Adult Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a proliferative histiocytic disorder of unknown cause originating from dendritic cells. The clinical presentation of LCH is highly variable. Although the features of this disease have been well described in children, they remain poorly defined in adults. Here, we review the current knowledge about adult LCH, focussing on clinical presentation, diagnosis, treatment, and prognosis.     

Successful treatment of Langerhans cell histiocytosis with 2-chlorodeoxyadenosine

Langerhans cell histiocytosis (LCH) is a rare disorder which frequently involves the lungs of affected adults. Recent evidence suggests it is a clonal neoplastic disorder. Prognosis in this disease is variable, but in its multisystem form or when associated with progressive respiratory dysfunction, prognosis is poor. Recent case reports and a phase II trial of the antimonocyte drug 2-chlorodeoxy-adenosine (2CDA) have described success in treating LCH. We used 2CDA to treat a young Australian man with LCH involving lungs and bone. A complete symptomatic remission was achieved with no evidence of recurrence some 5 years after completion of chemotherapy.     

Familial clustering of Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is considered a non-hereditary disorder. Evaluation of the few familial cases might provide insight into its aetiology and pathogenesis. We conducted a survey to identify familial LCH cases. Data on family history, zygosity assessment in twins, clinical and laboratory features, treatment outcome, and present status were collected. According to variable confidence for twins monozygosity assessment, we termed these pairs 'presumed monozygotic' (pMZ). Nine families had more than one affected relative: five with LCH-concordant twin pairs, four with LCH in siblings or cousins. Three twin pairs not concordant for LCH were also studied. Overall, four of five pMZ twin pairs and one of three dizygotic (DZ) pairs were concordant for LCH. The pMZ twins had simultaneous and early disease onset (mean age 5.4 months); onset was at 21 months in the DZ pair. Clinical features were similar in the pMZ pairs. One pair of DZ twins had disseminated LCH. The three healthy twins (one pMZ, two DZ) remain asymptomatic 0.3, 5.9 and 4.7 years, respectively, after disease onset in their co-twins. Of the two families with affected non-twin siblings, one had known parental consanguinity and the other possible consanguinity. Potential consanguinity was also present in one of the two families with affected first cousins. Our data support high LCH concordance rates in pMZ twins and add the finding of LCH concordance in one of three dizygotic pairs studied. Taken together with our identification of LCH in siblings and first cousins from known or possibly consanguineous families, and with prior reports of three affected parent-child pairs, the data support a role for genetic factor(s) in LCH. The work-up of newly diagnosed patients should include a careful, extensive family history and chromosome studies. When possible, constitutional and/or lesional DNA should be obtained for future study.     

Telomere length shortening in Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a clonal, proliferative disorder of phenotypically immature CD1a⁺ Langerhans cells (LC). The aetiology of LCH is unknown and data supporting an immune dysregulatory disorder as well as a clonal neoplasm have been reported. Telomere shortening has been associated with cancers and premalignant lesions as well as promoting chromosomal instability. To determine whether LCH LC have altered telomere lengths, we used dual detection of CD1a expression by immunofluorescence and telomere length by fluorescence in situ hybridization of LCH LC and lymphocytes in local, multisystem and systemic LCH and compared these with telomere lengths of LC and lymphocytes in reactive lymph nodes. LCH LC showed significantly shorter telomere lengths than LC from reactive lymph nodes or unaffected skin. Lymphocyte telomere lengths showed similar profiles among the different samples. These data show a significant telomere shortening in LCH LC in all stages of disease involvement compared with LC from reactive lymph nodes, suggesting that LCH may share mechanisms of telomere shortening and survival with clonal preneoplastic disorders and cancer, although an initiating infectious or immune event is still possible.     

成人脊柱朗格汉斯细胞组织细胞增生症误诊1例

脊柱朗格汉斯细胞组织细胞增生症发病率低,临床表现无特异性,且病理组织获得难度大,因此临床误诊及漏诊率高.本文对1例开始误诊为脊柱结核最终通过手术病理活检确诊为脊柱朗格汉斯细胞组织细胞增生症的病例进行报道,以提高对本病的认识,减少误诊率.     

吸烟与肺朗格汉斯细胞组织细胞增生症

肺朗格汉斯细胞组织细胞增生症的发生与吸烟有关.烟草糖蛋白可引起一系列细胞和细胞因子病理变化.戒烟可使部分患者病情稳定,改善影像学变化,甚至可使疾病(包括肺外病变)痊愈.     

