Juvenile xanthogranuloma (JXG)
- Kate B Püttgen, MD, FAAD
Kate B Püttgen, MD, FAAD
- Assistant Professor of Dermatology and Pediatrics
- Johns Hopkins University School of Medicine
Juvenile xanthogranuloma (JXG) is a benign, proliferative disorder of histiocytic cells of the dermal dendrocyte phenotype. JXG belongs to the broad group of non-Langerhans cell histiocytoses and is typically a disorder of early childhood. JXG typically presents in the first two years of life as a solitary, reddish or yellowish skin papule or nodule (picture 1D), most often on the head, neck, or upper trunk. Histologically, JXG is characterized by the presence of histiocytes, foam cells, and Touton giant cells. JXG generally follows a benign course with spontaneous resolution over a period of a few years. Less commonly skin lesions can be multiple (picture 2B). Extracutaneous or systemic forms are exceedingly rare and can be associated with considerable morbidity.
An overview of JXG will be presented here. Langerhans cell histiocytosis is discussed separately. (See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis" and "Langerhans cell histiocytosis (eosinophilic granuloma) of bone in children and adolescents".)
JXG is the most common of the non-Langerhans cell histiocytoses . The incidence is unknown. In a large tumor registry spanning 35 years, JXG accounted for 129 of 24,600 pediatric tumors (0.5 percent) . However, this figure may be an underestimate of the relative frequency of JXG since many cases are diagnosed on clinical grounds without histologic confirmation. In a survey of 122 dermatologists with an average of 12 years of practice, 2371 cases of JXG were reported (an average of less than two cases per dermatologist per year); only 7 cases had ocular involvement .
JXG may be present at birth . Between 40 and 70 percent of JXG arise in the first year of life . The median ages of onset in two large case series were 5 months (range 0 to 244 months) and 1 year (range 0 to 20 years) [2,6]. The male to female ratio was about 1.4:1.
The prognosis of JXG is generally good, with spontaneous resolution of skin and organ lesions over a few years. Rare fatalities have been reported in infants with central nervous system or massive hepatic involvement [2,6-9]. (See 'Prognosis' below.)
- Weitzman S, Jaffe R. Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses. Pediatr Blood Cancer 2005; 45:256.
- 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.
- Chang MW, Frieden IJ, Good W. The risk intraocular juvenile xanthogranuloma: survey of current practices and assessment of risk. J Am Acad Dermatol 1996; 34:445.
- Isaacs H Jr. Fetal and neonatal histiocytoses. Pediatr Blood Cancer 2006; 47:123.
- Hernandez-Martin A, Baselga E, Drolet BA, Esterly NB. Juvenile xanthogranuloma. J Am Acad Dermatol 1997; 36:355.
- 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.
- Freyer DR, Kennedy R, Bostrom BC, et al. Juvenile xanthogranuloma: forms of systemic disease and their clinical implications. J Pediatr 1996; 129:227.
- Azorín D, Torrelo A, Lassaletta A, et al. Systemic juvenile xanthogranuloma with fatal outcome. Pediatr Dermatol 2009; 26:709.
- Orsey A, Paessler M, Lange BJ, Nichols KE. Central nervous system juvenile xanthogranuloma with malignant transformation. Pediatr Blood Cancer 2008; 50:927.
- Caputo R, Marzano AV, Passoni E, Berti E. Unusual variants of non-Langerhans cell histiocytoses. J Am Acad Dermatol 2007; 57:1031.
- Samara WA, Khoo CT, Say EA, et al. Juvenile Xanthogranuloma Involving the Eye and Ocular Adnexa: Tumor Control, Visual Outcomes, and Globe Salvage in 30 Patients. Ophthalmology 2015; 122:2130.
- Vendal Z, Walton D, Chen T. Glaucoma in juvenile xanthogranuloma. Semin Ophthalmol 2006; 21:191.
- SANDERS TE. Intraocular juvenile xanthogranuloma (nevoxanthogranuloma): a survey of 20 cases. Trans Am Ophthalmol Soc 1960; 58:59.
- Cambiaghi S, Restano L, Caputo R. Juvenile xanthogranuloma associated with neurofibromatosis 1: 14 patients without evidence of hematologic malignancies. Pediatr Dermatol 2004; 21:97.
- Ferrari F, Masurel A, Olivier-Faivre L, Vabres P. Juvenile xanthogranuloma and nevus anemicus in the diagnosis of neurofibromatosis type 1. JAMA Dermatol 2014; 150:42.
- Fenot M, Stalder JF, Barbarot S. Juvenile xanthogranulomas are highly prevalent but transient in young children with neurofibromatosis type 1. J Am Acad Dermatol 2014; 71:389.
- Raygada M, Arthur DC, Wayne AS, et al. Juvenile xanthogranuloma in a child with previously unsuspected neurofibromatosis type 1 and juvenile myelomonocytic leukemia. Pediatr Blood Cancer 2010; 54:173.
