Unifocal Langerhans Cell Histiocytosis Research Articles

Clinical features, genomic profiling, and outcomes of adult patients with unifocal Langerhans cell histiocytosis

BackgroundLangerhans cell histiocytosis (LCH) is a rare highly heterogeneous histiocytosis, which can be divided into single system and multiple system disease according to site of involvement. There is a paucity of studies examining unifocal LCH in adults in the molecular era.ResultsWe retrospectively analysed records from 70 patients with unifocal LCH. The median age at diagnosis was 36 years (18–69). The most common organ involved was the bone (70.0%), followed by pituitary gland (7.1%). Target gene sequencing of lesion tissues was performed on 32 of the 70 patients. MAPK/PI3K pathway alterations were observed in 78.1% of the patients; the most common mutations included BRAFV600E (28.1%), MAP2K1 (18.8%) and PIK3CA (9.4%). After a median follow-up time of 39.4 months (0.7–211.8), 10 (14.3%) patients developed disease progression, of whom 4 had local recurrence, 2 progressed to single-system multifocal and 4 progressed to multiple system LCH. The 3-year progression-free survival (PFS) was 81.9%. Univariate analysis showed that age < 30 years at diagnosis was associated with worse 3-year PFS (52.2% vs. 97.0%, p = 0.005). The 3-year overall survival was 100%.ConclusionsIn our large cohort of adults with unifocal LCH, we found that prognosis of unifocal LCH in adults was very good, and age < 30 years at diagnosis was associated with increased relapse risk.

Long-term outcomes among adults with Langerhans cell histiocytosis

AbstractAdvances in the treatment of Langerhans cell histiocytosis (LCH) have resulted in a growing survivor population. There is a lack of data on long-term outcomes among adults with LCH. We conducted a retrospective record review of 219 adults (aged ≥18 years) with LCH. Most common presentation was multisystem (34.2%), followed by single-system pulmonary (32%), unifocal (28.3%), and single-system multifocal (5.5%) LCH. Risk organ involvement (the liver, spleen, or bone marrow) was seen in 8.7% of cases, and 40 of 88 (45.5%) tested cases were BRAFV600E. At a median follow-up of 74 months, 5-year progression-free survival (PFS) was 58.3% and estimated median PFS was 83 months. Median overall survival (OS) was not reached; 5- and 10-year OS rates were 88.7% and 74.5%, respectively. Risk organ involvement was associated with worse PFS (hazard ratio [HR], 4.5) and OS (HR, 10.8). BRAFV600E was not associated with risk organ involvement or survival. When compared with matched unaffected US population, individuals with LCH had a significantly higher risk of overall mortality (standardized mortality ratio [SMR], 2.66), specifically among those aged <55 years at diagnosis (SMR, 5.94) and those with multisystem disease (SMR, 4.12). Second cancers occurred in 16.4% cases, including diverse hematologic and solid organ malignancies. LCH-associated deaths constituted 36.1% of deaths and occurred within 5 years of diagnosis. After 5 years, non-LCH causes of death, including second cancers, chronic obstructive pulmonary disease, and cardiovascular diseases, predominated. Our study highlights, to our knowledge, for the first time, that adults with LCH experience early and late mortality from non-LCH causes and the need for development of targeted survivorship programs to improve outcomes.

Sonographic diagnosis of unifocal Langerhans cell histiocytosis of the skull

Sonographic diagnosis of unifocal Langerhans cell histiocytosis of the skull

Treatment and Outcomes of Unifocal and Multifocal Osseous Pelvic Langerhans Cell Histiocytosis Lesions in a Pediatric Population.

