Congenital aggressive variant of Langerhans cells histiocytosis with CD56+/E‐Cadherin− phenotype

In children <2 years of age, cutaneous involvement is the most frequent presentation of Langerhans cell histiocytosis (LCH). Cutaneous LCH can be localized or associated with dissemination and organ dysfunction. The clinical course is variable, ranging from spontaneous regression to a fatal outcome. We describe a female newborn presenting with congenital cutaneous lesions who rapidly developed pulmonary infiltrates and multiple osteolytic lesions. Skin biopsy showed a dermal infiltrate of medium to large cells morphologically and phenotypically consistent with LCH. The clinical course was rapidly fatal in spite of chemotherapy. No strict correlation between morphology and prognosis has been documented in LCH, but, in our case, distinct morphological and immunohistochemical features (CD56 expression and no E‐Cadherin expression) may have contributed to an aggressive clinical course. Pediatr Blood Cancer 2009;53:1107–1110. © 2009 Wiley‐Liss, Inc.     

Langerhans'-cell histiocytosis in adults

Guided by a long-term retrospective observation, the clinical course and treatment of Langerhans'-cell histiocytosis (LCH) in adult patients are represented. The series included 19 patients meeting the histopathologic criteria of presumptive LCH who were followed for 1.5–20 years (average 7.7 years). Most frequently, skeletal lesions (16 patients), diffuse interstitial lung infiltrates (seven patients), and pituitary gland involvement with diabetes insipidus (four patients) were present. Bone lesions of the skull and axial skeleton were associated with an infiltration of adjacent soft tissues in 10 of 16 patients. Liver, lymph node, and bone marrow involvement appeared sporadically. LCH was divided into localized or multifocal form. Localized disease took a benign course with remission of bone (n = 4) or lymph node lesions (n - 2). Also, in isolated pulmonary LCH (n = 2), spontaneous transition to inactive disease occurred. With the exception of isolated bone lesions (n = 27), which remained asymptomatic or showed a remission to treatment, multifocal LCH had a more aggressive course. Osseous lesions with adjacent soft tissue infiltration (n = 20) showed a relapse rate in excess of 80% independent of the treatment applied. Pulmonary involvement led to a more marked functional impairment compared to the isolated form, and systemic treatment yielded no convincing effect. In three patients with liver or bone marrow involvement, LCH showed a persistent, serious disease activity. One patient died of transition into acute monomyelocytic leukemia 18 months after diagnosis without preceding chemotherapy. In adults, LCH seems to be limited to a few organ systems. Multifocal LCH represents the more aggressive form with unfavorable prognosis in patients with bone lesions spreading into the adjacent soft tissue and liver or bone marrow involvement. © 1997 Wiley-Liss, Inc.     

Congenital Langerhans cell histiocytosis mimicking a "blueberry muffin baby"

Congenital Langerhans cell histiocytosis (LCH) is a rare condition with great diversity. A case of congenital skin-only LCH presenting as a "blueberry muffin baby" with a spontaneous regression by the age of 8 months is reported here. New insights into clinical manifestations and prognosis, which is not uniformly positive, are discussed. A thorough examination and a careful follow-up should be provided to these patients. Systemic therapy is warranted in multi-system disease; no consensus on treatment exists in case of LCH isolated to skin. The diagnosis of congenital self-healing LCH should be made only retrospectively.     

Cutaneous Langerhans cell histiocytosis in children under one year

BACKGROUND: To evaluate the clinical course and outcome of infants with Langerhans cell histiocytosis (LCH) involving skin and to estimate the incidence of progression to multi-system (M-S) disease in those with isolated skin involvement. METHODS: A retrospective review was conducted on 22 LCH patients who were younger than 12 months at the onset of their skin eruption. RESULTS: Twelve patients had isolated skin involvement at diagnosis and 10 were evaluable for progression. Four of the 10 (40%) evaluable patients progressed to multi-system (M-S) disease. Of the 10 patients with M-S disease at diagnosis, 5 had a history of a preceding skin eruption 2 to 13 months prior to diagnosis. Eleven of the 14 (79%) patients with M-S disease had risk organ involvement. The mortality rate of M-S disease was 50%. CONCLUSIONS: It is important for primary caregivers to recognize that isolated cutaneous LCH in infants is not always a benign disorder. The diagnosis of self-healing cutaneous LCH should only be made in retrospect. Careful, albeit non-invasive, follow-up is recommended to monitor for disease progression and development of long-term complications.     

