A previously healthy 14-month-old girl presents for evaluation following the gradual appearance and persistence of multiple 4- to 15-mm dome-shaped yellow papulonodules on the scalp, face, and upper trunk. Skin biopsy reveals that the lesions are composed primarily of lipid-laden histiocytes, with scattered Touton-type giant cells and small admixtures of eosinophils and lymphocytes. Predominant cells stained strongly with factor XIIIa immunostain, but did not stain with S-100. The remainder of the physical examination was normal. Specifically, neither organomegaly nor lymphadenopathy were clinically detected.
C. Complete blood count
The lesions depicted are clinically classic for juvenile xanthogranuloma (JXG), and the histologic and immunostaining pattern confirm that diagnosis. These benign, yellow to red-brown-colored histiocytic lesions of unknown etiology are more common in infants and children than in adults. Although JXG typically involutes within 3 to -6 years of initial appearance, spontaneous resolution is less common in the setting of multifocal cutaneous lesions. This tumor most often appears on the head and neck and upper torso. Extracutaneous lesions can occur and favor the iris of the eye. While ocular lesions develop in less than 0.5% of patients with skin lesions, they can have serious consequences, such as hyphema and glaucoma. JXG can usually be differentiated from other childhood histiocytic disorders by routine histology combined with immunostaining and electron microscopy (if needed). In particular, JXG can be reliably distinguished from Langerhans cell histiocytosis, as the latter consistently stains with S-100 and CD1a and fails to stain with factor XIIIa, the converse of the typical JXG immunostaining pattern.
The most interesting, and as yet unexplained, facet of JXG is the association of this skin lesion with neurofibromatosis (NF1) and leukemia. Some patients with JXG display an incomplete picture of NF1 and only have caf-au-lait macules, while others fulfill all criteria for the genodermatosis.[4,5] Even without concomitant NF1, there has been an association noted between JXG, especially when multiple, and leukemia in children (juvenile chronic myelogenous leukemia and juvenile myelomonocytic leukemia primarily, but not exclusively).[3,6,7] The so-called "triple association" of JGX, NF1, and myeloid leukemia has been well documented by extensive meta-analysis of medical literature; children with both JXG and NF1 have an estimated risk for leukemia that is 20 to 30 times higher than that in children with NF1 without JXG.
Even though most adult-onset JXG lesions, whether solitary or multiple, do indeed run a benign course there have been sporadic case reports suggesting that JXG in adults can also be associated with a variety of hematological malignancies.
In the case presented, multiple JXG lesions appeared in an eruptive fashion in a child. Because there is at least some statistically increased risk for juvenile leukemia when JXG develop (usually immediately before or concurrent with signs and symptoms of leukemia), an immediate complete blood count would be warranted. Due to the fact that there may be a delay in leukemia onset, periodic repeated assessments of hematologic status along with evaluation for hepatosplenomegaly, pallor, and bleeding diathesis (eg, petechiae to ecchymosis) should be done for several years.
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