TABLE 4.

Clinical Evaluations for Newly Diagnosed LCH

Initial Evaluation

• History, Physical examination • Laboratory Studies  ○ Complete blood count  ○ Serum chemistry  ○ Liver function test  ○ Sedimentation rate (ESR)  ○ Lactate dehydrogenase (LDH)  ○ Serum ferritin  ○ Immunoglobulin profile  ○ PT/INR, aPTT (with evidence of liver dysfunction) • Imaging  ○ Skeletal survey with 2 views of chest and 4 views of the skull (if PET/CT not obtained).

Confirmation of LCH and extent of disease evaluation

• PET/CT • Diagnostic Biopsy-excisional biopsy is preferred. Curettage of bone lesions is optimal and complete excision is not required. The presence of abnormal clusters of CD1a+/CD207+ histiocytes are diagnostic (Note: normal skin and lymph node biopsies may include scattered physiologic CD207+ Langerhans cells). CD163, fascin, and factor XII help identify mixed histiocytic lesions (such as JXG/LCH, ECD/LCH)

Additional studies(based on lab and/or clinical features)

• All patients < 2 years of age, any patients with cytopenias, liver and spleen involvement  ○ Bilateral bone marrow aspirate and biopsy • Any skull lesions (based on physical exam or lytic lesions on skull x-rays) -CT Skull/maxillofacial scans • CNS-risk lesions  ○ MRI brain with and without contrast for patients with CNS-Risk lesions  ○ For auditory canal or temporal bone involvement, also perform a hearing evaluation  ○ For clinical suspicion of DI, pituitary dysfunction, or thickened pituitary stalk on MRI brain- urine specific gravity, urine and serum osmolality/water deprivation test. (Note: If there is an isolated DI and thickened pituitary stalk without any other features suggestive of LCH, perform diagnostic LP for cytology and AFP/B-HCG to rule out germ cell tumor).  ○ Other endocrine evaluation as indicated  ○ Baseline neurocognitive evaluation for patients with DI or evidence of LCH-ND • Spinal cord or vertebral involvement-MRI spine with and without contrast • Pulmonary involvement-CT chest (chest x-rays and PET/CT may miss small pulmonary nodules, cysts, or thymic involvement). • Elevated transaminases, elevated direct bilirubin or decreased albumin-Abdominal US or MRI • History of malabsorption or hypoalbuminemia- Lower GI endoscopy