Tests
1st tests to order
CBC
Test
Abnormal blood counts may indicate bone marrow involvement in the context of multisystem disease or a concomitant second myeloid neoplasm (adults).
Abnormal result should be followed by bone marrow aspirate and biopsy.[2][53]
In adults, presence of peripheral blood count abnormalities may suggest bone marrow infiltration by LCH or another myeloid neoplasm.
Result
normal or may show neutropenia, anemia, monocytosis (adults), or thrombocytopenia
LFTs
Test
Elevated LFTs may suggest hepatic involvement in the context of multisystem disease.
Result
normal or elevated
serum albumin
Test
Decreased level may suggest hepatic involvement in the context of multisystem disease.
Result
normal or decreased
renal function
Test
Elevated creatinine or BUN may be due to concomitant glomerulonephritis or, more rarely, renal involvement.
Result
normal or may show renal impairment
serum electrolytes
Test
Deranged levels can be caused by dehydration or a concomitant glomerulonephritis.
Result
normal or deranged
serum calcium
inflammatory markers
Test
Inflammatory markers include CRP, erythrocyte sedimentation rate, and LDH.
Result
elevated in active disease
endocrine evaluation (adults)
Test
Recommended in newly diagnosed adults to detect pituitary involvement. Tests include: morning urine and serum osmolality to detect diabetes insipidus; follicle-stimulating hormone and luteinizing hormone; testosterone or estradiol; corticotropin and morning cortisol; thyrotropin and free thyroxine; prolactin; and insulin-like growth factor 1.[53]
Result
normal or deranged
BRAF V600E mutation analysis
Test
Most common genetic mutation in LCH cells. Analysis may be performed by immunohistochemical (IHC) analysis, polymerase chain reaction, or next-generation target capture sequencing. Negative or equivocal IHC results should be confirmed by another molecular method.[53]
Result
mutation detected
skeletal survey (children)
Test
Helps establish whether there is bone involvement and whether it is unifocal (single bone) or multifocal (>1 bone). The skull is the most common site for bone involvement.[10] Approximately 50% of bone lesions are asymptomatic and are only revealed on x-ray.[10][26]
Lesions in long bones may present with aggressive features and poorly defined borders, with or without a large soft-tissue mass that must also be distinguished from malignancy.
Result
punched-out lytic lesions without periosteal reaction or sclerosis
chest x-ray (children)
Test
Helps in ruling out multisystem disease and with diagnosing lung involvement.
Cysts may be visible within the infiltrates, predominating in the middle and upper lung fields, and sparing the costophrenic angles.[56]
In infants, lung involvement does not usually progress beyond the nodular pattern. In older patients, particularly smokers, interstitial infiltration of the lungs with cysts and bullous formation is typically seen.
Pneumothorax, or a lytic lesion in a rib, may also be visible.
Patients with an abnormal x-ray should also undergo pulmonary function tests and a high-resolution CT scan of the chest.[2]
Result
reticulo-micronodular infiltration
abdominal ultrasound (children)
Test
Helps in ruling out multisystem disease and diagnosing liver and/or spleen involvement.
Result
enlarged liver and/or spleen
fluorodeoxyglucose positron emission tomography (FDG-PET) (adults)
Test
Full-body (vertex to toes) FDG-PET is recommended to stage disease and determine a suitable biopsy site.[53]
Result
FDG-PET uptake is increased in affected regions
MRI head with contrast (adults)
Test
MRI head with gadolinium contrast is performed to detect central nervous system, dural, and orbital involvement, which may be asymptomatic.[53]
Result
may show enhancement of the pons, basal ganglia, and white matter of the cerebellum; dural lesions or pituitary stalk thickening
tissue biopsy
Test
For definitive diagnosis.
Usual areas of biopsy are skin or bone lesions, or lymph nodes.[63]
Sometimes the biopsy alone of a single bone lesion can be curative.
