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.

	Solitary skin lesion	116/174 (scalp: 20, face: 15, eyelid: 7, neck: 7, back: 13, abdomen: 8, chest: 6, axilla: 3, lower extremity: 19, upper extremity: 18)2, 94/129 (51/126 head and neck, 52/126 trunk, 10/126 upper extremity, 13/126 lower extremity)3
	subcutis/soft tissue	28/174 (25 subcutaneous and 3 deeper soft tissue)2, 19/129 (4 subcutaneous, 8 deep soft tissues, 7 in skeletal muscle)3
	multiple skin only	13/174 (10 cases involved the head or neck)2, 11/1293
	solitary extracutaneous	9/174 (sites include maxillary sinus, orbit, temporal bone, tongue, nasal cavity, salivary gland, bronchus and vertebra)2, 2/129 (isolated CNS lesions)3
	multiple skin and other systems	8/174 (sites include liver, lung, spleen, kidney, brain, gastrointestinal tract, pancreas and bone)2, 3/129 (sites include liver, spleen, intestines, lung, kidney, CNS and bone marrow)3

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:

		Early JXG	Classic JXG	Late (transitional) JXG	Combined JXG
	frequency	39/1443	68/1443	23/1443	14/1443
	histiocytes	smallish, limited cytoplasm	abundant cytoplasm	storiform pattern of spindle cells resembling benign fibrous histiocytoma, plus foamy and giant cells	combination of these patterns within one lesion
	lipid vacuoles	absent or fine	distinct vacuoles
	nuclei	small, round to oval, may be indented
	nucleoli	inconspicuous
	Touton giant cells	usually absent	foreign body and early (lack cytoplasmic vacuolation) and typical Touton giant cells	absent or rare
	mitotic figures	some
	eosinophils	scattered	few	few

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

	CD68	28/282, 8/83
	Factor XIIIa	28/282, 112/113 (diffuse cytoplasmic staining)3
	vimentin	28/282
	KI-M1P	121/121 (strong granular cytoplasmic staining)3
	CD1a	0/282, 1/11, 0/1223
	CD4	15/153
	S-100	8/28 (weak positivity in 8/28 cases)2, 7/122 (in seven cases, scattered cells stained)3
	SMA	positivity only in late JXG3

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