Long-term follow-up of Langerhans cell histiocytosis: 39 years’ experience at a single centre

Bernstrand, Cecilia; Sandstedt, Bengt; Åhström, L.; Henter, Jan‐Inge

doi:10.1080/08035250510028263

Cited by 48 publications

(38 citation statements)

References 27 publications

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“…(11,12) At the end of this study, 31 of the 37 patients (83.8%) had ' probable ' or ' definitive ' diagnoses. Of the 6 patients who remained with 'presumptive' diagnoses, 4 presented clinical manifestations highly suggestive of the disease, such as diabetes insipidus and multisystem disease.…”

Section: Discussionmentioning

confidence: 84%

Langerhans cell histiocytosis

Babeto¹,

Oliveira²,

Castro³

et al. 2011

Rev. Bras. Hematol. Hemoter.

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ObjectivesTo improve the level of 'definitive' diagnosis of Langerhans cell histiocytosis by immunohistochemical investigation of the CD1a surface antigen and to compare outcomes in respect to age, gender, stage of the disease, treatment response and level of diagnostic accuracy.MethodsA retrospective study was carried out of 37 children and adolescents with possible Langerhans cell histiocytosis between 1988 and 2008. The diagnoses were revisited using immunohistochemical investigations for CD1a, S-100 and CD68 in an attempt to reach definitive diagnoses for all cases.ResultsBefore the study, only 13 of 37 patients (35.1%) had a 'definitive' diagnosis; by the end of the study, this number rose to 25 patients (67.6%). All reviewed cases were positive for the CD1a antigen. Overall survival was 88.5%. Multisystem disease (Stage 2; n=19) and absence of response at the 6th week of therapy (n=5) were associated to significantly lower overall survival (p-value = 0.04 and 0.0001, respectively). All deaths occurred in patients with multisystem disease and organ dysfunction at diagnosis. Other potential prognostic factors were not significant. Reactivation episodes occurred in 75% of the patients with multisystem disease. Diabetes insipidus was the most common sequel (21.6%).ConclusionThe level of diagnostic accuracy was increased through immunohistochemistry. The overall survival rate was similar to international multicentric studies. Multisystem disease and absence of response at six weeks of treatment were the most important unfavorable prognostic factors. The frequency of reactivation for patients with multisystem disease was higher than described in the literature, probably because maintenance chemotherapy was used only in two cases.

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Section: Discussionmentioning

confidence: 84%

Langerhans cell histiocytosis

Babeto¹,

Oliveira²,

Castro³

et al. 2011

Rev. Bras. Hematol. Hemoter.

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“…The clinical course of LCH is remarkably varied, ranging from lesions that spontaneously resolve, to a chronic disease, or even to a widespread and sometimes lethal disease [1,7,8]. The pathophysiology of LCH remains enigmatic, but seems to be associated with abnormalities in the biology of Langerhans cells (LCs) and macrophages [5,9,10].…”