肺郎格罕细胞组织细胞增多症7例临床分析

目的探讨肺郎格罕(Langerhans)细胞组织细胞增多症的临床表现,以提高对本病的认识。方法回顾性分析1997—2006年北京协和医院确诊的7例肺郎格罕细胞组织细胞增多症的临床资料。结果7例患者均为男性,平均年龄26.7岁,其中4例吸烟,主要症状为咳嗽、活动后气短,5例在疾病过程中发生气胸。肺功能示阻塞性通气功能障碍3例、限制性通气功能障碍2例、混合性通气功能障碍2例,4例有不同程度的弥散功能障碍。胸部高分辨CT(HRCT)示6例表现为双上中肺野网格状改变及囊性变,仅有1例可见小结节影。外科肺活检标本病理学检查结果示7例光镜下均可见病理性郎格罕细胞浸润,6例可见囊样及气腔样结构。免疫组化阳性检出情况为7例S-100均为阳性;5例行CD1a检查者中4例阳性;6例行CD68检查者中5例阳性。结论肺郎格罕细胞组织细胞增多症常见于年轻吸烟男性,主要临床表现为咳嗽、活动后气短、反复气胸,胸部HTCT表现为双上中肺野为主的网结节或囊性变,肺功能无特异性改变,可伴有弥散功能异常,病理学检查可见病理性郎格罕细胞或免疫组化CD1a、S-100阳性可以明确诊断。     

Treatment of children with Langerhans cell histiocytosis with 2-chlorodeoxyadenosine

Langerhans cell histiocytosis (LCH) is a disorder characterized by proliferation of activated Langerhans cells. Immune dysregulation is believed to be part of the pathogenesis. Although current therapies are very effective at inducing remission, multiple recurrences and long-term sequelae are common for patients with low-risk disease, and a significant proportion of young patients die of their disease. More effective therapies based on the pathogenesis of LCH are needed. We investigated the use of 2-chloro-deoxyadenosine (2-CdA), a purine analogue with an antiproliferative effect on histiocytes and lymphocytes, in patients with recurrent or high-risk LCH. Six patients with recurrent LCH received 2-CdA (5-7 mg/m(2)/day for 5 days, repeated every 21-28 days). All patients achieved remission. With a median follow-up of 15 months (range, 3-25 months), 5 patients remain in remission. A patient with multisystem disease who recurred after 13 months, achieved a second remission with 2-CdA. Hematologic toxicity was minimal, and no infectious complications were documented. 2-CdA is among the most effective drugs for the treatment of LCH, and this is probably due to both its anti-proliferative and immunomodulatory effects. 2-CdA needs to be considered for the treatment of recurrent LCH. However, its incorporation into front-line treatment of patients with multi-system LCH needs further study.     

A case of adult Langerhans cell histiocytosis showing successfully regenerated osseous tissue of the skull after chemotherapy

Langerhans cell histiocytosis (LCH) is a proliferative disorder of Langerhans cells and extremely rare in adults. Adult LCH is often associated with osteolytic bone lesions, but large bone-defective lesions have been rarely reported. We report an adult case of LCH accompanied by large osteolytic lesions in the skull that successfully responded to chemotherapy. A 47-year-old woman with LCH who had multiple, large osteolytic areas of more than 3 cm in diameter in the skull was admitted to our hospital. She was treated with systemic chemotherapy consisting of prednisolone, vinblastine, and 6-mercaptopurine. Twelve months later, when she completed the treatment, osteolytic areas were covered with hard osseous tissue, and X-ray examination confirmed regeneration of the bone. This case indicates that chemotherapy can be effective even for the treatment of large osteolytic lesions in adult LCH patients.     

郎格汉斯组织细胞增多症的消化系表现、诊断及治疗

郎格汉斯组织细胞增多症是一种少见的全身多系统受侵犯的组织细胞异常增生性疾病,常见受累部位为骨、皮肤、肺脏、骨髓、淋巴结等,除此之外,尚可侵犯肝脏、胆道及胃肠道等消化器官,临床表现与其他消化系统疾病相比缺乏特异性,故诊断难度较大,一旦郎格汉斯组织细胞增多症患者明确诊断消化系统受累,则需要系统性治疗,甚至是肝脏移植.本文综述郎格汉斯组织细胞增多症的消化系统表现,从而对其早期诊断及治疗提供帮助.     

Management of severe pulmonary Langerhans cell histiocytosis in children

Patients with pulmonary Langerhans cell histiocytosis (LCH) typically have a benign course but may have extensive cystic lung disease with rare life‐threatening complications including multiple and recurrent pneumothoraces and respiratory failure. We report seven severely affected pediatric patients treated with chemotherapy, aggressive chest tube management, and pleurodesis of whom five survived. Patients with extraordinary amounts of pulmonary cystic disease and multiple pneumothoraces due to LCH can have remarkable, curative outcomes with early recognition, optimal LCH‐directed therapy, and supportive care.     