IntroductionLangerhans cell histiocytosis (LCH) is a rare, clonal disorder characterized by proliferation and tissue infiltration by myeloid dendritic cells, most commonly occurring in pediatric populations. It often manifests as skeletal lesions with possible pelvic involvement. Few studies have characterized and reviewed outcomes after treatment of isolated pelvic LCH lesions.MethodsA retrospective single-institution review was conducted on diagnoses of patients younger than 18 with a diagnosis of unifocal or multifocal skeletal LCH lesions involving the pelvis. Clinical presentations, lesion sites, focal classification, radiographic findings, treatments, complications, and recurrence rates were reviewed.ResultsTwenty patients had unifocal or multifocal LCH pelvic lesions (11 males, nine females). The median age at diagnosis was 3.5 years (0.8-21.6). Eight cases (40%) involved unifocal lesions, and twelve (60%) involved multifocal lesions, with the most common associated skeletal disease occurring at the ilium. 100% of cases had a lytic bone lesion with no pathologic fractures. All cases were treated nonoperatively with chemotherapy medications, corticosteroids, or observation alone. 75% of cases were treated with chemotherapy with a 100% resolution rate. The median length of follow-up was 4.5 years (0.4-16.7). ConclusionOur study found that chemotherapy alone or chemotherapy with corticosteroid supplementation are appropriate options for unifocal pelvic LCH lesions. In contrast, pelvic lesions that are part of a multifocal presentation may be managed adequately with varied chemotherapy regimens. Corticosteroid therapy and observation alone may also be reasonable for a single organ system, multifocal, skeletal lesions that are anatomically accessible for biopsy and small in number or size.

Pituitary Stalk Thickening: Causes and Consequences. The Children's Memorial Health Institute Experience and Literature Review.

BackgroundPituitary stalk thickening (PST) is a rare abnormality in the pediatric population. Its etiology is heterogeneous. The aim of the study was to identify important clinical, radiological and endocrinological manifestations of patients with PST and follow the course of the disease.Materials and MethodsIt is a study conducted in 23 patients (13 boys) with PST with/without central diabetes insipidus (CDI) diagnosed between 1990 and 2020 at Children’s Memorial Health Institute (CMHI) in Warsaw, Poland. We analyzed demographic data, clinical signs and symptoms, radiological findings, tumor markers, hormonal results, treatment protocols and outcomes.ResultsThe median age at the diagnosis of PST was 9.68 years (IQR: 7.21-12.33). The median time from the onset of the symptoms to the diagnosis was 2.17 years (IQR: 1.12-3.54). The most common initially reported manifestations were polydipsia, polyuria and nocturia (82.6%); most of the patients (56.5%) also presented decreased growth velocity. Hormonal evaluation at the onset of PST revealed: CDI (91.3%), growth hormone deficiency (GHD) (56.5%), hyperprolactinemia (39%), central hypothyroidism (34.8%), adrenal insufficiency (9%), precocious puberty (8.7%). The majority of the patients were diagnosed with germinoma (seventeen patients – 73.9%, one of them with teratoma and germinoma). Langerhans cell histiocytosis (LCH) was identified in three patients (multisystem LCH in two patients, and unifocal LCH in one patient). A single case of atypical teratoid rhabdoid tumor, suspected low-grade glioma (LGG) and lymphocytic infundibuloneurohypophysitis (LINH). The overall survival rate during the observational period was 87.0%.ConclusionsThe pituitary infundibulum presents a diagnostic imaging challenge because of its small size and protean spectrum of disease processes. Germinoma should be suspected in all children with PST, especially with CDI, even when neurological and ophthalmological symptoms are absent.

Phenotypes and prognostic factors in adults with Langerhans cell histiocytosis.

7049 Background: Langerhans cell histiocytosis (LCH) can manifest as single system (SS) disease, multisystem (MS) disease, or pulmonary LCH (smoking-related). There is a paucity of data on prognostic factors including risk organ (RO) involvement (liver, spleen, and bone marrow) in adult LCH, which we sought to address in this study. Methods: Single-center retrospective study of patients ≥18y diagnosed with LCH from 1998 to 2020. Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were conducted using age, sex, organ involvement, LCH subtype, year of diagnosis, BRAF V600E status, and treatments. Results: We included 219 patients with LCH; median age 43y (range 19-88), females 51%, SS unifocal (23%), SS multifocal (6%), pulmonary (31%) and MS (40%). Commonly involved organs included lung (53%), bone (42%), skin (24%), pituitary (16%), and CNS (12%). BRAF V600E was positive in 40/88 (46%). Median follow-up duration was 6.1y (95% CI, 5.1- 7.1). On univariate analysis, factors associated with worse PFS were bone LCH, RO involvement, multifocal/MS LCH, and radiation therapy alone; those with worse OS included RO involvement, MS disease, BRAF V600E+, and age ≥45y at diagnosis. In multivariate analysis, BRAF V600E and age ≥45y at diagnosis were associated with worse mortality (Table). Median PFS was not reached (NR-NR) for SS unifocal LCH, 5mo (0-12.7) for SS multifocal LCH, 110mo (84.7-135.3) for pulmonary LCH, and 27mo (17.2-36.8) for MS LCH. 5-year OS was 97.4% for SS unifocal LCH, 100% for SS multifocal LCH, 96.1% for pulmonary LCH, and 79.9% for MS LCH. 41 (18.7%) developed a second primary malignancy (SPM), of which 11 were hematologic neoplasms. There was a trend towards a higher prevalence of SPMs in patients with BRAF V600E (28% vs. 17%; p = 0.22). Conclusions: In our large single-center study, PFS for multifocal and MS LCH was worse than SS unifocal or pulmonary LCH. RO involvement was not associated with outcomes in multivariate analysis. Overall prognosis was excellent for all subtypes except MS LCH. BRAF V600E and older age were associated with worse OS. The prevalence of SPMs was very high and needs to be explored further.[Table: see text]

