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Definition of Organ Involvement

Author(s): Euro Histio Net Work Group for LCH Guidelines (see introduction page), Created: 2011/03/09, last update: 2014/02/09

Possibly involved organs: bone, skin, hematopoietic system, spleen, liver, lung, mucosea, eye, ear, pituitary, CNS, other; risk organs; special sites

Possibly Involved Organs

After the diagnosis of LCH has been made, involvement of other organs should be evaluated and defined according to the clinical, biological or radiological criteria shown in Table 5.

Risk Organs

Based on previous experience, disease involvement in the hematopoietic system, spleen, or liver is a marker of a less favorable prognosis, even of mortality if the patient doesn’t respond to standard therapy [Gadner et al 2001; Gadner et al 2008; Minkov et al 2002].
There is general agreement that lung involvement can also considerably worsen the prognosis and therefore is a risk for the patient [Tazi/Soler/Hance 2000; Vassallo et al 2000]. However, it is also generally agreed that lung involvement is no “risk organ involvement” in reference to the clinical trials for LCH. Additionally, lung involvement itself does not always justify systemic treatment (see Local Therapy / Observation). Thus lung involvement alone is no longer a criterion for inclusion in the “risk” disease category of the LCH clinical trials.
The risk organs are marked in Table 5.

“Special Sites”

Disease in some sites which are marked as “Special Sites” in Table 5 requires additional considerations.
In certain situations, such as odontoid peg and vertebral lesions with intraspinal soft tissue extension, lesions are located in functionally critical anatomical sites. These lesions may cause immediate risk to the patient because of the potential for disease progression and the hazards of attempting local therapy. Isolated disease in these “Special Sites” may justify systemic therapy, but does not require prolonged therapy once the immediate risk of neurologic compression is over. These lesions need to be distinguished from other bone lesions.
Other “Special Sites” are craniofacial bone lesions that are associated to diabetes insipidus. They are detailed in table 5, section “Bone”. Recent knowledge suggests that involvement or disease reactivation of these bones is statistically associated with diabetes insipidus which can either be present at diagnosis or develop later [Donadieu et al 2004b; Grois et al 2006; Haupt et al 2004].
CNS involvement although rare may have serious consequences. The natural history is not well understood and appropriate preventative and treatment options are not established. Therefore these patients need careful attention and follow-up and their management should be discussed with an expert. [Grois et al 2006].

Tab. 5. Criteria for Organ Involvement Definition in LCH

   
    

Bone

Special Site

Risk Organ

Agree- ment

  • General bone involvement: All radiological documented lesions, which are not mentioned below, confirmed by histological examination of the most accessible lesion.
  

+

  • Craniofacial bone involvement: Lesions in the orbital, temporal, mastoid, sphenoidal, zygomatic, or ethmoidal bones; the maxilla or paranasal sinuses; or cranial fossa; with intracranial soft tissue extension.

X

 

+

  • Vertebral involvement without soft tissue extension, e.g. vertebra plana.
  

+

  • Vertebral involvement with intraspinal soft tissue extension or lesions in the odontoid peg.

X

 

+

An abnormality on Tc Bone scan or an MRI hypersignal, not correlated with symptoms, or with an X-ray image is not considered bony disease!

  

+

Skin

Special Site

Risk Organ

Agree- ment

  • Any rash documented by histological examination   OR
  

+

  • Any lesion (erythematous and crusted macules, papules or nodules, with or without ulceration, or petechiae, or seborrhea-like picture) compatible with the diagnosis, if LCH is confirmed by biopsy of another organ
  

+

Hematopoietic - Mild:

Special Site

Risk Organ

Agree- ment

(both of the following categories should be present)

 

X

+

  • Hemoglobin between 10 g/dl and 7 g/dl (not due to other causes, e.g. iron deficiency)
  

+

  • Thrombocytopenia with platelets between 100.000 and 20.000/mm3.
  

+

Hematopoietic - Severe:

Special Site

Risk Organ

Agree- ment

(both of the following categories should be present)

 

X

+

  • Hemoglobin < 7 g/dl. Exclude iron deficiency.
  

