Pathology Quiz Case—Diagnosis

Juvenile xanthogranuloma was first described in 1905 by Adamson,¹ who noted multiple yellow cutaneous papules that eventually regressed spontaneously in a 2-year-old boy. It is a benign histiocytic lesion that most often involves the head and neck region, followed by the trunk, upper extremities, and lower extremities, respectively.² It usually presents as single or multiple yellow-orange to red-brown cutaneous lesions ranging in size from a few millimeters to several centimeters. Numerous extracutaneous sites within the head and neck region have been described, including the eye,³ oral cavity,⁴ temporal bone,⁵ nasopharynx,⁶ and larynx.⁷ The nasal cavity is an uncommon site of presentation, with few descriptions available in the English-language literature.^{4 ,8 - 9} Males are preferentially affected in the juvenile form (male-female ratio, 4:1), although a similar predilection does not exist in the adult form.² The lesion is 10 times more common in whites than in blacks. Despite the nomenclature, JXG has been found to arise in both pediatric and adult populations, with presentations most often occurring in the first year and third decade of life.² There is also a well-known association between JXG and neurofibromatosis 1 and acute myelogenous leukemia.¹⁰

Cutaneous lesions tend to be self-limited and undergo spontaneous involution. Frequently, no particular intervention is warranted. Surgical excision may be carried out for extracutaneous lesions if their location or size affects vital functions or if the diagnosis is in question. Some authors have advocated injected steroids and radiotherapy,¹¹ although effectiveness is difficult to gauge given the self-limited nature of these lesions. Any patient diagnosed as having JXG should undergo full ophthalmologic examination because of the high predilection for ocular involvement.

Histopathologically, JXG presents as a well-circumscribed, dome-shaped lesion with a dense, diffuse dermal infiltrate, composed predominantly of histiocytes with admixed lymphocytes, eosinophils, neutrophils, and plasma cells, abutting the undersurface of the epidermis but not invading it (Figure 1 and Figure 2). The histopathologic hallmark is the Touton giant cell, a multinucleated giant histiocyte whose rings of nuclei separate a central homogeneous core from a foamy periphery. The number of Touton giant cells within the lesion and the prominence of the foamy periphery are variable. Early in the evolution of JXG, Touton giant cells may be either absent or sparse and, if present, their foamy periphery may not be well formed, as in the present case (Figure 3).¹²

Differential considerations include other histiocytic lesions, Rosai-Dorfman disease, and infectious causes. The primary non-Langerhans histiocytic lesion to consider in this type of case is reticulohistiocytoma. Reticulohistiocytoma, in contrast to JXG, lacks Touton giant cells at all stages of its evolution and characteristically is composed of large histiocytes with ground glass cytoplasm. Immunohistochemical analysis is not particularly helpful in differentiating between reticulohistiocytoma and JXG. Staining with antibodies, especially with macrophage markers (eg, CD68 and KP-1), is an ancillary technique and is only helpful to broadly classify the lesion as histiocytic in origin.¹³ Juvenile xanthogranuloma should also be differentiated from Langerhans histiocytosis. This distinction is facilitated with the use of immunohistochemical markers, because, unlike non-Langerhans lesions, Langerhans histiocytic lesions stain positive for S100 protein and CD1. This is an important distinction as Langerhans histiocytosis tends to be progressive in contrast to the non-Langerhans histiocytic disorders, which are usually self-limited in nature. Rosai-Dorfman disease and infection are other potential considerations in the differential diagnosis. Rosai-Dorfman disease, however, does not demonstrate the Touton giant cells typical of JXG and is characterized by lymphocytophagocytosis (emperipolesis) by sinus histiocytes, which are not a specific but a constant feature. The well-circumscribed, dome-shaped appearance of the lesion, the infiltrate abutting but not invading the overlying epidermis, and the presence of Touton giant cells, all of which are characteristic of JXG, ruled out an infectious origin in the present case.