BRAFV600E frequency and impact on outcomes in adults with langerhans cell histiocytosis.

7050 Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm manifesting as unifocal, multifocal, multisystem (MS) or pulmonary LCH (smoking-related). In pediatric LCH, somatic BRAFV600E prevalence is reported at 55-70%, and associated with increased risk of multisystem disease and early treatment failure. Our aim was to describe the prevalence of BRAFV600E mutation and evaluate its association with clinical manifestations and outcomes in adults with LCH. Methods: A retrospective review of adult patients diagnosed with LCH consecutively seen at Mayo Clinic from 2011 to 2020 was performed.Evaluation of association of BRAFV600E mutational status and clinical factors was conducted by the Chi-square test for independence. Progression-free survival (PFS) and overall survival (OS) were analyzed via the Kaplan Meier method and compared with the log-rank test to assess the effect of BRAFV600E. Results: Of the total LCH cohort ( n= 128), 88 patients with available BRAFV600E results were included in the study. Median age at diagnosis was 41y (range 19 - 88); 52.3% were male. 40 (45.5%) patients had a BRAFV600E mutation. Increasing age was associated with BRAFV600E (10-year increase OR 1.42, 95%CI 1.07-1.89; p= 0.017). No correlation was observed between BRAFV600E status and site of disease, risk organ (RO: liver, spleen, marrow) involvement, or MS disease. Patients with BRAFV600E were 4 times more likely to receive targeted therapy ( BRAF inhibitor) than non- BRAFV600E patients ( p= 0.018). After a median follow up of 46 mo (95% CI 30.8-61.2), PFS was similar between BRAFV600E and non- BRAFV600E patients ( p= 0.167). However, patients with BRAFV600E had a worse 3-year OS compared with non- BRAFV600E patients (84% vs. 97.1%, p= 0.027). Patients who died had a significantly higher age at LCH diagnosis (median 62 vs. 38 years; p= 0.0002). Conclusions: In our cohort of adults with LCH, BRAFV600E was less frequent than reported in pediatric literature and was associated with worse OS. The frequency of BRAFV600E was positively correlated with increasing age. Contrary to reports in pediatric LCH, there were no significant associations between BRAFV600E and high-risk or multisystem disease.[Table: see text]

Langerhans Cell Histiocytosis of the Orbit: Spectrum of Clinical and Imaging Findings

To evaluate the clinical and imaging characteristics of orbital lesions of pediatric Langerhans cell histiocytosis (LCH). A retrospective analysis of clinical data and central review of magnetic resonance imaging scans in patients with LCH, enrolled into one of the consecutive international trials LCH I-III, or submitted for a second opinion between 1994 and2015. Data from 31 children (34 involved orbits) were analyzed. Orbital LCH was the only disease manifestation in 15, part of a multifocal skeletal in 5, or a multisystem LCH in 11 patients. Orbital LCH was part of the initial disease presentation in 23 or developed at relapse in 8 cases. Orbital involvement was unilateral in 28 and bilateral in 3 patients (34 affected orbits). Proptosis was present in 9 patients. Frontal and zygomatic bone were most commonly affected. All orbital lesions were extraconal. Associated extraorbital imaging findings were dural tail sign in 19, neurodegeneration in 8, and hypothalamic-pituitary mass in 3 patients. Sixteen patients (52%) had at least 1 documented disease relapse. Permanent consequences were prominent proptosis in 1, diabetes insipidus in 8, growth hormone deficiency in 2, radiologic neurodegeneration in 8, and clinical neurodegeneration in 3 patients. Predominantly unilateral orbital LCH can be the only disease manifestation or part of a disseminated disease. Orbital lesions in LCH are exclusively extraconal, typically located at the roof and the lateral wall of the orbit. The optimal treatment approach of unifocal LCH of the orbit remains controversial and warrants a prospective evaluation.

