The histopathology of Erdheim-Chester disease: A comprehensive review of a molecularly characterized cohort Journal Article


Authors: Ozkaya, N.; Rosenblum, M. K.; Durham, B. H.; Pichardo, J. D.; Abdel-Wahab, O.; Hameed, M. R.; Busam, K. J.; Travis, W. D.; Diamond, E. L.; Dogan, A.
Article Title: The histopathology of Erdheim-Chester disease: A comprehensive review of a molecularly characterized cohort
Abstract: Erdheim-Chester disease is a rare, non-Langerhans cell histiocytosis histologically characterized by multisystemic proliferation of mature histiocytes in a background of inflammatory stroma. The disease can involve virtually any organ system; most commonly the bones, skin, retroperitoneum, heart, orbit, lung, and brain are affected. Although a histiocytic proliferation is the histological hallmark of the disease, a wide range of morphological appearances have been described as part of case studies or small series. A comprehensive review of histopathological features in clinically and molecularly defined Erdheim-Chester disease has yet to be characterized. To address this issue and help guide clinical practice, we comprehensively analyzed the pathological spectrum of Erdheim-Chester disease in a clinically and molecularly defined cohort. We reviewed 73 biopsies from 42 patients showing involvement by histiocytosis from a variety of organ systems, including bone (16), retroperitoneum (11), skin (19), orbit (6), brain (5), lung (6), cardiac structures (2), epidural soft tissue (3), oral cavity (2), subcutaneous soft tissue (2), and testis (2). In eight patients, one or more bone marrow biopsies were performed due to clinical indication and an accompanying myeloid neoplasm was detected in six of them. Thirty-eight cases were investigated for genetic abnormalities. Somatic mutations involving BRAF (25/38), MAP2K1 (6/38), ARAF (2/38), MAP2K2 (1/38), KRAS (1/38), and NRAS (1/38) genes were detected. One of the cases with a MAP2K1 mutation also harbored a PIK3CA mutation. We have observed marked heterogeneity in histology and immunophenotype, identified site-specific features, overlap with other histiocytic and myeloid disorders and potential diagnostic pitfalls. We hope that broadening the spectrum of recognized pathologic manifestations of Erdheim-Chester disease will help practicing clinicians and pathologists to diagnose Erdheim-Chester disease early in the disease course and manage these patients effectively. © 2018 USCAP, Inc All rights reserved.
Journal Title: Modern Pathology
Volume: 31
Issue: 4
ISSN: 0893-3952
Publisher: Nature Publishing Group  
Date Published: 2018-04-01
Start Page: 581
End Page: 597
Language: English
DOI: 10.1038/modpathol.2017.160
PROVIDER: scopus
PUBMED: 29192649
DOI/URL:
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
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MSK Authors
  1. Meera Hameed
    139 Hameed
  2. Marc Rosenblum
    255 Rosenblum
  3. William D Travis
    552 Travis
  4. Klaus J Busam
    540 Busam
  5. Eli Louis Diamond
    90 Diamond
  6. Ahmet Dogan
    174 Dogan
  7. Benjamin Heath Durham
    63 Durham
  8. Neval   Ozkaya
    19 Ozkaya