Final Diagnosis -- solitary brain juvenile xanthogranuloma (parietal lobe lesion)

FINAL DIAGNOSIS:   SOLITARY BRAIN JUVENILE XANTHOGRANULOMA (JXG) WITHOUT SKIN INVOLVEMENT.

DISCUSSION: JXG is generally benign, self limited, non-Langerhans cell histiocytosis (LCH) lesion occurring in the skin predominantly of children and young adults, which may be a systemic disease, as well (1,2). The eye is the most common extracutaneous site. The isolated central nervous system lesion is unusual and rare. We have found only one reported case of a 13-year-old boy with a solitary JXG in the brain cortex (3). Systemic JXG combined with central nervous system involvement may follow a more aggressive course (2).

The usual microscopic pattern is a mixture of histiocytes, foamy cells, and giant cells of foreign body and Touton type. A moderate inflammatory infiltrate is usually present (4). The cells of JXG are believed to possibly derive from dermal dendrocytes, which usually express macrophage markers and are S-100 protein negative (5). Generally accepted difference between LCH and non-LCH, with JXG as the main member of the later group, had been immunohistochemical reactivity for S-100 protein and CD1a surface antigen, and the presence of Birbeck granules on the electron microscopic level in LCH (1,5). In our case, however, a lot of cells were strongly S-100 positive (Table1). Electron microscopic examination of our lesion did not demonstrate Birbeck granules.

Table 1. Antigenic profile of our case in comparison with JXG and LCH

Antibody	Our case	JXG	LCH
S-100	+/-	+/-	+
CD1a	-	-/(+)	+
CD68	+/-	+	-
MAC387	+/-	+/-	-

In the recent literature we have found a report of S-100 protein expression in the cells of JXG and related lesions (6). CD1a surface antigen expression in the same cells of JXG was also described (2). It seems that Birbeck granules are still an obligatory ultrastructural finding for differentiating LCH from JXG and related lesions.

The contemporary classification of histiocytic disorders of the WHO committee from 1997, which is related to the ontogeny of the histiocytes, put the JXG in a large group of disorders of varied biological behavior. Disorders that are considered to be malignant are excluded from this group, while it recognizes a wide scope of severity ranging from self limited (as for example JXG) to lethal diseases (Langerhans' cell histiocytosis with its many expressions), with obvious some phenotypical overlapping between these lesions (5).

Whenever JXG or similar lesions of central nervous system are diagnosed, especially in children and young adults, the LCH should be excluded by electron microscopy. Thoroughly screening of the skin is necessary, since cutaneous lesions often, though not always, precede or accompany the deep lesions.

REFERENCES:

1. Burgdorf HC, Zelger B (1996) The non-Langerhans' cell histiocytoses in childhood. Pediatr Dermatol 58: 201-207.
2. Freyer DR, Kennedy R, Bostrom BC, Kohut G, Dehner LP (1996) Juvenile xanthogranuloma: Forms of systemic disease and their clinical implications. J Pediatr 129: 227-237.
3. Schultz KD, Petronio J, Narad C, Hunter SB (1997) Solitary intracerebral juvenile xanthogranuloma. Pediatr Neurosurg 26: 315-21.
4. Hernandez-Martin A, Baselga E, Drolet BA, Esterly NB (1997) Juvenile xanthogranuloma. J Am Ac Dermatol 36: 355-369.
5. Favara BE, Feller AC with members of the WHO Committee on Histiocytic/Reticulum Cell Proliferations (1997) Contemporary classification of histiocytic disorders. Med Pediatr Oncol 29: 157-66.
6. Tomaszevski MM, Lupton GP (1998) Unusual expression of S-100 protein in histiocytic neoplasms. J Cutan Pathol 25: 129-35.

Contributed by Helena Gutnik, MD, Zvezdana Dolenc-Strazar, MD and Mara Popovic, MD, PhD