Clinical Features and Outcomes of Unifocal Adult Langerhans Cell Histiocytosis

Purpose: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder that presents with a wide spectrum of clinical diseases, ranging from single-organ lesions to systemic disease. Although previously thought of as an immune disorder, LCH was reclassified as an inflammatory myeloid neoplasm in the 2016 Histocyte Society classification after discovery of BRAF V600E or MAP2K1 gain-of-function mutations and evidence of clonality in most LCH patients. In this revised classification, LCH was divided into single-system LCH, pulmonary LCH, or multisystem LCH. However, there is a lack of data on clinical features and outcomes in the subgroup of "unifocal" non-pulmonary LCH in adults. In this study, we sought to address the gaps in knowledge for unifocal adult LCH utilizing our institution's experience over 20 years. Methods: We retrospectively reviewed the medical records of 189 adult patients (defined as &gt;18 years old at diagnosis) with histopathologically confirmed LCH who were seen at our tertiary referral center between 1997 and 2018. Of these, 44 met criteria for unifocal LCH at diagnosis after careful exclusion of other sites of disease involvement. Results: We included 44 adult patients with unifocal LCH at diagnosis, with median age 42 years (range 19 to 88) and 55% males. 84% were Caucasians and 50% were smokers. Most commonly involved disease sites included bone (43%), skin (25%), pituitary (14%), and gastrointestinal (11%), with common presenting symptoms of head pain/swelling (25%), skin rash (20%), abdominal pain/diarrhea (11%), and diabetes insipidus (9%). Resection/excision was the most common first line therapy in 24 patients (63%); none had local recurrence and 3 patients developed recurrence at a new site. Radiation was the second most common therapy in 6 patients, with an overall response rate of 83%; none had local recurrence and 1 patient had recurrence at a new site. Other less common first-line treatments included resection followed by radiation (2), topical immunosuppression (2), dexamethasone (1), cladribine (1), smoking cessation (1), and observation (1) (Table 1). Cladribine used as first-line therapy for pituitary LCH resulted in progressive disease, but cladribine used as second-line therapy in 2 cases (including one who had progressed to multisystem disease) resulted in partial remission with no further recurrence in both cases. Patients were followed for a median of 3.8 years (range 0.1 to 18.8), with 5 patients lost to follow-up. By time of last follow-up, 11 (28%) had developed recurrence: 1 had local recurrence, 5 developed disease at a new site within the same system (skin or bone), and 5 developed multisystem disease (Figure 1). Median time to recurrence was 2 years (range 0.2 to 6.6). 2 out of 5 patients tested for BRAF had a V600E mutation, both of whom had isolated unifocal bone disease and remained in complete remission following resection at time of last follow-up. Median overall survival (OS) from time of diagnosis was not reached and overall 5-year OS was 94%. 3 patients died, only 1 of progressive LCH. Conclusion: In our study, most patients with unifocal adult LCH achieved a complete remission with surgical resection or local radiation. None of the patients treated with resection or radiation developed local recurrence, but around 1 in 5 developed distant recurrence within 5 years. However, the overall prognosis was very good, and none of the patients in the cohort progressed to "high-risk" organ (liver, spleen, or bone marrow) involvement or pulmonary involvement. Further studies are warranted to assess the role of MAPK-ERK mutations in the prognosis of unifocal LCH. Disclosures Bennani: Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Adicet Bio: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding. Vassallo:Sun Pharmaceuticals: Research Funding; Sun Pharmaceuticals: Research Funding; Pfizer: Research Funding; Bristol Myers Squibb: Research Funding; Bristol Myers Squibb: Research Funding.

