Erdheim-Chester disease

Definition: Erdheim-Chester disease is a very rare xanthogranulomatous, non-Langerhans cell systemic histiocytosis with an unknown etiology and pathogenesis. It involves the marrow space of the long bones.

Extraosseous sites most commonly affected include the eyes, lungs, pituitary glands, and kidneys.

Images

 50 year old man with bone pain and bilateral symmetrical sclerotic lesions on plain films of his femurs

• https://twitter.com/judith_ferry/status/1110879322468962304

Erdheim-Chester disease (ECD) is a rare, potentially fatal multiorgan myeloid neoplasm occurring mainly in adults.

The diagnosis is established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a−, and frequently S100−.

Mutation BRAF-V600E is detected in 51% of cases. In a study, one patient had an ARAF-D228V mutation, and another patient had an activating ALK fusion.

Recent reports of BRAF-V600E mutation and MAPK pathway gene mutations in ECD cells have led to treatment with BRAF inhibitors and MEK inhibitors.

Erdheim-Chester disease is a rare, nonfamilial, systemic histiocytic disease of obscure etiology.

Patients typically present with XG lesions composed of non-Langerhans cell histiocytes in multiple organs, as well as osteosclerosis of the long bones.

Morphologically, xanthogranulomas show diffuse infiltration with large, foamy histiocytes in a background of fibrosis, lymphoid aggregates, and rare Touton-like giant cells.

The histiocytes are strongly CD68 and factor XIIIa positive, weakly S100 positive, and CD1a negative.

Lipid droplets are identified in the cytoplasm on electron microscopy.

The multifocal disease process lacking a neutrophilic infiltrate distinguishes this condition from xanthogranuloma.

Localization

 bones: symmetric osteosclerosis of the long bones

• bone marrow necrosis (11469352)

 extraskeletal lesions (more than 50%)

• retroperitoneal space (8037299), perirenal space (ureteral obstruction)
• mediastinum, periaortal space (10852289)
• lungs (11202482, 10912934) causing interstitial lung disease (17304381)
• kidneys
• brain (12687308, 17063320)
• pitutary (insipide diabetes, hypopituitarism)(11838810)
• cavernous sinus
• epidural space (17063320)
• retro-orbital space: orbital xanthogranuloma (14506422)
• heart (11755517), pericardium (pericardial effusion) (12186113)
• liver (12873197)
• dermal nodules, eyelid xanthelasma, pretibial dermopathy
• lips and buccal mucosa
• associated haematological abnormalities: normochromic normocytic anaemia, thrombocytopenia, eosinophilia
• breast (10752893, 16297093, 20216377)
• sinonasal region (10997572)
• muscle (10855472)

Associations

 A amylosis (11014995)

Microscopical synopsis

 fibrosing xanthogranulomatous infiltration of multiple organs
 diffuse infiltration with large, foamy histiocytes
 rare Touton-like giant cells
 lymphocytic aggregates
 fibrosis and fibrobastic cells
 extensive coagulative necrosis (11469352)

Immunochemistry

 CD68+
 CD1a-
 protein S-100- or S-100+ (10912934)
 factor XIIIa+ (10912934)

Ultrastructure

 lack of Birbeck granules

Cytogenetics

 balanced chromosomal translocation t(12;15;20)(q11;q24;p13.3) (17255779)

Differential diagnosis

 histiocytic infiltration

• fat necrosis
• histocytoses
  • systemic histiocytoses
    • non-Langerhans cell histiocytoses

 histiocytoid invasive carcinomas

Open references

 The clinical spectrum of Erdheim-Chester disease: an observational cohort study. http://www.bloodadvances.org/content/1/6/357

References

 Erdheim-chester disease presenting as bilateral clinically malignant breast masses. Provenzano E, Barter SJ, Wright PA, Forouhi P, Allibone R, Ellis IO. Am J Surg Pathol. 2010 Apr;34(4):584-8. PMID: 20216377

 Vencio EF, Jenkins RB, Schiller JL, Huynh TV, Wenger DD, Inwards CY, Oliveira AM. Clonal cytogenetic abnormalities in Erdheim-Chester disease. Am J Surg Pathol. 2007 Feb;31(2):319-21. PMID: 17255779

 Chetritt J, Paradis V, Dargere D, Adle-Biassette H, Maurage CA, Mussini JM, Vital A, Wechsler J, Bedossa P. Chester-Erdheim disease: a neoplastic disorder. Hum Pathol. 1999 Sep;30(9):1093-6. PMID: 10492045

 Egan AJ, Boardman LA, Tazelaar HD, Swensen SJ, Jett JR, Yousem SA, Myers JL. Erdheim-Chester disease: clinical, radiologic, and histopathologic findings in five patients with interstitial lung disease. Am J Surg Pathol. 1999 Jan;23(1):17-26. Review. PMID: 9888700

 Favara BE, Feller AC, Pauli M, Jaffe ES, Weiss LM, Arico M, Bucsky P, Egeler RM, Elinder G, Gadner H, Gresik M, Henter JI, Imashuku S, Janka-Schaub G, Jaffe R, Ladisch S, Nezelof C, Pritchard J. Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol. 1997 Sep;29(3):157-66. PMID: 9212839