Section: Introductionmentioning

confidence: 99%

Expansion of Regulatory T Cells in Patients with Langerhans Cell Histiocytosis

et al. 2007

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BackgroundLangerhans cell histiocytosis (LCH) is a rare clonal granulomatous disease that affects mainly children. LCH can involve various tissues such as bone, skin, lung, bone marrow, lymph nodes, and the central nervous system, and is frequently responsible for functional sequelae. The pathophysiology of LCH is unclear, but the uncontrolled proliferation of Langerhans cells (LCs) is believed to be the primary event in the formation of granulomas. The present study was designed to further investigate the nature of proliferating cells and the immune mechanisms involved in the LCH granulomas.Methods and FindingsBiopsies (n = 24) and/or blood samples (n = 25) from 40 patients aged 0.25 to 13 y (mean 7.8 y), were studied to identify cells that proliferate in blood and granulomas. We found that the proliferating index of LCs was low (∼1.9%), and we did not observe expansion of a monocyte or dendritic cell compartment in patients. We found that LCH lesions were a site of active inflammation, tissue remodeling, and neo-angiogenesis, and the majority of proliferating cells were endothelial cells, fibroblasts, and polyclonal T lymphocytes. Within granulomas, interleukin 10 was abundant, LCs expressed the TNF receptor family member RANK, and CD4+ CD25high FoxP3high regulatory T cells (T-regs) represented 20% of T cells, and were found in close contact with LCs. FoxP3+ T-regs were also expanded compared to controls, in the blood of LCH patients with active disease, among whom seven out of seven tested exhibited an impaired skin delayed-type hypersensitivity response. In contrast, the number of blood T-regs were normal after remission of LCH.ConclusionsThese findings indicate that LC accumulation in LCH results from survival rather than uncontrolled proliferation, and is associated with the expansion of T-regs. These data suggest that LCs may be involved in the expansion of T-regs in vivo, resulting in the failure of the host immune system to eliminate LCH cells. Thus T-regs could be a therapeutic target in LCH.

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“…This reflects an active therapeutic approach that is applied at an early stage at our institute, and this approach has recently been supported by the finding that early combination therapy is associated with a lower degree of reactivation in patients with single-system disease as compared with monotherapy [2, 11]. Treatment may include observation, local resection, irradiation, and systemic therapy.…”

Section: Discussionmentioning

confidence: 92%

“…Therefore, we agree with Longaker et al [19] that a long-term follow-up is indicated for all with LCH, including those with single-system involvement at diagnosis. Bernstrand et al [2] reported that patients with multiple bone lesions have a high rate of reactivation. Moreover, in patients with multiple bone lesions, the presence of skull lesions may be a marker for an increased incidence of reactivations [12], which seems to correlate with our finding, as 1 patient with multiple bone involvement experienced reactivation.…”

Section: Discussionmentioning

confidence: 99%

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Eosinophilic Granuloma of the Skull: A Retrospective Analysis

Park

Hwang

et al. 2007

Pediatr Neurosurg

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Background: The authors describe 9 cases of children with eosinophilic granuloma (EG) of the skull and report on their clinical manifestations, treatment, and prognosis. Method: Nine consecutive patients were diagnosed as EG of the skull and confirmed pathologically between 1996 and 2005. In the present study, multi- and single-system Langerhans’ cell histiocytosis without skull involvement were excluded. Patients with EG of the skull were divided into two groups: (1) those with only a single bone lesion and those with (2) multiple bone lesions. Surgical removal was performed between 2 and 10 years of age (mean, 4.2 years). Results: Eight (88.9%) of the study subjects were found to have a single bone lesion at diagnosis, and 1 had multiple bone lesions. Seven patients had a painless skull mass and 2 patients had a painful skull mass. Total removal was performed in all 9 patients. Eight patients received postoperative chemotherapy or indomethacin as adjuvant therapy. Of the 8 patients who received adjuvant therapy, 4 were treated with indomethacin and the remaining 4 received methotrexate-based chemotherapy. Eight patients did not experience EG recurrence, however, 1 patient developed additional lesions 2 years after surgical excision. Conclusions: EG of the skull is a clinicopathological entity with a good outcome. However, therapies and prognoses are dependent on age at diagnosis and the number of bony involvements.

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Long-term follow-up of Langerhans cell histiocytosis: 39 years’ experience at a single centre

Abstract: Multi-system LCH is associated not only with increased mortality but also pronounced propensity for severe late sequelae; 51% of the patients (multi-system=33%, single-system=67%) were alive without sequelae at follow-up. Among multi-system patients, at least 19% suffered CNS sequelae.

Cited by 48 publications

References 27 publications

Langerhans cell histiocytosis

Langerhans cell histiocytosis

Expansion of Regulatory T Cells in Patients with Langerhans Cell Histiocytosis

Eosinophilic Granuloma of the Skull: A Retrospective Analysis

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