Other inflammatory cells, such as lymphocytes and eosinophils, are usually present in lesions.
Result
presence of histiocytic infiltrate positive for CD1a and langerin (CD207); electron microscopy shows Birbeck granules
Tests to consider
endocrine evaluation (children)
Test
Early-morning urine specific gravity and osmolality (following an overnight fast), blood electrolytes, and water deprivation test are indicated in children if there is a history of polydipsia or polyuria, to detect central diabetes insipidus.[2] Additional pituitary function testing (e.g., follicle-stimulating hormone, luteinizing hormone, testosterone or estradiol, corticotropin and morning cortisol, thyrotropin and free thyroxine, prolactin, and insulin-like growth factor 1) may be indicated if another endocrine abnormality is suspected.[2]
Result
normal or deranged
coagulation studies (children)
Test
Should include INR, prothrombin time (PT), and fibrinogen.[54] Elevated result may be a sign of advanced liver disease.
Result
normal or elevated INR/PT, decreased fibrinogen
pulmonary function tests
Test
Indicated in patients with pulmonary symptoms or abnormal chest x-ray.
May show restrictive or obstructive patterns, or both.
A valuable tool in monitoring pulmonary disease, and a good complement to imaging if patient can cooperate.
Result
normal or decreased carbon monoxide diffusing capacity and decreased total lung capacity
echocardiogram
Test
Indicated in patients with pulmonary LCH to rule out pulmonary hypertension.
Result
normal or increased pulmonary arterial pressure
high-resolution CT chest
Test
Indicated in patients with pulmonary symptoms or abnormal chest x-ray.
Can help in ruling out multisystem disease, especially in the case of multifocal bone and skin disease.
Best modality to show cysts and micronodular infiltrates in lung disease.
In children with known multisystem LCH, low-dose CT is sufficient to assess lung involvement and minimizes radiation exposure.[2]
Result
may show isolated or multiple lesions in the lungs
audiometry
Test
Recommended in patients with ear involvement, to test for hearing loss.
Result
normal or hearing impairment
bone marrow aspirate and biopsy
Test
Indicated in patients with abnormal unexplained peripheral blood counts to rule out another underlying myeloid disease such as leukemia, myeloproliferative neoplasm, or myelodysplastic syndrome.
Establishes whether there is bone marrow involvement with LCH.
Result can sometimes be difficult to interpret.
Secondary hemophagocytic syndrome due to macrophage activation is one possible explanation for cytopenias.
Result
presence of clusters of large CD1a-positive cells in the marrow (rare); macrophage activation and hemophagocytosis are common in children; bone marrow fibrosis; myeloid neoplasm
MRI head with contrast (children)
Test
An MRI scan of the head should be requested for children with suspected craniofacial bone lesions (including the mandible and maxilla). MRI may characterize the bony lesions and detect involvement of the brain and pituitary gland. MRI head should also be performed for patients with visual, neurologic, or suspected endocrine abnormalities.[2][57]
Can be helpful in diagnosing early radiographic neurodegeneration.
Asymptomatic patients with these lesions should be monitored closely for clinical neurodegeneration.
Result
may show enhancement of the pons, basal ganglia, and white matter of the cerebellum; mass lesions, pineal gland enlargement, or pituitary stalk thickening
MRI spine
Test
MRI spine should be performed in all patients with suspected vertebral lesions, to exclude spinal cord compression and detect any soft-tissue masses.[2]
Result
may show soft-tissue mass or spinal cord compression
CT head
Test
CT of an affected craniofacial bone and the skull base should be performed if MRI is unavailable.[2]
Useful to delineate uncertain lesions on skull x-ray, particularly if orbital, ear, or mastoid involvement is suspected.
Contrast images will demarcate the soft-tissue involvement and periosteal reaction.
Result
may show lytic skull lesion with soft-tissue mass that extends intracranially, involving the epidural space and the adjacent dura
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