A case of multisystem Langerhans cell histiocytosis with primary hypothyroidism followed by type 1 diabetes mellitus

We report a case of a 13‐year‐old female with Langerhans cell histiocytosis (LCH) and primary hypothyroidism followed by type 1 diabetes mellitus (DM), both of which are rare complications. In LCH diagnosis, imaging studies showed an enlargement of the thyroid gland, suggesting the involvement of LCH cells. While the pancreas appeared normal, insulin secretion markedly deteriorated 11 months after cessation of chemotherapy. Even without direct pancreatic involvement, there is a possibility that LCH could induce DM as a part of its long‐term complications. In particular, thyroid involvement may be related to the onset of DM. Pediatr Blood Cancer 2009;53:232–234. © 2009 Wiley‐Liss, Inc.     

Punctate thymic calcification in infants with untreated Langerhans' cell histiocytosis: Report of four new cases

Four new cases of punctate thymic calcification in infants with untreated Langerhans' cell histiocytosis (LCH) are added to the four previously reported cases. All cases were shown on CT scans; plain films were rarely diagnostic. Pathologic correlation remains elusive since the usual biopsies of the LCH have been on skin or bone biopsies. A single prior pathologic study of the thymus in untreated LCH showed microscopic calcospherites. The thymic punctate calcific densities in patients with LCH may represent further accretion so that the calcospherites become macroscopic. The finding of such punctate calcific densities in an enlarged thymus of an infant with skin or bone or lung disease is strongly suggestive of LCH. Received: 1 February 1999 Accepted: 10 May 1999     

Successful treatment of refractory Langerhans cell histiocytosis with pulmonary aspergillosis by reduced‐intensity conditioning cord blood transplantation

Hatakeyama N, Hori T, Yamamoto M, Inazawa N, Hirako Y, Tsutsumi H, Suzuki N. Successful treatment of refractory Langerhans cell histiocytosis with pulmonary aspergillosis by reduced‐intensity conditioning cord blood transplantation.
Pediatr Transplantation 2010: 14: E4–E10. © 2009 Wiley Periodicals, Inc. Abstract: The prognosis of multisystem LCH in children with risk organ involvement is extremely poor when they fail to respond to conventional chemotherapy. In such patients, allogeneic SCT may produce complete and sustained remission; however, high‐dose myeloablative regimens are frequently associated with treatment‐related morbidity and mortality. More recently, allogeneic SCT following an RIC regimen has been performed as an alternative salvage approach. We describe a nine‐month‐old boy with refractory multisystem LCH with pulmonary aspergillosis who was successfully treated with reduced‐intensity cord blood transplantation.     

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.     

Long‐Term Extracorporeal Membrane Oxygenation as Bridging Strategies to Lung Transplantation in Rapidly Devastating Isolated Langerhans Cell Histiocytosis

Isolated pulmonary involvement in pediatric Langerhans cell histiocytosis (LCH) is extremely rare. While the multisystem‐LCH course varies from spontaneous remission to rapid deterioration with lethal outcome, single system involvement is generally associated with favorable prognosis. A child with isolated pulmonary LCH had an extremely rapid progression leading to respiratory failure, despite treatment with prednisone and vinblastine. Since lung hyperinflation and cystic degeneration contraindicated conventional mechanical ventilation, extracorporeal membrane oxygenation (ECMO) was chosen for 50 days as a bridge to lung transplantation. The mechanisms involved in disease progression and the usefulness of long‐term ECMO are discussed.     

Iodopovidone Pleurodesis for Isolated Pulmonary Langerhan’s Cell Histiocytosis in a Two Year Old Child

Isolated pulmonary involvement in Langerhans Cell Histiocytosis (LCH) is rare in childhood. The authors report a 2-y-old boy who presented with acute history of fever, cough and respiratory distress; later developed pneumothorax; whose CT thorax showed diffuse pulmonary cystic lucencies bilaterally. Lung biopsy confirmed pulmonary LCH with CD1a positivity. Recurrent spontaneous pneumothoraces are common in patients of pulmonary LCH; which necessitates rapid intervention. The authors share their experience of successfully using iodopovidone in pleurodesis for repeated pneumothorax episodes in this child with rare diagnosis of isolated pulmonary LCH.     

