Whole-body MRI of paediatric malignant tumours: comparison with conventional oncological imaging methods

Purpose: To evaluate the usefulness of whole-body (WB) MRI for detecting metastases from paediatric malignant tumours in comparison with conventional oncological imaging methods. Materials and methods: Using a 1.5-T system, a coronal short tau inversion recovery (STIR) sequence was obtained in all patients. In addition, sagittal fat-suppressed T2-weighted, sagittal STIR, or coronal fat-suppressed pre-contrast and post-contrast T1-weighted sequences were performed. Patients who underwent WB MRI and conventional oncological imaging within 15 days were enrolled in the study. In total, 58 bone scintigraphies, 26 iodine-123 (¹²³I) meta-iodo-benzylguanidine (MIBG) scintigraphies, and 48 CT scans were available for comparison in 36 patients (median age 3.5 years; 21 boys, 15 girls) who underwent 82 WB MRI examinations. Skeletal and extraskeletal metastases were evaluated for a variety of tumour types. Results: Concordance rate of WB MRI between two readers was 74%. In detecting metastases, WB MRI had higher sensitivity (99%) and PPV (94%) than bone scintigraphy (26 and 76%, respectively). In detecting skeletal metastases, WB MRI revealed higher sensitivity (100%) than ¹²³I-MIBG scintigraphy (25%) and CT (10%). In contrast, WB MRI showed lower PPV in detecting skeletal and extraskeletal metastases (8 and 57%, respectively) than ¹²³I-MIBG scintigraphy (100%), and lower sensitivity (60%) in detecting extraskeletal metastases than CT (100%). In 2 of 11 untreated patients, tumour staging was upgraded from stage 3 to 4 according to WB MRI findings. In 3 patients, WB MRI revealed early treatment responses (<1 year) of skeletal metastases. Conclusions: WB MRI can substitute for bone scintigraphy in detecting skeletal metastases of paediatric malignant tumours, and it is useful in evaluating initial tumour staging and early treatment responses. However, it still has only a complementary role in detecting extraskeletal metastases.     

Intralesional steroids in Langerhans cell histiocytosis of bone

Langerhans cell histiocytosis may involve single or multiple organ systems. Bone involvement is the most common feature. We have examined retrospectively the effects of 20 intralesional injections of steroids into bone in seven patients seen at our department from 1988 to 1993. Most of these injections (75%) relieved the symptoms, and no side-effects were observed. However, injections into the jaw were seldom effective. Our results suggest that the dose of the steroids administered is of importance.     

PET-CT in pediatric Langerhans cell histiocytosis

Our objective was to assess the utility of PET-CT in five pediatric patients with Langerhans cell histiocytosis (LCH) who underwent PET-CT imaging for clinical staging and determination of lesion activity at various stages of treatment and follow-up. PET-CT combines the anatomic detail of CT and the physiologic activity of ¹⁸F-FDG imaging. We conclude that PET-CT information is clinically useful to evaluate disease activity and response to therapy and provides information that cannot be obtained from technetium 99m methylene diphosphonate bone scans or radiographs.     

朗格罕斯细胞组织细胞增多症发病机制及治疗

朗格罕斯细胞组织细胞增多症是一种少见病,大量朗格罕斯细胞组织聚集于多种脏器,导致不同的临床表现,但其发病机制尚未完全阐明.文章将该病发病机制及治疗作一阐述,以提高临床医师对该病的认识.     

Hungarian experience with Langerhans cell histiocytosis in childhood

The Langerhans cell histiocytosis (LCH) in children is relatively rare and the long-term analysis of therapy results has not been done yet in Hungary. The aim of this study was to investigate the incidence, clinical features, prognostic risk factors, and treatment results of children's LCH in Hungary in a 20-year period. Children less than 18 years of age with newly diagnosed LCH in Hungary were entered in this study. Clinical data of all children with LCH were reported to the National Childhood Cancer Registry in Hungary from 1981 to 2000. The clinical files were collected and abstracted for information regarding age at diagnosis, gender, disease characteristics, treatment, and outcome of treatment. Median follow-up duration of surviving patients is 10.98 years. Between January 1981 and December 2000, 111 children under 18 years of age were newly diagnosed with LCH in Hungary. The annual incidence of LCH in children younger than 18 years of age was 2.24/million children. The male-female ratio was 1.36:1; the mean age was 4 years 11 months. Thirty-eight children had localized disease and in 73 cases systemic dissemination was found already at the time of diagnosis. Twenty-two patients were treated only by local surgery, 7 by surgery with local irradiation, and 5 children got only local irradiation. In 2 cases remission was achieved with local steroid administration. Seventy-five patients received chemotherapy. In the 20 years of the study 14 children died, 9 due to the progression of the disease. Sixteen patients had relapse with a mean of 2.16 ± 1.29 years after the first diagnosis. Three patients with relapse got chemotherapy generally used in lymphoma and remission was achieved. The overall survival of all patients (n = 111) was 88.3 ± 3.1% at 5 years and 87.3 ± 3.2% at 10 and 20 years. Childhood LCH is a well-treatable disease and the survival rate is high. Even disseminated diseases have a quite good prognosis in childhood.     