+

  • Platelets < 20.000/mm3
  

+

Spleen

Special Site

Risk Organ

Agree- ment

> 3 cm below the costal margin at the mid clavicular line, confirmed by ultrasound

 

X

+

Liver

Special Site

Risk Organ

Agree- ment

  • Enlargement > 3 cm below the costal margin at the mid clavicular line, confirmed by ultrasound  OR
 

X

+

  • Dysfunction documented by: hyperbilirubinemia > 3 times normal, hypoalbuminemia (< 30 g/dl), γ GT increased > 2 times normal, ALT - AST> 3 times normal, ascites, edema   OR
 

X

+

  • Intra hepatic nodular mass
 

X

+

The patient can also show a combination of these symptoms.

   

Lung

Special Site

Risk Organ

Agree- ment

  • Typical imaging (nodules or cysts) on CT scan
 

(X)1

+

  • Any atypical mass needs to be explored by BAL or biopsy in order to have histopathological / cytological diagnosis
 

(X)1

+

Mucosae

Special Site

Risk Organ

Agree- ment

  • Oral involvement with lesions in the oral mucosa, gums
  

+

  • Genital or anal involvement
  

+

Eye

Special Site

Risk Organ

Agree- ment

  • Orbital involvement with proptosis or exophthalmos

X

 

+

Ear

Special Site

Risk Organ

Agree- ment

  • Ear involvement with external otitis, otitis media, or otorrhea

X

 

+

Pituitary

Special Site

Risk Organ

Agree- ment

  • Any pituitary hormone deficiency   OR
  

+

  • Tumor appearance in the hypothalamic pituitary axis
  

+

Central nervous system (CNS)

Special Site

Risk Organ

Agree- ment

  • Tumoral: All intracerebral expansive lesions predominantly affecting the brain or meninges.

X

 

+

  • Neuro degeneration on MRI: MRI imaging compatible with neuro degenerative disease2, i. e. abnormal signal intensity localized in the dentate nuclei or cerebellum or cerebral atrophy NOT explained by corticosteroids.

X

 

+

  • Clinical neuro degeneration: Presence of suggestive symptoms (either cerebellar syndrome or learning difficulty) with compatible MRI imaging.

X

 

+

  1. See Risk Organs
  2. The term radiological neurodegeneration has been coined to describe a certain pattern of MRI findings, but this terminology may be misleading as it does not necessarily correlate with histopathology.
  3. Abbreviations: ALT (SGPT), alanine transaminase (serum glutamic pyruvic transaminase); AST (SGOT), aspartate transaminase (serum glutamic oxaloacetic transaminase); BAL, bronchoalveolar lavage; CT, computed tomography; MRI, magnetic resonance imaging.
References

[Gadner et al 2001] Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S, Histiocyte Society: A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. The Journal of pediatrics 2001, 138: 728 [PMID: 11343051]

[Gadner et al 2008] Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S, Histiocyte Society: Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood 2008 Mar 1; 111: 2556 [PMID: 18089850]

[Minkov et al 2002] Minkov M, Grois N, Heitger A, Pötschger U, Westermeier T, Gadner H, DAL-HX Study Group: Response to initial treatment of multisystem Langerhans cell histiocytosis: an important prognostic indicator. Medical and pediatric oncology 2002, 39: 581 [PMID: 12376981]

[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]

[Donadieu et al 2004b] Donadieu J, Rolon MA, Thomas C, Brugieres L, Plantaz D, Emile JF, Frappaz D, David M, Brauner R, Genereau T, Debray D, Cabrol S, Barthez MA, Hoang-Xuan K, Polak M, French LCH Study Group: Endocrine involvement in pediatric-onset Langerhans' cell histiocytosis: a population-based study. The Journal of pediatrics 2004, 144: 344 [PMID: 15001940]

[Grois et al 2006] Grois N, Pötschger U, Prosch H, Minkov M, Arico M, Braier J, Henter JI, Janka-Schaub G, Ladisch S, Ritter J, Steiner M, Unger E, Gadner H, DALHX- and LCH I and II Study Committee: Risk factors for diabetes insipidus in langerhans cell histiocytosis. Pediatric blood & cancer 2006, 46: 228 [PMID: 16047354]

[Haupt et al 2004] Haupt R, Nanduri V, Calevo MG, Bernstrand C, Braier JL, Broadbent V, Rey G, McClain KL, Janka-Schaub G, Egeler RM: Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group. Pediatric blood & cancer 2004, 42: 438 [PMID: 15049016]