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Year : 2016  |  Volume : 17  |  Issue : 1  |  Page : 71-74

Juvenile xanthogranuloma with multiple lesions in central nervous system: A rare case report

1 Department of Dermatology, Care Hospitals, Banjara Hills, Hyderabad, Telangana, India
2 Department of Pediatrics and Pediatric Hemato Oncology, Rainbow Children's Tertiary Care Centre, Banjara Hills, Hyderabad, Telangana, India
3 Department of Pathology, Care Hospitals, Nampally, Hyderabad, Telangana, India

Date of Web Publication4-Jan-2016

Correspondence Address:
Priyanka M Jain
Department of Dermatology, Care Out Patient Centre, Banjara Hills Road No.10, Hyderabad - 500 034, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2319-7250.172466

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Juvenile xanthogranuloma (JXG) preferentially occurs in childhood and is usually benign and limited to the skin. The systemic form is rare and may be associated with severe morbidity and mortality. We describe a three and a half year old boy with disseminated papular skin lesions and neurological signs and symptoms. Diagnostic workup revealed multiple brain lesions. Skin and brain biopsy was suggestive of systemic JXG. Treatment with prednisolone, vinblastine, and methotrexate caused regression of skin and central nervous system (CNS) lesions. However, 6 months after completion of chemotherapy, cutaneous but not CNS lesions relapsed. Few case reports have been published in the past, particularly with multiple lesions in CNS, which as in our case, is an extremely rare finding.

Keywords: Central nervous system, juvenile xanthogranuloma, papular

How to cite this article:
Jain PM, Chandravathi P L, Siddaiahgari SR, Tourani VK. Juvenile xanthogranuloma with multiple lesions in central nervous system: A rare case report. Indian J Paediatr Dermatol 2016;17:71-4

How to cite this URL:
Jain PM, Chandravathi P L, Siddaiahgari SR, Tourani VK. Juvenile xanthogranuloma with multiple lesions in central nervous system: A rare case report. Indian J Paediatr Dermatol [serial online] 2016 [cited 2020 Jul 7];17:71-4. Available from: http://www.ijpd.in/text.asp?2016/17/1/71/172466

  Introduction Top

Juvenile xanthogranulomas (JXG) are benign tumors of histiocytic cells that are usually limited to skin, occurring predominantly in infancy and early childhood with usual spontaneous regression. Histologically, JXG is composed of collections of foamy histiocytes and Touton giant cells with a distinct immunohistochemistry (IHC) staining pattern (positive CD68, alpha-1-antitrypsin, factor XIIIa and lysozyme; S100 and CD1a - negative).[1] Systemic JXG is rare, and extracutaneous involvement usually includes eyes, lung, liver, spleen, and central nervous system (CNS). Although there are some reports on intracranial involvement,[2],[3],[4] occurrence of multiple brain lesions and relapsing cutaneous lesions after chemotherapy is extremely rare.

  Case Report Top

Three and a half year old boy suffered from numerous, asymptomatic well demarcated, yellowish maculopapular lesions over the face, neck, trunk, flexural areas and upper extremities [Figure 1] which were firm to rubbery in consistency. Six months later he was admitted to a tertiary care hospital with frontal headache, projectile vomitings and left sided weakness. Hemiparesis, polydipsia and polyuria were evident. Nail, hair and mucous membrane examination did not reveal any abnormality. His medical and family history was otherwise unremarkable.
Figure 1: (a and b) Multiple asymptomatic yellowish to skin colored maculopapular lesions which were firm to rubbery in consistency over the neck and face

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Magnetic resonance imaging (MRI) brain demonstrated multiple discrete and enhancing lobulated lesions in cerebral, cerebellar, subcortical and ependymal regions; a large lesion in right cerebellopontine angle causing compression of fourth ventricle with mild hydrocephalus and distortion of brain stem [Figure 2]. Further diagnostic workup for detecting possible systemic involvement at other sites such as hematological and biochemical parameters including lipid profile, ophthalmological checkup, abdominal ultrasound, skeletal survey, chest X-ray, cerebrospinal fluid examination, bone marrow aspiration and biopsy were performed and did not show any abnormality.
Figure 2: High magnification histopathology (hematoxylin and eosin stain) of the cutaneous lesion showing cells with multiple nuclei grouped in a wreath like arrangement near the center of the cell i.e; Touton giant cell (a). Multiple foamy histiocytes with inflammatory infiltrate (b). Immunohistochemistry showing negative CD1a (c). and positive CD68 stained cells (d)

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Skin lesion biopsy showed epidermal atrophy, focal infiltrates of foamy histiocytes and macrophages; few Touton type giant cells and mild infiltration by lymphocytes and eosinophils in the dermis. Histopathologic examination of the brain biopsy showed diffuse infiltrates with sheets of histiocytic cells and occasional giant cells consistent with the dermal specimen. IHC labeling of both the specimens revealed CD68-positive and CD1a-negative cells [Figure 3].
Figure 3: Magnetic resonance imaging brain. (a and b) scan showing discrete and enhancing lobulated lesions in a multifocal distribution