Analysis of the Incidence and Diagnostic Pattern of Langerhans Cell Histiocytosis from the Population-Wide Healthcare Database in Korea

Introduction Langerhans cell histiocytosis (LCH) is a rare disease involving clonal proliferation of Langerhans cells. The reported incidence of LCH ranges from 0.5-5.4 cases per million persons per year, according to the prospective registry-based reports. However, due to the rarity of the disease and the limitation of prospective registries, the comprehensive understanding of nation-wide epidemiology has been limited. This study aimed to analyze the incidence by age and diagnostic patterns of LCH using the population-wide healthcare database in Korea. M ethods The claims data of the Health Insurance Review and Assessment (HIRA) contain information of 46 million patients per year, which accounts for about 95% of the total population of South Korea. The data include information regarding diagnoses, hospitalization, and prescription drugs. Since 2005, the "National cancer registration and reimbursement program" has been implemented, which reimburse for 90% of the medical expenses of patients with malignant diseases, including LCH. Therefore, all the patients with LCH have been registered in the database after a definite diagnosis. From the HIRA open data source, we extracted a claim data of patients corresponding to diagnosis codes of C95.0 (Multifocal and multisystemic -disseminated LCH), C96.5 (Multifocal and unisystemic LCH), or C96.6 (Unifocal LCH) during the period of 2010-2017. Data for 2010-2011 was used as a reference for overlapping patients, and the actual analysis was conducted with data from 2012 to 2017. Results During the period, a total of 59,929 insurance statements were issued, and 53,446 statements with only one identical diagnostic code and confirmative workups were selected for final analysis. The total incidence cases during the period of 2012 to 2017 were 899 cases, and the average number of the annual incidence was 150 cases. The incidence was 3.0 cases per million persons per year. There was a male predominance with a male-to-female ratio of 1.63:1 (558 cases:341 cases) in a whole cohort. For the detailed diagnosis codes, C96.6 was the most frequent as 93.4%, followed by C96.0 as 4.9%, and C96.5 as 1.7%. The average age at diagnosis was 26.6 years (range, 0.2~87 years) in all incidence cases, and 26.6 years for C96.0 group, 29.5 years for C96.5 group, and 25.9 years for C96.6 group, respectively. When patients were grouped by age at diagnosis, the age group of 0-4 years showed the highest annual incidence of 17.9 cases per million, followed by the group of 5-9 years as 8.9 cases per million, and the age group over 70 years showed the lowest annual incidence of 1.1 cases per million (Figure 1). There were no seasonal trends in the diagnosis of LCH. At diagnosis, 21.6% of patients were diagnosed at the department of neurosurgery, 21.5% at pediatrics, 19.3% at internal medicine, and 16.8% at orthopedic surgery. For examinations conducted at the time of diagnosis, simple radiography was conducted in 84.9% of patients, computed tomography in 32%, magnetic resonance imaging in 39.6%, bone scan in 47.1%, and bone marrow examination in 22.9% of patients. For treatment, most of the patients (93.7%) received at least one modality of treatments after diagnosis; 42.7% of patients underwent surgery only, 30.4% received topical steroids only, 12.6% underwent surgery followed by chemotherapy, and 10.5% received chemotherapy. For chemotherapy, vinblastine was the most frequently prescribed drug as used in 82.9% of patients who received chemotherapy, followed by methotrexate in 39.4%, and mercaptopurine in 38.9%. Conclusions This study was the first big data analysis regarding LCH in Korea, and the annual incidence of LCH was 3.0 cases per million persons per year. The incidence was highest at 0-4 years of age, and the incidence was significantly decreased with age. We plan to conduct further research on the treatment and outcomes of Korean LCH patients in conjunction with the data of ongoing prospective registry. Figure 1. The annual incidence of Langerhans Cell Histiocytosis by age at diagnosis Figure 1 Disclosures No relevant conflicts of interest to declare.

Adult Langerhans cell histiocytosis: A contemporary single-institution series of 186 patients.

