Juvenile xanthogranuloma, JXG, nevoxanthoendothelioma

Definition

A histiocytic disorder of childhood, grouped with Langerhans' cell granulomatosis as a "dendritic cell related" proliferation. These are contrasted with the "macrophage related proliferations" (papular xanthoma, benign cephalic histiocytosis, sinus histiocytosis with massive lymphadenopathy [Rosai-Dorfmann disease] and haemophagocytic syndromes). Spindle cell xanthogranuloma, progressive nodular histiocytosis, xanthoma disseminatum and generalized eruptive histiocytosis may all be variants of juvenile xanthogranuloma.

Epidemiology

This is predominantly a disorder of the first two decades of life, 45%2 to 75%3 of patients developing the lesions as infants, 95% by the age of 10 years3. There is a reported association with neurofibromatosis type I and juvenile myelomonocytic leukaemia2.

Clinical features

Skin is the most commonly involved site, with a predilection for the head and neck. Most cases involve a solitary skin lesion. About 8% of the cutaneous cases are multiple; these patients are predominantly male infants. There is seldom progression form solitary to multiple skin lesions. A few patients present with plaques.

A minority of patients show single or multi-organ disease, with or without skin involvement. There is a predilection for the head and neck and soft tissue tumours are most common in infants.

Macroscopic appearances

Skin lesions most commonly present as yellow to red papules measuring less than 1 cm.

Histopathology

The lesions are fairly well demarcated but not encapsulated: there are often small projections into the surrounding tissue. Skin lesions usually consist of Touton giant cells and lipidised or non-lipidised mononuclear cells. In 20% of cases, there is a spindle cell component2. 10% of cases show some nuclear atypia and mitotic activity. There may be an infiltrate of eosinophils, lymphocytes and rarely plasma cells. There may be involvement of the papillary dermis and/or epidermis, with acanthosis (may be central flattening with peripheral acanthosis), parakeratosis, hypergranulosis or ulceration.

Three stages in the evolution of lesions have been described3:

Soft tissue lesions are dominated by mononuclear cells and more commonly show mitotic activity.

Extracutaneous visceral lesions tend to be composed solely of mononuclear cells2. There is a variable spindle cell component. Enlarged hyperchromatic nuclei may be seen, but without mitoses.

Immunohistochemistry

Ultrastructure

Birbeck granules are never seen.

Differential diagnosis

• Early JXG: cutaneous: Langerhans cell histiocytosis; positive for S-100 and CD1a but negative for FXIIIa and only weakly positive for macrophages markers. Juvenile xanthogranuloma may sometimes be positive for S-100 and may rarely be positive for CD1a.

• round cell sarcoma

• haematopoietic malignancy

Management

Prognosis

Solitary skin lesions recur after apparent complete excision in 7% of cases3. Spontaneous regression of multiple skin lesions has been inconsistently reported. Soft tissue lesions rarely recur, even when excision is incomplete. The systemic condition may prove fatal3. Infants may develop fatal giant cell hepatitis2.

References

1Andersen, W.K., Knowles, D.M. and Silvers, D.N. CD1 (OKT6)-positive juvenile xanthogranuloma. OKT6 is not specific for Langerhans cell histiocytosis (histiocytosis X). J Am Acad Dermatol 1992;26:850-4.

2Dehner, L.P. Juvenile xanthogranulomas in the first two decades of life: a clinicopathologic study of 174 cases with cutaneous and extracutaneous manifestations. Am J Surg Pathol 2003;27:579-93.

3Janssen, D. and D. Harms (2005). "Juvenile xanthogranuloma in childhood and adolescence: a clinicopathologic study of 129 patients from the kiel pediatric tumor registry." Am J Surg Pathol 29(1): 21-8.

This page last revised 13.1.2005.

©SMUHT/PW Bishop