The clinical impact of serum soluble CD25 levels in children with Langerhans cell histiocytosis.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics, as well as prognosis, in pediatric LCH. METHODS: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regimens. We further assessed the predictive value for the prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. RESULTS: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000pg/ml). sCD25 level was significantly higher in multi-system and risk organ positive (MS RO+) LCH patients compared to single-system(SS) LCH patients (p < 0.001). Patients with elevated sCD25 were more likely to have involvement of risk organs, skin, lung, lymph nodes, or pituitary (all p < 0.05). sCD25 level could predict LCH progression and relapse, with an area under the ROC curve of 60.6 %. The optimal cutoff value was determined at 2921 pg/ml. Patients in the high-sCD25 group had significantly worse progression-free survival compared to those in the low-sCD25 group (p < 0.05). CONCLUSION: Elevated serum sCD25 level at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 level can predict the progression/recurrence of LCH following first-line chemotherapy.

Targeted Therapy With Vemurafenib in Brazilian Children With Refractory Langerhans Cell Histiocytosis: Two Case Reports and Review of Literature.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a clonal myeloid neoplasm with inflammatory component. Refractory disease is a challenge, but vemurafenib has emerged as a therapeutic option. We will delineate the cases of two Brazilian children suffering from refractory LCH with a positive response to vemurafenib. CASES: Both cases had a diagnosis of multisystem disease with involvement of organs at risk and had not responded to standard and second-line treatment. After refractoriness to classic treatment regimens, the BRAF mutation was investigated and found to be positive in both patients, and target therapy with vemurafenib was sought. The first case has been using vemurafenib for about 2 years and the second case has been using it for about 3 years, having had an attempt to suspend the medication after concomitant use with maintenance therapy. However, the disease returned 4 months after stopping the medication. Fortunately, the disease returned to remission status after the medication was reintroduced. CONCLUSION: These cases represent the first reported instances of off-label vemurafenib use in Brazil for the treatment of LCH and both patients have demonstrated excellent responses to the medication. However, the long-term side effects are unknown in children, and prospective studies are needed. In addition, there is a lack of epidemiological data on histiocytosis in Brazil and studies evaluating the budgetary impact of incorporating BRAF mutation research and the use of vemurafenib into the public health system. These reports could be a starting point.

Histiocitosis de células de Langerhans en un paciente con lesión perianal. Caso clínico / Langerhans cell histiocytosis in a patient with perianal lesion. A case report

La histiocitosis de células de Langerhans es una expresión de células dendríticas mieloides, asociada a un componente inflamatorio significativo y compromiso sistémico variado. La edad más frecuente de presentación es entre 1 y 4 años, y predomina en el sexo masculino. Se comunica el caso de un niño de 5 años de edad cuya forma de presentación fue una lesión granulomatosa con fístula perianal, afectación pulmonar y de oído externo. El abordaje interdisciplinario permitió llegar al diagnóstico, realizar las intervenciones necesarias e iniciar el tratamiento adecuado.

Langerhans cell histiocytosis is an expression of myeloid dendritic cells, associated with a significant inflammatory component and varied systemic involvement. The most common age at presentation is between 1 and 4 years, and it prevails among male subjects. Here we describe the case of a 5-year-old boy who presented with a granulomatous lesion with perianal fistula and lung and external ear involvement. An interdisciplinary approach helped to make a diagnosis, provide the necessary interventions, and start an adequate treatment.

Langerhans Cell Histiocytosis Mimicking a Meningeal Lesion with Temporal Bone and Muscle Compromise in an Adult Patient: A Case Report.

