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An Atlas of Lumps and Bumps, Part 31: Juvenile Xanthogranuloma

Alexander K.C. Leung, MD1,2, Benjamin Barankin, MD3, Joseph M. Lam, MD4, Kin Fon Leong, MD5

Volume 63 - Issue 9 - September 2023

Juvenile xanthogranuloma is a benign proliferative disorder of dendritic histiocytes that mostly affects the skin.1,2 It is the most common form of non-Langerhans cell histiocytosis in childhood.3-5 The true incidence is not known but is likely higher than is generally appreciated.  This is because of the natural history of spontaneous resolution, the other skin conditions that it can mimic, and the fact that small and solitary lesions may go unrecognized.3 In the Kiel Pediatric Tumor Registry in Germany between 1965 and 2001, 129 (0.52%) of 24,600 patients were documented to have juvenile xanthogranuloma.6 As the studied population was highly selected, the results are not generalizable.  Juvenile xanthogranuloma is more commonly observed in Caucasians than in other ethnic groups.4,7 The disease typically affects infants and young children.3 Approximately 15% of juvenile xanthogranulomas occur at birth and 75% appear during the first year of life.3,8 Adult onset is reported infrequently.7 In children, the male to female ratio is approximately 1.5 to 1.4,9,10 In adults, there is no sex predilection.11-13 Most cases are sporadic.14  

The exact etiopathogenesis is not known. It is believed that the condition results from a benign reactive proliferation and granulomatous reaction of dendritic histiocytes in response to an undefined stimulus.4,7,9 There may be a genetic predisposition as the condition has been reported in monozygotic twins.14   

Typically, juvenile xanthogranuloma presents as an asymptomatic, well-demarcated, dome-shaped, firm, rubbery, round to oval papule or nodule.1,4,5,7 The size usually ranges from 5 to 20 mm in diameter (Fig. 1).2,10,15

image1
Fig. 1. Typically, juvenile xanthogranuloma presents as an asymptomatic, well-demarcated, dome-shaped, firm, rubbery, round to oval papule or nodule, ranging from 5 to 20 mm in diameter.

At first, the lesion is pink to red with a yellow tinge.4,5 Over time, it acquires a yellow-brown or orange hue (Fig. 2) and will often flatten.2,16

2
Fig. 2. Over time, juvenile xanthogranuloma acquires a yellow-brown or orange hue

Occasionally, fine telangiectases can be seen on the surface of the lesion.2,7 The lesion is solitary in 60 to 82% of cases (Fig. 3).4 Sites of predilection include the head and neck, followed by the upper torso, followed by the proximal extremities.4,7,17

fig3
Fig. 3. Sites of predilection include the head and neck, followed by the upper torso, followed by the proximal extremities.

Atypical clinical presentations, such as generalized, lichenoid, infiltrative, keratotic, pedunculated, subcutaneous, intramuscular, clustered, linear, segmental, atrophic, lichenoid, plaque-like, horn-like, and giant (size greater than 2 cm in diameter) variants have been reported.4,8,15,16,18-23 These variants are rare and may pose a diagnostic challenge. Giant exophytic lesions appear to be the most at risk of ulceration.24

Cutaneous lesions are the most common form of classic juvenile xanthogranulomas.18 Extracutaneous or systemic forms (involvement of the eyes, lungs, lymph nodes, liver, spleen, pericardium, adrenal glands, bone, breasts, gonads, and gastrointestinal tract) are rare.2,25 Ocular involvement (especially the iris) is the most common extracutaneous association.3,8,25 Risk factors for extracutaneous involvement are age under two years and multiple lesions.15

The diagnosis is mainly clinical, based on the history (age of onset and natural history of spontaneous regression) and physical findings (color, shape, and location).1 The diagnosis can be aided by dermoscopy which shows the "setting sun" sign consisting of a yellow-orange central area surrounded by a peripheral pink or erythematous halo with fine, branched and/or linear vessels.5,26,27 Additional features include "clouds" of paler yellow, orange-yellow, orange-pink, or red globules, shiny white streaks, irregularly distributed different types of vascular structures.5,27 Reflectance confocal microscopy typically shows large round and ovoid cells with a foamy cytoplasm, large, multinucleated cells with a hyperrefractile peripheral rim in a granulomatous formation.28,29 A skin biopsy for histology and immunohistochemical stains should be considered if the diagnosis is in doubt.

Patients with juvenile xanthogranuloma are at risk for neurofibromatosis type 1, diabetes mellitus type 1, urticaria pigmentosa, aquagenic pruritus and, rarely, juvenile myelomonocytic leukemia, B-cell lymphoma, and monoclonal gammopathy.2,8,17,25,30 Juvenile xanthogranuloma may herald the diagnosis of Erdheim-Chester disease.31 Generally, the prognosis of patients with exclusive cutaneous involvement is excellent as spontaneous regression is the rule, although the process of resolution may take 1 to 5 years.2,15 In some cases, there may be a residual hyperpigmented or atrophic scar.2,15 In contrast to other xanthomatous diseases, juvenile xanthogranulomas are not associated with lipid or metabolic disorders except for diabetes mellitus type 1.3

AFFILIATIONS:
1Clinical Professor of Pediatrics, the University of Calgary, Calgary, Alberta, Canada
2Pediatric Consultant, the Alberta Children’s Hospital, Calgary, Alberta, Canada
3Dermatologist, Medical Director and Founder, the Toronto Dermatology Centre, Toronto, Ontario, Canada
4Associate Clinical Professor of Pediatrics, Dermatology and Skin Sciences, the University of British Columbia, Vancouver, British Columbia, Canada.
5Pediatric Dermatologist, the Pediatric Institute, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia

CITATION:
Leung AKC, Barankin B, Lam JM, Leong KF. An atlas of lumps and bumps, part 31: Juvenile Xanthogranuloma. Consultant. 2023;63(9):e7. doi:10.25270/con.2023.08.000014.

CORRESPONDENCE:
Alexander K. C. Leung, MD, #200, 233 16th Ave NW, Calgary, AB T2M 0H5, Canada (aleung@ucalgary.ca)

EDITOR’S NOTE:
This article is part of a series describing and differentiating dermatologic lumps and bumps. To access previously published articles in the series, visit: https://www.consultant360.com/resource-center/atlas-lumps-and-bumps.

References

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