颅骨和脊椎朗格汉斯组织细胞增生症

目的：探讨颅骨和脊椎朗格汉期组织细胞增生症（LCH）的诊断和治疗。方法：总结5例中经手术后病理证实的颅骨和脊椎LCH15例，男10例，女5例，年龄1．5年－10岁，颅骨损害11例（单发9例，多发2例），颅骨合并脊椎损害2例，脊椎损害伴椎旁软组织肿块2例。影像学上均表现为骨质破坏，颅骨单发和多发损害，术后化疗，不作放疗，颅骨伴脊椎损害和脊椎损害伴椎管内外软组织肿块，脊椎放疗化化疗，结果：全部病例随访0．5－4．5年，无一例死亡，2例颅多骨多发损害，术后化疗期间，颅骨有新病灶出现，改用环磷酰胺，病灶消失，无复发，结论：病变组织活检是明确诊断的依据。术后化疗，放疗应视疾病程度而定，颅骨和脊椎LCH预后较好。     

超声诊断儿童朗格汉斯组织细胞增生症颅骨病变的价值

目的本研究旨在分析超声诊断颅骨朗格汉斯组织细胞增生症的声像图特征。方法回顾性分析经病理证实的19例颅骨朗格汉斯组织细胞增生症患儿的超声表现,总结其声像图特征,并与CT、MRI的特征进行比较。结果 19例患儿共发现颅骨病变25个部位,4例为颅骨多发病变。其中颞部12个,顶部7个,枕部5个,颊部1个。超声表现为颅骨膨胀性破坏,颅骨内外板分离呈斜坡状或呈阶梯形,破坏的骨质边缘锐利,形态不规则。所有病变同时伴有软组织低回声肿块,2例伴有无回声区。肿块内可见丰富的短棒状血流信号。CT和MRI结果:19例行CT检查,4例行MRI检查,表现为局部骨质破坏伴软组织肿块。CT发现胸椎椎体病变1例。结论颅骨朗格汉斯组织细胞增生症的超声表现具有一定的特征性。超声因其具有不具放射性、方便及经济的优点,可以作为颅骨朗格汉斯组织细胞增生症的首选检查方法。     

儿童朗格汉斯细胞组织细胞增生症病因和治疗进展

朗格汉斯细胞组织细胞增生症(LCH)是一种以大量未成熟树突状细胞在组织中异常积累为特征的罕见疾病。LCH的病因与发病机制随着BRAFV600 E基因突变的发现已逐渐明朗,但LCH多样化的临床表现仍导致其治疗困难。文章综述近年来有关LCH的病因与发病机制和治疗的最新进展。     

骨朗格汉斯细胞组织细胞增生症108例临床病理分析

目的 探讨小儿骨朗格汉斯细胞组织细胞增生症(LCH)的临床特点、病理形态学、免疫表型特征、鉴别诊断及预后.方法 回顾性分析108例小儿骨LCH的临床资料,其中40例行免疫组织化学染色.按2000年WHO分类标准重新分类,并随访.结果 108例小儿骨LCH中累及单块骨73.14%(79/108例),累及多块骨(伴或不伴皮肤受累)25%(27/108例),累及多个脏器(骨、肝、脾及其他)1.9%(2/108例).累及单块骨及多块骨5 a生存率均为100%,累及多个脏器2例,随访25个月2例均死亡.免疫组织化学染色显示,40例小儿骨LCH中CD1a阳性100%(40/40例),Vim阳性90%(36/40例),S100阳性90%(36/40例),CD68阳性67.5%(27/40例),Lys阳性40%(16/40例),MAC387阳性30%(12/40例),CK、 EMA 均阴性.结论 小儿骨LCH是一种病因不明的肿瘤性增生性疾病,在病理学上具有特殊的形态学表现及免疫组织化学表型.疾病的预后与骨病损范围和病理分型有关,大部分病例预后好.     

多系统累及朗格汉斯细胞组织细胞增生症治疗进展

朗格汉斯细胞组织细胞增生症(Langerhans cell histiocytosis,LCH)是一种罕见的树突细胞和网状细胞系统增生性疾病,目前分为单系统LCH(SS-LCH)和多系统LCH(MS–LCH)。MS-LCH的预后较差,及时有效地干预是患者存活的关键。目前有化学治疗、免疫治疗、造血干细胞移植治疗等多种治疗方案。文章就MS-LCH相关治疗方案的进展进行综述。     

新生儿朗格汉斯细胞组织细胞增生症一例

患儿，男，34d，因“额部肿物1个月”入新生儿外科病房。患儿为足月顺产，生后即发现额部肿物，暗红色，逐渐增大至鸡蛋黄大小，病来未经治疗，曾破溃一次，周身同时伴有皮疹，时多时少，无发热，吃奶好，大小便正常。母孕期正常。体检：体温37℃，脉搏125次／min，呼吸35次／min．     

