Guideline sources The following summarized guidelines for the evaluation and management of langerhans cell histiocytosis (LCH) are prepared by our editorial team based on guidelines from the Histiocyte Society (HS 2022). 1 Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s Guidelines 1. Screening and diagnosis Diagnosis: suspect LCH in the presence of characteristic clinical/radiologic features, even when histopathologic review is equivocal. B https://web.pathway.md/diseases/recPaw2vHmvXxIqk4 1/5 6/29/23, 5:52 AM Langerhans cell histiocytosis Pathway 2. Diagnostic investigations Laboratory testing: Obtain laboratory tests to assess for liver insufficiency, cytopenias, markers of inflammation (CRP) at diagnosis. A Obtain laboratory tests to rule out diabetes insipidus and anterior pituitary function in patients with polyuria/polydipsia or involvement of pituitary/hypothalamus axis on cranial imaging. A Diagnostic imaging: obtain baseline full-body (vertex-to-toes) FDG-positron emission tomography/CT, including the distal extremities, to aid in diagnosis and define extent of disease. B Show 3 more Pulmonary function testing: obtain pulmonary function testing (spirometry with lung volumes, diffusion capacity and plethysmography) at the time of diagnosis in all patients with pulmonary LCH. A Echocardiography: obtain resting TTE to screen for pulmonary hypertension in all patients with pulmonary LCH being symptomatic or having abnormal diffusing capacity for CO. B Right heart catheterization: consider performing right-sided heart catheterization and vasoreactivity testing in selected patients with echocardiographically demonstrated pulmonary hypertension to assess its severity and aid with further management. C Cholangiopancreatography: perform MRCP or ERCP in patients with elevated serum cholestasis markers or sono-morphologically dilated bile ducts, to evaluate for sclerosing cholangitis related to LCH. A 3. Diagnostic procedures Biopsy: perform a biopsy of lesional tissue even in circumstances of highly suggestive clinical and imaging features to confirm LCH diagnosis and to establish BRAF or other MAPK-ERK pathway mutational status. A Show 5 more Mutational analysis: consider obtaining molecular analysis of tissue for BRAF and MAPK-ERK pathway mutations for the diagnosis of questionable lesions. C Show 4 more 4. Medical management Management of unifocal LCH: offer observation or local therapies, such as surgical excision, intralesional corticosteroids, or radiation as first-line treatments in patients with unifocal LCH (except diabetes insipidus). B Show 2 more https://web.pathway.md/diseases/recPaw2vHmvXxIqk4 2/5 6/29/23, 5:52 AM Langerhans cell histiocytosis Pathway Management of pulmonary LCH: advise cessation of smoking, vaping, inhalation of marijuana or other substances as first-line therapy in patients with single-system pulmonary LCH. A Show 2 more Management of multifocal LCH: offer radiotherapy (< 3 lesions safely amenable to radiation), bisphosphonates or systemic chemotherapy as treatment options in patients with multifocal osseous LCH. B Show 4 more 5. Follow-up and surveillance Assessment of treatment response: Decide on the type and frequency of response assessments and follow-up examinations depending on the degree of involvement with LCH. A Obtain repeated FDG-FDG positron emission tomography-based imaging study for assessment of disease response after 2-3 months of initiation of therapy in patients with initially FDG-FDG positron emission tomography-avid LCH. Decide on subsequent imaging frequency individually based on specific clinical scenario. A Clinical findings Symptoms Past medical history Back pain Diabetes inspidus Bone pain Spontaneous pneumothorax Chest pain Superior vena cava syndrome Cough Vital signs Dysarthria Dysphagia Tachypnea Fatigue O2 saturation Fever Ocular exam Gait disturbance Headache Exophthalmos Hemoptysis Hoarseness Dental exam Loss of appetite Gingivitis Malaise Nausea Abdominal exam Neck pain Night sweats Abdominal distension Personality or behavioral changes Ascites Hepatomegaly Polydipsia Splenomegaly https://web.pathway.md/diseases/recPaw2vHmvXxIqk4 3/5 6/29/23, 5:52 AM Langerhans cell histiocytosis Pathway Polyuria Lymphatic exam Seizure Lymphadenopathy Shortness of breath Skin rash Lab findings Tremor Vomiting serum osmolality Weight loss urine osmolality Social history Imaging findings Cigarette smoking Upper-lobe predominant ILD Neurological exam Ataxia Focal neurologic deficits Torticollis ICP Head and neck exam Oral mass Oral ulcers Otorrhea Proptosis Respiratory exam Rales Musculoskeletal exam Limping spinal ROM Integument exam Jaundice Pallor Petechiae Skin nodules Vesicular rash Hematological findings blood neutrophil count Genetic testing B f V600E t ti https://web.pathway.md/diseases/recPaw2vHmvXxIqk4 4/5 6/29/23, 5:52 AM Langerhans cell histiocytosis Pathway References 1. Gaurav Goyal, Abdellatif Tazi, Ronald S Go et al. Expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults. Blood. 2022 Mar 10;blood.2021014343. Open https://web.pathway.md/diseases/recPaw2vHmvXxIqk4 5/5