Case 8 -

Juvenile Xanthogranuloma Omar Sangueza

Clinical History: The patient is a 14-day-old newborn female infant weighing 3.22 kg referred to the hospital for evaluation of a growing right groin mass, present since birth. Diagnosis: Juvenile Xanthogranuloma. Juvenile xanthogranuloma (JXG) is included within the group of non-X histiocytoses. JXG is a benign histiocytic proliferation which probably represents a reactive process and usually resolves spontaneously. Most examples occur in childhood and adolescence as solitary circumscribed and cutaneous nodules. JXG may be present at birth. Although virtually any body surface site may be affected, the trunk and head and neck region are the most common anatomic sites. Rarely, JXG involves deep soft tissues or visceral organs. [1, 2, 3] While all lesions of JXG have similar clinical features, the histopathologic presentations of JXG lesions vary and most likely represent lesions at different stages of evolution. Numerous foamy histiocytes and Touton giant cells characterize "classic", well-developed xanthogranulomas; these features are absent in "early" lesions which presumably have not had time to "lipidize". [4] Patients with early JXG lesions are usually younger than 2 years of age at the time of biopsy (range 5 days to 16 months). Such lesions may represent an "infantile" variant of JXG. Later lesions may be fibrohistiocytic with prominent storiform patterns and spindled cells. [1] Immunohistochemically, JXG regardless of stage show uniform and strong labeling of histiocytes and Touton giant cells with CD68, HAM56, Factor 13a, and vimentin. [1, 5] HAM56 and CD68 are markers with specificity for tissue macrophages including Kupffer cells of the liver, spleen, gut and alveolar macrophages. MIB (Ki-67) detects proliferating cells in a wide range of normal tissues. In most cases of JXG shows less than 5% positivity, suggesting that JXG have a low proliferative rate. The uniform positive staining with CD68, HAM56 suggest that the histiocytes in JXG lesions have monocytic/macrophagic differentiation and most likely represent a reactive process to an unknown stimulus. The histologic and immunohistochemical features of JXG and the other non-X histiocytoses overlap considerably and comprise a spectrum of diseases. Moreover, the features distinguishing between Langerhan's cell histiocytosis (histiocytosis X) (LCH) and the non-X histiocytoses are not only more distinct but also more clinically relevant. Whereas most non-X histiocytoses are self-limited without extracutaneous manifestations, LCH is often progressive and potentially fatal due to extracutaneous involvement. One of the most useful differentiating features between X and non-X histiocytoses is the staining with S100 protein, which is positive in LCH and negative in non-X histiocytoses such as JXG. CD1a (OKT6) is an antigen which shares structural similarities with human leukocyte antigen (HLA) class I molecules and was once considered specific for the diagnosis of LCH; it is usually negative in JXG. [1] The differential diagnosis of JXG also includes Spitz nevi. While S100 is positive in Spitz nevi and HX lesions, it is negative in JXG lesions. In addition, macrophage markers are absent in Spitz nevi. Janssen D, Harms D. Juvenile xanthogranuloma in childhood and adolescence. Am J Surg Pathol 2005;29:21-28. Janney CG, Hurt MA, Santa Cruz DJ. Deep Juvenile Xanthogranuloma. Am J Surg Pathol 1991;15:150-159. de Graaf JH, Timens W, Tamminga RYJ, Molenaar WM. Deep juvenile xanthogranuloma: A lesion related to indeterminate cells. Human Pathol 1992;23:905-910. Shapiro PE, Silvers DN, Treiber RK, et al., Juvenile xanthogranuloma with inconspicuous or absent foam cells and giant cells. J Am Acad Dermatol 1991;24:1005-1009. Cerio R, Spaull J, Oliver GF, Wilson Jones E. A study of Factor XIIIa and MAC 387 immunolabeling in normal and pathological skin. Am J Dermatopathol 1990;12:221-233.