Systemic Histiocytosis (Langerhans Cell Histiocytosis, Erdheim–Chester Disease, Destombes–Rosai–Dorfman Disease): from Oncogenic Mutations to Inflammatory Disorders

Papo, Matthias; Cohen‐Aubart, Fleur; Tréfond, Ludovic; Bauvois, Adeline; Amoura, Zahir; Émile, Jean-François; Haroche, Julien

doi:10.1007/s11912-019-0810-6

Cited by 59 publications

(60 citation statements)

References 97 publications

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“…1 While rare BRAF, KRAS, and MAP2K aberrations have been infrequently reported in RDD, clonality studies including analysis of polymorphisms at the androgen receptor locus on the X chromosome and genomic hybridization studies have failed to definitively confirm a neoplastic origin in most cases, resulting in the prevailing theory that RDD may be a reactive and nonneoplastic process. 1,[30][31][32][33] It is our hope that this article will remind practitioners of breast pathology that extranodal RDD of the breast exists, that it can present as a concerning breast mass, and that careful light microscopic review combined with ancillary testing may allow for specific diagnosis and appropriate management.…”

Section: Discussionmentioning

confidence: 99%

Mammary Extranodal Rosai-Dorfman Disease With and Without Associated Axillary Lymphadenopathy: Insights for Practitioners of Breast Pathology

et al. 2020

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Rosai-Dorfman disease is a rare proliferative histiocytic disorder of lymph nodes that is descriptively known as sinus histiocytosis with massive lymphadenopathy. Extranodal involvement of the parenchyma of the breast is uncommonly reported, with fewer than 50 cases of mammary extranodal disease detailed in the English-language literature. We characterize a retrospective series of adult female patients from a single institution with Rosai-Dorfman disease of the breast and axillary lymph nodes. Because Rosai-Dorfman disease of the breast and axillary lymph nodes may clinically, radiographically, and histologically mimic breast carcinoma and other conditions, we present an illustrated review of the disease and its relevant differential diagnoses in hopes of raising awareness and allowing for accurate management of affected patients.

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Section: Discussionmentioning

confidence: 99%

Mammary Extranodal Rosai-Dorfman Disease With and Without Associated Axillary Lymphadenopathy: Insights for Practitioners of Breast Pathology

et al. 2020

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“…Given the complexity of M ontogeny, the histogenesis of these disorders has been long debated, and is still the object of active research. 65,66 Specifically, the BRAF V600E mutation was found in CD34 + cells of several LCH and ECD patients, as well in circulating monocytes. 61,69 In addition, genetic fingerprinting revealed that histiocytes in ECD often exhibit mutations typically observed in clonal hematopoiesis.…”

Section: Ecd Histiocytes Harbor Activating Oncogenic Mutationsmentioning

confidence: 98%

“…Indeed, combined whole exome and transcriptome analyses of several ECD tissue samples revealed additional mechanisms leading to ERK activation, including MAP2K1 (encoding MAPK kinase 1 [MAP2K1, alternatively termed MEK1], 32% of patients), NRAS (16%), KRAS mutations (11%), and ARAF (3%) 63,64 . In addition, in‐frame fusions involving several kinases including BRAF , ALK , and NTRK1 were identified in ECD patients without BRAF , MAP2K1 , or N/KRAS point mutations (reviewed in 6, 65, 66). Finally, mutations affecting other signaling pathways such as PIK3CA were also found in 11% of ECD patients 63 .…”

Section: Ecd Pathogenesis: At the Crossroad Between Inflammation And mentioning

confidence: 99%

Erdheim-Chester disease: An in vivo human model of Mϕ activation at the crossroad between chronic inflammation and cancer

Cavalli

Dagna

Biavasco

et al. 2020

Journal of Leukocyte Biology

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Erdheim-Chester disease (ECD) is a rare histiocytosis characterized by infiltration of multiple tissues by CD68 + foamy M s (or 'histiocytes'). Clinical manifestations arise from mass-forming lesions or from tissue and systemic inflammation. ECD histiocytes harbor oncogenic mutations along the MAPK-kinase signaling pathway (BRAF V600E in more than half of the patients), and secrete abundant pro-inflammatory cytokines and chemokines. Based on these features, ECD is considered an inflammatory myeloid neoplasm, and is accordingly managed with targeted kinase inhibitors or immunosuppressive and cytokine-blocking agents. Evidence is emerging that maladaptive metabolic changes, particularly up-regulated glycolysis, represent an additional, mutation-driven feature of ECD histiocytes, which sustains deregulated and protracted proinflammatory activation and cytokine production. Besides translational relevance to the management of ECD patients and to the development of new therapeutic approaches, recognition of ECD as a natural human model of chronic, maladaptive M activation instructs the understanding of M dysfunction in other chronic inflammatory conditions.

