langerhans cell histiocytosis i2 王鐘慶. introduction accumulation and infiltration of monocytes,...
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Langerhans Cell Histiocytosis
I2 王鐘慶
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Introduction
Accumulation and infiltration of monocytes, macrophages, and dendritic cells in the affected tissues
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Classification of Histiocytosis Syndromes in Children
Class Syndrome
I LCH
II Histiocytosis of mononuclear phagocytes other than Langerhans cells
Hemophagocytic lymphohistiocytosis (familial and reactive)
Sinus histiocytosis with massive lymphadenopathy (Rosai- Dorfman disease)
Juvenile xanthogranuloma
Reticulohistiocytoma
III Malignant histiocytic disorders
Acute monocytic leukemia (FAB M5)
Malignant histiocytosis
True histiocytic lymphoma
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Classification of Histiocytosis
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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.
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EM demonstrating ultrastructural Birbeck granules (cluster between two arrows).
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Writing Group of the Histiocyte Society : diagnosis of class I LCH
Presumptive diagnosis - Light morphologic characteristics Designated diagnosis - Light morphologic features plus 2 or
more supplemental positive stains for the following: 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
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Categories of Langerhans’ Cell Histiocytosis (LCH)
Based on the severity and extent of involvement 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) Restricted LCH
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 i
nsipidus, adjacent lymph node involvement, or rash Extensive LCH
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
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Unifocal LCH (eosinophilic granuloma of bone)
Age: 5-15 years Solitary calvarial lesion in young adu
lts; other sites of involvement include the vertebra, the rib, the mandible, the femur, the ilium, and the scapula .
Asymptomatic or painful.
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Multifocal LCH (Hand-Schuller-Christian disease) Age: 2-10 years Fever, diffuse eruption(scalp, ear canal), o
titis 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
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Acute disseminated LCH (Letter-Siwe disease) Age: <2 y/o Aggressive systemic disorder fever; anemia; thrombocytopenia;
pulmonary infiltrates; skin lesions; and enlargement of the lymph nodes, the spleen, and the liver
Rapid fatal if untreated With intensive chemotherapy, 5-year survival
is about 50%
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Clinical Presentation
Bone Skin Hypothalamic/Pituitary axis Other endocrinopathies CNS Lymph nodes Hepatic enlargement Others
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Bone
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.
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Skin
Up to 50% with multisystem disease may initially present with a rash.
Often the first sign of multisystem LCH Scaly, erythematous, seborrhea-like brown t
o red papules, presenting in a fashion similar to contact dermatitis
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Hypothalamic/Pituitary axis
Hypothalamic involvement:disturbances in behavior, appetite, temperature regulation, or sleep patterns.
Posterior pituitary involvement: DI
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Other endocrinopathies
Growth retardation Thyroid hormone deficiency Precocious or delayed puberty, ameno
rrhea, and hypocortisolism
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CNS
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
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Lymph node
Lymph nodes are sometimes enlarged in LCH patients (less than 10%), with those from the head and neck region preferentially affected
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Hepatic enlargement
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
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Lung disease
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
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Others
Otitis Hypertrophic gingivitis Oral manifestations may result in bleeding g
ums, early eruption, or even loss of teeth GI involvement rare (the most common pre
senting sign is "failure to thrive" due to malabsorption)
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Treatment Single-agent chemotherapy is the first l
ine therapy.(carboplatin, 2-chlorodeoxyadenosine, chlorambucil, cyclophosphamide, cytosin, arabinoside, daunomycin, etoposide, mercaptopurine, methotrexate, mechlorethamine, procarbazine, vinblastine, vincristine, vindesine)
Topical steroid, intralesional injection of steroids, NSAID, phototherapy, bone marrow allografting, hematopoietic stem cell transplantation, cyclosporin A,prednisoe.