Features Of Langerhans Cell Histiocytosis Research Articles

Langerhans Cell Histiocytosis Following Hodgkin Lymphoma in Adult: A Case Report

Introduction: Langerhans cell histiocytosis (LCH) is a very rare disorder, and usually considered a disease of childhood. It is rarely observed in adults. Its etiopathogenesis remains to be elucidated. One possible etiological cause is a reactive proliferation of Langerhans cells following chemotherapy or radiotherapy for Hodgkin's disease (HD). Eosinophilic granuloma is the benign accumulation of histiocytes located primarily in the bones, but which also affects other organs, including the skin, lungs and lymph nodes. The time interval between LCH occurrence and previous lymphoma is variable. The occurrence of eosinophilic granuloma in a patient with Hodgkin disease has rarely been reported. Objective: This case report aimed to describe the clinic-pathological, histopathological, immunohistochemical and other features of LCH and to analyze LCH clinical features for improving diagnosis and decreasing misdiagnosis rate. Case report: In this report, a 38-year-old female presented with LCH twenty-two months after diagnosis and treatment of nodular sclerosing HD. The patient presented with generalized lymphadenopathy and general weakness. The Langerhans cells diffusely infiltrated in the inguinal lymph node and the tumor cells were positive for CD1a and S-100 expression. The patient received chemotherapy and show complete remission. Conclusion: LCH has a very rare occurrence following HD in adult. The definitive diagnosis depends on pathological biopsy and immunohistochemistry. Although specific therapeutic approach hasn't been well established, combined chemotherapy for multisystem lesions and surgical operation or radiotherapy for unifocal lesions may improve the therapy.

Endocrine features of Langerhans cell histiocytosis in paediatric patients: A 30-year review.

To document the incidence of endocrine features in paediatric patients with LCH, treated at a tertiary paediatric centre in Victoria, Australia. Retrospective chart review of electronic medical records and oncology database of patients with LCH managed at a tertiary paediatric centre. Patients were excluded if a biopsy did not suggest LCH or if records were incomplete. One hundred seventy-one patients were identified and 141 records of patients diagnosed with LCH over the last 30 years were assessed for endocrinopathies, from diagnosis to last documented follow-up. Mean age at diagnosis was 5 years 8 months. Of these, 15% (n = 21) had CDI, 7% had growth hormone deficiency (GHD) (n = 10) and 8% (n = 11) had more than one endocrinopathy noted during follow-up. Forty percent (n = 57) were pre-pubertal at the time of audit or upon discharge from tertiary services. Ongoing pituitary assessment, in addition to CDI, is required to detect evolving deficiencies of GHD and gonadotropins as these can be subtle, late or missed. Close follow-up of growth and progression through puberty, even if discharged from tertiary care, is essential.

Clinical and prognostic features of Langerhans cell histiocytosis in adults.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by clonal expansion of CD1a+ CD207+ myeloid dendritic cells. The features of LCH are mainly described in children and remain poorly defined in adults; therefore, we conducted a nationwide survey to collect clinical data from 148 adult patients with LCH. The median age at diagnosis was 46.5 (range: 20-87) years with male predominance (60.8%). Among the 86 patients with detailed treatment information, 40 (46.5%) had single system LCH, whereas 46 (53.5%) had multisystem LCH. Moreover, 19 patients (22.1%) had an additional malignancy. BRAF V600E in plasma cell-free DNA was associated with a low overall survival (OS) rate and the risk of the pituitary gland and central nervous system involvement. At a median follow-up of 55 months from diagnosis, six patients (7.0%) had died, and the four patients with LCH-related death did not respond to initial chemotherapy. The OS probability at 5 years post-diagnosis was 90.6% (95% confidence interval: 79.8-95.8). Multivariate analysis showed that patients aged ≥60 years at diagnosis had a relatively poor prognosis. The probability of event-free survival at 5 years was 52.1% (95% confidence interval: 36.6-65.5), with 57 patients requiring chemotherapy. In this study, we first revealed the high rate of relapse after chemotherapy and mortality of poor responders in adults as well as children. Therefore, prospective therapeutic studies of adults with LCH using targeted therapies are needed to improve outcomes in adults with LCH.

Classic cytomorphological features of Langerhans cell histiocytosis with osseous involvement.

Classic cytomorphological features of Langerhans cell histiocytosis with osseous involvement.