儿童朗格罕细胞组织细胞增生症BRAFV600E突变对预后的影响

目的 探讨BRAFV600E突变在儿童朗格罕细胞组织细胞增生症（LCH）中的预后意义以及影响儿童LCH的预后因素。方法 回顾性纳入首都医科大学附属北京儿童医院2016年1月1日至2017年12月31日收治的初治LCH患儿,采用数字PCR方法检测患儿病灶组织中的BRAFV600E突变,分析突变与临床特征和预后的相关性,影响预后的因素。结果 140例LCH患儿纳入研究,诊断时中位年龄为2.2（0.1~15.7）岁,男89例（63.6%）,女51例。临床分型为单系统（SS）60例（42.9%）,多系统无危险器官受累（MS RO－）47例（33.6%）,多系统有危险器官受累（MS RO+）33例（23.6%）。中位随访时间34.1（0.9~50.7）月,随访期内70例（50.0%）出现进展或复发,12例（9.6%）出现持续性后遗症,死亡3例（2.1%）。总体3年无进展生存率（PFS）、无事件生存率（EFS）和总生存率（OS）分别为（48.9±4.5）%、（46.6±4.4）%和（97.8±1.2）%。①儿童LCH中BRAFV600E突变阳性率67.1%（94/140）。②BRAFV600E突变与患儿临床分型明显相关,突变阳性率MS RO+患儿（90.9%）高于MS RO－患儿（53.2%）或SS患儿（65.0%）（P=0.001）;皮肤受累患儿中突变阳性率（77.8%）高于非皮肤受累的患儿（P=0.042）;③BRAFV600E突变阳性患儿进展/复发率（57.4%）高于突变阴性患儿（34.8%）,P=0.019。3种临床分型中突变阳性和阴性患儿的预后差异均无统计学意义。④多因素分析结果表明,危险器官受累是影响LCH患儿PFS的独立预后因素（HR=2.702,P=0.003）,垂体受累（HR=3.582,P<0.001）、危险器官（HR=2.321,P=0.008）和耳部受累（HR=2.093,P=0.013）是EFS的独立预后因素。结论 LCH患儿BRAFV600E突变与危险器官受累密切相关,突变阳性患儿的进展/复发率高于突变阴性患儿,BRAFV600E不是儿童LCH的独立预后因素。     

Concurrent Langerhans cell histiocytosis and nephroblastoma

Both Langerhans cell histiocytosis (LCH) and nephroblastoma are rare in children. We report herein the first case of a patient with both diseases concurrently. A 2‐year‐old female presented with bone pain and swelling of the right humerus. As a result of the local incision biopsy, she was diagnosed as LCH. A nephroblastoma of the left kidney was discovered during her staging work‐up. After complete resection of the nephroblastoma, she received standard chemoradiotherapy for nephroblastoma. She is alive without relapse 14 months after initial presentation. Pediatr Blood Cancer 2009;52:662–664. © 2009 Wiley‐Liss, Inc.     

Fetal and neonatal histiocytoses

PURPOSE: The histiocytoses are a group of disorders of the monophagocytic system having a variety of clinical and pathological findings. They occur less often during the perinatal period than later in life. Their biologic behavior, response to therapy, and histologic types are not the same. METHODS: The study consisted of 221 fetuses and neonates collected from the literature and from personal files. RESULTS: Langerhans' cell histiocytosis (LCH), the hemophagocytic lymphohistiocytoses (HLH), and juvenile xanthogranuloma (JXG), in order of rank, were the main histiocytoses occurring in the perinatal period. HLH accounted for the highest mortality (74%) followed by disseminated LCH (52%) and JXG (11%). All neonates with LCH and JXG limited to the skin and/or subcutaneous tissue survived with or without treatment. CONCLUSIONS: This study suggests that there is an increased incidence of spontaneous regression of certain histiocytic lesions in neonates as compared to older individuals. Cutaneous forms JXG and LCH had the highest incidence of regression followed by infection associated HLH.     

Langerhans cell histiocytosis mimicking molluscum contagiosum: A case series

Langerhans cell histiocytosis (LCH) is a disorder characterized by accumulation of Langerhans‐like cells in one or various organs. A correct staging work‐up is essential since there are multiorgan presentations with a poor prognosis. We report three patients with LCH skin lesions mimicking molluscum contagiosum in association with both high and low risk organ involvement. This peculiar cutaneous presentation can be a clue for the diagnosis of LCH, a disease with potentially severe systemic involvement.     

A phase II trial using thalidomide for Langerhans cell histiocytosis

BACKGROUND: Few new drugs for treatment of Langerhans cell histiocytosis (LCH) have been studied. Tumor necrosis factor-alpha (TNF-alpha) is a prime therapeutic target since it appears to be present in elevated amounts in LCH lesions. Thalidomide inhibits TNF-alpha production by affecting the gene promoter as well as other anti-cytokine effects. PROCEDURES: A Phase II trial of thalidomide for treatment of LCH patients who had failed primary and at least one secondary regimen was conducted. Sixteen patients were enrolled: nine males and seven females ranging in age from 19 months to 45 years. Six patients were high risk (HR) because of spleen, liver, lung, or bone marrow involvement. The low risk (LR) patients included six with bone/skin LCH, one with multiple bone, one with skin/bone/pituitary, one with skin/bone/brain, and one with skin only disease involvement. Fifteen patients remained on treatment from 3 weeks to over 1 year. RESULTS: Among the LR patients there were four complete responses, three partial responses, and two with no response to thalidomide. No HR patient responded to thalidomide and all died of pulmonary, liver, or bone marrow failure. Thalidomide may have played a role in the pulmonary failure. Other toxicities that required stopping therapy included neutropenia, peripheral neuropathy, and fatigue. CONCLUSIONS: Thalidomide is an effective therapy for some LR patients with LCH, but showed no significant responses in HR patients. Dose-limiting toxicities may reduce its efficacy in LR patients. Additional trials with improved anti-TNF therapies would appear warranted.     

