Differentials
Seborrheic dermatitis
SIGNS / SYMPTOMS
No differentiating signs and symptoms from LCH with skin involvement, especially in newborns.
INVESTIGATIONS
Tissue biopsy: negative for CD1a and langerin (CD207).
Juvenile xanthogranuloma (JXG)
SIGNS / SYMPTOMS
Can mimic LCH very closely in a number of tissue sites (especially the skin), and sometimes can be multisystemic.
Dermal JXG can be seen in children after LCH.[64]
INVESTIGATIONS
Tissue biopsy: negative for CD1a and S100; positive for factor XIIIa, fascin, CD68, CD163, and CD14.
Rosai-Dorfman disease (RDD)
SIGNS / SYMPTOMS
Also called sinus histiocytosis with massive lymphadenopathy.
Most patients present with bilateral painless cervical lymphadenopathy with fever, night sweats, and weight loss.
Extranodal disease occurs in 40% of patients, with skin, lung, liver, central nervous system, and bone being most commonly involved.[65]
Bone RDD may mimic the lesions of healing and involuting LCH. Coexistence of LCH and RDD has been reported.[66]
INVESTIGATIONS
White blood cell count: leukocytosis.
Serum electrophoresis: hypergammaglobulinemia.
Tissue biopsy: positive for intracytoplasmic emperipolesis of lymphocytes, neutrophils, and plasma cells. Negative for CD1a and langerin (CD207).
Osteomyelitis
SIGNS / SYMPTOMS
Difficult to distinguish clinically from LCH with bone involvement.
Chronic multifocal osteomyelitis can be confused with multifocal bone disease and may have few or no constitutional symptoms.
INVESTIGATIONS
Tissue biopsy: negative for CD1a and langerin (CD207).
Cultures from biopsy sample: positive for bacteria or atypical mycobacteria.
Ewing sarcoma
SIGNS / SYMPTOMS
Difficult to distinguish clinically from LCH with bone involvement.
INVESTIGATIONS
Tissue biopsy: negative for CD1a and langerin (CD207).
X-ray: aggressive radiologic features such as significant periosteal reaction, poorly defined borders, and onion-skinning are typical. With healing LCH lesions, there is recalcification and development of a well-defined sclerotic rim.
Osteosarcoma
SIGNS / SYMPTOMS
Difficult to distinguish clinically from LCH with bone involvement.
INVESTIGATIONS
Tissue biopsy: negative for CD1a and langerin (CD207).
X-ray: with healing LCH lesions, there is recalcification and development of a well-defined sclerotic rim.
Tuberculosis (TB)
SIGNS / SYMPTOMS
Disseminated TB may mimic multisystem disease.
Progressive fever and weight loss are usually present.
INVESTIGATIONS
Sputum smear: positive for acid-fast bacilli.
Sputum culture: positive.
Tuberculin skin testing: millimeters of induration.
Chest x-ray: normal; abnormal typical for TB; abnormal atypical for TB.
Tissue biopsy: caseating granulomas typically seen, negative for CD1a and langerin (CD207).
Acute lymphoblastic leukemia
SIGNS / SYMPTOMS
Can be confused with multisystem disease in the presence of hepatosplenomegaly, lymphadenopathy, fever, pallor, and petechial rash.
INVESTIGATIONS
Bone marrow aspirate and biopsy: bone marrow hypercellularity and infiltration by lymphoblasts.
Peripheral blood smear: leukemic lymphoblasts with or without hyperleukocytosis.
Serum electrolytes: hyperuricemia, hyperkalemia, hyperphosphatemia.
Acute myelogenous leukemia
SIGNS / SYMPTOMS
Neonatal acute monoblastic leukemia can present with skin rash that can mimic LCH with skin involvement.
INVESTIGATIONS
Bone marrow aspirate and biopsy: bone marrow hypercellularity and infiltration by myeloblasts.
Peripheral blood smear: myeloblasts, hyperleukocytosis, or pancytopenia.
Non-Hodgkin lymphoma
SIGNS / SYMPTOMS
Can be difficult to differentiate from LCH in the presence of lymphadenopathy and systemic symptoms.
INVESTIGATIONS
Tissue biopsy: negative for CD1a and langerin (CD207) and positive for T- or B-cell markers.
Pituitary adenoma
SIGNS / SYMPTOMS
Can also cause central diabetes insipidus.
No history of skin rash, bone pain, or recurrent otitis.
INVESTIGATIONS
CT/MRI pituitary with contrast: sellar mass.
Craniopharyngioma
SIGNS / SYMPTOMS
Can also cause central diabetes insipidus.
No history of skin rash, bone pain, or recurrent otitis.
Macrocephaly and hydrocephalus.
INVESTIGATIONS
MRI brain with contrast: variable; T1 signal (T1 hyperintensity secondary to high protein content in cystic component); mixed solid and cystic components with enhancement of the solid component and cyst wall; T2 and fluid attenuation inversion recovery show heterogeneous signal in the solid components and cyst hyperintensity; calcification has low signal on T2.
Biopsy and histology: adamantinous/squamous epithelial tumor; calcification.
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