Methotrexate and Cytarabine for Adult Patients with Newly Diagnosed Langerhans Cell Histiocytosis: A Single Arm, Single Center, Prospective Phase 2 Study

Backgroud: Langerhans cell histiocytosis (LCH) is a rare, heterogeneous histiocytic disorder occurring in patients of all ages from neonates to the elderly. The features of LCH are well described in children, however, they remain poorly defined in adults. There is no standard first-line treatment for adult LCH. The current standard treatment protocol for children is vinblastine plus prednisone, which has never been proven effective for adults in a prospective study. Considering the relatively high frequency of pituitary involvement and late onset of neurodegenerative symptoms, patients may benefit from the combination of cytarabine and methotrexate as both these drugs cross the blood-brain barrier. Methods: This phase 2, prospective, single-center study enrolled 83 newly diagnosed adults multisystem (MS)-LCH or LCH with multifocal single system (SS-m) involved between January 2014 and March 2019 (NCT 02389400). The methotrexate (1g/m2by 24-hour infusion on day 1) and cytarabine (100 mg /m2by 24-hour infusion for 5 days) was administered every 35 days for a cycle and 6 cycles totally. The primary endpoint was event-free survival (EFS). Events were defined as a poor response to chemotherapy, reactivation after chemotherapy or death from any cause. Results: The median age was 33 years (range 18-65 years). Forty-nine patients were male (59.0%). Six patients were SS-m LCH (7.2%), 77 patients were MS LCH (92.8%). The most common organ involved in the total cohort was bone (78.3%), followed by lung (67.5%), pituitary (62.7%) and lymph nodes (38.6%). Twenty-three patients had liver involvement (27.7%), 11 patients with spleen involvement (13.3%), no patients had hematologic involvement. All patients received at least one course of chemotherapy, with median 6 (1-6) courses. Overall 69 patients (83.1%) completed protocol treatment, 14 patients (16.9%) went off protocol (13 patients' decision, 1 poor response). The overall response rate was 87.9%. including 43 patients (51.8%) as having non-active disease and 30 patients (36.1%) as active disease (AD)/better. After a median of 23 months (range 7-79 months) follow-up, one patient died of disease progression and 25 patients had reactivation of the disease. The estimated 3-year OS and EFS were 97.7% and 68.0% separately (Figure 1). To evaluate the prognostic factors of EFS using univariate analysis, liver, spleen, lung and skin involvement at baseline had significantly shorter EFS. EFS were also evaluated using multivariate Cox regression model, liver involvement remained predictive of poorer EFS (P = 0.012; HR 0.339, 95% CI 0.146-0.784). The most common toxicity was hematologic adverse events. All patients experienced neutropenia and thrombocytopenia. Thirty-five patients (42.2%) had grade 4 neutropenia, 43 patients (51.8%) had grade 3 neutropenia. Fourteen patients (16.9%) had grade 4 thrombocytopenia, 13 patients (15.7%) had grade 3 thrombocytopenia. No patients received prophylactic antimicrobial treatment during any of the cycles. Forty patients (48.2%) experienced febrile neutropenia, including 38 (45.8%) grade 3 and 2 (2.4%) grade 4. The most common non-hematological toxicities were gastrointestinal complications. Two patients developed grade 3 nausea. Grade 3 alanine aminotransferase increased occurred in in two patients. No treatment related death. One patient had secondary primary malignancy (oral squamous cell carcinoma), 56 months after the last course of MA regimen. Fifty-two of 82 surviving patients experienced sequelae to the disease that were not influenced by therapy. Forty-eight patients had diabetes insipidus and 4 presented with hypothyroidism. Conclusion: Methotrexate and cytarabine is an efficient and safe regimen for newly diagnosed adult LCH. The involvement of liver at baseline indicates a worse prognosis in adult LCH. Disclosures No relevant conflicts of interest to declare.

BRAF V600E and Pten deletion in mice produces a histiocytic disorder with features of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is characterized by the accumulation of Langerin (CD207)-expressing histiocytes. Mutational activation of mitogen-activated protein kinase pathway genes, in particular BRAF, drives most cases. To test whether activated BRAF is sufficient for the development of LCH, we engineered mice to express BRAF V600E under the control of the human Langerin promoter. These mice have shortened survivals, smaller lymphoid organs, absent Leydig cells, and fewer epidermal LCs than controls, but do not accumulate histiocytes. To test whether the absence of histiocyte proliferation could be due to oncogene-induced senescence, we engineered homozygous Pten loss in the same cells that expressed BRAF V600E. Like mice with intact Pten, these mice have shortened survivals, smaller thymi, and absent Leydig cells. However, loss of Pten also leads to the accumulation of CD207+ histiocytes in spleen, thymus, and some lymph nodes. While many CD207+ histiocytes in the thymus are CD8-, reminiscent of LCH cells, the CD207+ histiocytes in the spleen and lymph nodes are CD8+. These mice also accumulate large numbers of CD207- cells in the lamina propria (LP) of the small intestine. Both the lymphoid and LP phenotypes are likely due to human Langerin promoter-driven BRAF V600E expression in resident CD8+ dendritic cells in the former and LP dendritic cells in the latter and confirm that Pten loss is required to overcome inhibitory pathways induced by BRAF V600E expression. The complex phenotype of these mice is a consequence of the multiple murine cell types in which the human Langerin promoter is active.