克拉屈滨治疗儿童难治性朗格罕细胞组织细胞增生症并发肝损伤1例并文献复习

目的讨论并鉴别克拉屈滨引起的少见的不良反应—药物性肝损伤(DILI),提高克拉屈滨治疗儿童难治性朗格罕细胞组织细胞增生症(LCH)的临床用药安全性。方法回顾性分析1例1岁5月男性难治性LCH,经LCH-Ⅲ诱导方案、Japan LCH-SG 96 B诱导方案两次诱导后治疗反应差,评估病情再活动,转入更为强烈的LCH-S-2005方案:克拉屈滨9mg/(m~2·d)联合阿糖胞苷1g/(m~2·d)治疗,一个疗程共5d,并复习相关文献。结果该病例在用药后出现严重肝脏毒性,表现为肝大、显著高胆红素血症、肝酶不高,CT影像改变肝大,密度减低,门静脉周围见条状低密度影,临床表现类似肝窦闭塞综合征(SOS)。该病例同时发生了4级血液学毒性最后死于肺部感染。结论临床医师需注意克拉屈滨引起药物性肝损伤的问题,而且可能在原来存在肝脏基础疾病的患者中更易出现。克拉屈滨治疗前肝功能的充分评估、治疗过程中肝功能的密切监测、血药浓度监测、及时的病理学诊断、剂量的个体化调整等,是今后克拉屈滨应用过程中需要重视和关注的要点。     

儿童朗格汉斯细胞组织细胞增生症免疫状态检测及其意义

目的 研究不同临床类型的朗格汉斯细胞组织细胞增生症(LCH)患儿初诊时的免疫功能变化,探讨免疫功能检测在LCH发病机制及病情预后评估中的意义.方法 应用流式细胞术分析30例LCH患儿初诊时外周血各淋巴细胞亚群(T细胞、B细胞、NK细胞、NKT细胞、Th细胞、Ts细胞、Th/Ts比值、Treg细胞)比例,同时应用化学发光...     

儿童朗格汉斯细胞组织细胞增生症的临床及BRAF基因突变研究

目的 总结朗格汉斯细胞组织细胞增生症(LCH)患儿临床特征,分析BRAF基因突变与临床特征的关系。方法 回顾性性分析2019年—2021年湖南省儿童医院收治的46例LCH患儿临床资料,采用下一代基因测序方法检测BRAF基因突变,分析其与临床特征的关系。结果 28例(61%)病灶组织检测出BRAF基因突变,其中26例为V600E突变。BRAF突变与年龄、性别、RO+、MS无关。9例出现疾病进展,均为MS-LCH,其中8例加用阿糖胞苷化疗(其中5例口服达拉非尼治疗),6例好转,1例处于中间反应状态,1例放弃后死亡。结论 LCH患儿BRAF基因突变率高,其临床意义需进一步探讨。达拉非尼可能有助于提高二线治疗BRAF基因突变患儿的好转率。     

儿童噬血细胞淋巴组织细胞增生症诊治进展

噬血细胞淋巴组织细胞增生症(hemophagocytic lymphohistiocytosis,HLH)是以发热、肝脾大、血细胞减低、高甘油三脂血症及低纤维蛋白原血症为特点的一组临床综合征,是免疫异常基础上严重威胁患儿生命的过度炎症反应性疾病,免疫化疗使该病的生存率得到显著提高.随着对HLH认识的不断深入,诊断为该病的患儿也在逐年增多,发病率要远高于以往的认识.除遗传性HLH外,感染、肿瘤、结缔组织疾病等多种疾病均可继发HLH,近几年在高致病性禽流感H5N1患者中也发现了继发HLH.由于与HLH相关的疾病种类繁多,对患儿所造成的危害极为严重,使得明确HLH发病机制并探究更有效的治疗迫在眉睫.     

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.     

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.     

