Langerhans cell histiocytosis

Blesa, Joan Manel Gasent; Candel, Vicente Alberola; Vercet, Carlos Solano; Canales, Juan Laforga; Semler, Christof; Antolí, M. Rosa Pérez; Rodríguez‐Galindo, Carlos

doi:10.1007/s12094-008-0275-9

Cited by 15 publications

(6 citation statements)

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“…These granuloma are therefore heterogeneous in cellular composition as well as anatomical distribution. The pathophysiology of LCH is largely unknown [10], [14], although a genetic component is suggested by a higher concordance rate between monozygotic twins compared with dizygotic twins [15]. The tropism of skin lesions to flexures also suggests that external stimuli may trigger inflammation [16].…”

Section: Introductionmentioning

confidence: 99%

“…Of note, the clinical features of LCH are not typical of cancer [10], [14] and LCH lesions frequently regress, either spontaneously or after local treatment [1], [4], [5]. In addition, LCH CD1a+ cells, which are presumed to be pathologic, very slowly proliferate in most patients [12], while the expansion of a monocyte or dendritic cell compartment, which represent candidate precursors for these CD1a+ cells of the granuloma, was not consistently observed in the blood of LCH patients [12], [27].…”

Section: Introductionmentioning

confidence: 99%

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B-RAF Mutant Alleles Associated with Langerhans Cell Histiocytosis, a Granulomatous Pediatric Disease

et al. 2012

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BackgroundLangerhans cell histiocytosis (LCH) features inflammatory granuloma characterised by the presence of CD1a+ dendritic cells or ‘LCH cells’. Badalian-Very et al. recently reported the presence of a canonical V600EB-RAF mutation in 57% of paraffin-embedded biopsies from LCH granuloma. Here we confirm their findings and report the identification of two novel B-RAF mutations detected in LCH patients.Methods and ResultsMutations of B-RAF were observed in granuloma samples from 11 out of 16 patients using ‘next generation’ pyrosequencing. In 9 cases the mutation identified was V600EB-RAF. In 2 cases novel polymorphisms were identified. A somatic 600DLATB-RAF insertion mimicked the structural and functional consequences of the V600EB-RAF mutant. It destabilized the inactive conformation of the B-RAF kinase and resulted in increased ERK activation in 293 T cells. The 600DLATB-RAF and V600EB-RAF mutations were found enriched in DNA and mRNA from the CD1a+ fraction of granuloma. They were absent from the blood and monocytes of 58 LCH patients, with a lower threshold of sequencing sensitivity of 1%–2% relative mutation abundance. A novel germ line T599AB-RAF mutant allele was detected in one patient, at a relative mutation abundance close to 50% in the LCH granuloma, blood monocytes and lymphocytes. However, T599AB-RAF did not destabilize the inactive conformation of the B-RAF kinase, and did not induce increased ERK phosphorylation or C-RAF transactivation.ConclusionsOur data confirmed presence of the V600EB-RAF mutation in LCH granuloma of some patients, and identify two novel B-RAF mutations. They indicate that V600EB-RAF and 600DLATB-RAF mutations are somatic mutants enriched in LCH CD1a+ cells and absent from the patient blood. Further studies are needed to assess the functional consequences of the germ-line T599AB-RAF allele.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

B-RAF Mutant Alleles Associated with Langerhans Cell Histiocytosis, a Granulomatous Pediatric Disease

et al. 2012

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“…LCH has an extremely variable presentation that depends on abnormal proliferation and dissemination of histiocytes. Therefore, LCH has numerous clinical forms that affect different systems or different sites in the same system with variable outcomes (2). LCH occurs in the bones, skin and mucous membranes in children, and occasionally in other organs in adults.…”

Section: Introductionmentioning

confidence: 99%

“…Positive cluster of differentiation (CD)1a and/or Langerin (CD207) staining in lesional cells is required for definitive diagnosis (4). LCH has variable clinical symptoms, as it affects a wide variety of systems (2). Specific symptoms include pain, swelling, skin rashes, otorrhea, irritability, fever, loss of appetite, diarrhea, polydipsia, dyspnea and behavioral and neurological changes (5).…”

Section: Introductionmentioning

confidence: 99%

Langerhans cell histiocytosis misdiagnosed as liver cancer and pituitary tumor in an adult: A case report and brief review of the literature

Jiang

Chen

et al. 2014

Oncology Letters

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Langerhans cell histiocytosis (LCH) is a rare proliferative disorder in which pathological Langerhans cells accumulate in a variety of organs. LCH usually affects the bone, skin and lymph nodes of children; however, LCH occasionally affects vital organs, including the liver, spleen and pituitary gland. The present study reports a case of an adult LCH patient with marked liver damage, splenomegaly and pituitary damage treated using a new therapeutic strategy. This case was misdiagnosed as liver cancer and pituitary tumor on the basis of abdominal ultrasound, abdominal magnetic resonance imaging (MRI) and head MRI. The final diagnosis was established by identifying the proliferation of cluster of differentiation 1a-positive LCs in liver tissues. A new regimen of combined 12-week therapy of prednisolone/desmopressin/vincristine and 10 months of maintenance therapy of prednisolone/vinblastine/6-mercaptopurine improved symptoms, liver function and blood cell tests.

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“…It displays a heterogeneous clinical feature that ranges from the involvement of a single organ system (SS) (primarily skin or bone) to the involvement of multiple organ systems (MS) complicated by organ dysfunction 1 2. Only about 20 cases of Langerhans cell sarcoma (LCS) have been previously reported in English literature,1 3 4 which can be considered as a higher-grade variant of LCH, and it can present de novo or progress from antecedent LCH.…”

Section: Introductionmentioning

confidence: 99%