytic proliferation, which usually a selflimited disorder that occurs in children with a predilection for the head and neck region. It has been first described in 1905 and 1912 by Adamson and McDonagh, respectively [1,3]. It is the most common form of non-Langerhans cell histiocytosis. However, the true etiology of this disease is currently unknown [2]. JXG can be defined by the clinical setting as solitary to disseminated lesions, the areas of the body involved, and the patient’s age [3]. That is, It usually presents in the first year of life with one, several, or even numerous red to yellow cutaneous nodules that typically involve the head and neck area. These nodules usually range in size between 0.5 to 1.0 cm in diameter and are often self-limited. Extracutaneous dissemination is infrequent, primarily affecting the uveal tract of the eye [3]. Nevertheless, isolated lesion involving the Central Nervous System (CNS) without cutaneous involvement is extremely rare [4]. We are presenting a case of an 11-year-old female who presented with multiple primary intracranial and spinal JXGs without cutaneous manifestations.

Case Presentation

An 11-years old male child presented with long-standing right ear pain and erythema for two months that progressed into a decreased hearing with right facial nerve weakness and headache. Despite medical therapy, the patient had developed severe headaches and, subsequently tonic-clonic seizures. Physical examination showed right facial paralysis. All other sensory and motor functions were intact. No cutaneous lesions or bone tenderness were observed. Brain Magnetic Resonance Imaging (MRI) revealed multiple extra-axial and intraaxial supratentorial moderately enhancing lesions, including dural based, leptomeningeal based, and frontal region (Figure 1A,1B). In addition, bilateral vestibular lesions were seen in the internal auditory canals and the right trigeminal nerve (Figure 1C,1D). The largest lesion was dural-based and was located in the right temporal lobe. Spinal MRI exhibited multiple moderately enhancing spinal cord lesions at the level of C7, along the middle and lower thoracic, at the conus medullaris, the cauda equina, and the lower part of the theca’ sac at the level of S1 and S2 (Figure 1E,1F). No sclerotic or lytic bone lesions were identified on Positron Emission Tomography Computed Tomography (PET/CT). A chest, abdomen, and pelvis CT scans were negative for any organ involvements. A craniotomy approach with a dural-based lesional biopsy showed an inflammatory mass composed predominantly of histiocytes with scattered lymphocytes and occasional eosinophils. There were scattered clusters of Toutontype giant cells (Figure 2A). The tissue was negative for Glial Fibrillary Acidic Protein (GFAP) immunohistochemical stain excluding glial neoplasms. Additional staining with Acid-fast bacilli (AFB), Periodic Acid-Schiff (PAS), and Grocott’s Methenamine Silver (GMS) stain were also negative, excluding tuberculosis and infections causes. Positive immunohistochemical reaction for CD68 confirmed the histiocytic nature of the lesion, while negative reaction for S100 and CD1a excluded Rosai-Dorfman Disease (RDD) and Langerhans Cell Histiocytosis (LCH), respectively (Figure 2B-2D). Molecular study for BRAFV600E mutation and immunohistochemical stain for Anaplastic Lymphoma Kinase (ALK) were both negative, confirming the diagnosis of JXG and excluding Erdheim-Chester Disease (ECD) and ALK-positive histiocytosis, respectively (Figure 2E). The patient’s condition progressed despite chemo-radiotherapy, and he passed away 30 months from the time of initial diagnosis.

Citation: Almanea AK, Alqazlan MS, Bardisi MM, Alotaibi F and Alshakweer W. Multiple Primary Intracranial and Spinal Juvenile Xanthogranuloma: A Case Report. Austin Surg Case Rep. 2021; 6(1): 1043.