Langerhans cell histiocytosis with digestive tract involvement

Gastrointestinal tract (GIT) involvement in Langerhans cell histiocytosis (LCH) is not commonly described. We present two children presenting with GIT involvement with LCH, one successfully treated on standard protocol and other being treated on a protocol for relapsed disease. A review of literature showed almost 95% children were less than 2 years of age and 62% were females. Vomiting, abdominal pain, constipation, intractable diarrhea, malabsorption, bloody stools, protein‐losing enteropathy, and even intestinal perforation are some of the reported symptoms. More than 50% patients died within 18 months from diagnosis. Pediatr Blood Cancer. 2010;55:748–753. © 2010 Wiley‐Liss, Inc.     

Growth of children with Langerhans cell histiocytosis

Diseases in childhood have an impact on growth. The influence of Langerhans cell histiocytosis (LCH) on growth has never been studied well. Recently a patient with LCH was treated with human growth hormone (GH) because of severe GH deficiency due to LCH involvement of both the hypothalamus and pituitary. This led us to review our charts from 1971 onward for evaluation of the growth patterns in patients with LCH. Here the long-term growth of 22 patients with LCH is reported, the median follow up being 7 years and 1 month. The height data were converted into standard deviation scores (SDS). At diagnosis the mean SDS of patients with isolated LCH at diagnosis was 0.04 and –0.37 in patients with disseminated LCH. Of the total group, 12 patients did not show any influence from the LCH or therapy on their growth. The remaining 10 patients reached, after a minimum of 3 years, a percentile clearly higher than that at diagnosis. However all the ten above mentioned patients, either isolated or disseminated LCH, had a lesion in the facial side of the skull.Conclusion GH deficiency is not a common manifestation of LCH in childhood and GH provocation tests are only indicated when there is a poor or decelerating growth rate. In our patients the number of organs involved and/or the treatment modality did not influence the growth in all but one.Both authors made equal contributions to this work and are listed in alphabetical order     

Biliary wall calcification in Langerhans cell histiocytosis: report of two cases

Langerhans cell histiocytosis (LCH) is a disorder of unknown pathogenesis affecting one or more organs (unifocal or disseminated form) due to clonal proliferation of Langerhans cells. Liver involvement is more frequent in the disseminated form and the radiological findings of end-stage liver disease due to LCH are similar to those of sclerosing cholangitis. We present the multidetector CT findings in two children with LCH liver involvement and the unique finding of calcification of the biliary wall.     

Thymic Langerhans cell histiocytosis mimicking lymphoma

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal expansion of antigen presenting Langerhans cells. Different clinical features can be seen according to the involved organs and systems. Multisystem disease with organ dysfunction is more common in infants, whereas single system disease is usually observed in older children. The disease can affect any system or organ throughout the body. Thymus is a rarely involvement site reported in LCH and usually is accompanied by skin, bone or lung disease. Here we report a 12-year-old male with thymic involvement by LCH clinically mimicking lymphoma.     

Response to subcutaneous therapy with mistletoe in recurrent multisystem Langerhans cell histiocytosis

We report a case of histologically proven multisystem (MS) Langerhans cell histiocytosis (LCH) with recurrent disease reactivations after systemic chemotherapy. Through the use of subcutaneous therapy with mistletoe (MT), an inactive disease state was achieved.     

Recurrent pneumomediastinum and pneumothorax in Langerhans cell histiocytosis

Pneumothorax is an unusual complication of pulmonary Langerhans cell histiocytosis. We report three children who developed recurrent intrathoracic air leaks. In one case, bilateral pneumothoraces may have been precipated by intermittent positive pressure ventilation during general anaesthesia. Chemical pleurodesis was unsuccessful in preventing recurrence of pneumothoraces in two children. The use of extracorporeal membrane oxygenation as an alternative to intermittent positive pressure ventilation in children with respiratory failure from Langerhans cell histiocytosis is discussed. Med. Pediatr. Oncol. 29:139–142, 1997. © 1997 Wiley-Liss, Inc.     

