eMedicine Specialties > Dermatology > Pediatric Diseases

Juvenile Xanthogranuloma (Nevoxanthoendothelioma)

Author: Caroline DS Piggott, MD, Resident, Department of Medicine, Division of Dermatology, University of California, San Diego
Coauthor(s): Michael L Smith, MD, Associate Professor of Medicine (Dermatology) and Pediatrics, Vanderbilt University School of Medicine; Consulting Staff, Vanderbilt University Hospital; Hunter H Sams, MD, Consulting Staff, Denver Dermatology Consultants, PC
Contributor Information and Disclosures

Updated: Oct 23, 2009

Introduction

Background

Juvenile xanthogranulomas (JXGs) are benign; usually asymptomatic; self-healing; red, yellow, or brown papules and nodules composed of histiocytic cells that predominantly occur in infancy and childhood. Papules or nodules occur in the skin, eyes, and viscera. JXG is the most common form of non–Langerhans cell histiocytosis.

Smooth, domed, yellow-brown, 5-mm papule on right...

Smooth, domed, yellow-brown, 5-mm papule on right arm of a 6-month-old boy.

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Smooth, domed, yellow-brown, 5-mm papule on right...

Smooth, domed, yellow-brown, 5-mm papule on right arm of a 6-month-old boy.


Adamson first reported JXG in the English literature in 1905. He presented a child who developed numerous yellow-white papules on the body in the first 2 weeks of life. He named the entity congenital xanthoma multiplex.

In 1912, McDonagh presented the first case review and renamed the condition nevoxanthoendothelioma (although the condition is not associated with nevi or endothelial cells). In 1954, Helwig and Hackney again retermed it juvenile xanthogranuloma, reflecting its histopathologic appearance. Laurb and Lain first reported JXG with visceral involvement in 1937. Blank et al first described ocular involvement in 1949.

Pathophysiology

The etiology of juvenile xanthogranuloma (JXG) is not fully known. The papules and nodules of JXG represent collections of differentiated non–Langerhans cell histiocytes. The consensus is that the cells of origin are dermal dendrocytes. As postulated, JXG may be a granulomatous reaction of histiocytes to an unidentified stimulus, possibly of either physical or infectious etiology. Evidence from Kraus et al,1 however, suggests a possible CD4+ plasmacytoid monocyte origin. Inhibition of cellular apoptosis appears to play a minor role in the growth of xanthogranulomas.2

The appearance of giant cells and foamy lipid-laden histiocytes generally occurs late and apparently is a secondary event, possibly in response to cytokine production by histiocytes. Serum lipid levels are normal and remain normal.

Race

Juvenile xanthogranuloma (JXG) occurs in whites approximately 10 times more frequently than in African Americans.

Sex

In childhood, juvenile xanthogranuloma (JXG) occurs predominately in males (1.4:1). Equal incidence occurs in adult males and females. Multiple cutaneous lesions occur predominantly in males (12:1).

Age

Approximately 35% of cases of juvenile xanthogranuloma (JXG) occur at birth, with as many as 71% of cases occurring in the first year. The mean age at presentation is 22 months. Most JXGs resolve by age 5 years. Despite the term juvenile in the disease name, 10% of cases manifest in adulthood.

Clinical

History

  • Patients with juvenile xanthogranuloma (JXG) usually present in infancy or early childhood with an asymptomatic; smooth; round; yellow, red, or brown papule or papules. Lesions are usually asymptomatic.

Physical

  • The most frequent site of juvenile xanthogranuloma (JXG) occurrence is on the head and neck, followed the trunk and upper extremities; however, JXG may occur anywhere on the skin.
  • Up to 81% of cutaneous JXG cases manifest as a solitary lesion. This form is also more common in cases of adult xanthogranulomas.
  • Involvement is rare on mucous membranes, the tongue, palms, and soles.
  • Both papular and nodular forms of JXG have been described.
    • The papular form consists of multiple, 2- to 5-mm, smooth, firm papules that initially are red-brown, then quickly change to yellow.
    • The rarer nodular form consists of round, 0.5- to 2-cm, translucent, red-to-yellow, rubbery nodules with telangiectasias (nodules change to yellow-brown with time).
  • Giant JXG refers to nodules and masses greater than 2 cm (largest reported mass was 10 X 5 cm).3,4
  • Rarer variants include a mixed form characterized by both papular and nodular lesions, in which grouped papules coalesce, and a subcutaneous form (approximately 5%), with a single deep nodule or mass formation.
  • Extracutaneous JXG is rare (3.9%) and most commonly involves the eye (<1%) and periorbital region.5 Ocular JXG most commonly manifests in the iris. Following in frequency are lung and liver manifestations of JXG.6
  • Rarely, lesions occur in the adrenal gland, appendix, bones, bone marrow,6 central nervous system,7 gonads, kidney, larynx, myocardium, pericardium, retroperitoneum, small and large intestines, and spleen. Only 50% of systemic lesions are accompanied by cutaneous JXG, and these cutaneous lesions tend to appear as multiple, rather than solitary, papules or nodules. The size of a cutaneous lesion does not correlate with the presence or absence of systemic JXG.
  • Café au lait macules occur in approximately 20% of patients with papular JXG.