Pulmonary Langerhans cell histiocytosis: a variable disease in childhood

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is rare in childhood but occurs most commonly in children with multisystem (MS) LCH. In adults, by contrast, the lung is the most common and usually the sole organ affected. This retrospective study describes the clinical manifestation, course, and outcome of PLCH in children consecutively diagnosed at two Canadian institutions. PROCEDURE: The medical records of children (<18 years of age) consecutively diagnosed with LCH at the two institutions, were examined to ascertain the demographic details, pathological diagnosis, and organs involved. Further clinical details including, the clinical manifestation, details of therapy, course of lung disease, and clinical outcome were extracted for patients with PLCH. Initial and follow-up lung radiographs and CT scans were re-reviewed. RESULTS: Of the 178 patients with LCH, 40 (22.5%) presented with MS disease. Thirteen (7.3%) had PLCH, seven at initial diagnosis, and six at the time of disease progression. The median age was 10.1 months and mean was 11.9 months at diagnosis of PLCH. Lung involvement was always in the context of MS LCH, and half of the patients had no respiratory symptoms. Disease-free survival was around 70%, with a mean follow-up duration of 7 years. Of the four patients who died, three had other risk-organ involvement. Five of the nine surviving patients have had complete radiological resolution of PLCH. CONCLUSION: PLCH is seen in less than 10% of childhood LCH, but more than 30% of MS LCH. About half of children with PLCH may be asymptomatic, and the prognosis appears to depend on the presence or absence of other risk-organ involvement. The MS PLCH found in children appears to be a different disease from the single system (SS) PLCH seen in adults.     

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.     

Haploidentical parental hematopoietic stem cell transplantation in pediatric refractory Langerhans cell histiocytosis

Children with MS‐LCH that fail to respond to conventional chemotherapy have poor outcomes. HSCT represents a potential salvage approach. It has been applied in over 50 cases in recent years. HSCT can achieve greater disease control than chemotherapy, but it carries a high risk of transplant‐related mortality; thus, the haploidentical parental HSCT is used infrequently in pediatric refractory LCH. We report the first successful haploidentical parental HSCT, with no T‐cell depletion, in two girls, aged 26 months and five months, with refractory MS‐LCH. The mothers were donors with 5/6 and 4/6 HLA matches, respectively. The conditioning regimen included busulfan + cyclophosphamide + etoposide + antithymocyte‐globulin ± fludarabine; the GVHD prophylaxis was based on cyclosporine + methotrexate ± mycophenolate‐mofetil ± zenapax. In both cases, the stem cells were sourced from peripheral blood and BM, which included CD34+ cells (13.17 × 10⁶/kg and 40.23 × 10⁶/kg, respectively). These patients survived and showed no signs of disease activity in 54‐ and 44‐month post‐HSCT follow‐ups. Our results indicated that, for patients that fail chemotherapy delivered early in the disease, but do not show organ dysfunction progression, it may be possible to achieve successful haploidentical parental HSCT with a strong myeloablative regimen.     

Successful treatment of refractory Langerhans cell histiocytosis by allogeneic peripheral blood stem cell transplantation

We describe a six-yr-old boy who exhibited typical signs and symptoms of LCH with EBV-associated hemophagocytic syndrome from the age of 15 months. Multiple courses of conventional chemotherapy achieved only marginal improvement over the ensuring five yr. During this period, this boy experienced recurrent episodes of hemophagocytic syndrome associated with CMV infection. Five yr after the first diagnosis of LCH, the patient was treated with allogeneic PBSCT from his HLA-identical eight-yr-old brother. PBSCT was performed using a TBI-incorporating conditioning regimen comprising TBI, busulfan, and cyclophosphamide. Diabetes insipidus, typically a permanent consequence of LCH, was well controlled by DDAVP therapy. At the time of writing, this boy is alive and well, and had been disease-free for more than two yr after the PBSCT.     

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.     

Anti-CD52 antibody, alemtuzumab, binds to Langerhans cells in Langerhans cell histiocytosis

BACKGROUND: The humanized anti-CD52 monoclonal antibody, alemtuzumab (or Campath-1H), has been shown to potently deplete lymphocytes in human patients. It has been used to successfully treat graft versus host disease and chronic lymphocytic leukemia (CLL). CD52 is expressed on normal lymphocytes, monocytes, and some dendritic cell subsets. However, normal Langerhans cells (LC's) in the skin do not bind alemtuzumab. We sought to determine whether the pathologic LC's of Langerhans cell histiocytosis (LCH) express CD52 and thus could be targeted by this antibody. METHODS: Immunohistochemistry was performed on both frozen and fixed/paraffin-embedded tissue specimens using either Campath-1G (the parental rat isotype) or Campath-1H (the humanized version of Campath in clinical use). RESULTS: Both Campath-1H and Campath-1G were found to bind to the pathologic LC's in LCH, but not the normal LC's of skin. Specific staining was demonstrated in all (13 of 13) LCH specimens examined, though staining was somewhat variable among specimens, and tended to be weaker in paraffin-embedded specimens. CONCLUSIONS: Expression of CD52 by the pathologic LC's seen in LCH suggests that alemtuzumab may represent a new, targeted therapy for this disease. Such therapy is particularly needed for patients with refractory, high-risk disease. Further investigation of the possible clinical use of this antibody in these patients is warranted.