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“…Promoter swapping with multiple partner genes leads to upregulation of USP6 Langerhans Cell Histiocytosis [71][72][73][74][75] BRAF V600E mutations N/A Dysregulation of MAPK pathway Fibrous Dysplasia [76][77][78][79] GNAS activating mutations N/A Constitutive cAMP elevations lead to alteration in expression levels of multiple targets Low-Grade Central Chondrosarcoma [3,4,[80][81][82] Somatic mutations in IDH1 and IDH2 N/A Altered 2-hydroxyglutarate levels Low-Grade Peripheral Chondrosarcoma [3,4] Somatic mutations in EXT1 and EXT2 genes N/A Deficiency of heparin sulfate glycotransferases Low-Grade Central Osteosarcoma/ Parosteal Osteosarcoma [3,[83][84][85][86][87] N/A Supernumerary ring and giant chromosome markers with amplification of 12q13-15, including MDM2, FRS2, and CDK4…”

Section: Cdh11-usp6mentioning

confidence: 99%

“…Rosai-Dorfman Disease [75,[179][180][181][182] KRAS and MAP2K1 mutations MAPK pathway alteration Erdheim Chester Disease & [71,75,183] BRAF V600E MAPK pathway alteration FUS/EWSR1-NFATC2 rearrangements have recently been described in a significant proportion of simple bone cysts indicating that these rearrangements are neither specific to NFATC2 sarcomas, nor do they necessarily indicate a malignant process. & Erdheim Chester shows bone involvement in nearly 95% of cases making it common to bone; however, it also commonly displays systemic involvement and is exceedingly rare overall, thus it is classified here under rare lesions rather than primary bone tumors.…”

Section: Variousmentioning

confidence: 99%

Genetic characteristics and molecular diagnostics of bone tumors

Suster¹,

Suster²

2021

JCMT

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The diagnosis of primary tumors of bone relies heavily on clinicopathological and radiological correlation and is often best performed in a multidisciplinary setting. Bone tumors comprise a heterogenous category of human lesions ranging from benign to malignant neoplasms. These tumors affect a wide age range and can become problematic for diagnosis when less common entities are encountered. Traditionally the pathological diagnosis of many bone tumors has been based primarily on the evaluation of hematoxylin and eosin-stained glass slides, sometimes combined with ancillary diagnostic techniques such as immunohistochemistry, conventional cytogenetics, fluorescence in situ hybridization, and polymerase chain reaction-based assays. More recently, the advent of massively parallel sequencing-based techniques has opened new avenues for diagnostic testing in bone tumors; however, these new testing modalities are sensitive to traditional decalcification procedures that are commonly used in the routine processing of bony specimens. Herein we provide a focused review concentrating on the molecular genetic features of bone tumors with specific, recurrent genetic alterations that make them appealing targets for directed ancillary testing by conventional or molecular techniques. In addition, specimen handling with regards to decalcification procedures are discussed and the different types of testing modalities available are reviewed.

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Systemic Histiocytosis (Langerhans Cell Histiocytosis, Erdheim–Chester Disease, Destombes–Rosai–Dorfman Disease): from Oncogenic Mutations to Inflammatory Disorders

Cited by 59 publications

References 97 publications

Mammary Extranodal Rosai-Dorfman Disease With and Without Associated Axillary Lymphadenopathy: Insights for Practitioners of Breast Pathology

Mammary Extranodal Rosai-Dorfman Disease With and Without Associated Axillary Lymphadenopathy: Insights for Practitioners of Breast Pathology

Erdheim-Chester disease: An in vivo human model of Mϕ activation at the crossroad between chronic inflammation and cancer

Genetic characteristics and molecular diagnostics of bone tumors

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