Reactivation and risk of sequelae in Langerhans cell histiocytosis

OBJECTIVE: To evaluate disease reactivation in patients with Langerhans cell histiocytosis (LCH) and its impact on adverse sequelae. MATERIALS AND METHODS: A retrospective evaluation of 300 patients diagnosed with LCH between 1987 and 2002 with complete response to initial treatment was performed. RESULTS: Mean age at diagnosis was 5.3 years. With a mean follow-up of 4.8 years, reactivation of the disease occurred in 29.7% (89/300) of the patients, with two or more reactivations in 34.8% (31/89) of those. Reactivation occurred in 17.4, 36.8, 46.5, and 53.5% of the patients with single-system unifocal disease (Group A: 161 patients), single-system multifocal disease (Group B: 53 patients), multi-system disease without (Group C: 58 patients), and with (Group D: 28 patients) risk-organ involvement, respectively. The differences between the incidence rates of Groups A and B (P < 0.0004), A and C (P < 0.0001), and A and D (P < 0.0001) were highly significant. The most common reactivation sites involved were bone, middle ear, and skin; reactivation was rare in risk organs (9.5%). The median time between initial complete response and the first reactivation episode was 1 year for Group A, 1.3 years for Group B, and 9 months for Groups C and D. Most reactivation episodes (88%) occurred within the first 2 years of follow-up. Adverse sequelae were recognized in 242/300 patients: 71% (49/69) of patients with and 25.4% (44/173) without reactivations developed these adverse sequelae (P < 0.0001), respectively. Sites most commonly showing sequelae were bone, middle ear, and hypothalamus (Diabetes Insipidus). CONCLUSIONS: Incidence of reactivation correlates with the stage of the disease at diagnosis. Incidence of sequelae correlates with the occurrence of reactivations.     

82例朗格罕斯细胞组织细胞增生症临床分析

目的 分析82例郎格汉斯细胞组织细胞增生症（LCH）患儿的治疗效果,旨在了解LCH的长期预后.方法 收集2001年6月-2011年5月我院收治的初治LCH患儿,其中2001年6月-2005年12月发病者按改良DAL-HX 83/90方案治疗,设为DAL-HX 83/90组,共27例;2006年1月-2011年5月发病者按LCH-Ⅲ方案治疗,设为LCH-Ⅲ组,共55例.所有患儿均按国际组织细胞协会疗效标准评价疗效.结果 82例患儿化疗结束后总有效率为87％,其中DAL-HX83/90组治疗总有效率为82％,LCH-Ⅲ组治疗总有效率为89％,两者比较差异无显著性（P=0.54）.82例患儿5年无事件生存率（EFS）为82％,5年总生存率（OS）为95％.DAL-HX 83/90组和LCH-Ⅲ组患儿复发率分别为22％和16％ （x2=0.12,P=0.73）,3年EFS分别为78％和84％（x2=0.14,P=0.71）.结论 采用改良DAL-HX 83/90方案和LCH-Ⅲ方案的近、远期疗效相仿,均可获得与国外研究近似的有效率和生存率.对有高危脏器累及、复发难治LCH患儿的治疗,仍是目前临床难题.     

Liver involvement in Langerhans cell histiocytosis

Liver involvement in Langerhans cell histiocytosis (LCH) typically presents with hepatomegaly and other signs of liver dysfunction. We present an 11-month-old child having only minimally elevated liver enzymes as an indication of liver involvement. Using sonography as the initial diagnostic tool followed by MRI, LCH of the liver was revealed. A review of sonographic, CT, MRI and MR cholangiopancreatography findings in liver LCH is presented. We recommend that physicians consider sonography and MRI screening for liver involvement in patients with newly diagnosed LCH, as periportal involvement may be present with little or no liver function abnormality present, as in this patient.     

