Association of Langerhans Cell Histiocytosis with Erdheim-Chester Disease: How Close Monocyte/Macrophage and Dendritic Cell Lineages Are?

Histiocytoses are a heterogeneous group of diseases that can be classified into either Langerhans cell histiocytosis (LCH) or non-Langerhans cell histiocytosis. The latter includes Erdheim-Chester disease (ECD). This study investigated the clinical association between LCH and ECD.

This retrospective study included 16 patients (10 males, 6 females, median age 41 years) treated at twelve different university hospitals between 1970 and 2010. Inclusion criteria were biopsy-proven LCH in association with two or more diagnostic signs of ECD.

LCH and ECD were diagnosed simultaneously in 4/16 cases, whereas LCH preceded ECD in 12/16 cases. The median time interval was 7.5 years (range 2–22) in these cases. Major organs involved in LCH were the bones (n=12), skin (n=8) and lungs (n=3). ECD mainly affected the large vessels (n=11), bones (n=11) and retroperitoneum (n=9). Non-biopsy proven central nervous system (n=6) and pituitary gland (n=6) involvement also occurred. No specific histologic features were identified in the 65 biopsies studied, including platelet-derived growth factor receptor β expression. Between one and four lines of treatment were required in nine patients diagnosed with LCH. Nine patients were treated with interferon α-2a after the diagnosis of ECD was made. A partial improvement occurred in all assessable patients concerning ECD (n=5) and/or LCH (n=2). These 16 patients were compared with a monocentric cohort of 48 ECD patients; the only difference between the groups was a lower frequency of bone involvement in ECD patients with concomitant LCH (9/13 vs 47/48, p<0.003).

This study suggests that a pathogenic link exists between LCH and ECD. Although the mechanisms responsible for both diseases remain unknown, the present association could argue for transitions between monocyte/macrophage and dendritic cell lineages. The patient characteristics of LCH in association with ECD were similar to those in patients with LCH alone, whereas bone involvement may have been less common in ECD when it was in association with LCH. Clinicians should be aware of this association and should consider the possibility of ECD in patients with LCH, especially in the case of treatment resistance.

No relevant conflicts of interest to declare.