Table 4 Specific clinical scenarios: recommended additional testing

History of polyuria or polydipsia:

D2

• Urine and Plasma osmolality

• Water deprivation test

• MRI of the head

Suspected Other Endocrine Abnormality:

D2

• Endocrine assessment (including dynamic tests of the anterior pituitary, MRI of the head)

Bi- or Pancytopenia, Or Persistent Unexplained Single Cytopenia:

D2

• Any other cause of cytopenia has to be ruled out according to standard medical practice

• Bone marrow aspirate and trephine biopsy to exclude causes other than LCH

• In case of morphological signs of hemophagocytosis additional tests like serum-ferritin should be performed (criteria of HLH)

Liver Or Spleen Abnormalities:

D2

• In case of any unclear sonographically pathology CT, PET-CT, MRI or Scans should be added (the choice is depending on the sonomorphology – discuss with your radiologist)

• Visuable lesions of the liver should be biopsied if possible

• Other causes of splenomegaly has to be ruled out before it may be assigned to LCH

• ERCP (Endoscopic Retrograde Cholangiopancreatography) or MRCP (Magnetic Resonance Cholangiopancreatography) should be performed in case of elevated serum cholestasis markers or sonomorphologically dilatated bile ducts. Primary biliary cirrhosis and primary sclerosing cholangitis have to be ruled out.

Unexplained Chronic Diarrhea, Weight loss, Evidence Of Malabsorption Or Hematochezia

D2

• GI-Exploration (Endoscopy with biopsies, capsule endoscopy)

Enlarged Lymph Nodes (LN):

D2

• If found by screening ultrasound or physical examination the best suitable LN should be extirpated. A LN needle biopsy should be avoided.

• CT scans or a PET-CT should be performed additionally

Lung Involvement - In case of abnormal Chest X Ray or symptoms/signs suggestive for lung involvement or suspicion of a pulmonary infection:

D2

• Lung high resolution computed tomography (HR-CT)

• Lung function tests (Spirometry, Diffusing capacity, Oxygen desaturation during exercise (6MWT), blood gases)

• Bronchoalveolar lavage (BAL): > 5% CD1a + cells in BAL fluid may be diagnostic of LCH

• Lung biopsy (if BAL is not diagnostic), ideally Video-assisted thoracoscopic surgery (VATS)

Osseous Disease:

D2

• CT +/- MRI should be performed in case of craniofacial or vertebral lesions or signs of additional soft tissue involvement

• Biopsies should be taken from the most suitable region in case of multifocal bone disease

Skin, Oral And Genital Mucosa lesions:

D2

• Biopsies should be taken

Aural Discharge Or Suspected Hearing Impairment / Mastoid Involvement:

D2

• Formal hearing assessment

• MRI of head