Langerhans cell histiocytosis in neonates

BACKGROUND: To study the incidence, clinical patterns, course, and outcome of neonatal Langerhans cell histiocytosis (LCH). PROCEDURE: Retrospective analysis of the data of the Austrian/German/Swiss/Netherlands LCH Study Group. The incidence of neonatal LCH was estimated with the data from the population-based German Childhood Cancer Registry. RESULTS: The estimated incidence of neonatal LCH (LCH diagnosed within 28 days after birth) in the population-based registry was 1-2/1,000,000. In 61/1,069 trial patients (6%), the first disease manifestations were observed in the neonatal period. However, in only 20 of them, the diagnosis was established within this period. There was a preponderance of multisystem (MS)-LCH 36/61 (59%). Cutaneous changes were the most common initial manifestation in both, single-system (SS)-LCH (92%), and MS-LCH (86%). In 72% of the MS-LCH patients, risk organs (ROs) were involved at diagnosis as well. The probability of survival at 5 years was 94% in SS-LCH and 57% in MS-LCH, which is significantly lower than in older age groups. CONCLUSIONS: In contrast to the available literature, neonatal LCH is characterized by a clear predominance of MS-LCH. Cutaneous changes are the most common initial manifestation in neonates with both SS-LCH and MS-LCH. Prompt evaluation of disease extent upon diagnosis is mandatory for risk-adapted treatment. The disease course is unpredictable upon diagnosis. Close monitoring for disease progression is mandatory if isolated cutaneous LCH is managed by the "wait and see" approach. Neonates with MS-LCH, especially those with RO involvement at diagnosis, have less favorable prognosis compared to infants and older children, and need systemic therapy.     

36例朗格罕细胞组织细胞增生症的临床与病理分析

目的分析朗格罕细胞组织细胞增生症(langerhans cell histiocytosis,LCH)传统分型和单系统/多系统分型及Lavin-Osband分级之间的联系,观察LCH病理结果,并对比临床和预后中的不同。方法回顾性调查36例LCH,分析比较其临床、病理及预后。结果36例LCH中14例单系统LCH,Lavin-OsbandⅠ、Ⅱ级,治疗后痊愈或好转12例。22例多系统LCH,多为Ⅲ、Ⅳ级;治疗后未愈或恶化9例,死亡2例。病理检查17/17例CD1a阳性;电镜6/10例找到Birbeck颗粒;12/12例Fascin染色阳性。结论现行分型分级利于直观评估病情、预后。CD1a染色比电镜找Bir-beck颗粒更简便易行。Fascin在LCH诊断中有一定作用,但其价值需大样本量的试验证实。     

Evaluation and treatment of Langerhans cell histiocytosis patients with central nervous system abnormalities: Current views and new vistas

Central nervous system (CNS) involvement in Langerhans cell histiocytosis (LCH) can include mass lesions of the hypothalamic pituitary axis, choroid plexus, cerebrum, and cerebellum or magnetic resonance imaging (MRI) signal abnormalities of the cerebellum, pons, and basal ganglia. The term neurodegenerative (ND) CNS‐LCH has been given to the MRI signal abnormalities and neurologic dysfunction, although initially patients may have no clinical symptoms. Standardized evaluations to better understand the natural history and response to therapy are needed. We propose guidelines for clinical, radiologic, and physiologic tests as a framework for developing the best methods of evaluation, which can then be tested in prospective treatment protocols.     

DOR-1, A novel CD10+ stromal cell line derived from progressive Langerhans cell histiocytosis of bone

BACKGROUND: Langerhans cell histiocytosis (LCH) is granulomatous proliferative disorder characterized by the presence of activated Langerhans cells admixed with macrophages, lymphocytes, and eosinophils. In an effort to obtain an LCH ex vivo model, we succeeded in establishing the DOR-1 cell line from an LCH lesion of bone in a 3-year-old girl. PROCEDURE: The DOR-1 cell line was established from a CD1a immunoreactive LCH lesion of bone maintained in long-term cell culture. The phenotypic characteristics were assessed by immuno-cytochemistry and fluorescence activated cell sorter (FACS) analysis. Cytogenetic analysis was performed by RHG-banding that was supplemented by fluorescence in situ hybridization (FISH). RESULTS: The DOR-1 cells grew in vitro as a poorly differentiated mesenchymal-like cells with a doubling time between 72 and 96 hr. The cells exhibited pleomorphism and consistent immuno-reactivity for CD10 (50%), CD13 (55%), CD68 (65%), and CD117 (70%) while CD1a, Langerin and HLA-DR were not detected. By RHG-banding, several aberrant chromosomes were detected including the t (9; 17) (p23; p13) translocation and a pair of long dicentric marker chromosomes indicating clonal abnormality. Functionally, exposure to 33 nM 12-O-tetradecanoyl phorbol mirystate-13-acetate (TPA) induced DOR-1 cell differentiation with appearance of cytoplasmic extensions. CONCLUSIONS: The DOR-1 cell line exhibits distinct immuno-cytochemical features and carries the t (9; 17) (p23; p13) translocation suggesting involvement of stromal-like cell lineage in LCH initiation and progression.