An otherwise healthy 8-month-old girl presented to the pediatric dermatology clinic for evaluation of an enlarging lesion on her right cheek. The child’s mother first noticed this “bump” a month prior to presentation and denied any inciting event. The lesion had increased in size since it was first noted but was not symptomatic. No bleeding was noted. Perinatal history and review of systems were unremarkable.
On physical examination, a solitary, well-demarcated, 3-mm yellow erythematous papule with central erosion was noted on the right upper cheek (Figure 1). No other lesions were identified. Lymph node examination was unremarkable. Clinical observation was recommended, with excision if significant enlargement or atypical features developed. Two months later, the lesion remained asymptomatic but had grown to 9 mm in size (Figure 2). The central erosion persisted but no bleeding occurred.
Juvenile xanthogranuloma (JXG), the most common form of non-Langerhans cell histiocytosis, is a self-limited cutaneous disorder that is rarely associated with systemic manifestations.1 The true incidence of JXG is not known because they are often mistaken for other benign lesions and most often regress within several years. The prevalence is greater in whites than in other ethnic groups, with a male predominance. Up to 70% of reported cases of JXG appear within the first year of life, although onset during adulthood is known to occur.2,3
Clinical findings usually include a well-demarcated, dome-shaped, yellow to erythematous papule or nodule on the head or neck of an infant or child.3,4 Over time, these lesions may develop a yellow-brown hue and telangiectasias.2 These asymptomatic lesions are often small but can be several centimeters in size. Figures 3 and 4 provide additional clinical examples.
A 2-year-old girl with a 1-year history of an 8-mm yellow-orange papule on the forehead along the hairline.
Two yellow-orange adjacent papules present since the first month of life were noted on the left lateral hip of an 8-month-old girl.
A JXG may occasionally ulcerate or bleed. The vast majority of patients with JXG have a solitary lesion, although multiple lesions in the head and neck are more often observed in children younger than 6 months of age.3 The head and neck region is the most common location for JXG, but they may also be observed in the upper torso, upper extremities, and lower extremities.2,3
Because of its yellowish-brown-erythematous color, JXG can be mistaken for other xanthomatous lesions, a mastocytoma, a Spitz nevus, a dermatofibroma, or Langerhans cell histiocytosis.4 Molluscum contagiosum, with its central umbilication, is a diagnostic consideration in cases with a central erosion or ulceration. Histologic findings showing Touton giant cells, considered pathognomonic for this entity, with dense dermal infiltrate of foamy histiocytes confirm the diagnosis of JXG.3 Nevertheless, several clinical clues may assist in differentiating between some of the clinical mimics of JXG. Xanthomatous lesions often occur in multiples and have characteristic distribution associated with dyslipidemia, and an urticarial reaction, Darier’s sign is often seen after rubbing a solitary mastocytoma. The yellow color of a JXG may help differentiate this from a Spitz nevus, but often when uncertain about these two diagnoses, an excision with histopathologic examination is performed.
Although the etiology of JXG remains unclear, it is considered to be a benign reactive proliferation of cells of dermal dendrocyte origin. The development of JXG has been linked to physical trauma and viral infection such as cytomegalovirus or varicella.2 Despite cholesterol being the major lipid in the JXG histiocyte, JXG is not associated with hyperlipidemia or other metabolic abnormalities.1 However, systemic JXG do occur. The eye, particularly the iris, is the most common extracutaneous site affected by systemic JXG. Eye involvement is almost always associated with multiple JXGs, which should prompt an ophthalmologic evaluation even in the absence of ocular symptoms. Other extracutaneous sites for JXG include the liver and lungs.3,4 Despite some reports of systemic JXG causing fatal outcomes, visceral lesions regress similar to their cutaneous counterparts.2–4
There is a well-recognized association among JXG, neurofibromatosis 1 (NF-1), and juvenile myelomonocytic leukemia (JMML).1 Formerly known as juvenile chronic myelogenous leukemia (JCML), chronic myelomonocytic leukemia of infancy, and infantile monosomy,7 JMML is a rare myelodysplastic and myeloproliferative disorder estimated to be 20- to 30-times more frequent in patients with both JXG and NF-1 than NF-1 alone. However, studies relating the association of JMML with NF-1 and JXG must be interpreted cautiously as the incidence of this triple finding remains controversial.4,5 Dysregulation of the Ras pathway causing reduced apoptosis of several cell lines, including myeloid progenitor cells, has been speculated as the link among JXG, NF-1, and JMML.1 A diagnosis of JXG in patient with NF-1 should nonetheless signal a clinician to be on alert for this possibility.4,5
JXG is often excised for diagnostic or cosmetic reasons, but spontaneous resolution often occurs within months to years. The lesion may leave behind a small atrophic scar or a hyperpigmented patch. Ocular JXG has been successfully treated with topical, intralesional, and systemic steroids, as well as radiation therapy.2 Vinca alkaloid and a systemic steroid regimen used for Langerhans cell histiocytosis has also been used for the treatment of symptomatic systemic JXG with favorable outcomes.6
A primary care provider can render the diagnosis in most cases of solitary cutaneous JXG. Referral to a dermatologist is recommended when unusual features are noted, especially when multiple skin lesions are present, to exclude other diseases. Although there is controversy regarding routine ophthalmologic screening in patients with JXG, referral to an ophthalmologist is advisable in patients with multiple lesions and younger than 2 years of age.2