7018 Background: Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm driven by MAPK-ERK mutations in majority of patients. Contemporary data on treatments and outcomes in adult LCH are lacking. Hence, we undertook this study to analyze a large cohort of adult LCH patients. Methods: This was a retrospective study of adult (≥18 years) LCH patients seen at our institution between 1998 and 2018. Results: We included 186 patients with adult LCH (median age 43; 19-88), and 54% were females. 70% of patients were diagnosed after 2007. Common presenting symptoms were cough/dyspnea (30%), rash (17%), pain/swelling in head (17%), and diabetes insipidus (10%). 70 (38%) patients had multisystem LCH, 62 (33%) had isolated pulmonary LCH, and 35 (19%) had unifocal LCH. Common sites of involvement included lung (59%), bone (37%), skin (21%), and nervous system (16%). 121 (65%) were smokers; 48% of these had lung disease, while 52% had multisystem disease. 18 of 31 tested (58%) patients had BRAF-V600E mutation. Most common first-line treatment was smoking cessation in 24 patients, and led to an overall response rate (ORR) of 83% in pulmonary lesions. Radiation therapy was used in 11 patients, and led to an ORR 82%. Surgical resection of lesion was done in 23 patients, with relapses in 24%. Systemic therapies were used in 78 (42%) patients (Table). Most common first-line systemic therapy was cladribine with ORR of 78%. Vemurafenib was used in 3 patients with BRAF-V600E, leading to an ORR of 67% . After a median follow-up of 23 months (0-261), 21 patients had died. Of these, 10 died of progressive LCH. Median OS was not reached, and mean OS was 196 months. Conclusions: This is the largest contemporary series of adult LCH. It shows that diverse clinical spectrum, ranging from benign course to a progressive multisystem disease. Although smoking cessation was an effective treatment for pulmonary LCH, a large subset required systemic chemotherapy. [Table: see text]

Spontaneous resolution of unifocal Langerhans cell histiocytosis of the skull: potential role of ultrasound in detection and imaging follow-up

Langerhans cell histiocytosis is a tumor-like condition characterized by idiopathic proliferation of Langerhans cells. The disease may involve the skeleton as well as other organs systems. Bone involvement may be solitary or multifocal. Unifocal osseous Langerhans cell histiocytosis may involve virtually any bone, with the calvarium being most frequently involved. Plain radiography, computed tomography and magnetic resonance imaging are the most used techniques for detection and characterization of the lesion. The use of ultrasound is less known, although it may be a valuable technique in detection and follow-up of superficially located lesions such as calvarial lesions. This case report describes an 8-year-old girl, in whom the lesion was initially detected by ultrasound. Furthermore, ultrasound was used to evaluate spontaneous resolution of the lesion. The knowledge of ultrasound characteristics may be important to avoid unnecessary radiation and gadolinium administration, particularly in a pediatric population.

Langerhans cell histiocytosis of the orbit: A study of eight cases.

BACKGROUND:Langerhans cell histiocytosis (LCH) of the orbit is a rare clinical entity with a diagnostic and therapeutic dilemma.MATERIALS AND METHODS:This was a retrospective study of eight patients with orbital LCH.RESULTS:All eight patients in our series were male, and the mean age at presentation was 8 years (median 6 years; range, 7 months–23 years). All of them had unilateral disease, and the most common presenting complaint was upper eyelid swelling (n = 6). The mean duration of symptoms was 6 weeks (median, 3 weeks; range, 2–20 weeks). Visual acuity was unaffected in seven cases. Clinical diagnosis included rhabdomyosarcoma (n = 4), malignant lacrimal gland tumor (n = 2), orbital cysticercosis (n = 1), and orbital tuberculosis (n = 1). The diagnosis of orbital LCH was confirmed by incisional biopsy (n = 7) or fine-needle aspiration cytology (n = 1). Four cases underwent careful limited curettage and received intralesional steroid, and four cases were treated with intralesional steroid alone after incisional biopsy. Complete tumor resolution was achieved in seven cases after receiving a mean of one intralesional steroid injection (median, 1; range, 1–2), while one patient was advised systemic chemotherapy for residual tumor. No tumor recurrence was noted in any case at a mean follow-up duration of 30 months (median, 23 months; range, 7–96 months). None of the cases developed diabetes insipidus or multisystem disease during the follow-up period.CONCLUSION:Minimal local intervention with intralesional steroids with/without careful curettage achieves complete tumor resolution in unifocal orbital LCH.

Clinicopathological pattern of cranial unifocal Langerhans cell histiocytosis: A study at medical college hospital.

