Juvenile Xanthogranuloma Clinical Presentation

Updated: Dec 19, 2022
  • Author: Bhupendra C K Patel, MD, FRCS; Chief Editor: Michael Taravella, MD  more...
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Presentation

History

Most individuals with juvenile xanthogranuloma (JXG) are asymptomatic. JXG predominantly affects the skin. Although a minority of patients with JXG have ocular involvement, recognition of this condition is important because a treatment delay can lead to complications such as glaucoma and hyphema.

Ocular lesions usually are discovered incidentally or following spontaneous hyphema. They may be noted by observant parents or primary care physicians. Among children with JXG, 10%-40% demonstrate cutaneous lesions characteristic of the condition.

Screening for ocular involvement generally is not performed because of its low incidence. The eye probably is affected in only about 0.5% of patients with cutaneous JXG, [9] although some early studies found an incidence as high as 10%. [10, 11]

Those at greatest risk are children younger than 2 years with multiple skin lesions. [7]

The most common ocular presentation involves the iris. Iris tumors may be diffuse or localized and lead to heterochromia, uveitis, spontaneous hyphema, and secondary glaucoma. [12]

Other ocular tissues are involved much less frequently, and orbital tumors are rare.

Nearly all cases are unilateral, and spontaneous regression of lesions is uncommon.

An association with neurofibromatosis type 1 (NF-1) and juvenile chronic myelogenous leukemia (JCML) has been reported. A recent retrospective review by Cambiaghi of 77 patients younger than 3 years with NF-1 yielded 17 (22%) with JXG, but none developed JCML or other hematologic abnormalities. [13]

Conjunctival, eyelid, and orbital JXG are rare and are more benign than iris JXG.

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Physical

Skin lesions are well-demarcated, rubbery, tan-orange papulonodules (dome-shaped) ranging from 1-20 mm in size, usually between 2 and 5 mm. They may be single or multiple and usually occur on the head and neck, but they may appear at any site on the body surface. [14]  Initially pink to red, they subsequently turn yellow. See the image below.

Juvenile xanthogranuloma. Photograph of an 18-mont Juvenile xanthogranuloma. Photograph of an 18-month-old presenting with a firm, nodular, tan-yellow lesion that has grown since first noticed 6 months ago. An examination under anesthesia did not reveal any ocular abnormalities. Excision of the lesion confirmed that this was a juvenile xanthogranuloma.

Other forms of presentation include one or more large nodules measuring 1 to 2 centimeters, giant juvenile xanthogranuloma, cutaneous horn-like JXG, atrophic plaques, and subcutaneous masses.  [15]

Extracutaneous involvement has been reported in every organ system in the body, including the central nervous system, [16] eye, salivary glands, larynx, lung, pericardium, myocardium, liver, spleen, colon, retroperitoneum, kidney, adrenal gland, gonads, bone, periosteum, muscle, and mucous membranes.

Ocular lesions usually involve the iris, but they may occasionally be seen in the eyelids, conjunctiva, cornea, limbal tissue, sclera, retina, choroid, optic nerve, and orbit. Cases are usually unilateral, but bilateral cases have been reported.

Iris lesions most often resemble isolated cutaneous lesions in color and appearance. They may be single or multiple and localized or diffuse. Tumors have been described to increase in thickness and lighten in color with maturation.

Iris JXG also may present as diffuse conjunctival injection with uveitis, congenital or acquired heterochromia iridis, spontaneous hyphema, or secondary glaucoma. Involvement of other uveal tissue is very uncommon.

The second most commonly affected ocular site is the eyelid. [17] Lesions appear as typical cutaneous tumors. Subcutaneous forms are rare, but they can mimic a recurrent/nonresolving chalazion. They can cause deprivational amblyopia or refractive amblyopia if they induce significant astigmatism.

Intraocular lesions rarely have been reported in the posterior pole.

Cutaneous lesions may appear before or after an ocular diagnosis has been made, with a delay of up to 8-10 months. Cutaneous and iris JXG present at a mean age of 3.3 years. Periocular JXG presents later, at a mean age of 6.5 years.

Although ocular involvement in patients with cutaneous JXG is rare, visual sequelae can lead to loss of vision. Therefore, all patients who present with typical JXG cutaneous lesions should be referred for a complete ophthalmologic examination.

Spontaneous hyphema is a common presenting sign in iris JXG. The differential diagnoses of hyphema in childhood include trauma, neoplastic conditions such as retinoblastoma, medulloepithelioma, leukemia, retinopathy of prematurity, and blood dyscrasias. These disorders should be excluded before JXG can be diagnosed.

When a spontaneous hyphema is the presenting finding, iris JXG appearing as nodular or diffuse lesions can be seen. Nodular iris JXG appears as a well-circumscribed, thickened, orange-colored lesion. Diffuse iris JXG appears as a thin coating or film on the iris surface, blunting the normal iris crypts.

Orbital lesions are extremely uncommon. They usually appear as infiltrative soft tissue tumors and often cause proptosis of the globe. At least one case has been described as a locally aggressive lesion causing bony destruction with intracranial extension.

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Causes

The etiology of JXG is unknown, but a genetic basis has been suggested given the multiple sites of occurrence. However, familial cases have not been observed.

The transformation of benign cephalic histiocytosis (a related disorder) into JXG has been reported infrequently. A recent report postulated this progression could be virally mediated.

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Complications

The primary complication of ocular JXG is spontaneous hyphema and its sequelae, mainly glaucoma and amblyopia.

4% of children with JXG will have systemic juvenile xanthogranulomas with a mortality of 5% to 10%: fatalities are caused by progressive central nervous system (CNS) disease or liver failure.  [6]  CNS complications include the development of seizures, raised intracranial pressure, developmental delay, and diabetes insipidus. 

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