Introduction Langerhans cell histiocytosis (LCH) is a rare proliferative systemic disease characterized by the growth of abnormal dendritic cells and wide-ranging organ involvement. This condition can affect individuals of all ages, but most commonly children, with a peak incidence in toddlers. Symptoms may vary depending on the affected organ or system. Case Report A 43-year-old man presented with a left temporal stabbing headache unresponsive to management with therapy and nonsteroidal anti-inflammatory drugs. Initial evaluation revealed a contrast-enhanced left temporal extra-axial lesion with bone and muscle compromise. Differential diagnoses, including multiple myeloma, were explored. Initial laboratory tests and imaging studies showed no other abnormalities, except for splenomegaly and a residual granuloma in the left lung. En bloc resection of the lesion was recommended. The patient underwent surgical intervention, which included resection of the dural lesion and all borders of an infiltrating tumor within the temporalis muscle and the affected portion of the left temporal bone. Posterior pathological examination revealed LCH. Postoperative course was uneventful. Follow-up appointments were scheduled after pathology results confirmed the diagnosis. Patient has continued follow-up for the following 3 months after the surgical procedure. Further evaluations are pending. Discussion This case report corresponds to a patient with LCH. These patients are individualized and stratified based on local or systemic involvement to determine the most appropriate type of management. This is a rare case as LCH is rare in older patients and the initial presented lesion initially mimicked a meningioma; however, its atypical behavior and associated lytic compromise led to consideration of possible differential diagnoses. Conclusion LCH can present with lytic bone lesions, mimicking other conditions, including infiltrative neoplastic lesions. Early diagnosis and appropriate surgical management are essential for optimal patient outcomes. Long-term follow-up is crucial to monitor disease progression and response to treatment.

Congenital Juvenile Xanthogranuloma in the Perioral Region: A Case Image.

Juvenile xanthogranuloma (JXG) is the most common form of non-Langerhans cell histiocytosis in childhood. It often presents with cutaneous involvement and exhibits a predilection for the head and neck region. This article illustrates a case of congenital JXG in a 5-month-old boy, characterized by a solitary, well-circumscribed nodule above the left upper lip. Histopathologically, the lesion exhibited histiocytes with eosinophilic cytoplasm and Touton giant cells. Immunohistochemistry revealed histiocytes positive for CD68 and Factor XIIIa, while negative for S-100 protein. Clinicians should become familiar with the broad clinical spectrum of cutaneous JXG, particularly its congenital presentation, in order to ensure timely and accurate management.

Increased AXLhigh myeloid cells as pathognomonic marker in Langerhans cell histiocytosis and Langerin expression dependence of mTOR inhibition.

Langerhans cell histiocytosis (LCH) is characterized by an expansion and accumulation of pathological histiocytes expressing langerin (CD207) and CD1a in different organs under an inflammatory milieu. The origin of pathognomonic precursors of LCH is widely debated, but monocytes and pre-dendritic cells (pre-DC) play a significant role. Remarkably, we found an expansion of AXLhigh cells in the CD11c+ subset of patients with active LCH, which also express the pathognomonic CD207 and CD1a. Moreover, we obtained a monocyte-derived LC-like (mo-LC-like) expressing high levels of AXL when treated with inflammatory cytokine, or plasma of patients with active disease. Intriguingly, inhibiting the mTOR pathway at the initial stages of monocyte differentiation to LC-like fosters the pathognomonic LCH program, highly increasing CD207 levels, together with NOTCH1 induction. We define here that AXLhigh could also be taken as a strong pathognomonic marker for LCH, and the release of Langerin and NOTCH1 expression depends on the inhibition of the mTOR pathway.

Langerhans cell histiocytosis in a patient with perianal lesion. A case report. / Histiocitosis de células de Langerhans en un paciente con lesión perianal. Caso clínico.

Langerhans cell histiocytosis is an expression of myeloid dendritic cells, associated with a significant inflammatory component and varied systemic involvement. The most common age at presentation is between 1 and 4 years, and it prevails among male subjects. Here we describe the case of a 5-year-old boy who presented with a granulomatous lesion with perianal fistula and lung and external ear involvement. An interdisciplinary approach helped to make a diagnosis, provide the necessary interventions, and start an adequate treatment.

La histiocitosis de células de Langerhans es una expresión de células dendríticas mieloides, asociada a un componente inflamatorio significativo y compromiso sistémico variado. La edad más frecuente de presentación es entre 1 y 4 años, y predomina en el sexo masculino. Se comunica el caso de un niño de 5 años de edad cuya forma de presentación fue una lesión granulomatosa con fístula perianal, afectación pulmonar y de oído externo. El abordaje interdisciplinario permitió llegar al diagnóstico, realizar las intervenciones necesarias e iniciar el tratamiento adecuado.

