Is Langerhans cell histiocytosis a neoplasia?

Braier, Jorge

doi:10.1002/pbc.26267

Cited by 7 publications

(6 citation statements)

References 9 publications

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“…Initially, the patient didn't meet the clinical criteria of HLH; however, after his second cycle of intensive chemotherapy he developed the disorder. This supports the argument by Jorge Braier [17] who questioned the role of chemotherapy agents in LCH patients and whether they induce cytotoxicity against the clonal infiltration of multisystem LCH in organs, or promote immunosuppression that modulates the cytokine storm; which, in our opinion, might explain the gradual emergence of HLH in our patient.…”

Section: Discussionsupporting

confidence: 91%

The Challenges of Bone Marrow Biopsy in Diagnosing Multisystem Langerhans Cell Histiocytosis

Allen¹,

Bem²

2018

Int J Clin Pathol Diagn

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Langerhans Cell Histiocytosis (LCH) is a disease characterized by infiltration of Langerhans-type histiocytes of one or more organ systems, most commonly bone, skin, lymph nodes, liver, or lung. While localized disease tends to follow a more indolent course, multiorgan involvement is usually common in infants and portends a worse prognosis, with dysfunction of the involved organs and a mortality rate nearing twenty percent. Bone marrow involvement often presents clinically with cytopenias, however in such cases the presence of bone marrow infiltration by Langerhans cells is infrequent. We are presenting a case of a 10-month-old male child with significant pancytopenias, marked hepatosplenomegaly and scalp lesions on initial presentation. Bone marrow biopsies showed aggregates of histiocytes and evidence of hematophagocytosis without clinically meeting the diagnostic criteria for Hemophagocytic Lymphohistiocytosis (HLH). The child further developed, during his second cycle of chemotherapy, secondary HLH. Ultimately, a definitive diagnosis of multisystem Langerhans cell histiocytosis was only made following biopsy of an occipital mass, which initially was clinically considered to be a hemangioma. This case report highlights the bone marrow findings and the challenges in diagnosing multisystem Langerhans cell histiocytosis with high-risk organ involvement. It also illustrates the relationship between multisystem LCH and macrophage activation/ secondary HLH.

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Section: Discussionsupporting

confidence: 91%

The Challenges of Bone Marrow Biopsy in Diagnosing Multisystem Langerhans Cell Histiocytosis

Allen¹,

Bem²

2018

Int J Clin Pathol Diagn

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“…7 There has been many progresses in characterization and management of LCH since then, but its nature and biology is still less understood. 1,[3][4][5][6][8][9][10][11][12][13][14] LCH can be diagnosed at any age but it is mainly a childhood disease and its incidence is around 3-5 cases per million children. 6,[8][9][10]13,15 Due to rarity of the disease, the incidence in adults (1 to 2 per milion) may be underestimated and should be revealed.…”

Section: Introductionmentioning

confidence: 99%

Langerhans Cell Histiocytosis: Excellent Local Control with Low Dose Radiotherapy

Kıraklı¹

2019

UHOD

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Langerhans cell histiocytosis (LCH) is a rare disorder. Uncontrolled clonal proliferation of langerhans cells leads to a diversity of clinical manifestations. Low dose Radiotherapy (RT) is used mainly for osseous manifestations as a sole treatment or in combination with surgery/chemotherapy/steroids. Altough the mechanism of action of RT is an unresolved issue, it's usually used in adjuvant/palliative settings, also as first-line local therapy with curative intent in unresectable or resectable cases in case surgery would result in functional compromise. This study is conducted to review indications, dose-fractionation schedules, clinical characteristics and outcomes of LCH patients received local RT mainly for osseous lesions. The medical records of biopsy proven all LCH patients referred to our center and treated with RT between 2000-2016 were evaluated retrospectively. Disease-free survival (DFS), local control and side effects were defined as study end-points. There was 35 patients, 21 of them were children. At presentation 65.7% had single systemsingle bone, 20% had single system-multiple bone, 15% had multisystem disease.Soft tissue extension were detected in 16 children, 4 adults (p= 0.013).Mean radiation dose was 10.8 Gy. Median follow-up from the date of biopsy was 105 months (range= 8-204) in children and 88 (range:31-245) in adults (log rank p:0.029).Complete response rate was 97%. 11 children and 1 adult experienced relapse (p= 0.05), median interval for relapse was 9months in children, 19months in adults. The most common relapse pattern was as single system-multiple bone (58.3%). Local control was 97.1%. Median disease free survival was 85 months. Low dose local RT seems to be effective and safe in multidisciplinary management of LCH.

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“…LCH cells carry few genetic alterations beyond BRAF V600E or another oncogenic driver in the MAPK pathway (MAP2K1, ARAF), and they show no progressive accumulation of recurrent somatic mutations (9). Instead, high levels of inflammatory infiltrate suggest that cell-extrinsic, immunologic stimuli could be key contributors to the formation of LCH lesions (10)(11)(12). LCH is lethal in up to 20% of patients with risk organ-positive, multisystem disease treated according to current standard of care.…”

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confidence: 99%

Epigenomics and Single-Cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis

et al. 2019

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Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a hybrid position between cancers and inflammatory diseases, which makes it an attractive model for studying cancer development. To explore the molecular mechanisms underlying the pathophysiology of LCH and its characteristic clinical heterogeneity, we investigated the transcriptomic and epigenomic diversity in primary LCH lesions. Using single-cell RNA sequencing, we identified multiple recurrent types of LCH cells within these biopsies, including putative LCH progenitor cells and several subsets of differentiated LCH cells. We confirmed the presence of proliferative LCH cells in all analyzed biopsies using IHC, and we defined an epigenomic and generegulatory basis of the different LCH-cell subsets by chromatin-accessibility profiling. In summary, our single-cell analysis of LCH uncovered an unexpected degree of cellular, transcriptomic, and epigenomic heterogeneity among LCH cells, indicative of complex developmental hierarchies in LCH lesions. SIGNIFICANCE:This study sketches a molecular portrait of LCH lesions by combining single-cell transcriptomics with epigenome profiling. We uncovered extensive cellular heterogeneity, explained in part by an intrinsic developmental hierarchy of LCH cells. Our findings provide new insights and hypotheses for advancing LCH research and a starting point for personalizing therapy.

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Is Langerhans cell histiocytosis a neoplasia?

Cited by 7 publications

References 9 publications

The Challenges of Bone Marrow Biopsy in Diagnosing Multisystem Langerhans Cell Histiocytosis

The Challenges of Bone Marrow Biopsy in Diagnosing Multisystem Langerhans Cell Histiocytosis

Langerhans Cell Histiocytosis: Excellent Local Control with Low Dose Radiotherapy

Epigenomics and Single-Cell Sequencing Define a Developmental Hierarchy in Langerhans Cell Histiocytosis

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