Evaluation of Clinicopathologic Characteristics and the BRAF V600E Mutation in Erdheim-Chester Disease Among Chinese Adults
Authors: Cao Xin-xin , Sun Jian , Li Jian , Zhong Ding-rong , Niu Na , Duan Ming-hui , Liang Zhi-yong , Zhou Dao-bin 
Published: October 2019

Abstract
Objectives Erdheim-Chester disease (ECD) is a rare form of histiocytosis with a broad, non-specific clinical spectrum. Here, we retrospectively evaluated the clinical and pathologic characteristics, presence of the BRAF V600E mutation, treatment options and outcomes of Chinese patients diagnosed with ECD at our center.
Methods Patients diagnosed with ECD between January 2010 and April 2015 at Peking Union Medical College Hospital were included for study. We evaluated baseline characteristics, reviewed histological material, and tested for the presence of the BRAF V600E mutation using immunohistochemistry and polymerase chain reaction (PCR).
Results Sixteen patients were diagnosed with ECD. Median age at diagnosis was 47 years (range, 22-61 years). Median disease duration (from the first symptom to diagnosis) was 22.5 months (range, 3-100 months). The main sites of involvement included bone (93.8%), cardiovascular region (43.8%), skin (31.3%), central nervous system (25.0%), and ¡°hairy kidney¡± (25%). Thirteen patients displayed characteristic histological features, including foamy histiocyte infiltration of polymorphic granuloma and fibrosis or xanthogranulomatosis, with CD68-positive and CD1-¦Á- negative immunostaining. Three patients (designated 3, 5 and 10) displayed CD68-positive and CD1¦Á- negative histiocyte infiltration, but not the above histological characteristics, and were thus initially misdiagnosed as Rosai-Dorfman disease. All three cases were BRAFV600E mutation-positive, leading to revision of diagnosis as ECD. Diagnosis of ECD in each case was additionally supported by typical radiographic findings. The BRAF V600E mutation was detected in 68.8% patients using PCR and 50.0% patients with immunohistochemistry. Ten patients (62.5%) received IFN-¦Á as first-line treatment, 3 patients showed improvement, 3 remained stable, 3 were too early for evaluation and 1 died. Three patients (5, 10 and 11) underwent transsphenoidal pituitary lesion surgery but were not subjected to systemic treatment, owing to the absence of symptoms and disease activity post-surgery and remained stable after a median of 16 months (range, 6-30 months) from diagnosis. Thirteen patients (81.3%) were still alive at median follow-up of 14.5 months.
Conclusion ECD remains a largely overlooked disease, and increased recognition by clinicians and pathologists is necessary for effective diagnosis and treatment. The presence of the BRAF V600E mutation may facilitate discrimination of ECD from other non-Langerhans cell histiocytoses.
Table 1. Characteristics and treatment of 16 patients with ECD Patient Sex/ age, years Disease duration, mo Main sites of involvement BRAF IH BRAF V600E Therapy Vital Status OS£¬mo 1 M/33 5 B N/A - IFN-6 MIU 3/wk Alive 15 2 M/22 43 S, B - - IFN-3 MIU 3/wk Alive 11 3 M/25 18 B, LN, CNS - + Pred Dead 13 4 F/28 3 S, B + + None Alive 16 5 M/60 27 B, PIT + + Surgery Alive 15 6 F/61 5 B, H, LV, R£¬CNS, MS, S N/A + IFN-6 MIU 3/wk Dead 25 7 F/23 67 S, B, H, LV - - IFN-3 MIU 3/wk Alive 19 8 M/60 43 B, P, LV, R N/A + IFN-6 MIU 3/wk Alive 14 9 M/46 84 CNS, B + + IFN-6 MIU 3/wk Alive 22 10 F/51 7 PIT + + Surgery Alive 6 11 F/36 72 PIT, B + + Surgery Alive 30 12 M/55 100 B, S, CNS, PIT - + IFN-6 MIU 3/wk Alive 3 13 F/50 11 B, H N/A + IFN-6 MIU 3/wk Alive 5 14 F/46 8 B, LV, P + + IFN-6 MIU 3/wk Alive 1 15 M/52 30 B, LV, R, P£¬E - - IFN-6 MIU 3/wk Alive 1 16 M/47 4 B, LV, R, LN - - None Dead 36
Age is at diagnosis£»disease duration is from the first symptom to diagnosis
IH, immunohisochemistry; B, long bones; LN, lymph nodes; LV, large vessels; H, heart; S, skin; CNS, central nervous system; MS, maxillary sinus; PIT, pituitary gland; R, retroperitoneal; P, pericardial effusion; E, Exophthalmos; MIU, million international units; N/A, not available

Disclosures
No relevant conflicts of interest to declare.