Ophthalmic histiocytic lesions (diseases of the L group): A multicenter clinicopathological study of 18 cases and review of literature.

INTRODUCTION: Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are rare histiocytic disorders in the L (Langerhans) group diseases. They range from self-limited benign diseases to lethal disseminated forms. METHODS: This retrospective study was conducted in 3 tertiary hospitals in Saudi Arabia and Brazil. Histopathological records were searched for all patients diagnosed with ocular and periocular histiocytic disorders from January 1993 to December 2018. Histopathological slides and medical files were reviewed for data collection and simple analysis of demographics, clinical manifestations, and management. The relevant literature is reviewed. RESULTS: Twenty-two eyes of 18 patients with biopsy-proven histiocytic disorders in the L group were included. Female-to-male ratio was 1.25:1. Average age at presentation was 14 years (range, 1-54). LCH was diagnosed in 14 eyes, while eight eyes had ECD. All LCH cases were unilateral and confined to the bone as cases of eosinophilic granuloma (EG), while patients with ECD were bilateral. Commonest presentations in EG and ECD were eyelid swelling (85.7%) and periocular xanthomas (75%), respectively. Orbit was involved in 100% of EG cases, with bony erosion in 54.5%. Relevant systemic involvement was found in 100% of ECD and 21% of EG cases. Surgical intervention was needed in 16 of the 22 eyes (72.7%). All EG and 25% of patients with ECD required surgical excision. CONCLUSIONS: Histiocytic disorders are a rare group of diseases, including the L group. Relevant systemic associations require specific and selective therapy. A high clinical index and multidisciplinary collaboration are essential for the proper evaluation and management of these patients.

Histiocitose de células de Langerhans: relato de caso clínico / Langerhans cell histiocytosis: clinical case report

A Histiocitose de células de Langerhans (HCL) é uma doença caracterizada pela proliferação anormal dessas células dentríticas em um tecido, que podem acometer uma única estrutura ou órgão ou ainda ocorrer simultaneamente em mais de uma região. Na cavidade oral geralmente a HCL pode se apresentar como uma hipertrofia gengival e ulceração da mucosa, provocando dor, edema, mobilidade, perda dentária, e destruição do tecido ósseo da maxila e da mandíbula. O objetivo desse trabalho foi de reportar a evolução clínica de um caso de HCL com lesões maxilo-mandibulares em uma paciente adulta. A paciente de 27 anos, feoderma, sexo feminino, foi admitida na Clínica de Estomatologia e Cirurgia Bucomaxilofacial do Hospital Metropolitano Odilon Behrens (HMOB), onde foi diagnosticada com HCL. Houveram cinco manifestações da doença desde 2012 até 2022, sendo todas restritas ao tecido ósseo e se estendendo aos tecidos moles mucogengivais, acometendo duas vezes a mandíbula, duas vezes a maxila, e uma vez na região occiptal do crânio, este último caso tratado pela neurologia. A paciente foi submetida ao tratamento cirúrgico e quimioterápico. O tratamento cirúrgico consistiu na exérese das manifestações da HCL em mandíbula e maxila, sendo que na mandíbula E, foi realizada a ressecção segmentar com margem de segurança após fratura patológica da mandíbula. No momento a paciente encontra-se em acompanhamento pelas clínicas de Cirurgia BMF e Médica Oncológica, realizando novo regime quimioterápico, devido a constantes recidivas. A HCL pode apresentar aspectos clínicos e radiográficos comuns a outras patologias que são encontrados com frequência na clínica odontológica, portanto, é de extrema importância que o cirurgião dentista saiba reconhecer as características clínicas e imaginológicas que possam sugerir o diagnóstico de HCL para melhor conduzir o caso afim de se obter o diagnóstico precoce dessa patologia.

