Group of disorders that have in common, as a primary
event, the accumulation and infiltration of histiocytes, monocytes,
macrophages, and dendritic cells in the affected tissues. Involves mainly
the skin, bones, brain, lungs, spleen, and liver. Presents as nonmalignant
growths that represent accumulation of histiocytes. Poor prognosis (70%
Ulceration, infiltrates, and bronzing of the skin in a 3-month-old girl
with congenital, self-healing histiocytosis.
Langerhans Cell Histiocytosis; LCH.
Estimated annual incidence ranges from 0.5-5.4: 1,000,000
persons per year, but this probably is underestimated.
Male-to-female ratio is 2:1.
Consanguinity has been reported.
LCH could arise secondary to a somatic mutation of
a gene with clonal proliferation of the specific cells as a consequence.
LCH cells synthesize various cytokines, including interleukin (IL)-1, tumor necrosis factor-α, and
granulocyte-macrophage colony-stimulating factor (GM-CSF), which can explain certain systemic signs of the disease.
Clinically evocated and confirmed by laboratory
investigations. Different levels of probability have been described for the
- Presumed: Light morphologic characteristics
- Probable: Light morphologic features plus two or more supplemental positive stains
for the following: adenosinetriphosphatase, S-100, α-d-mannosidase protein, and peanut lectin
- Definitive: Light morphologic characteristics plus Birbeck granules in the lesional
cell (electron microscopy) and/or staining positive for CD1a antigen (T6) on
the lesional cell.
Because of the dissemination of the disease,
clinical signs are multiple and can involve a large part of the body.
Bones (78%): Typical punched-out cavity. Lesions can be asymptomatic or revealed by
pathologic fracture or regional complications (loss of teeth, pain,
periosteal inflammation). Most frequently involved bones are skull (49%),
innominate bone 23%, femur 17%, orbit 11%, and ribs 8%.
Skin (50%): Lesions occur during the first months of life. Rash is frequent. Bronzing
of the skin can occur. Infiltrates (maculoerythematous, petechial
xanthomatous, nodular papula) have a predilection for the midline of the
trunk and the peripheral and flexural areas of skin. Scalp lesion can lead
to alopecia. There is no pruritus.
Chest (20-40%): Interstitial syndrome (nodular images) caused by a restrictive syndrome
with clinical manifestations such as cough tachypnea and dyspnea. Diagnosis
is based on bronchoalveolar washing. Pulmonary fibrosis and pneumothorax can
Digestive System: Relatively rare, ranging from focal intestinal infiltration without any
signs to severe serous diarrhea or bleeding. Liver can be variously
involved, from simple, moderate biologic signs to hepatomegaly or even
sclerosing cholangitis complicated by biliary cirrhosis and, finally,
Nervous System: Rare; cerebral tumor or parenchymatous infiltration (usually the
cerebellum) that could lead to intracranial hypertension, localization
signs, ataxia, or seizures. Pituitary gland can be involved, causing
diabetes insipidus and deficit of growth hormone and/or thyroid-stimulating