Langerhans Cell
Histiocytosis
I2 王鐘慶
Introduction
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Accumulation and infiltration of
monocytes, macrophages, and dendritic
cells in the affected tissues
Classification of Histiocytosis
Syndromes in Children
Class
Syndrome
LCH
I
Histiocytosis of mononuclear phagocytes other than Langerhans
II
cells
Hemophagocytic lymphohistiocytosis (familial and reactive)
Sinus histiocytosis with massive lymphadenopathy (RosaiDorfman disease)
Juvenile xanthogranuloma
Reticulohistiocytoma
III
Malignant histiocytic disorders
Acute monocytic leukemia (FAB M5)
Malignant histiocytosis
True histiocytic lymphoma
Classification of Histiocytosis
H&E (left) demonstrates characteristic giant cells (large arrow), eosinophil infiltrate
(eosinophil demonstrated between two small arrows), as well as lymphocytes (single
small arrow). Positive CD1a immunohistochemistry (right) demonstrates characteristic
membranous staining.
EM demonstrating ultrastructural Birbeck granules
(cluster between two arrows).
Writing Group of the Histiocyte Society :
diagnosis of class I LCH
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Presumptive diagnosis - Light morphologic
characteristics
Designated diagnosis - Light morphologic features plus 2
or more supplemental positive stains for the following:
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Adenosinetriphosphatase
S-100 protein
a-D-Mannosidase
Peanut lectin
Definitive diagnosis - Light morphologic characteristics
plus Birbeck granules in the lesional cell with electron
microscopy and/or staining positive for CD1a antigen (T6)
on the lesional cell
Categories of Langerhans’ Cell
Histiocytosis (LCH)
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Based on the severity and extent of involvement
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Letterer-Siwe disease
Eosinophilic granulomas
Hand-Schuller-Christian disease
Hashimoto-Pritzker disease
Evaluate the extent of involvement and its relationship to prognosis (modified
from Egeler and D'Angio classification)
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Restricted LCH
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Extensive LCH
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Skin lesions without any other site of involvement
Monostotic lesion with or without diabetes insipidus, adjacent lymph node involvement, or rash
Polyostotic lesions involving several bones or more than 2 lesions in one bone, with or without
diabetes insipidus, adjacent lymph node involvement, or rash
Visceral organ involvement with or without bone lesions, diabetes insipidus, adjacent lymph node
involvement, and/or rash but without signs of organ dysfunction of the lungs, liver, or hemopoietic
system
Visceral organ involvement with or without bone lesions, diabetes insipidus, adjacent lymph node
involvement, and/or rash but with signs of organ dysfunction of the lungs, liver, or hematopoietic
system
Location of lesions and extent of the disease have a significant effect on the
course of the disease and prognosis
Unifocal LCH (eosinophilic
granuloma of bone)
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Age: 5-15 years
Solitary calvarial lesion in young
adults; other sites of involvement
include the vertebra, the rib, the
mandible, the femur, the ilium, and
the scapula .
Asymptomatic or painful.
Multifocal LCH (HandSchuller-Christian disease)
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Age: 2-10 years
Fever, diffuse eruption(scalp, ear canal),
otitis media, mastoiditis, URI, bone
lesions, mild lymphadenopathy,
hepatomegaly, and splenomegaly.
Diabetes insipidus (posterior stalk of the
hypothalamus)
Hand-Schűller-Christian triad: calvarial
bone defects, diabetes insipidus,
exophthalmos
Acute disseminated LCH
(Letter-Siwe disease)
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Age: <2 y/o
Aggressive systemic disorder
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fever; anemia; thrombocytopenia;
pulmonary infiltrates; skin lesions; and
enlargement of the lymph nodes, the
spleen, and the liver
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Rapid fatal if untreated
With intensive chemotherapy, 5-year survival
is about 50%
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Clinical Presentation
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Bone
Skin
Hypothalamic/Pituitary axis
Other endocrinopathies
CNS
Lymph nodes
Hepatic enlargement
Others
Bone
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The most common manifestation (80~100% )
Skull (27%), femur (13%), mandible/maxilla
(11%), pelvis (10%), vertebral bodies (8%),
ribs (8%), humerus (5%), and tibia (3%)
The bones of the hands and feet usually
spared.
Skin
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Up to 50% with multisystem disease may
initially present with a rash.
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Often the first sign of multisystem LCH
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Scaly, erythematous, seborrhea-like brown
to red papules, presenting in a fashion
similar to contact dermatitis
Hypothalamic/Pituitary axis
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Hypothalamic involvement:disturbances in
behavior, appetite, temperature regulation,
or sleep patterns.
Posterior pituitary involvement: DI
Other endocrinopathies
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Growth retardation
Thyroid hormone deficiency
Precocious or delayed puberty,
amenorrhea, and hypocortisolism
CNS
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Cognitive impairment, emotional lability,
changes in behavior, neurologic dysfunction,
pyramidal signs, cerebellar symptoms, and
cranial nerve palsy (causing difficulties in
speech and swallowing)
The most common manifestation is
cerebellar symptoms, followed by pyramidal
signs and cranial nerve palsy
Lymph node
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Lymph nodes are sometimes enlarged
in LCH patients (less than 10%), with
those from the head and neck region
preferentially affected
Hepatic enlargement
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Very common in people with disseminated
disease (up to 1/3 to 1/2 of children with
disseminated disease have hepatomegaly)
Signify a later stage of multisystemic
disease or a manifestation of a more
fulminant disease process
Lung disease
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Respiratory distress with tachypnea,
retraction, and persistent cough
lung disease is most common in adult LCH
patients.
Children with uncontrolled LCH may
develop chronic respiratory failure,
presenting with cysts or bullae
Others
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Otitis
Hypertrophic gingivitis
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Oral manifestations may result in bleeding
gums, early eruption, or even loss of teeth
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GI involvement rare (the most common
presenting sign is "failure to thrive" due to
malabsorption)
Treatment
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Single-agent chemotherapy is the
first line therapy.(carboplatin, 2chlorodeoxyadenosine, chlorambucil,
cyclophosphamide, cytosin, arabinoside,
daunomycin, etoposide, mercaptopurine,
methotrexate, mechlorethamine, procarbazine,
vinblastine, vincristine, vindesine)
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Topical steroid, intralesional injection of
steroids, NSAID, phototherapy, bone
marrow allografting, hematopoietic stem
cell transplantation, cyclosporin
A,prednisoe.