Langerhans cell histiocytosis (LCH) is a disease characterized by the abnormal proliferation of these dendritic cells in a tissue, which can affect a single structure or organ or even occur simultaneously in more than one region. In the oral cavity, LCH can usually present as gingival hypertrophy and mucosal ulceration, causing pain, swelling, mobility, tooth loss, and destruction of bone tissue in the maxilla and mandible. The objective of this work was to report the clinical evolution of a case of LCH with maxillomandibular lesions in an adult patient. The patient of 27 years old, female, feoderm, was admitted to the Clinic of Stomatology and Oral and Maxillofacial Surgery at the Metropolitan Hospital Odilon Behrens (MHOB), where she was diagnosed with LCH. There were five manifestations of the disease from 2012 to 2022, all of which were restricted to bone tissue and extended to mucogingival soft tissues, affecting twice the mandible, twice the maxilla, and once in the occipital region of the skull, the latter case treated by neurology. The patient underwent surgical and chemotherapy treatment. The surgical treatment consisted of the excision of the manifestations of LCH in the mandible and maxilla, and in left mandible, segmental resection was performed after a pathological fracture of the mandible. At the moment, the patient is being followed up by the BMF Surgery and Medical Oncology clinics, undergoing a new chemotherapy regimen, due to constant recurrences. LCH can present clinical and radiographic aspects common to other pathologies that are frequently found in the dental practice, therefore, It is extremely important that the dental surgeon knows how to recognize the clinical and imaging characteristics that may suggest the diagnosis of LCH in order to better manage the case in order to obtain an early diagnosis of this pathology.

Langerhans cell histiocytosis simulating endodontic periapical lesion: Are we prepared to diagnose and manage it? A case report.

Many aggressive non-endodontic radiolucent lesions show very similar clinical and radiographical features to periapical lesions of endodontic origin. Since the treatments of endodontic and non-endodontic lesions differ markedly, a precise diagnosis is imperative. Thus, the present study aimed at presenting a clinical case on the diagnosis and management of a Langerhans cell histiocytosis (LCH) lesion mimicking a periapical lesion of endodontic origin. A 51-year-old male patient was referred to a private dental office due to slight pain from the region of tooth 36. Although no sign of prosthetic or endodontic failure was noted, radiographical examination revealed a radiolucent image with poorly defined borders associated with the periapical region of the tooth. Apicoectomy and bone curettage were then performed and, given the clinical and laboratory features, the definitive diagnosis of solitary eosinophilic granuloma was made. The surgical treatment was sufficient for the remission of the symptoms, and recurrence was not observed. Given the current case, dentists should be aware of LCH lesions as they may mimic endodontic periapical pathoses, leading to misdiagnosis and therapeutic complications. Moreover, alveolar bone lesions may be the first or only sign of LCH in many cases.

Oral Juvenile Xanthogranuloma: A Clinicopathological, Immunohistochemical and BRAF V600E Study of Five New Cases, with Literature Review.

Juvenile xanthogranuloma (JXG) is the most common form of non-Langerhans cell histiocytosis and oral mucosal involvement is exceedingly rare. Histiocytic disorders harbor activating mutations in MAPK pathway, including the report of BRAF V600E in JXG of extracutaneous site. However, no information is available for oral JXG. Herein, the clinicopathological and immunohistochemical features of five new oral JXG were evaluated in conjunction with literature review. Also, we assessed the BRAF V600E in oral samples. Five oral JXG were retrieved from pathology archives. Morphological and immunohistochemical analyses were performed. The BRAF V600E status was determined with TaqMan allele-specific qPCR. The series comprised of three female and two male patients, most of them adults, with a median age of 39 years (range 13-68 years). Clinically, the lesions appeared as asymptomatic solitary nodules, measuring until 2.5 cm, with more incident to the buccal mucosa. Morphologically, most of the cases presented classical histological features of JXG, with histiocytic cells consistent with the non-Langerhans cell immunophenotype. BRAF V600E was not detected in the cases tested. This is the first and largest published series of oral JXG affecting adults and a Brazilian population. The molecular pathogenesis of oral JXG remains unknown. Clinicians and pathologists must recognize JXG to avoid misdiagnoses with oral benign or malignant lesions.

Erdheim-Chester disease presenting at the central nervous system.

