Langerhans cell histiocytosis, LCH, histiocytosis X

Definition

A neoplasm of Langerhans cells expressing CD1a, S-100 and containing Birbeck granules.

Equivalent normal cell

Langerhans cells are found in the epidermis, cervix, vagina, stomach and oesophagus. They have a dendritic morphology and contain Birbeck granules, show low levels of lysosomal enzymes and play a key role in antigen presentation. They are CD1a+/S-100+/CD21-/CD35-/CD86-. Veiled cells are Langerhans cells or interstitial dendritic cells which have migrated to local lymphoid tissue following antigen capture; they lack Birbeck granules and complex interdigitating cell junctions¹.

Epidemiology

The incidence is 5 per million. This is predominantly a disease of childhood, with a male predominance. There is an association of systemic LCH with acute lymphoblastic leukaemia, lymphoma (FL¹), germ cell tumours¹. and with solvent exposure. LCH of the lung is an adult condition, strongly associated with tobacco smoking and may represent a separate reactive entity.

Clinical features

• solitary eosinophilic granuloma. Usually involves bone (skull, femur, pelvis, ribs), less often lymph nodes, skin or lung.

• Hand-Schüller-Christian disease; multifocal unisystem disease. Almost always involves bone.

• Letterer-Siwe disease; multiple organ systems involved, including bone, skin, liver, spleen and lymph nodes.

Histopathology

Langerhans cells predominate, with grooved nuclei. There are variable numbers of eosinophils, mononuclear and multinucleate histiocytes, neutrophils and small lymphocytes. There may be eosinophil microabscesses. Involvement of lymph nodes is commonly sinusoidal¹.

Immunohistochemistry; see the immunohistochemical differentiation of histiocytic and dendritic cell neoplasms

both should be positive	S-100	positive0; 17/171
	CD1a	positive0; 17/171
fascin		34/34 (sites included bone, soft tissue, lymph node, thyroid, orbit, and extradural cranial tissue)2
vimentin		usually positive0
HLA-DR		usually positive0
peanut agglutinin lectin		usually positive0
placental alkaline phosphatase		usually positive0
CD45		variably weakly positive0, 10/15 (Expression variable)1
CD68		variably weakly positive0, 16/171
lysozyme		variably weakly positive0, 15/16 (Expression usually weak / minority of cells)1
CD4		may be positive0
myeloid markers: should be negative0	myeloperoxidase	0/151
	CD34	0/121
FDC-markers	CD21	almost always negative0, 0/171
	CD35	almost always negative0, 1/16 (focally positive in one case)1
	CNA.42	5/171
T-lineage markers: should be negative0	CD3	0/161
B-lineage markers: should be negative0	CD20	0/141
	CD79a	0/111
	CD35	almost always negative0, 0/161
others	CD15	usually negative0
	CD30	0/141

Ultrastructure

Birbeck granules are present in most cases. Complex interdigitating cellular processes are absent¹. Desmosomes and lysosomes may be seen¹.

Differential diagnosis

• Other histiocytic and dendritic cell neoplasms; see the immunohistochemical differentiation of histiocytic and dendritic cell neoplasms

Prognosis

About one third of cases prove fatal¹.

References

⁰World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

¹Pileri, S.A., Grogan, T.M., Harris, N.L., et al. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 2002;41:1-29.

² Pinkus GS, Lones MA, Matsumura F, et al. Langerhans cell histiocytosis immunohistochemical expression of fascin, a dendritic cell marker. Am J Clin Pathol 2002; 118:335-43

This page last revised 16.7.2005.

©SMUHT/PW Bishop