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This extensive diagnostic workup along with clinical correlation confirmed the diagnosis of JXG involving skin and brain in a multifocal manner. The patient was treated by oncologist with Langerhans cell histiocytosis-III (LCH) chemotherapy protocol comprising of induction with methotrexate, vinblastine and prednisolone followed by addition of 6-mercaptopurine and oral weekly methotrexate in maintenance phase over a period of 2 years. Desmopressin puffs were administered for diabetes insipidus. Cutaneous lesions showed good clinical response and healed with mild atrophic scarring. The follow-up MRI brain scans taken at the completion of treatment showed gradual regression of all lesions [Figure 4].
Figure 4: (a) Before chemotherapy magnetic resonance imaging brain scan. (b) Postchemotherapy magnetic resonance imaging scan showing resolution of central nervous system lesions

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However, 6 months after completion of chemotherapy he developed similar cutaneous lesions which were confirmed histologically as JXG. A repeat MRI brain revealed no significant change as compared to previous postchemotherapy scan. Further diagnostic workup for detecting possible new systemic involvement at other sites was performed and was unremarkable. So a diagnosis of JXG with cutaneous relapse postchemotherapy was made.

At present patient is showing normal growth and mental development and is being conservatively managed with regular follow-ups as no new systemic involvement was detected.

  Discussion Top

JXG is one of the most common non-LCH in children.[4] In 1954, JXG was placed under non-Langerhans histiocytosis group as an archetype of non-Langerhans histiocytosis with factor XIIIa+ dermal dendrocytes as the strongest candidate originating cells; however, this concept has been challenged recently and plasmacytoid monocyte has been proposed as the putative origin of JXG.[5]

The cutaneous presentation consists of two main clinical forms: Papular and Nodular. The papular form as in our case is characterized by numerous asymptomatic firm, yellowish hemispheric lesions 2–5 mm in diameter located mainly in the upper part of the body. They are usually believed to be benign and regress spontaneously leaving a flat, atrophic scar or an area of altered pigmentation. An extremely rare extracutaneous manifestation of the papular variant is CNS involvement.[6]

The pathological changes in the brain may originate from mesenchymal stem cells of the dura mater, from the intracerebral perivascular soft tunica vaginalis or the wall of brain vessels themselves. The lesions can be solitary or multiple. In CNS involvement, JXG can induce epilepsy, mental and growth retardation, diabetes insipidus, ataxia, and hemiplegia. According to the literature, JXG appears in the CNS either secondary to the skin, soft tissues, lung and pancreas which have been involved for several months or years or rarely as a primary manifestation.[7] In our case, cutaneous lesions were present 6 months before the occurrence of hemiplegia and diabetes insipidus.

Although systemic JXG without organ damage can have a benign course, CNS disease may be difficult to treat and is associated with severe morbidity and mortality.[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] Patients with systemic JXG have fared well with LCH-based chemotherapy because both LCH and JXG are dendritic cell-related disorders.[9] The inclusion of a vinca alkaloid and steroid is associated with better overall response rate.[10] Our patient had JXG with disseminated CNS involvement and appeared to have had a good response to LCH-based regimens that included induction with both corticosteroids and vinca alkaloids, with resolution of the brain lesions. As to whether the recurrence of cutaneous but not CNS lesions till date after stopping chemotherapy suggests a resistant form of the cutaneous disease is an enigma.

Although CNS involvement is rare, a high degree of clinical suspicion is warranted when patients present with a papular variant of JXG. A baseline MRI brain can help to rule out CNS involvement. An abnormality if found should warrant further investigations and involvement of concerned specialties.

Overall, our knowledge of systemic JXG is still very limited; more experience in its diagnosis and treatment is necessary and expected because of the low, but potentially serious risk of internal organ involvement. More individual cases reports and multicenter coordination should be encouraged.

Declaration of Patient Consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial Support and Sponsorship


Conflicts of Interest

There are no conflicts of interest.

  References Top

Chu AC. Histiocytosis. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rooks Textbook of Dermatology. 8th ed. Oxford: Wiley Blackwell; 2010. p. 55.15-55.16.  Back to cited text no. 1
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
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. 3
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. 4
Fan R, Sun J. Neonatal systemic juvenile xanthogranuloma with an ominous presentation and successful treatment. Clin Med Insights Oncol 2011;5:157-61.  Back to cited text no. 5
Gelmetti C. Non-Langerhans cell histiocytosis. In: Goldsmith L, Katz S, Gilchrist B, Paller A, Lefell D, Wolff K, editors. Fitzpatrick's Dermatology in General Medicine. 8th ed. New York: McGraw Hill; 2012. p. 1797-8.  Back to cited text no. 6
Sun LP, Jin HM, Yang B, Wu XR. Intracranial solitary juvenile xanthogranuloma in an infant. World J Pediatr 2009;5:71-3.  Back to cited text no. 7
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
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
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]


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