The complete evaluation of any patient, whether presenting with single-system or multisystem disease, should include the following:
History and physical exam: A complete history and physical exam with special attention to the skin, lymph nodes, ears, oral pharynx, gingiva, tongue, teeth, bones, lungs, thyroid, liver and spleen size, bone abnormalities, growth velocity, and history of excessive thirst and urination.
It is possible that the main title of the report Multiple Endocrine Neoplasia Type 2 is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
BRAF V600E: Although BRAF mutation assessment is not a required part of the workup for Langerhans cell histiocytosis (LCH), the BRAF mutation can be detected by either immunohistochemistry or molecular diagnostic methods.
Urine tests: Urine tests include urinalysis and a water-deprivation test if diabetes insipidus is suspected. Water deprivation tests in very young children, especially infants, is performed under medical monitoring.
Bone marrow aspirate and biopsy: The bone marrow aspirate and biopsy is indicated for patients with multisystem disease who have unexplained anemia or thrombocytopenia. The biopsy should be stained with anti-CD1a and/or anti-CD207 (langerin) and anti-CD163 immunostains to facilitate the detection of LCH cells.
Radiologic and imaging tests: Radiologic tests for the first level of screening include skeletal survey, skull series, bone scans, and chest X-ray. Newer diagnostic imaging modalities, such as somatostatin analog scintigraphy or fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET) scans, augment, but do not replace the standard tests.[2,3,4,5,6]
Computed tomography (CT) scan: CT scan of the head may be indicated if orbital, mastoid, or other maxillofacial involvement is suspected. Imaging tests may include magnetic resonance imaging (MRI) scan with gadolinium contrast of the brain for patients with diabetes insipidus or suspected brain or vertebral involvement.
CT scan of the lungs may be indicated for patients with abnormal chest X-rays or pulmonary symptoms. High-resolution CT scans may show evidence of pulmonary LCH when the chest X-ray is normal, thus in infants and toddlers with normal chest X-rays, a CT scan may be considered.
LCH causes fatty changes in the liver or hypodense areas along the portal tract, which can be identified by CT scans.
18F-FDG PET scan: 18F-FDG PET scan abnormalities have been reported in the brains of seven patients with LCH, with neurologic and radiographic signs of neurodegenerative disease. There was good correlation with MRI findings in the cerebellar white matter, but less so in the caudate nuclei and frontal cortex. It was suggested that PET scans of patients at high risk for developing neurodegenerative LCH could show abnormalities earlier than MRI. PET scans often demonstrate lesions not found by other modalities and show a decrease of activity after 6 weeks of therapy, thus providing a better assessment of response to therapy than bone scans or plain X-rays.
MRI: MRI findings of patients with diabetes insipidus include thickening and nodularity of the pituitary stalk with loss of the posterior pituitary bright spot reflecting absence of anti-diuretic hormone. Later in the course, the stalk generally atrophies but this should not be used as evidence of response to therapy.
All patients with vertebral body involvement need careful assessment of associated soft tissue, which may impinge on the spinal cord.
MRI findings of central nervous system LCH include T2 fluid attenuated inversion recovery (FLAIR) enhancement in the pons, basal ganglia, white matter of the cerebellum, and mass lesions or meningeal enhancement. In a report of 163 patients, meningeal lesions were found in 29% and choroid plexus involvement in 6%. Paranasal sinus or mastoid lesions were found in 55% of patients versus 20% of controls, and accentuated Virchow-Robin spaces in 70% of patients versus 27% of controls.
Biopsy: Lytic bone lesions, skin, and lymph nodes are the most frequent sites biopsied for diagnosis of LCH. A liver biopsy is indicated when a child with LCH presents with hypoalbuminemia not caused by gastrointestinal LCH or other etiology. These patients usually have elevated levels of bilirubin or liver enzymes. An open lung biopsy may be necessary for obtaining tissue for diagnosis of pulmonary LCH when bronchoalveolar lavage is nondiagnostic.
A pathologic diagnosis is always required to make a definitive diagnosis. However, this may sometimes be difficult or contraindicated, such as in isolated pituitary stalk disease when the risk outweighs the benefit of a firm diagnosis. LCH cells are large cells with abundant pink cytoplasm and a bean-shaped nucleus on hematoxylin and eosin. LCH cells should stain positively with antibodies to CD1a and/or anti-langerin (CD207) to confirm the diagnosis of LCH.
Haupt R, Minkov M, Astigarraga I, et al.: Langerhans cell histiocytosis (LCH): guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years. Pediatr Blood Cancer 60 (2): 175-84, 2013.
Calming U, Jacobsson H, Henter JI: Detection of Langerhans cell histiocytosis lesions with somatostatin analogue scintigraphy--a preliminary report. Med Pediatr Oncol 35 (5): 462-7, 2000.
Calming U, Bemstrand C, Mosskin M, et al.: Brain 18-FDG PET scan in central nervous system langerhans cell histiocytosis. J Pediatr 141 (3): 435-40, 2002.
Binkovitz LA, Olshefski RS, Adler BH: Coincidence FDG-PET in the evaluation of Langerhans' cell histiocytosis: preliminary findings. Pediatr Radiol 33 (9): 598-602, 2003.
Phillips M, Allen C, Gerson P, et al.: Comparison of FDG-PET scans to conventional radiography and bone scans in management of Langerhans cell histiocytosis. Pediatr Blood Cancer 52 (1): 97-101, 2009.
Ribeiro MJ, Idbaih A, Thomas C, et al.: 18F-FDG PET in neurodegenerative Langerhans cell histiocytosis : results and potential interest for an early diagnosis of the disease. J Neurol 255 (4): 575-80, 2008.
Grois N, Prayer D, Prosch H, et al.: Course and clinical impact of magnetic resonance imaging findings in diabetes insipidus associated with Langerhans cell histiocytosis. Pediatr Blood Cancer 43 (1): 59-65, 2004.
Ha SY, Helms P, Fletcher M, et al.: Lung involvement in Langerhans' cell histiocytosis: prevalence, clinical features, and outcome. Pediatrics 89 (3): 466-9, 1992.
Prasad SR, Wang H, Rosas H, et al.: Fat-containing lesions of the liver: radiologic-pathologic correlation. Radiographics 25 (2): 321-31, 2005 Mar-Apr.
Prayer D, Grois N, Prosch H, et al.: MR imaging presentation of intracranial disease associated with Langerhans cell histiocytosis. AJNR Am J Neuroradiol 25 (5): 880-91, 2004.
Chikwava K, Jaffe R: Langerin (CD207) staining in normal pediatric tissues, reactive lymph nodes, and childhood histiocytic disorders. Pediatr Dev Pathol 7 (6): 607-14, 2004 Nov-Dec.
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