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Specific Clinical Scenarios and Recommended Additional Testing

Author(s): Euro Histio Net Work Group for LCH Guidelines (see introduction page), Created: 2011/03/09, last update: 2013/08/28

History of polyuria or polydipsia; bicytopenia, pancytopenia, or persistent unexplained single cytopenia; liver dysfunction; lung involvement; suspected craniofacial bone lesions including maxilla and mandible; vertebral lesions (even if only suspected); Visual or neurological abnormalities; Suspected other endocrine abnormality; aural discharge or suspected hearing impairment / mastoid involvement; unexplained chronic diarrhea, failure to thrive, or evidence of malabsorption

After having performed the baseline clinical evaluation, certain scenarios might require additional testing. Recommended laboratory investigations, imaging or specialized clinical assessments are shown in Table 4.

Tab. 4. Specific Clinical Scenarios: Recommended Additional Testing

 
  

History of Polyuria or Polydipsia

Agreement

  • Early morning urine specific gravity and osmolality

+

  • Blood electrolytes

+

  • Water deprivation test if possible

+

  • MRI of the head (details see here)

+

Bicytopenia, Pancytopenia, or Persistent Unexplained Single Cytopenia

Agreement

  • Any other cause of anemia or thrombocytopenia has to be ruled out according to standard medical practice. If no other causes are found, the cytopenia is considered as LCH-related.

+

  • Bone marrow aspirate and trephine biopsy to exclude causes other than LCH.1

+

  • Hemophagocytic biological feature (coagulation, including factor I / fibrinogen, triglycerides, and ferritin) to evaluate macrophage activation and hemophagocytic syndrome.2

+

Liver Dysfunction

Agreement

  • Consult a hepatologist and consider liver MRI that is preferable to retrograde cholangiography in case of frank liver dysfunction (liver enzymes > 5 fold normal / bilirubinemia > 5 fold normal range)

+

  • Liver biopsy is only recommended if there is clinically significant liver involvement and the result will alter treatment (i.e. to differentiate between active LCH and sclerosing cholangitis)

+

Lung Involvement

Agreement

A testing is only needed in case of abnormal Chest X Ray or symptoms/signs suggestive for lung involvement, or lung findings not characteristic of LCH or suspicion of an atypical infection:

 
  • Lung high resolution computed tomography (HR-CT) or preferably low dose multi-detector HR-CT if available. Note that cysts and nodules are the only images typical of LCH; all other lesions are not diagnostic. In children already diagnosed with MS-LCH low dose CT is sufficient in order to assess extent of pulmonary involvement, and reduce the radiation burden.

+

  • Lung function test (if age appropriate)

+

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

O3

  • Lung biopsy (if BAL is not diagnostic)

+

Suspected Craniofacial Bone Lesions Including Maxilla and Mandible

Agreement

  • MRI of the head (details see here) including the brain, hypothalamus-pituitary axis and all craniofacial bones. If MRI not available, CT of the involved bone and the skull base is recommended.

+

Vertebral Lesions (Even if only Suspected)

Agreement

  • MRI of spine to exclude spinal cord compression and to assess for soft tissue masses

+

Visual or Neurological Abnormalities

Agreement

  • MRI of the head (details see here)

+

  • Neurological assessment

+

  • Neuropsychometric assessment

+

Suspected Other Endocrine Abnormality

Agreement

(i.e. short stature, growth failure, hypothalamic syndromes, precocious or delayed puberty)

 
  • Endocrine assessment (including dynamic tests of the anterior pituitary and thyroid)

+

  • MRI of the head (details see here)

+

Aural Discharge or Suspected Hearing Impairment / Mastoid Involvement

Agreement

  • Formal hearing assessment

+

  • MRI of the head (details see here) or HR-CT of temporal bone

+

Unexplained Chronic Diarrhea, Failure to Thrive, or Evidence of Malabsorption

Agreement

  • Endoscopy

+

  • Biopsy

+

  1. The clinical significance of CD1a positivity in the bone marrow remains to be proven. An isolated finding of histiocytic infiltration on the bone marrow with no cytopenia is not a criterion for diagnosis or reactivation [McClain et al 1983; Minkov et al 2007].
  2. Hemophagocytic syndrome with macrophage activation is a common finding in patients with hematological dysfunction [Favara/Jaffe/Egeler 2002; Galluzzo et al 2010].
  3. See discussion in references [Tazi/Soler/Hance 2000; Vassallo et al 2000].
  4. Abbreviations: (HR-)CT, (high resolution) computed tomography; MRI, magnetic resonance imaging.
References

[McClain et al 1983] McClain K, Ramsay NK, Robison L, Sundberg RD, Nesbit M Jr: Bone marrow involvement in histiocytosis X. Medical and pediatric oncology 1983, 11: 167 [PMID: 6602270]

[Minkov et al 2007] Minkov M, Pötschger U, Grois N, Gadner H, Dworzak MN: Bone marrow assessment in Langerhans cell histiocytosis. Pediatric blood & cancer 2007 Oct 15; 49: 694 [PMID: 17455318]

[Favara/Jaffe/Egeler 2002] Favara BE, Jaffe R, Egeler RM: Macrophage activation and hemophagocytic syndrome in langerhans cell histiocytosis: report of 30 cases. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2002 Mar-Apr; 5: 130 [PMID: 11910507]

[Galluzzo et al 2010] Galluzzo ML, Braier J, Rosenzweig SD, Garcia de Dávila MT, Rosso D: Bone marrow findings at diagnosis in patients with multisystem langerhans cell histiocytosis. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2010 Mar-Apr; 13: 101 [PMID: 19863448]

[Tazi/Soler/Hance 2000] Tazi A, Soler P, Hance AJ: Adult pulmonary Langerhans' cell histiocytosis. Thorax 2000, 55: 405 [PMID: 10770823]

[Vassallo et al 2000] Vassallo R, Ryu JH, Colby TV, Hartman T, Limper AH: Pulmonary Langerhans'-cell histiocytosis. The New England journal of medicine 2000 Jun 29; 342: 1969 [PMID: 10877650]