- Shin HT, Harris MB, Orlow SJ. Juvenile myelomonocytic leukemia presenting with features of hemophagocytic lymphohistiocytosis in association with neurofibromatosis and juvenile xanthogranulomas. J Pediatr Hematol Oncol 2004; 26:591.
- Benessahraoui M, Aubin F, Paratte F, et al. [Juvenile myelomonocytic leukaemia, xanthoma, and neurofibromatosis type 1]. Arch Pediatr 2003; 10:891.
- Larrègue M, Belaïch S, Delzant O, Degos R. [Xanthomatoleukemia in young children and Recklinghausen's disease]. Ann Dermatol Syphiligr (Paris) 1972; 99:373.
- Royer P, Blondet C. Xantholeucemie du nourrisson et neurofibromatose de Recklinghausen. Ann Pediatr (Paris) 1958; 24:1504.
- Paulus S, Koronowska S, Fölster-Holst R. Association Between Juvenile Myelomonocytic Leukemia, Juvenile Xanthogranulomas and Neurofibromatosis Type 1: Case Report and Review of the Literature. Pediatr Dermatol 2017; 34:114.
- Burgdorf WH, Zelger B. JXG, NF1, and JMML: alphabet soup or a clinical issue? Pediatr Dermatol 2004; 21:174.
- Song M, Kim SH, Jung DS, et al. Structural correlations between dermoscopic and histopathological features of juvenile xanthogranuloma. J Eur Acad Dermatol Venereol 2011; 25:259.
- Breier F, Zelger B, Reiter H, et al. Papular xanthoma: a clinicopathological study of 10 cases. J Cutan Pathol 2002; 29:200.
- Chen CG, Chen CL, Liu HN. Primary papular xanthoma of children: a clinicopathologic, immunohistopathologic and ultrastructural study. Am J Dermatopathol 1997; 19:596.
- Fonseca E, Contreras F, Cuevas J. Papular xanthoma in children: report and immunohistochemical study. Pediatr Dermatol 1993; 10:139.
- Caputo R, Gianni E, Imondi D, et al. Papular xanthoma in children. J Am Acad Dermatol 1990; 22:1052.
- Busam KJ, Granter SR, Iversen K, Jungbluth AA. Immunohistochemical distinction of epithelioid histiocytic proliferations from epithelioid melanocytic nevi. Am J Dermatopathol 2000; 22:237.
- Caputo R, Veraldi S, Grimalt R, et al. The various clinical patterns of xanthoma disseminatum. Considerations on seven cases and review of the literature. Dermatology 1995; 190:19.
- Park M, Boone B, Devos S. Xanthoma disseminatum: case report and mini-review of the literature. Acta Dermatovenerol Croat 2014; 22:150.
- Gianotti F, Caputo R. Histiocytic syndromes: a review. J Am Acad Dermatol 1985; 13:383.
- Stover DG, Alapati S, Regueira O, et al. Treatment of juvenile xanthogranuloma. Pediatr Blood Cancer 2008; 51:130.
- Nakasu S, Tsuji A, Fuse I, Hirai H. Intracranial solitary juvenile xanthogranuloma successfully treated with stereotactic radiosurgery. J Neurooncol 2007; 84:99.
- De Paula AM, André N, Fernandez C, et al. Solitary, extracutaneous, skull-based juvenile xanthogranuloma. Pediatr Blood Cancer 2010; 55:380.
- Müller RP, Busse H. [Radiotherapy in juvenile xanthogranuloma of the iris]. Klin Monbl Augenheilkd 1986; 189:15.
- Wang B, Jin H, Zhao Y, Ma J. The clinical diagnosis and management options for intracranial juvenile xanthogranuloma in children: based on four cases and another 39 patients in the literature. Acta Neurochir (Wien) 2016; 158:1289.
- Rajendra B, Duncan A, Parslew R, Pizer BL. Successful treatment of central nervous system juvenile xanthogranulomatosis with cladribine. Pediatr Blood Cancer 2009; 52:413.
- Maintz L, Wenzel J, Irnich M, et al. Successful treatment of systemic juvenile xanthogranulomatosis with cytarabine and 2-chlorodeoxyadenosine: case report and review of the literature. Br J Dermatol 2017; 176:481.
- Bailey KM, Castle VP, Hummel JM, et al. Thalidomide therapy for aggressive histiocytic lesions in the pediatric population. J Pediatr Hematol Oncol 2012; 34:480.
- Hu WK, Gilliam AC, Wiersma SR, Dahms BB. Fatal congenital systemic juvenile xanthogranuloma with liver failure. Pediatr Dev Pathol 2004; 7:71.
- CLINICAL MANIFESTATIONS
- Clinical presentation
- Clinical course
- Ocular JXG
- ASSOCIATED CONDITIONS
- DIFFERENTIAL DIAGNOSIS
- Cutaneous JXG
- Subcutaneous and soft tissue JXG
- Ocular JXG
- Symptomatic systemic JXG
- SUMMARY AND RECOMMENDATIONS