Background:Eosinophilic granuloma (EG) of bone refers to a generally benign form of Langerhans cell histiocytosis localized to the bone. Patients may present with a solitary lesion (monostotic) or multiple sites of involvement (polyostotic).Materials and Methods:This study was done to evaluate the clinicopathological pattern of 6 cases of EGs of the skull diagnosed at a tertiary care hospital. All patients of EG were included with the help of medical records over a 5-year period that is, November 2009 to November 2014. They all had been preoperatively evaluated by skull X-ray and computed tomography. To rule out a multifocal disease scintigraphy was performed in all cases preoperatively. Surgical excision was performed, and EG was diagnosed on histopathology and immunohistochemistry.Results:There was a male predominance. Parietal bone was the most common affected bone. Total excision of the lesion was performed in all cases. No patient received postoperative radiotherapy. The follow-up period ranged from 6 months to 3 years. No tumor recurrence was noted.Conclusion:With an unknown etiology, nonspecific clinical and radiological findings with diagnosis possible only on histopathological examination, EG needs to be considered in the differential diagnosis as a skull mass, especially in children.

男児の下顎骨に生じたランゲルハンス細胞組織球症の1例

Langerhans’-cell histiocytosis （LCH） is caused by monoclonal proliferation of Langerhans’ cells, a type of antigen-presenting cell, and affects multiple organs. We report a case of LCH arising in the mandible of a young boy.The patient was an 11-year-old boy who referred to our hospital because of swelling of the right cheek. Computed tomographic examination showed a destructive bony lesion extending from the right mandibular body to the mandibular angle, with resorption of the buccal and lingual cortical plate. Gadolinium-enhanced T1-weighted magnetic resonance imaging showed contrast enhancement in a large portion of the right mandibular body, with soft tissue extension. A biopsy of the lesion was performed with the patient under general anesthesia because the radiographic findings suggested malignancy. Histopathological examination revealed that the lesion was composed of eosinophilic cells and histiocytes, which were positive for S-100 and CD1a immunohistochemically. These findings led to the diagnosis of LCH. PET-CT showed no evidence of lesions in other organs or bone.Patients with unifocal LCH arising in one organ generally have a high chance of spontaneous remission and favorable outcomes. The present case spontaneously remitted 3 months after the biopsy, without additional treatment. Currently, 1 year 9 months after the biopsy, the patient has made favorable progress, with no recurrence.

Approaches to Treatment of Unifocal Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH) is a variable disorder involving either single bone or multiorgan systems. The most effective treatment of unifocal osseous lesions is debated in the literature. This study describes the treatment approaches for LCH and demonstrates the effectiveness of biopsy in providing symptom resolution. Records of 61 patients diagnosed with LCH at a single institution over an 11-year period were reviewed. Thirty-nine patients with biopsy-confirmed diagnoses of unifocal osseous LCH were included in the analysis. At this institution, lesions are surgically treated by incisional biopsy, trocar biopsy, or curettage and grafting. Patients receive chemotherapy on a case-by-case basis, depending on the lesion location and size. A Kaplan-Meier analysis was used to compare time with symptom resolution across treatment groups. In the 39 patients with unifocal osseous LCH, treatment approaches included incisional biopsy (n = 18, 46.15%), trocar biopsy (n = 8, 20.51%), incisional biopsy and chemotherapy (n = 8, 20.51%), and biopsy with bone grafting (n = 5, 12.82%). The median time from biopsy to symptom resolution was 5.43 weeks, with an average length of follow-up of 1.59 years. The median time to symptom resolution was 3.86 weeks with incisional biopsy, 5.43 weeks with biopsy and grafting, 5.64 weeks with trocar biopsy, and 16.57 weeks with biopsy and chemotherapy. Overall, there was a significant difference (P = 0.0262) in the time to symptom resolution across the different treatment approaches. Time to symptom resolution was significantly different between incisional biopsy and chemotherapy treatment compared with the incisional biopsy treatment (P = 0.0027), as well as biopsy with grafting treatment (P = 0.0264). Symptom resolution occurred rapidly after biopsy and did not significantly differ among patients who received incisional biopsy, trocar biopsy, or biopsy with grafting. Unifocal osseous LCH likely does not require aggressive surgical or medical management. Biopsy alone both confirms the diagnosis and precedes a predictable resolution of symptoms. Level III, retrospective comparative therapeutic study.

