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Year : 2019  |  Volume : 20  |  Issue : 3  |  Page : 271-275

Disseminated juvenile xanthogranulomas with systemic involvement: A rare presentation

Department of Pediatric Dermatology, B J Wadia Hospital for Children, Mumbai, Maharashtra, India

Date of Web Publication28-Jun-2019

Correspondence Address:
Dr. Preeti K Sheth
B J Wadia Hospital for Children, Parel, Mumbai - 400 012, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpd.IJPD_121_18

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Juvenile xanthogranuloma is a self-healing non-Langerhans cell histiocytosis. It primarily manifests with cutaneous lesions which may have systemic associations. We report a case of a 6-month-old child who presented with multiple orangish papules and nodules all over the body with eye and liver involvement, which is a rare entity. The diagnosis was confirmed with dermoscopy and histopathological assessment, including immunohistochemical study. He responded to medical line of therapy.

Keywords: Juvenile xanthogranuloma, non-Langerhans cell histiocytosis, xanthogranulomas with systemic involvement

How to cite this article:
Sheth PK, Vasani R, Parikh D, Shah M, Jadhav R. Disseminated juvenile xanthogranulomas with systemic involvement: A rare presentation. Indian J Paediatr Dermatol 2019;20:271-5

How to cite this URL:
Sheth PK, Vasani R, Parikh D, Shah M, Jadhav R. Disseminated juvenile xanthogranulomas with systemic involvement: A rare presentation. Indian J Paediatr Dermatol [serial online] 2019 [cited 2020 Jul 4];20:271-5. Available from: http://www.ijpd.in/text.asp?2019/20/3/271/261869

  Introduction Top

Juvenile xanthogranuloma (JXG) is a self-limiting, benign, non-Langerhans cell histiocytosis, presenting with yellow-orange papules and nodules in the skin with or without systemic involvement.[1] JXG predominantly presents with a single cutaneous lesion. However, multiple skin lesions with or without systemic manifestations may also be seen.[2] The diagnosis is usually made on clinical examination followed by histopathology. It is confirmed with immunohistochemistry showing CD68 positivity and CD1a and S100 negativity.[3] We present a rare case of a child with multiple, cutaneous xanthogranulomas since 1 month of age with associated involvement of liver and eyes. He improved with medical line of therapy.

  Case Report Top

A 6-month-old male child, the first born of a nonconsanguineous marriage, presented with multiple orange-brown raised lesions on the body since 1 month of age. They first appeared on the face, followed by the limbs and the trunk, progressively increasing in size and number over 3 months with no further progression thereafter. The lesions were essentially asymptomatic, and there were no associated systemic complaints. The child had normal physical, mental, and developmental growth parameters and was vaccinated for age. There was no history of any antenatal, intrapartum, or postpartum complications in the mother.

On examination, there were multiple papules and nodules, ranging from a few millimeters to as large as 3 cm, present on the scalp, face, upper and lower limbs, axillae, chest, and back with the involvement of palms and soles [Figure 1] and [Figure 2]. The smaller papules and larger nodules were seen in different stages of evolution. The early papules and nodules showed a lighter uniform orange-brown color with peripheral rim of erythema while the evolved ones showed a central dark brown color with yellow stippling in the periphery and a lighter brown rim. The regressing nodules showed a decreased induration, darker hue, and lighter peripheral rim. The nodules had a disc-like deeper component with a firm consistency. The skin overlying the dome-shaped nodules was tense and shiny while the larger ones on the dorsum of the left foot showed the presence of central erosion and crusting and radiating telangiectasia. The intervening skin was normal. In addition, there were two café au lait macules on the body, one on the flexor aspect of the left forearm surrounding a nodule, measuring 3 cm and the other on the left side of the umbilicus with serrated margin, measuring 3.5 cm. There were no neurofibromas or freckles in the axillae or palms. Furthermore, multiple Mongolian spots were present, sacrally and extrasacrally (upper and lower back). Oral and genital mucosae were normal. There was no lymphadenopathy or organomegaly. Systemic examination was unremarkable. Dermatoscopy of an evolved lesion showed the presence of an oval structure with an orange-brown background with a peripheral rim of erythema and clouds of pale yellow deposits within suggestive of the xanthogranulomatous infiltrate [Figure 3].
Figure 1: Papules and nodules of varying sizes

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Figure 2: Nodules on the scalp

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Figure 3: Oval structure with orange-brown background, peripheral rim of erythema, and clouds of yellow deposits

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Ophthalmoscopic examination revealed xanthogranulomatous lesions in the anterior segment. No Lisch nodules were present. Complete blood count with peripheral smear examination, lipid profile, radiography of the chest and the whole body, and two-dimensional echocardiography were normal. Ultrasonography of the abdomen revealed xanthogranulomas in the liver. Histopathology of cutaneous lesions showed fibroblastic and histiocytic proliferation in the entire dermis up to the subcutaneous tissue surrounding the adnexal structures with lymphocytes and few Touton giant cells [Figure 4] suggestive of JXG. Immunohistochemistry was positive for CD68, CD31, and vimentin.
Figure 4: Touton giant cells

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The parents were also subjected to a lipid profile, which was normal, to rule out familial dyslipidemia.