Causes

  • Coexistence of café au lait macules and juvenile xanthogranuloma (JXG) has been associated with epilepsy.
  • Niemann-Pick disease has been associated with JXG.
  • Urticaria pigmentosa has been associated with JXG.
  • Neurofibromatosis type 1 (NF1) has been associated with JXG.8,9,10,11,12 A retrospective study has estimated that as many as 1 in 5 children with NF1 before age 3 years will develop JXG.
  • Juvenile chronic myelogenous leukemia, now primarily referred to as juvenile myelomonocytic leukemia (JMML), has been observed in association with multiple JXGs,10,11,13 and the prevalence is especially high in patients with coexistent neurofibromatosis. Statistics regarding this triple association are controversial; estimates indicate that patients with NF1 and JXG have a 20- to 32-times increased risk of developing JMML than patients with NF1 alone. Patients have also been diagnosed with JMML and JXG, but without NF1.

More on Juvenile Xanthogranuloma (Nevoxanthoendothelioma)

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Treatment & Medication: Juvenile Xanthogranuloma (Nevoxanthoendothelioma)
Follow-up: Juvenile Xanthogranuloma (Nevoxanthoendothelioma)
Multimedia: Juvenile Xanthogranuloma (Nevoxanthoendothelioma)
References
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References

  1. Kraus MD, Haley JC, Ruiz R, Essary L, Moran CA, Fletcher CD. "Juvenile" xanthogranuloma: an immunophenotypic study with a reappraisal of histogenesis. Am J Dermatopathol. Apr 2001;23(2):104-11. [Medline].

  2. Mancini AJ, Prieto VG, Smoller BR. Role of cellular proliferation and apoptosis in the growth of xanthogranulomas. Am J Dermatopathol. Feb 1998;20(1):17-21. [Medline].

  3. Campbell L, McTigue MK, Esterly NB, Rosenbaum M. Giant juvenile xanthogranuloma. Arch Dermatol. Nov 1988;124(11):1723-4. [Medline].

  4. Imiela A, Carpentier O, Segard-Drouard M, Martin de Lassalle E, Piette F. Juvenile xanthogranuloma: a congenital giant form leading to a wide atrophic sequela. Pediatr Dermatol. Mar-Apr 2004;21(2):121-3. [Medline].

  5. Chang MW, Frieden IJ, Good W. The risk intraocular juvenile xanthogranuloma: survey of current practices and assessment of risk. J Am Acad Dermatol. Mar 1996;34(3):445-9. [Medline].

  6. Chantranuwat C. Systemic form of juvenile xanthogranuloma: report of a case with liver and bone marrow involvement. Pediatr Dev Pathol. Nov-Dec 2004;7(6):646-8. [Medline].

  7. Flach DB, Winkelmann RK. Juvenile xanthogranuloma with central nervous system lesions. J Am Acad Dermatol. Mar 1986;14(3):405-11. [Medline].

  8. Cambiaghi S, Restano L, Caputo R. Juvenile xanthogranuloma associated with neurofibromatosis 1: 14 patients without evidence of hematologic malignancies. Pediatr Dermatol. Mar-Apr 2004;21(2):97-101. [Medline].

  9. Newell GB, Stone OJ, Mullins JF. Juvenile xanthogranuloma and neurofibromatosis. Arch Dermatol. Feb 1973;107(2):262. [Medline].

  10. 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. Sep 2004;26(9):591-5. [Medline].

  11. Zvulunov A, Barak Y, Metzker A. Juvenile xanthogranuloma, neurofibromatosis, and juvenile chronic myelogenous leukemia. World statistical analysis. Arch Dermatol. Aug 1995;131(8):904-8. [Medline].

  12. Raygada M, Arthur DC, Wayne AS, Rennert OM, Toretsky JA, Stratakis CA. Juvenile xanthogranuloma in a child with previously unsuspected neurofibromatosis type 1 and juvenile myelomonocytic leukemia. Pediatr Blood Cancer. Sep 25 2009;[Medline].

  13. Cooper PH, Frierson HF, Kayne AL, Sabio H. Association of juvenile xanthogranuloma with juvenile myeloid leukemia. Arch Dermatol. Mar 1984;120(3):371-5. [Medline].