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis (LCH) that affects different body systems. It was recently recognized as a neoplastic disorder after identifying an activating mutation of the MAPK pathway. Neurological presentations of ECD are rare. We present a case of a 35-year-old male who presented to the emergency department with neck pain, headache and vomiting for 2 months; MRI showed multiple heterogeneous intracranial masses. Neurosurgery performed a suboccipital craniotomy, partially resected the cerebellar mass, and placed a parietal to frontal shunt catheter. Biopsy results from the cerebellar mass demonstrated cerebellar tissue involved by a diffuse proliferation of foamy histiocytes and spindle cells admixed with prominent lymphoplasmacytic infiltrate and positive for CD68, CD163, Factor XIIIa and Fascin. PET scan showed hypermetabolic uptake within the medullary portions of the diffuse abnormal lesions of the distal femurs, tibias, and fibulas, and cardiac MRI was nonsignificant. The patient was started on vemurafenib and continued to show improvement in a 3-month outpatient follow-up.

Concomitant Langerhans cell histiocytosis of cervical lymph nodes in adult patients with papillary thyroid carcinoma: A report of two cases and review of the literature.

OBJECTIVE: : Langerhans cell histiocytosis (LCH) is an uncommon entity of unknown etiology. It contains a wide range of clinical presentations. The discovery of oncogenic BRAF V600E mutation in LCH has provided additional evidence that LCH is a neoplasm. Papillary thyroid carcinoma is the most common cancer of the thyroid characterized by a high incidence of BRAF V600E mutations. LCH with concomitant PTC is rare, with few cases reported in the literature. CASES SUMMARY: We identified two cases of LCH with concomitant papillary thyroid carcinoma in adult patients. The first was a 49-year-old female with a thyroid nodule diagnosed with papillary thyroid carcinoma. Later, the patient had a left neck mass; Ultrasound-guided lymph node FNA was diagnosed with Langerhans histiocytosis. Subsequently, a chest CT scan revealed signs of Langerhans cell histiocytosis in the lung. The second case refers to a 69-year-old male who presented with a left thyroid nodule diagnosed on FNA cytology as papillary thyroid carcinoma. The patient was found to have multiple bone lytic lesions. Biopsies revealed Langerhans cell histiocytosis. Later, the patient experienced LCH involvement of the bone marrow with associated secondary myelofibrosis. CONCLUSIONS: LCH is rare in adults; the association with papillary thyroid carcinoma is reported and should be considered in the presence of Langerhans cell groups along with PTC, whether in the thyroid gland or cervical lymph nodes. Once LCH has been diagnosed, pulmonary involvement should also be investigated. This will direct treatment plans for patients with pulmonary or systemic disease involvement.

Paediatric Langerhans Cell Histiocytosis Disease: Long-Term Sequelae in the Hypothalamic Endocrine System.

Langerhans cell histiocytosis (LCH) is a disorder of the mononuclear phagocyte system that can affect almost any organ and system. The most common central nervous system (CNS) manifestation in LCH is the infiltration of the hypothalamic-pituitary region leading to destruction and neurodegeneration of CNS tissue. The latter causes the most frequent endocrinological manifestation, that is, central diabetes insipidus (CDI), and less often anterior pituitary hormone deficiency (APD). The reported incidence of CDI is estimated between 11.5 and 24% and is considered a risk factor for neurodegenerative disease and APD. Three risk factors for development of CDI are recognized in the majority of the studies: (1) multisystem disease, (2) the occurrence of reactivations or active disease for a prolonged period, and (3) the presence of craniofacial bone lesions. Since CDI may occur as the first manifestation of LCH, differential diagnosis of malignant diseases like germ cell tumours must be made. APD is almost always associated with CDI and can appear several years after the diagnosis of CDI. Growth hormone is the most commonly affected anterior pituitary hormone. Despite significant advances in the knowledge of LCH in recent years, little progress has been made in preventing long-term sequelae such as those affecting the hypothalamic-pituitary system.

Additive Prognostic Impact of Gastrointestinal Involvement in Severe Multisystem Langerhans Cell Histiocytosis.