Langerhans cell histiocytosis in a premature baby presenting with skin-isolated disease: case report and literature review

Langerhans cell histiocytosis (LCH) in premature babies is extremely rare as is a vesicular skin rash, while gastrointestinal involvement is associated with a poor outcome. We report a case of LCH in a premature baby presented with isolated vesiculo-papulo-macular skin lesions and insidiously developed gastrointestinal symptoms, haematological and severe pulmonary involvement. We also reviewed a few cases of LCH in premature babies in the English language medical literature. LCH in preterm babies appears to be a severe systemic disease, usually lethal in-utero or post delivery. CONCLUSION: Careful observation should be applied to newborns with skin-only Langerhans cell histiocytosis in order to identify in time progression to potentially fatal systemic disease.     

Langerhans cell histiocytosis in a patient with stage 4 neuroblastoma receiving oral fenretinide

Langerhans cell histiocytosis (LCH) has previously been reported in association with other malignancies. The pathogenesis of LCH and its relationship to other malignancies is poorly understood. We present a novel case of a child who developed an LCH bone lesion while receiving a Phase I protocol therapy with oral fenretinide/Lym‐X‐Sorb (4‐HPR/LXS) powder for neuroblastoma. Pediatr Blood Cancer 2009;53:1111–1113. © 2009 Wiley‐Liss, Inc.     

Haploidentical stem cell transplantation with posttransplant cyclophosphamide for refractory systemic juvenile xanthogranuloma

Juvenile xanthogranuloma (JXG) is a generally benign, self‐limited histiocytic disorder, which belongs to non‐Langerhans cell histiocytoses (non‐LCH). However, systemic JXG can be fatal in rare cases. We present the case of an 11‐year‐old female with systemic JXG, who experienced repeated vertebral compression fractures and did not fully respond to systemic chemotherapy. Based on its reported efficacy in LCH, the patient underwent human leukocyte antigen‐haploidentical hematopoietic stem cell transplantation (HSCT) with posttransplant cyclophosphamide. The patient did not suffer major complications and has not experienced relapse for 13 months since HSCT. HSCT may be a potential treatment option for patients with refractory non‐LCH.     

Spontaneous remission in congenital leukemia is not related to (mosaic) trisomy 21: case presentation and literature review

Congenital leukemia is seldomly diagnosed. Cases should be differentiated from transient leukemoid reaction, which is noted in Down syndrome. Outcome in congenital leukemia is poor, but spontaneous remissions have been described. The authors report on a female neonate with myeloid leukemia of the skin; no blood and bone marrow involvement was noted. Constitutional 47,XX,+21 was excluded. In situ hybridization on a paraffin-embedded skin biopsy sample did not show trisomy 21 in the leukemia lesions. No antileukemia therapy was given. During follow-up, small nodules (diameter up to 3 mm) on the soles of both feet came and went over a 3-month period. The child is now 3.5 years old and well. To date, 18 cases of congenital leukemia showing spontaneous remission have been described in the literature, almost exclusively myeloid leukemia (FAB M4 and M5). Congenital leukemia confined to the skin was described in only 4 cases. On follow-up, 6 cases relapsed; only one of them initially had skin involvement only. The data from this patient and literature indicate that cytostatic treatment should start only if the malignancy interferes with vital parameters. In case of relapse or progression, initial postponement of chemotherapy in these frail neonates will result in less toxicity and probably a better survival.     

Colon involvement in Langerhans' cell histiocytosis.

BACKGROUND: Langerhans' cell histiocytosis (LCH), a granulomatous disorder of unknown cause, most often affects the bony skeleton and skin. Obvious gut involvement is uncommon, and colon involvement has been cited in only a small number of case reports, probably because most patients who have LCH with diarrhoea and/or failure to thrive are not investigated by colonoscopy and biopsy. The current study was conducted to determine the incidence of symptomatic colon involvement among patients with multisystem LCH treated at a single institution. METHOD: A retrospective review of cases in hospital records and the literature. RESULTS: Of the 275 children with LCH in the database, 5 were identified as having biopsy-confirmed colonic involvement. Another 14 cases were identified by a literature review. CONCLUSION: Colonic involvement in patients with multisystem LCH is probably more common than currently recognised. In addition to the other investigations recommended by the Writing Group of the Histiocyte Society, it is recommended that patients with any symptoms suggestive of gut involvement undergo colonoscopy and biopsy of the colonic mucosa.