  14. Rodriguez-Jurado R, Duran-McKinster C, Ruiz-Maldonado R. Benign cephalic histiocytosis progressing into juvenile xanthogranuloma: a non-Langerhans cell histiocytosis transforming under the influence of a virus?. Am J Dermatopathol. Feb 2000;22(1):70-4. [Medline].

  15. Janney CG, Hurt MA, Santa Cruz DJ. Deep juvenile xanthogranuloma. Subcutaneous and intramuscular forms. Am J Surg Pathol. Feb 1991;15(2):150-9. [Medline].

  16. Haughton AM, Horii KA, Shao L, Daniel J, Nopper AJ. Disseminated juvenile xanthogranulomatosis in a newborn resulting in liver transplantation. J Am Acad Dermatol. Feb 2008;58(2 Suppl):S12-5. [Medline].

  17. Unuvar E, Devecioglu O, Akcay A, et al. Successful therapy of systemic xanthogranuloma in a child. J Pediatr Hematol Oncol. Jun 2007;29(6):425-7. [Medline].

  18. Burgdorf WH, Zelger B. JXG, NF1, and JMML: alphabet soup or a clinical issue?. Pediatr Dermatol. Mar-Apr 2004;21(2):174-6. [Medline].

  19. Vendal Z, Walton D, Chen T. Glaucoma in juvenile xanthogranuloma. Semin Ophthalmol. Jul-Sep 2006;21(3):191-4. [Medline].

  20. Hu WK, Gilliam AC, Wiersma SR, Dahms BB. Fatal congenital systemic juvenile xanthogranuloma with liver failure. Pediatr Dev Pathol. Jan-Feb 2004;7(1):71-6. [Medline].

  21. Caputo R, Grimalt R, Gelmetti C, Cottoni F. Unusual aspects of juvenile xanthogranuloma. J Am Acad Dermatol. Nov 1993;29(5 Pt 2):868-70. [Medline].

  22. Cohen BA, Hood A. Xanthogranuloma: report on clinical and histologic findings in 64 patients. Pediatr Dermatol. Dec 1989;6(4):262-6. [Medline].

  23. 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. May 2003;27(5):579-93. [Medline].

  24. Dehner LP. Reawakening to the existence of juvenile xanthogranuloma. Am J Surg Pathol. Jan 2005;29(1):119-20. [Medline].

  25. Hernandez-Martin A, Baselga E, Drolet BA, Esterly NB. Juvenile xanthogranuloma. J Am Acad Dermatol. Mar 1997;36(3 Pt 1):355-67; quiz 368-9. [Medline].

  26. Iyengar V, Golomb CA, Schachner L. Neurilemmomatosis, NF2, and juvenile xanthogranuloma. J Am Acad Dermatol. Nov 1998;39(5 Pt 2):831-4. [Medline].

  27. 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. Jan 2005;29(1):21-8. [Medline].

  28. Ringel E, Moschella S. Primary histiocytic dermatoses. Arch Dermatol. Dec 1985;121(12):1531-41. [Medline].

  29. Roper SS, Spraker MK. Cutaneous histiocytosis syndromes. Pediatr Dermatol. Nov 1985;3(1):19-30. [Medline].

  30. Weitzman S, Jaffe R. Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses. Pediatr Blood Cancer. Sep 2005;45(3):256-64. [Medline].

  31. Zimmerman LE. Ocular lesions of juvenile xanthogranuloma. Nevoxanthoedothelioma. Am J Ophthalmol. Dec 1965;60(6):1011-35. [Medline].

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Further Reading

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Keywords

juvenile xanthogranulomas, nevoxanthoendothelioma, xanthoma multiplex, juvenile xanthoma, multiple xanthoma in infancy, congenital xanthoma tuberosum, xanthoma naviforme, juvenile giant cell granuloma

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Contributor Information and Disclosures

Author

Caroline DS Piggott, MD, Resident, Department of Medicine, Division of Dermatology, University of California, San Diego
Disclosure: Nothing to disclose.

Coauthor(s)

Michael L Smith, MD, Associate Professor of Medicine (Dermatology) and Pediatrics, Vanderbilt University School of Medicine; Consulting Staff, Vanderbilt University Hospital
Michael L Smith, MD is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, and Society for Pediatric Dermatology
Disclosure: Nothing to disclose.

Hunter H Sams, MD, Consulting Staff, Denver Dermatology Consultants, PC
Hunter H Sams, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, and American Society for Dermatologic Surgery
Disclosure: Nothing to disclose.

Medical Editor

Jean Paul Ortonne, MD, Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France
Jean Paul Ortonne, MD is a member of the following medical societies: American Academy of Dermatology and American Dermatological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio
Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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