OBJECTIVE: To evaluate the prognostic impact of gastrointestinal involvement on the survival of children with Langerhans cell histiocytosis (GI-LCH) registered with the international clinical trials of the Histiocyte Society. STUDY DESIGN: This was a retrospective analysis of 2414 pediatric patients registered onto the consecutive trials DAL-HX 83, DAL-HX 90, LCH-I, LCH-II, and LCH-III. RESULTS: Among the 1289 patients with single-system LCH, there was no single case confined to the GI tract; 114 of 1125 (10%) patients with multisystem LCH (MS-LCH) had GI-LCH at initial presentation. GI-LCH was significantly more common in children aged <2 years at diagnosis (13% vs 6% in those aged >2 years; P < .001) and in those with risk organ involvement (15% vs 6% in those without risk organ involvement; P < .001). The 5-year overall survival (OS) in patients without risk organ involvement was excellent irrespective of GI disease (98% vs 97% in patients with GI-LCH; P = .789). In patients with risk organ involvement, the 5-year OS was 51% in 70 patients with GI-LCH vs 72% in 394 patients without GI-LCH (P < .001). CONCLUSIONS: GI-LCH has an additive unfavorable prognostic impact in children with MS-LCH and risk organ involvement. The emerding need for more intensive or alternative treatments mandates prospective evaluation.

High prevalence of BRAFV600E in patients with cholestasis, sclerosing cholangitis or liver fibrosis secondary to Langerhans cell histiocytosis.

Targeted therapies with MAPK inhibitors have proven to modulate the clinical manifestations of patients with Langerhans cell histiocytosis (LCH). We explored the presence of BRAFV600E mutation in our cohort of patients with LCH and cholestasis, sclerosing cholangitis, or liver fibrosis that presented resistance to chemotherapy. The BRAFV600E mutation was detected either in the diagnosis (skin and bone) or liver biopsy in our cohort of 13 patients. Thus, we observed a high incidence of BRAFV600E mutation in 100% either in diagnostic biopsy (skin and bone) or liver biopsy in patients with progressive liver disease, sequela, or liver transplant requirement.

Histiocytosis in the pediatric spine: a clinical and radiographic analysis of 50 patients.

STUDY DESIGN: Descriptive, retrospective. Scientific level of evidence IV. OBJECTIVES: The aim of this study was to evaluate a consecutive case series of 50 pediatric patients with LCH of the spine. Langerhans cell histiocytosis (LCH) is a rare disease characterized by abnormal proliferation of Langerhans cells in different organs. Incidence in children range from 2 to 10 cases per million. In the current literature, few series evaluate LCH in the pediatric spine. MATERIAL AND METHODS: A consecutive case series of 50 pediatric patients with LCH of the spine treated at our hospital between 1984 and 2016, with a follow-up of at least 2 years, was analyzed. Sex, age, clinical and radiographic presentation, number of lesions, treatment, complications, and outcome were assessed. RESULTS: Fifty patients, 26 boys and 24 girls, were evaluated. Mean age was 5 years and 2 months (6 months to 13 years and 3 months). 27 patients had a single spinal lesion while 23 had 2 or more lesions. A total of 100 vertebrae were involved. The thoracic spine was the most affected. The most frequent lesion location was in the vertebral body in 88% of the cases. The symptoms were pain (87%), reduced range of motion, deformity, and neurologic deficit. Biopsy was performed in 48 patients. Thirty-nine patients received medical treatment, 28 used orthoses and six required surgery. Six patients (12%) recurred at a mean of 3 years and 5 months (range 2-12 years). In all cases, neurological symptoms, torticollis, and deformities resolved after medical or surgical treatment. CONCLUSIONS: Because of the variable presentation of the disease, ranging from a solitary isolated vertebral lesion to polyostotic and multisystemic involvement, a multidisciplinary team is required to have an adequate management of these patients and to obtain good results.

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

OBJECTIVE: To evaluate the clinical and imaging characteristics of orbital lesions of pediatric Langerhans cell histiocytosis (LCH). STUDY DESIGN: 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 and 2015. RESULTS: 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. CONCLUSIONS: 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.