A rare co-existence of langerhans cell histiocytosis and lichen planus

Langerhans cell histiocytosis (LCH) is the commonest of the histiocytic disorders. Owing to the relative rarity of the condition, it remains a disease in which the diagnosis is often delayed or missed. Commonly seen in infancy or early childhood, the disorder is characterized by proliferation of abnormal and clonal Langerhans cells in skin, bone, lymph nodes, lungs, liver, spleen, and bone marrow. Lichen planus presents as purple, polygonal, pruritic, papular eruption of unknown etiology affecting skin, mucous membranes and nails. Despite of thourough literature search, we could not find any association of lichen planus with LCH. Hereby, we report a case of five year old child with acute onset of polymorphic eruptions all over the body which on histopathology and Immunohistochemistry showed features of Langerhans cell histiocytosis and lichen planus on bilateral lower limb.

Clinical Analysis of 122 Cases of Langerhans Cell Histiocytosis.

Objective To investigate the features of Langerhans cell histiocytosis (LCH). <b>Method</b> Skin lesions,systemic involvement,imaging characteristics,laboratory tests,immunophenotying,treatment response,and survival of 122 LCH patients treated at our center from February 1983 to August 2013 were retrospectively analyzed. Results LCH was associated with diverse skin lesions. Lung was the most involved organ,followed by bone,skin,lymph nodes,liver,spleen,oral cavity,and thyroid. Multisystem LCH was more common than single-system LCH. Single-system LCH was mostly treated by surgery,whereas multisystem LCH by combined chemotherapy. Conclusion LCH has diverse clinical manifestations,with lungs being the most often involved organ. Surgery or chemotherapy is the mainstream treatment.

MRI and clinical features of Langerhans cell histiocytosis (LCH) in the pelvis and extremities: can LCH really look like anything?

To assess clinical and MRI features of Langerhans cell histiocytosis in the pelvis and extremities. The MRI and clinical features of 21 pathologically proven cases of LCH involving the pelvis and extremities were studied. Multiple characteristics of the lesions were evaluated (location, size, T1/ T2/post-contrast features, perilesional bone and soft tissue signal, endosteal scalloping, periosteal reaction, soft tissue mass, pathologic fracture). Pre-biopsy radiologic diagnoses were collected from the original clinical reports. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), temperature, and white blood cell count (WBC) were collected at the time of diagnosis when available. The locations of the LCH lesions included five humerus, four femur, five ilium, one tibia, one clavicle, and three scapula. Lesional size ranged from 1.8 to 7.1 cm, with a mean of 3.6 cm. All lesions demonstrated perilesional bone marrow edema, periosteal reaction, endosteal scalloping, and post-contrast enhancement. An associated soft tissue mass was present in 15/21 (71.4 %). Clinically, the WBC, ESR, and CRP were elevated in 2/14 (14 %), 8/12 (67 %), and 4/10 (40 %) of cases, respectively. Fever was documented in 1/15 (7 %) patients and pain was reported in 15/15 (100 %). The clinical and radiologic features of LCH in the pelvis and extremities overlap with infection and malignancy, but LCH must be considered in the differential diagnosis, as it routinely presents with aggressive MRI features, including endosteal scalloping, periosteal reaction, perilesional edema, and a soft tissue mass. Furthermore, an unknown skeletal lesion at presentation without aggressive MRI features is unlikely to represent LCH.