The patient was counseled regarding the benign nature of the lesions and was asked for a regular follow-up. On the follow-up at 3 months, the patient was noticed to have ulcerations over the larger lesions on the scalp, and hence, the patient was started on oral prednisolone 1 mg/kg which was tapered off over 3 months. Complete healing of the ulcerations and flattening of the nodules was seen. Ophthalmic examination and ultrasonography of the abdomen were repeated. The xanthogranulomas found in the anterior segment of the eyes and liver had disappeared posttherapy. On dermatoscopy of the resolved lesions, the orange-brown color was replaced by a darker hue of brown with a significant decrease in the number of the pale-yellow clouds, suggesting resolving xanthogranulomatous infiltrate [Figure 5]. Further, the erythematous rim was replaced by a light brown rim.
Figure 5: Dark brown structure with decreased yellow clouds

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On the follow-up after 3 months of corticosteroid therapy, there was increase in disease activity in the form of increase in lesion size. We decided to start methotrexate 0.3 mg/kg of body weight per week. The lesions responded very well to methotrexate within 3 weeks of therapy [Figure 6].
Figure 6: Reduction in the size of lesions on the face and body after 3 weeks of methotrexate therapy

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  Discussion Top

JXG is the most common type of histiocytosis, accounting for nearly 80%–90% of all non-Langerhans cell histiocytosis. It is a benign and self-healing disease, originating from the dermal dendritic cells. Adamson described it as congenital xanthoma multiplex way back in the 1900s, and Helwig and Hackney gave the condition its present name in 1954.[4] The incidence of JXG in pediatric patients from India is limited to few case reports.[5]

JXG is primarily a disease of the childhood. It begins in infancy in nearly 40%–70% of patients. The cutaneous features may be seen right after birth in 5%–17% of the cases.[6] Multiple cutaneous lesions are seen more commonly in children <6 months of age.[7] The incidence of JXG is higher in boys (1.4:1).[8]

Our patient is a male child with multiple cutaneous lesions, who developed them in the 1st month of life.

The etiology is poorly understood. It is hypothesized to be due to macrocytic multiplication resulting from an unknown injury (physical or infectious).[9]

Clinically, the disease manifests as well-defined, asymptomatic papules, and nodules ranging from a few millimeters to few centimeters in size, usually imparting a yellow-orange color. They may be solitary or multiple in number. Although any site may be involved, they are particularly seen on the head, neck, and upper trunk. Mucosae are usually spared. There are two types of JXG, micronodular and macronodular form. The micronodular form is multiple in number with size <10 mm, occurring frequently. Macronodular form consists of a few nodules (roughly 1–12), measuring between 10 and 20 mm in size.[10] Rarely, Cyrano type of JXG and lichenoid JXG may be encountered where the lesions attain a size up to 10 cm, which disfigure the face.[11]

Our case manifested with multiple papules and nodules of an orange-brown hue with varied sizes ranging from few millimeters to centimeters. The color is on the darker side in patients with Fitzpatrick skin Types IV, V, and VI. The lesions were found all over the body, not just the head and neck. Both the micro- and macro-nodular forms were found in our patient. The scalp and axillae lesions depicted ulcerations and crusting.

Multiple cutaneous lesions are associated with internal organ involvement. Extracutaneous involvement occurs in 4% of children and in 5%–10% overall. The most frequently targeted extracutaneous organ is the eye, followed by the brain, lungs, liver, and spleen. Other organs that may be affected are heart, gastrointestinal tract, bone, bone marrow, adrenal gland, pituitary gland, and kidney.[12]

The eyes may also be involved without any cutaneous manifestations. The iris is particularly the predominant site implicated in the disease. About 0.5% of the cases of JXG have ocular involvement in the form of irritation, hyphema, uveitis, and photophobia. Secondary glaucoma and bleeding in the anterior chamber of the eye are potential complications in the later stages. In fact, there is a high propensity for eye involvement in children <2 years of age associated with multiple lesions.[13] Our patient had multiple cutaneous lesions with xanthogranulomas in the anterior segment of the eye and liver.

Certain diseases are known to be associated with JXG such as neurofibromatosis Type 1, myelomonocytic leukemia, diabetes mellitus, and Niemann–Pick disease.[14] Our case had two CALMs but showed no other evidence of neurofibromatosis Type 1. Besides, complete blood count and peripheral smear of the patient were normal, ruling out leukemia.