Causes of treatment failure for children with LCH in Morocco

Abstract Background : Langerhans Cell Histiocytosis (LCH) is a rare disease with high survival rate. We noted poor outcomes in Morocco and thus this study was conducted to identify causes of preventable treatment failure in children. Patients & Methods : This study includes cases of children LCH followed in six Pediatric Oncology Units part of the Moroccan LCH Study Group (Groupe Marocain d'Etude de l'Histiocytose) between 2000 and 2009. Patients were categorized into risk group or low risk group as per the International Histiocyte Society classification. Results: Forty-two patients were included in the present study. The median age at diagnosis was 20.5 months. The sex-ratio M/F was 5. The onset symptom was a skin lesion in 20% of the cases and bone involvement in 17%. Seventeen patients had unifocal LCH (40%). The most common site of unifocal LCH was bone (65%) and the mean duration of the first episode treatment was 3 months. Complete or partial remission was achieved in 58% of the cases. Among 20 patients who had risk organ involvement, 11 died from progressive disease and 2 died from septic shock. The overall survival rate was 40% at 5 years. Conclusion : The most common cause of treatment failure was refractory disease in 26%. However, toxic death and abandonment caused an additional 24% of patients to fail treatment. Reducing this preventable failure requires carefully designed interventions. Thus, the Moroccan LCH Study Group was established in March 2010 and set as main objective the improvement of the therapeutic management

Sudden Sensorineural Hearing Loss as First Presenting Symptom of Unifocal Langerhans Cell Histiocytosis in the Temporal Bone

*Clinic for Otorhinolaryngology and Maxillofacial Surgery, Otologic Department; and †University of Belgrade, Faculty of Medicine, Institute for Pathology, Clinical Centre of Serbia, Belgrade, Serbia Address correspondence and reprint requests to Bojana Bukurov M.D., Clinic for Otorhinolaryngology and Maxillofacial Surgery, Clinical Centre of Serbia, Pasterova 2, 11 000 Belgrade, Serbia; E-mail: [email protected] The authors disclose no conflicts of interest.

Does Adjunctive Chemotherapy Reduce Remission Rates Compared to Cortisone Alone in Unifocal or Multifocal Histiocytosis of Bone?

Langerhans cell histiocytosis (LCH) is a rare disorder that can affect almost any organ, including bone. Treatment options include local corticosteroid infiltration in isolated bone lesions and oral corticosteroids and chemotherapy in multifocal bone lesions. Several studies show local corticosteroid injection in unifocal bone lesions heal in more than 75% of patients with minimal side effects. Therefore, it is unclear whether chemotherapy adds materially to the healing rate. We therefore compared overall survival, remission rate, and recurrence rate in patients with bone LCH treated with chemotherapy and corticosteroids or corticosteroids alone. We retrospectively reviewed the records of 198 patients with LCH since 1950. Median age at diagnosis was 5 years, male-to-female ratio was 1.33, and the most frequent symptom was local pain (95%). We recorded the disease presentation, demographics, treatment, and clinical evolution of each patient. Minimum followup was 4 months (median, 24 months; range, 4-360 months). The survival rate of the systemic disease group was 76.5% (65 of 85) while the survival rate in the unifocal and multifocal bone involvement groups was 100% at a median 5-year followup. All patients with unifocal bone involvement and 40 of 43 (93%) with multifocal bone involvement had complete remission. One of 30 patients with multifocal bone involvement treated with chemotherapy and oral corticosteroids did not achieve remission whereas two of six receiving only corticosteroids did not achieve remission. Our observations suggest intralesional corticosteroid injection without adjunctive chemotherapy achieves remission in unifocal bone LCH but may not do so in multifocal single-system bone involvement. Larger series would be required to confirm this observation. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Rare case of unifocal Langerhans cell histiocytosis in four-month-old child

Langerhans cell histiocytosis (LCH) comprises a group of disorders, the common feature of which is Langerhans cell proliferation. The clinical presentation is highly varied. The severity and prognosis of the disease are dependent on the type and extent of organ involvement. This paper reports a rare case of a four-month-old white male with unifocal LCH limited exclusively to the mandible, discussing the diagnosis, radiographic and immunohistochemical aspects, treatment and monitoring multidisciplinary of the case.