H syndrome with histological features of Langerhans cell histiocytosis

H syndrome with histological features of Langerhans cell histiocytosis

A clinicopathological analysis of 160 cases of adult Langerhans cell histiocytosis

目的观察成人朗格汉斯细胞组织细胞增生症(LCH)患者的临床特征，以提高其早期诊断与治疗水平。方法对1992年1月至2013年12月间年龄≥18岁的160例LCH患者资料进行回顾性分析。结果160例患者中男110例，女50例（男、女比例为2.2∶1），中位年龄33(18~73)岁。160例患者共有222个病变部位，包括骨骼172处(77.5%)，淋巴结13处(5.8%)，口腔8处(3.6%)，皮肤及肝脏各5处(2.2%)，眼眶及肺各4处(1.8%)，胸锁关节3处(1.4%)，消化道、耳及甲状腺各2处(0.9%)，肾上腺及舌下腺各1处(0.5%)。1个脏器受累150例(93.8%)，2个以上脏器受累10例(6.2%)。外院临床误诊77例(48.1%)，其中骨肿瘤（包括骨巨细胞瘤、纤维结构不良、软骨母细胞瘤、骨母细胞瘤及骨肉瘤）28例，骨结核13例，脑膜瘤9例，骨囊肿、慢性骨髓炎及尿崩症各5例，皮肤病及恶性淋巴瘤各4例，皮肤慢性溃疡、慢性中耳炎、肺癌及口腔癌各1例。结论成人LCH患者以男性居多，以单系统病灶占绝对优势，多发生于骨骼系统。成人LCH临床表现多样化，易于延误诊断。

Langerhans Cell Histiocytosis of the Clavicle in a 13-Year-Old Boy

Langerhans Cell Histiocytosis (LCH) is a rare neoplasm characterized by abnormal proliferation of histiocytic cells. In this case report, we describe a unique case of a 13-year-old boy who presented to the clinic with an insidious onset of mid-clavicular pain. The provisional radiologic diagnosis of Langerhans Cell Histiocytosis of the clavicle was confirmed by an incisional biopsy of the left mid-clavicle lesion. The patient's lesion was treated by curettage, bone grafting, and internal fixation, due to the presence of pathologic fracture. At the 2-year followup, the patient was asymptomatic, and the lesion showed complete resolution without recurrence. The case report highlights the characteristic features of Langerhans Cell Histiocytosis in an unusual location, the knowledge of which would help avoid delayed or missed diagnosis in the future.

18F-Fluoride PET/CT Aspect of an Unusual Case of Erdheim-Chester Disease With Histologic Features of Langerhans Cell Histiocytosis

We report the case of a 63-year-old woman with Erdheim-Chester disease (ECD) and histologic features of Langerhans cell histiocytosis, both extremely rare histiocytic proliferations responsible of skeletal and extraskeletal involvement. 18F-Fluoride PET/CT revealed multiple intense focal uptake scattered throughout the skeleton. We also performed an 18F-FDG PET/CT which point out visceral and vascular involvement. This case illustrates the interest of PET/CT in ECD, a rare polymorphus and systemic disease, and in our knowledge, this is the first reported illustration of 18F-fluoride PET/CT findings in this pathology.

Langerhans cell histiocytosis: a clinicopathologic and immunohistochemical analysis of 258 cases

To observe the clinicopathologic features of Langerhans cell histiocytosis (LCH), and to evaluate the values of langerin, CD1a and S-100 protein expression in diagnosis of the tumor. Total 258 cases of Langerhans cell histiocytosis in the past 18 years (from 1992 to 2008) were collected, morphologic review and immunohistochemical staining were performed. In all 258 cases, the ages of patients older than 16 years or younger than 2 years were 126 (48.8%) and 37 (14.3%), respectively, in the remaining 95 (36.8%) of the cases, the age of the patients ranged from 2 to 16 years. For all of 258 cases, there were 364 diseased sites. Bony lesions accounted for 77.2% (281 cases), especially the skull (112 cases, 39.9%), followed by lymph node (25 cases, 6.9%) and skin (14 cases, 3.8%). Clinically, unisystem or unifocal disease was predominant (201 cases, 77.9%), followed by unisystem and multifocal disease (21 cases, 8.1%), multi-system disease (26 cases, 10.1%), isolated pulmonary LCH (2 cases, 0.8%), and unclassified (8 cases, 3.1%). Histologically, variable number of Langerhans cells was present in 265 samples of 258 cases. Multinucleated giant cells were found in 166 (62.6%) of the samples. Eosinophils were the major infiltrating non-neoplastic cells, and eosinophilic abscess was seen in 57 cases (21.5%). Coagulative necrosis and dead bone were detected in 29 (10.9%) and 124 (46.8%) of the cases, respectively. Immunohistochemically, the expression of S-100 protein, CD1a and langerin was 99.1% (209/211), 100% (206/206) and 98.5% (193/196), respectively, and the sensitivity of them had no statistical difference. In this group of LCH cases, the ratio of adult patients is high, but the proportion of multi-organ lesion is low. No significant difference of the sensitivity is found among langerin, CD1a and S-100 expression in diagnosis of LCH.