Conditions that need to be differentiated are benign cephalic histiocytosis, generalized eruptive histiocytoma, progressive nodular histiocytosis, and xanthoma disseminatum. Benign cephalic histiocytosis is seen in children <2 years of age as yellow-brown small-sized papules and nodules most commonly affecting the face and head. These remit spontaneously without affecting internal organs. Generalized eruptive histiocytoma is essentially seen in adults but may be found in children too. It presents as multiple orange-brown nodules on the face, trunk, and extremities. Tendency is toward self-healing but may persist for a long time. Progressive nodular histiocytosis manifests as yellow-brown papules and nodules targeting the face, trunk, and extremities. It is a disease of young adults but may be observed in children. Spontaneous resolution is never seen. However, internal organs are spared. Xanthoma disseminatum, again a condition of adults, presents as multiple orange-yellow papules showing affinity for the flexures. Considerable overlap is seen in all the above conditions, both clinically and histopathologically. However, extracutaneous spread is most commonly observed in JXG. Immunohistochemistry clinches the diagnosis.

Histopathologically, JXG is divided into three stages, early, classical, and late. Early JXG shows histiocytes with scanty cytoplasm and absent lipid vacuoles. Nuclei are small, round, or oval with insignificant nucleoli. Eosinophils are present, but Touton giant cells are absent. Increased cytoplasm with prominent nuclei of histiocytes is found in the classical JXG. Foreign bodies and Touton giant cells now predominate the picture with few eosinophils. Late JXG reveals histiocytes being arranged in a storiform pattern of spindle cells. Foamy cells are present, but Touton giant cells are absent.[15] The histopathology report of our patient was consistent with the late stage of JXG.

Markers that are positive on immunochemistry are CD68, factor XIIIa, and vimentin. CD1a is negative but S100 may be positive in few cases.[16] Our patient showed positivity for CD68, CD31, and vimentin.

The course of JXG with solely cutaneous features is usually a favorable one. Skin nodules spontaneously resolve within 6 months to 3 years. Large nodules may be excised for cosmetic reasons.[17] Although systemic JXG without organ damage can have a benign course, central nervous system disease may be difficult to treat and is associated with severe morbidity and mortality. Severe cutaneous involvement with ulcerating lesions as in our case and symptomatic systemic involvement would warrant treatment. Systemic involvement needs treatment in the form of immunosuppression (corticosteroids, cyclosporine, or methotrexate), chemotherapy, or radiotherapy with or without surgery.[11]

Our patient was put on a short tapering course of oral corticosteroids, owing to the ulcerative and necrotic changes of the lesions on the scalp. Within 3 months, ulcers healed and other lesions showed flattening and lightening of color. The xanthogranulomas of the eye and liver also disappeared. The patient had a relapse of disease activity after stopping of corticosteroid. He later responded to methotrexate within 3 weeks on initiation. He is on the regular follow-up.

This case had ulcerating lesions suggesting severe cutaneous involvement warranting medical management with associated systemic involvement which is a rarity. This case also demonstrates dermatoscopic findings of evolved and resolving lesions of xanthogranuloma in Indian skin.

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.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Carlo G. Non-langerhans cell histiocytosis. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors. Fitzpatrick's Dermatology in General Medicine. 8th ed. USA: McGraw Hill Medical; 2012. p. 1795-808.  Back to cited text no. 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. 2
Yamamoto Y, Kadota M, Nishimura Y. A case of S-100-positive juvenile xanthogranuloma: A longitudinal observation. Pediatr Dermatol 2009;26:475-6.  Back to cited text no. 3
Helwig EB, Hackney VC. Juvenile xanthogranuloma (nevo-xanthoendothelioma). Am J Pathol 1954;30:625-6.  Back to cited text no. 4
Kar C, Das K, Barua JK. Uncommon presentation of a common histiocytic tumor: A Rare entity. Indian J Dermatol 2015;60:301-4.  Back to cited text no. 5
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Hernandez-Martin A, Baselga E, Drolet BA, Esterly NB. Juvenile xanthogranuloma. J Am Acad Dermatol 1997;36:355-67.  Back to cited text no. 8
Seo IS, Min KW, Mirkin LD. Juvenile xanthogranuloma. Ultrastructural and immunocytochemical studies. Arch Pathol Lab Med 1986;110:911-5.  Back to cited text no. 9
Gianotti F, Caputo R. Histiocytic syndromes: A review. J Am Acad Dermatol 1985;13:383-404.  Back to cited text no. 10
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Szczerkowska-Dobosz A, Kozicka D, Purzycka-Bohdan D, Biernat W, Stawczyk M, Nowicki R, et al. Juvenile xanthogranuloma: A rare benign histiocytic disorder. Postepy Dermatol Alergol 2014;31:197-200.  Back to cited text no. 14
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. 15
Zelger B, Cerio R, Orchard G, Wilson-Jones E. Juvenile and adult xanthogranuloma. A histological and immunohistochemical comparison. Am J Surg Pathol 1994;18:126-35.  Back to cited text no. 16
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]


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