General clinical approach to LCH
| Clinical approach to LCH . |
|---|
| Initial consideration of diagnosis of LCH |
| • Physical examination, history, or other clinical or laboratory tests suggest possibility of LCH |
| Initial evaluation |
| • Assess need for biopsy, optimal site for biopsy, and possible alternative diagnoses (eg, lymphoma, infection) |
| • Complete blood count, chemistries, liver function, coagulation studies, sedimentation rate, immunoglobulins, LDH, uric acid, ferritin |
| • Skeletal survey with 2 views of chest and 4 views of skull |
| Suspicion for LCH |
| • PET/CT scan (recommended) |
| • Diagnostic biopsy: open biopsy with curettage is optimal (complete excision is NOT required) |
| • Intralesion corticosteroid injection if single bone lesion is suspected |
| Pretherapy baseline studies and special circumstances* |
| Bone marrow biopsy and aspirate |
| • All patients under 2 y |
| • Any patient with cytopenias |
| CT skull/maxillofacial scan |
| • CNS-risk lesions |
| • Baseline neurocognitive evaluation |
| • Baseline MRI brain |
| • Baseline hearing evaluation if auditory canal or temporal bones are involved |
| MRI brain |
| • History concerning for DI or pituitary dysfunction |
| • Urine-specific gravity and urine and serum osmolality/water deprivation test |
| • Diagnostic LP (cytology and AFP/β-HCG for isolated pituitary mass) |
| • Endocrine evaluation (as directed by history) |
| MRI spine |
| • Concern for spinal cord involvement |
| CT chest scan |
| • Concern for pulmonary involvement |
| Abdominal imaging (U/S or MRI) |
| • Elevated transaminases, direct bilirubin or decreased albumin |
| Lower GI endoscopy |
| • Decreased albumin or history of malabsorption |
| Experimental |
| • BRAF/MAP2K1 genotyping of tumor (sequencing methods may yield false negative due to relatively low “LCH” cell infiltrate in lesions) |
| • BRAFV600E qPCR of tumor. If mutation detected or no tumor tissue available, BRAFV600E qPCR of peripheral blood (and bone marrow, if applicable) |
| Monitor response to therapy and toxicity |
| Single lesion (not CNS-risk) or skin-limited disease: |
| • Chemotherapy is not necessary in many cases, and disease may be monitored by focused imaging and/or clinical examination |
| For patients requiring chemotherapy: |
| Every cycle: |
| • Complete blood count |
| • Liver function |
| • Sedimentation rate (if initially abnormal) |
| • Chemistries/osmolality (if initially abnormal) |
| After 6-8 wk (depending on therapy/protocol): |
| • PET/CT scan and/or specific imaging from initial staging |
| • Bone marrow biopsy/aspirate (if initially positive) |
| • Experimental: circulating BRAF-V600E in blood and bone marrow aspirate (if initially positive) |
| Clinical concern for progression or relapse: |
| • Repeat 6- to 8-wk evaluations |
| End of therapy: |
| • Repeat 6- to 8-wk evaluations |
| Brain MRI for patient with CNS-risk lesions |
| Off-therapy management |
| 3 mo: |
| • PET/CT scan or focused imaging of original site of disease at 3 mo off-therapy |
| • Office visit every 3 mo through 1 y |
| • Focused imaging for clinical concerns |
| 1 y: |
| • Comprehensive clinical evaluation every 6 mo through 3 y off therapy, then annual |
| Clinical approach to LCH . |
|---|
| Initial consideration of diagnosis of LCH |
| • Physical examination, history, or other clinical or laboratory tests suggest possibility of LCH |
| Initial evaluation |
| • Assess need for biopsy, optimal site for biopsy, and possible alternative diagnoses (eg, lymphoma, infection) |
| • Complete blood count, chemistries, liver function, coagulation studies, sedimentation rate, immunoglobulins, LDH, uric acid, ferritin |
| • Skeletal survey with 2 views of chest and 4 views of skull |
| Suspicion for LCH |
| • PET/CT scan (recommended) |
| • Diagnostic biopsy: open biopsy with curettage is optimal (complete excision is NOT required) |
| • Intralesion corticosteroid injection if single bone lesion is suspected |
| Pretherapy baseline studies and special circumstances* |
| Bone marrow biopsy and aspirate |
| • All patients under 2 y |
| • Any patient with cytopenias |
| CT skull/maxillofacial scan |
| • CNS-risk lesions |
| • Baseline neurocognitive evaluation |
| • Baseline MRI brain |
| • Baseline hearing evaluation if auditory canal or temporal bones are involved |
| MRI brain |
| • History concerning for DI or pituitary dysfunction |
| • Urine-specific gravity and urine and serum osmolality/water deprivation test |
| • Diagnostic LP (cytology and AFP/β-HCG for isolated pituitary mass) |
| • Endocrine evaluation (as directed by history) |
| MRI spine |
| • Concern for spinal cord involvement |
| CT chest scan |
| • Concern for pulmonary involvement |
| Abdominal imaging (U/S or MRI) |
| • Elevated transaminases, direct bilirubin or decreased albumin |
| Lower GI endoscopy |
| • Decreased albumin or history of malabsorption |
| Experimental |
| • BRAF/MAP2K1 genotyping of tumor (sequencing methods may yield false negative due to relatively low “LCH” cell infiltrate in lesions) |
| • BRAFV600E qPCR of tumor. If mutation detected or no tumor tissue available, BRAFV600E qPCR of peripheral blood (and bone marrow, if applicable) |
| Monitor response to therapy and toxicity |
| Single lesion (not CNS-risk) or skin-limited disease: |
| • Chemotherapy is not necessary in many cases, and disease may be monitored by focused imaging and/or clinical examination |
| For patients requiring chemotherapy: |
| Every cycle: |
| • Complete blood count |
| • Liver function |
| • Sedimentation rate (if initially abnormal) |
| • Chemistries/osmolality (if initially abnormal) |
| After 6-8 wk (depending on therapy/protocol): |
| • PET/CT scan and/or specific imaging from initial staging |
| • Bone marrow biopsy/aspirate (if initially positive) |
| • Experimental: circulating BRAF-V600E in blood and bone marrow aspirate (if initially positive) |
| Clinical concern for progression or relapse: |
| • Repeat 6- to 8-wk evaluations |
| End of therapy: |
| • Repeat 6- to 8-wk evaluations |
| Brain MRI for patient with CNS-risk lesions |
| Off-therapy management |
| 3 mo: |
| • PET/CT scan or focused imaging of original site of disease at 3 mo off-therapy |
| • Office visit every 3 mo through 1 y |
| • Focused imaging for clinical concerns |
| 1 y: |
| • Comprehensive clinical evaluation every 6 mo through 3 y off therapy, then annual |
AFP, alpha-fetoprotein; β-HCG, beta-subunit of human chorionic gonadotropin; GI, gastrointestinal; LP, lumbar puncture; U/S, ultrasound.
For patients enrolled on study (eg, LCH-IV), follow protocol-specific requirements.