Langerhans cell histiocytosis following childhood acute lymphoblastic leukemia.

Langerhans cell histiocytosis (LCH) is a clonal proliferation of Langerhans cells of unknown etiology that results in a range of clinical manifestations. LCH has been known to be associated with a variety of malignant diseases. A 7-year-old boy was treated for standard-risk acute lymphoblastic leukemia (ALL) at age 2 years, on a Children's Cancer Group chemotherapy protocol for 3 years and developed LCH 2 years after completion of chemotherapy. The case and a review of literature on the association of LCH and ALL are presented.     

Relapses of multisystem/multifocal bone Langerhans cell histiocytosis in paediatric patients: Data analysis from the JLSG-96/02 study

We assessed relapse patterns in paediatric patients with relapsed Langerhans cell histiocytosis (LCH) who were initially treated with the JLSG-96/02 protocol. We analysed 187 relapse events in 101 relapsed LCH patients [31 with multifocal bone (MFB) and 70 with multisystem (MS) at LCH diagnosis] among a total 317 patients enrolled in JLSG-96/-02 studies. Relapse of LCH was defined as an exacerbation of the non-active disease (NAD) condition. Of the 317 patients, 101 (31.9%) had the first relapse at 1.5 years after initiation of therapy. The first relapse and subsequent relapses did not differ between patients with MFB and MS disease. Of the 187 relapse events, relapse occurred as a single-system disease (n = 159; 85%), in which isolated bone relapse (n = 104; 55%) was the most common. Relapse at MS disease with the risk of organ involvement is extremely rare. After relapse(s), most patients underwent chemotherapy (122/187; 65%) and 87% of them achieved NAD status again. The incidence of permanent consequences was significantly higher in patients with relapses than in those without relapses. In the JLSG cohort, bone relapse most occurred in both MFB and MS patients. Most relapses could be effectively controlled by repeated administration of the initial chemotherapy.     

Specific polymorphisms of cytokine genes are associated with different risks to develop single-system or multi-system childhood Langerhans cell histiocytosis

Cytokines and chemokines determine mobilisation of Langerhans cells and their dysregulation is implicated in the pathogenesis of Langerhans cell histiocytosis (LCH). Twenty point mutations of 12 different cytokine genes were studied in 41 Italian children, 15 with single-system (SS) and 26 with multi-system disease. The allele and genotype distributions of interleukin-4 (IL-4) and interferon-gamma (IFNgamma) were significantly different in patients vs. 140 controls (P = 0.007, and P = 0.018). Older children with single-system disease shared the 'anti-inflammatory profile' determined by the intermediate producer genotype IFNgamma +874A/T (P = 0.029) and the high-producer genotypes IL-4 -590C/T and T/T (P = 0.029). Our findings suggest that specific cytokine gene variants affect susceptibility to LCH and its clinical heterogeneity.     

Management of adult Langerhans cell histiocytosis based on the characteristic clinical features

To find out the most appropriate management, clinical features of 18 cases of adult multisystem langerhans cell histiocytosis (LCH) have been analyzed. The patients comprising of 9 males and 9 females were median age of 36 years, ranging from 18-53 years at diagnosis. Regarding the initial symptoms, 7 patients (2 males and 5 females) showed central diabetes insipidus (CDI) and other endocrine symptoms with thickened pituitary stalk or a mass at the hypothalamic region. Additional 2 patients initiated the disease with CDI with no immediate diagnosis. In the remaining patients, the disease begun with single (n = 3) or multiple (n = 1) spinal bone lesion(s) in 4 patients (all males), with multiple bone lesions in 3 patients (1 male and 2 females), with single skull lesion in one female patient and with ambiguous symptoms including hypothyroidism in the remaining one male patient. We also recognized the correlation between pregnancy/childbirth and LCH in 4 patients. In terms of treatment, 9 patients received systemic immuno-chemotherapy alone, of which the majority received vinblastine-based chemotherapy while 4 received 2-chlorodeoxyadenosine. Five had a combination of immuno-chemotherapy with surgical resection or radiotherapy, 2 had immunotherapy alone, 2 had surgical resection followed by observation alone to date. Three patients received hematopoietic stem cell transplantation after extensive chemotherapy. In terms of outcome, 15 patients are alive (9 with active disease, 6 without active disease), with a median of 66 mo (range 17-166 mo), two died of disease while the remaining 1 lost to follow-up. Based on these results, we think that early diagnosis and rapid introduction of appropriate treatment are essential, in order to overcome the problems relevant to adult LCH.