Mediastinal Mass and Paraparesis as the Sole Presenting Features of Langerhans Cell Histiocytosis

Ganesan, Prasanth MD*; Kaushal, Seema MD†; Thulkar, Sanjay MD‡; Bakhshi, Sameer MD* Author Information

Oral Langerhans cell histiocytosis in Malaysian children: a 40‐year experience

Oral Langerhans cell histiocytosis is generally seen in children. To determine the clinicopathological features of oral LCH in Malaysian paediatric patients. A retrospective study was carried out to determine the clinicopathological features of Langerhans cell histiocytosis (LCH), Letterer-Siwe disease, Hand-Schuller-Christian disease, eosinophilic granuloma, and histiocytosis X occurring in the oral cavity in children, diagnosed histologically in the main oral histopathology laboratory in Malaysia from 1967 to 2007. There were 17 cases (eight girls and nine boys) with age ranging from 1 to 7 years. There were ten Malays, four Chinese, two Indians, and one of other ethnicity. Thirteen cases presented as gingival swellings with six of these cases accompanied with mobility of the teeth. Nine cases involved the mandible, two in the maxilla, and two cases in both the maxilla and mandible. The radiographic findings were mentioned only in nine cases with presence of bony erosion or destruction of the jaw bones. Four cases had punched-out radiolucencies of the skull. The patients also had other systemic signs and symptoms: skin lesions (n = 5), hepatosplenomegaly (n = 2), prolonged fever (n = 2), diabetes insipidus (n = 1), and exophthalmos (n = 1). Two cases were known cases of systemic LCH. The histopathologic features of LCH are easily recognized; however, with the development of immunostaining, the use of CD1a helps in confirming the diagnosis.

Imaging Features of Thyroid Involvement by Langerhans Cell Histiocytosis

A 2-year-old male presented with fever, rash, right upper quadrant pain, and hyperbilirubinemia and was diagnosed with Langerhans cell histiocytosis (LCH). Periportal, hepatic, pulmonary, thymic, and thyroid involvement was noted on initial imaging. Thyroid gland involvement by LCH is rare. This case illustrates computed tomography, ultrasonography, and magnetic resonance imaging features of LCH of the thyroid.

Incidence and clinical features of Langerhans cell histiocytosis in the UK and Ireland

Objectives:There are few published studies on the epidemiology of Langerhans cell histiocytosis (LCH). We undertook a survey to ascertain all newly diagnosed cases aged 0–16 years in the UK and...

Langerhans cell histiocytosis of mediastinal node

The predominant clinical and radiological features of Langerhans Cell Histiocytosis (LCH) in children are due to osseous involvement. Extra-osseous disease is far less common, occurring in association with bone disease or in isolation. In the present study, LCH was presumptively diagnosed on Ultrasound guided Fine needle aspiration cytology (FNAC) of the mediastinal lymph node in a 18 month-old child. The diagnosis was confirmed by histological examination of the biopsy material.S-100 protein localization in the LCH cells is often positive on immunohistochemistry.

In vivo transformation of mouse conventional CD8α+ dendritic cells leads to progressive multisystem histiocytosis

Division and proliferation of dendritic cells (DCs) have been proposed to contribute to homeostasis and to prolonged antigen presentation. Whether abnormal proliferation of dendritic cells causes Langerhans cell histiocytosis (LCH) is a highly debated topic. Transgenic expression of simian virus 40 (SV40) T antigens in mature DCs allowed their transformation in vivo while maintaining their phenotype, function, and maturation capacity. The transformed cells were differentiated splenic CD8 alpha-positive conventional dendritic cells with increased Langerin expression. Their selective transformation was correlated with higher steady-state cycling compared with CD8 alpha-negative DCs in wild-type and transgenic mice. Mice developed a DC disease involving the spleen, liver, bone marrow, thymus, and mesenteric lymph node. Surprisingly, lesions displayed key immunohistologic features of Langerhans cell histiocytosis, including expression of Langerin and absence of the abnormal mitoses observed in Langerhans cell sarcomas. Our results demonstrate that a transgenic mouse model with striking similarities to aggressive forms of multisystem histiocytosis, such as the Letterer-Siwe syndrome, can be obtained by transformation of conventional DCs. These findings suggest that conventional DCs may cause some human multisystem LCH. They can reveal shared molecular pathways for human histiocytosis between humans and mice.