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Year : 2012  |  Volume : 8  |  Issue : 2  |  Page : 311-313

Systemic juvenile xanthogranuloma with multiple central nervous system lesions

1 Neurosciences Research Center, Tabriz University of Medical Science, Tabriz; Department of Neurosurgery, Shohada Hospital, Shahid Beheshti Medical University, Tehran, Iran
2 Department of Neurosurgery, Shohada Hospital, Shahid Beheshti Medical University, Tehran, Iran
3 Department of Pathology, Shohada Hospital, Shahid Beheshti Medical University, Tehran, Iran
4 Department of Neurosurgery, Medical School, Hannover, Germany
5 Neurosciences Research Center, Tabriz University of Medical Science, Tabriz, Iran

Date of Web Publication26-Jul-2012

Correspondence Address:
Amir Hamdi
Neurosciences Research Center, Tabriz University of Medical Sciences, Imam Reza Medical Center, Golgasht Street, Tabriz, Eastern Azerbaijan 5166614756
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.99001

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 > Abstract 

Juvenile xanthogranulomatosis (JXG) is an uncommon histiocytic disorder that is usually benign and limited to the skin. The systemic form of JXG is rare and may be associated with severe morbidity and mortality especially in central nervous system (CNS) involvement. Here, we describe a six-year-old boy with disseminated skin lesions and neurological signs and symptoms. Diagnostic work up revealed multiple brain lesions. A skin biopsy and a stereotactic brain biopsy considered suggestive of systemic JXG. Treatment with prednisolone, vinblastine and methotrexate was successful with regression of skin and CNS lesions. The patient has been in remission for almost three years.

Keywords: Central nervous system, juvenile xanthogranuloma, langerhans cell histiocytosis

How to cite this article:
Meshkini A, Shahzadi S, Zali A, Tajeddini A, Mirzayan J, Hamdi A. Systemic juvenile xanthogranuloma with multiple central nervous system lesions. J Can Res Ther 2012;8:311-3

How to cite this URL:
Meshkini A, Shahzadi S, Zali A, Tajeddini A, Mirzayan J, Hamdi A. Systemic juvenile xanthogranuloma with multiple central nervous system lesions. J Can Res Ther [serial online] 2012 [cited 2022 Jan 19];8:311-3. Available from: https://www.cancerjournal.net/text.asp?2012/8/2/311/99001

 > Introduction Top

Juvenile xanthogranuloma (JXG) is an uncommon proliferative disorder of histiocytes [1] which is typically a benign dermatosis that occurs predominantly in children. Systemic JXG is rare and with a benign clinical course but it occasionally has a poor prognosis. [1],[2] Extracutaneous involvement usually includes eyes, lung, liver, spleen and central nervous system (CNS). Although there are some reports on intracranial involvement, [1],[2],[3],[4],[5] occurrence of multiple brain lesions is extremely rare. Here, we report the successful treatment of a six-year-old boy with disseminated, cutaneous and intracranial lesions.

 > Case Report Top

This six-year-old boy suffered from multiple, disseminated maculopapular cutaneous lesions of the trunk [Figure 1] and upper eyelids eight months before recent admission to the hospital. Sporadic periods of transient fever during last months have been reported by his parents. At admission, he presented with headache, nausea, vomiting and dizziness. Hemiparesis on the left side, convulsion, polydipsia, polyuria and photophobia were evident. His medical and family history was unremarkable.
Figure 1: Disseminated maculopapular cutaneous lesions of the trunk

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Computed tomographic scans of the brain demonstrated multiple isodense small lesions with moderate enhancement following contrast medium injection. Magnetic resonance imaging (MRI) studies confirmed multiple small intra-axial lesions, both infra- and supratentorially. The lesions appeared hypointense on T 1 weighted sequences and hyperintense on T 2 weighted sequences. Following the administration of gadolinium, homogenous enhancement occurred [Figure 2].
Figure 2: Contrast-enhanced T1-weighted images. A Axial view, B coronal view, C sagittal view

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Further diagnostic work-up detecting possible systemic involvement at other sites were performed. No pathologic result was found in the following laboratory investigation. Abdominal ultrasound did not reveal any involvement of the liver, spleen, gall bladder, common bile duct, pancreas, kidney and urinary bladder. Chest X-ray was unremarkable. A skeletal survey showed no significant abnormality. Bone marrow aspiration did not show any abnormality or signs of storage disease.

