Multisystemic histiocytosis with risk organ involvement

Diagnosis

Multisystemic histiocytosis with risk organ involvement

History

Seven month old girl with skull lesions, anemia and cervical adenopathies.

Findings

Multiple lymph nodes involving predominantly the bilateral cervical regions but also the axillary regions, liver hilum and inguinal regions with high uptake (SUVmax 9.0). Diffuse high activity (SUVmax 8.3) in an enlarged thymus with irregular contours. Homogeneous spleen hypermetabolism (SUVmax 2.2).

Multiple hypermetabolic foci in skull corresponding to lytic lesions. There are also lesions near sella turcica and in mandible. Diffuse high bone marrow activity (SUVmax 8.4) with bone marrow expansion.

DDx

Multisystemic histiocytosis

Lymphoma/leukemia

Discussion

Langerhans Cell Histiocytosis is a rare disorder affecting children with a mean age of four years old. This disease is characterized by proliferation and accumulation of a subtype of dendritic cells (Langerhans cells) in various organs. The clinical presentation is highly variable and histopathology does not discriminate clinical course.

The pathogenesis of LCH is poorly understood and there is still controversy on the pathogenetic mechanism. Demonstration of a clonal disease has been made, suggesting neoplastic disorder. Moreover, BRAF mutation was reported in approximately 50-60% of LCH. However, occurrence of spontaneous remission suggests clonal reactive process rather than malignant process.

Because of the variable clinical course ranging from spontaneous regression to rapid lethal deterioration, finding predictive factors was necessary. Early observations revealed correlation between disease extent together with localization at presentation and prognosis. It was also shown that disease confined to skeleton did not evolve to into severe life-threatening form. On the other hand, multisystemic disease involving liver, spleen or hematopoietic system has the worst prognosis. Findings lead to the current clinical classification which divides patients in two groups: single-system LCH (SS-LCH) and multisystem LCH (MS-LCH) (Table 1).

Table 1

Single system LCH (SS-LCH)

One organ/system involved (uni or multifocal)

-Bone (unifocal or multifocal)

-Skin

-Lymph node (excluding draining lymph node of another LCH lesion), single or multiple

-Lungs

-CNS

-Other (e.g. thyroid, thymus)

Multisystem LCH (MS-LCH)

Two or more organs/systems involved

With or without involvement of risk organs (e.g. liver, spleen, hematopoietic system)

Unifocal SS-LCH has the best prognosis while MS-LCH with risk organ involvement has the worse. Multifocal SS-LCH and MS-LCH without risk organ involvement are in between in term of prognosis.

The recent LCH III study from the Histiocyte Society stratified patients in three groups with indication of systemic therapy (Table 2).

Table 2

Multisystem LCH (MS-LCH) with risk organ involvement

Risk organ: liver, spleen, hematopoietic system

Multisystem LCH (MS-LCH) without risk organ

Multifocal bone disease and ''special sites''

''special sites'' refers to

1-vertebral lesions with significant intraspinal soft tissue component

2-''CNS risk lesions''' (lesions in facial bones and skull base with intracranial soft tissue extension)

FDG  PET/CT has been demonstrated to be a useful tool for identification of active lesion, stratification of disease, monitoring therapeutic response and detection of recurrence. Phillips et al. concluded that FDG PET was able to detect LCH activity and early response to therapy with greater accuracy than other imaging modalities. Kaste et al. also found usefulness of FDG PET/CT to evaluate disease activity and therapy response, providing information not obtained from bone scan or radiographs.

References

Kaste et al. : PET-CT in pediatric Langerhans cell histiocytosis. Pediatr Radiol. 2007 Jul;37(7):615-22

Phillips et al.: Comparison of FDG-PET scans to conventional radiography and bone scans in management of Langerhans cell histiocytosis. Pediatr Blood Cancer. 2009 Jan;52(1):97-101

LCH III. Langerhans cell histiocytosis. Evaluation and treatment guidelines. Histiocyte Society. April 2009.

Lee et al.: The usefulness of F-18 fluorodeoxyglucose positron emission tomography/computed tomography in patients with Langerhans cell histiocytosis. Ann Nucl Med. 2012 Nov;26(9):730-7

LCH IV. International collaborative treatment protocol for children and adolescent with Langerhans cell histiocytosis. November 2012.

Mueller et al. : The diagnostic value of 18F-FDG PET and MRI in paediatric histiocytosis. Eur J Nucl Med Mol Imaging. 2013 Feb;40(3):356-63

Agarwal et al. : 18F-Fluorodeoxyglucose PET/CT in Langerhans cell histiocytosis: spectrum of manifestations. Jpn J Radiol. 2016 Apr;34(4):267-76