Skin lesion biopsy showed dermal aggregation of histiocytes and macrophages, some multinucleated Touton cell type, epidermal atrophy and mild dermal infiltration by lymphocytes and eosinophyles [Figure 3]. Histopathologic examination of the brain stereotactic biopsy showed foci of chronic inflammatory cell infiltration with numerous histiocytes consistent with the dermal examples [Figure 4]. Reactive gliosis was present to some degree.
Figure 3: The skin tissue with dermal aggregation of histiocytes and macrophages and some multinucleated Touton cell type (H&E stain, ×40)

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Figure 4: Brain tissue with chronic inflammatory cell infiltration and histiocytes (H&E stain, ×200)

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These extensive diagnostic work-up confirmed the diagnosis of systemic JXG involving the skin and brain in a multifocal manner. The patient was treated with prednisolone (40 mg oral daily for 7 days), vinblastine (2mg/m 2 i.v. every second week for two months) and methotrexate (300 mg/m 2 i.v. every week for two months). Over the following 3 months, his skin lesions showed a good clinical response. The follow-up MRI brain scans [Figure 5] showed gradual regression of all lesions within 13 months after the treatment. The patient is 8 years old now and shows normal growth and normal mental development.
Figure 5: Thirteen-month follow-up contrast-enhanced T1-weighted images. a Axial view, b coronal view, c sagittal view

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 > Discussion Top

JXG is one of the most common non-Langerhans cell histiocytosis (LCH) in children. [6],[7] Cutaneous presentation consists of benign, usually asymptomatic, self-healing, red, yellow or brown maculopapular lesions primarily involving the head, neck, and trunk. [7] Cutaneous JXG lesions are usually believed to be benign and will regress spontaneously leaving a flat, atrophic scar or an area of altered pigmentation. Although systemic JXG without organ damage can have a benign course, [7] CNS disease may be difficult to treat and is associated with severe morbidity and mortality. [1],[3],[4]

In a review of 26 patients with CNS JXG, a variety of chemotherapy, radiotherapy, surgery, or immunosuppressive therapies or combinations of these modalities have been used to treat these patients. [8] Although surgical excision appears to be curative in well-defined and accessible lesions, disseminated CNS lesions are not good enough to be removed surgically and have been considered for systemic therapies using agents with activity against LCH, such as corticosteroids, cyclosporine, vinca alkaloids, etoposide and methotrexate. [5],[9]

Dolken et al., [5] reported successful treatment of a seven-month-old girl with systemic JXG and multiple lesions in the CNS using systemic prednisolone, vinblastine and etoposide, intrathecal methotrexate and prednisolone, and also surgical removal of the larger CNS lesion. Orsey et al., [8] used prednisolone, vinblastine and methotrexate and etoposide to treat a JXG patient with diffuse involvement of the CNS that did not respond and died because of progression into a clonal histiocytic neoplasm.

Patients with systemic JXG have fared well with LCH-based chemotherapy because the both LCH and JXG are dendritic cell-related disorders. [9] Inclusion of a vinca alkaloid and steroid is associated with better overall response rates in patient with systemic JXG. [10] Our patient had JXG with disseminated CNS involvement and appeared to have had an excellent response to LCH-based regimens that include both corticosteroids and vinca alkaloids with resolution of the brain lesions.

In summary, this report describes a patient with systemic JXG and multiple CNS lesions treated successfully using established chemotherapeutic regimens for LCH.

 > References Top

1.Dehner LP. Juvenile xanthogranulomas in the first two decades of life: A clinicopathologic study of 174 cases with cutaneous and extracutaneous manifestations. Am J Surg Pathol 2003;27:579-93.  Back to cited text no. 1
2.Janssen D, Harms D. Juvenile xanthogranuloma in childhood and adolescence: A clinicopathologic study of 129 patients from the kiel pediatric tumor registry. Am J Surg Pathol 2005;29:21-8.  Back to cited text no. 2
3.Ernemann U, Skalej M, Hermisson M, Platten M, Jaffe R, Voigt K. Primary cerebral non-Langerhans cell histiocytosis: MRI and differential diagnosis. Neuroradiology 2002;44:759-63.  Back to cited text no. 3
4.Caputo R, Ermacora E, Gelmetti C, Gianni E. Fatal nodular xanthomatosis in an infant. Pediatr Dermatol 1987;4:242-6.  Back to cited text no. 4
5.Dolken R, Weigel S, Schroder H, Hartwig M, Harms D, Beck JF. Treatment of severe disseminated juvenile systemic xanthogranuloma with multiple lesions in the central nervous system. J Pediatr Hematol Oncol 2006;28:95-7.  Back to cited text no. 5
6.Favara BE, Feller AC, Pauli M, Jaffe ES, Weiss LM, Arico M, et al. Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol 1997;29:157-66.  Back to cited text no. 6
7.Freyer DR, Kennedy R, Bostrom BC, Kohut G, Dehner LP. Juvenile xanthogranuloma: Forms of systemic disease and their clinical implications. J Pediatr 1996;129:227-37.  Back to cited text no. 7
8.Orsey A, Paessler M, Lange BJ, Nichols KE. Central nervous system juvenile xanthogranuloma with malignant transformation. Pediatr Blood Cancer 2008;50:927-30.  Back to cited text no. 8
9.Nakatani T, Morimoto A, Kato R, Tokuda S, Sugimoto T, Tokiwa K, et al. Successful treatment of congenital systemic juvenile xanthogranuloma with Langerhans cell histiocytosis-based chemotherapy. J Pediatr Hematol Oncol 2004;26:371-4.  Back to cited text no. 9
10.Stover DG, Alapati S, Regueira O, Turner C, Whitlock JA. Treatment of juvenile xanthogranuloma. Pediatr Blood Cancer 2008;51:130-3.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

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