non-Langerhans Cell Histiocytosis Research Articles

Cladribine chemotherapy of multifocal, multisystemic form of Rosai–Dorfman disease: literature review and case report

Rosai–Dorfman disease is the most frequent variant of non-Langerhans cell histiocytosis. Local forms can be resected or irradiated. If the process involves multiple organs, systemic chemotherapy can cure some patients. This article includes literature review and a case report of a 34-year-old patient with multifocal, multisystemic form of Rosai–Dorfman disease with bone and pleural involvement. The diagnosis was based on histological, immunohistochemical, and molecular studies of tumor tissue. Since November 2021, 6 courses of chemotherapy with cladribine and 8 infusions of zolendronic acid were carried out with achievement of durable remission. The tolerance was acceptable.

A CASE REPORT ON JUVENILE XANTHOGRANULOMA

Introduction: Juvenile Xanthogranuloma is a rare, benign, asymptomatic and commonly self-healing histiocytic disorder. It is a type of Non-Langerhans cell histiocytosis affecting primarily first two decades of life as a solitary cutaneous lesion occurring most frequently on trunk and upper extremities. There can also be involved internal organs such as lungs, kidney, gastrointestinal tract etc. Most common extracutaneous location is eye. Case presentation: Here presenting case of 5 month old male child with complain of firm, mobile, non-tender swelling just proximal to the left wrist joint since 4 months. Conclusion: Cytomorphological diagnosis of benign fibrohistiocytic lesion with possibility of Juvenile Xanthogranuloma was made & later confirmed by histological examination.

Facial cutaneous Rosai-Dorfman disease: a case report

BackgroundRosai-Dorfman disease (RDD) is a form of non-Langerhans cell histiocytosis in which the activated histiocytes of the lymph nodes and other organs begin to accumulate following excessive production. Bilateral, massive, and painless lymphadenopathy are classic presentations. Systemic RDD is already known to be a rare condition, but isolated cutaneous RDD is extremely rare. We presented a rare and unusual presentations of a disease.Case presentationA 35-year-old Thai female with a 6-month history of a small acne-like lesion that rapidly progressed to 5 cm tumor-like lesions on the face within 3 months. Tissue histology showed a dense dermal infiltration of histiocytes with emperipolesis phenomenon. Immunohistochemistry was positive for S100 protein and CD68 and negative for CD1a. Oral prednisolone (50 mg/day) was initiated with a favorable outcome at the one-month follow-up. However, prednisolone yielded a partial response at 2-month follow-up, leading to application of another modality.ConclusionAlthough cutaneous Rosai-Dorfman disease is considered benign and well medical responded disease, patients with atypical presentation and rapid growing lesion may necessitate aggressive multimodal treatment.

Erdheim Chester Histiocytosis: About a New Case Reveled after Ten Years History of Diabetes Insipidus

Erdheim-Chester Disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by the proliferation of lipid-rich histiocytes and foam-like tissue cells. Here, we present a case report of a 31-year-old male patient with ECD who initially presented with nonspecific symptoms including diabetes insipidus. Histopathological analysis confirmed the diagnosis, showing typical histological features of ECD. Treatment with Anakinra and corticosteroids led to significant improvement in symptoms. Additionally, we provide a comprehensive literature review summarizing the clinical manifestations, diagnostic criteria, pathological features, and treatment options for ECD. This case highlights the importance of considering ECD in the differential diagnosis of patients presenting with multisystem involvement and underscores the challenges in managing this rare disease.

Spectrum of Neuroimaging Features of Histiocytosis Syndromes in Children

Histiocytosis syndromes are a group of disorders characterized by abnormal accumulation and infiltration of organs by mononuclear phagocytic cells. The 2021 World Health Organization CNS tumor classification reorganized this group and included only 5 histiocytosis types that show frequent CNS involvement. Langerhans cell histiocytosis is the most common and well-known member of the group. However, it is also important to be familiar with the classic imaging characteristics of the remaining 4 subtypes. Although in some cases histiocytosis can be strongly considered with typical findings on neuroimaging, in other cases, the imaging findings will be nonspecific and pose a diagnostic challenge. The differential diagnosis can be narrowed at such times when information such as the patient’s clinical presentation and age is considered. This review presents imaging examples with current literature to comprehensively describe the neuroimaging spectrum of CNS involvement by histiocytoses.Learning Objective: To discuss neuroimaging findings of Langerhans and non-Langerhans cell histiocytosis in children, with illustrative case examples

The use of topical Rapamycin in successfully treating non-Langerhans cell histiocytosis in a pediatric patient

Non-Langerhans cell histiocytosis (non-LCH) refers to a collection of medical conditions distinguished by the excessive growth of histiocytes in bodily tissues. It is important to note that these conditions do not meet the established diagnostic criteria for Langerhans cell histiocytosis (LCH). Juvenile xanthogranuloma (JXG) and benign cephalic histiocytosis (BCH) represent the prevailing forms of cutaneous non-LCH. We present a case of JXG which responded to topical treatment with a 0.1% topical ointment of Rapamycin. Rapamycin, an immunosuppressive and antineoplastic agent, can thus be a viable alternative non-invasive topical modality for managing JXG. However, it is imperative to conduct prolonged observations to evaluate the efficacy and potential adverse reactions.

Successful treatment of xanthoma disseminatum with pulsed dye laser: A case report.

Xanthoma disseminatum is a rare form of non-Langerhans cell histiocytosis with limited treatment options due to its unknown aetiology and diffuse skin lesions. This case report presents the successful treatment of a 31-year-old male with severe pan-facial xanthoma disseminatum lesions following a facial burn and traumatic brain injury resulting from a car accident. After 5 sessions of monthly pulsed dye laser treatment, there was a clinically significant reduction in the lesions. Over the course of 3 years, the patient underwent a series of monthly pulsed dye laser treatments, and the lesions were almost cleared. These findings suggest that pulsed dye laser therapy may offer an effective treatment option for managing xanthoma disseminatum. This is the first report on use of the pulsed dye laser for treatment of xanthoma disseminatum.

Selected Case From the Arkadi M. Rywlin International Pathology Slide Seminar: Involvement of Skin and Soft Tissue by Erdheim-Chester Disease.

Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis that preferentially involves long bones but can affect a variety of other organs. Initial presentation with extraskeletal involvement is not unusual and is most commonly observed in the central nervous system, heart, retroperitoneum, lungs, and skin. Initial presentation of the disease as a subcutaneous soft tissue mass is exceedingly rare and may pose difficulties for diagnosis. We describe a case of Erdheim-Chester disease that initially presented as a cutaneous and subcutaneous soft tissue mass in the right posterior shoulder of a 52-year-old man.

P18 Giant Periocular Juvenile Xanthogranulomas Treated with Trametinib

Abstract Juvenile Xanthogranuloma (JXG), the commonest type of non-Langerhans cell histiocytosis, is regarded as a benign self-limiting condition of infancy, characterised by asymptomatic yellow brown papulonodular lesions, usually confined to the skin but occasionally affecting the eyes or internal organs. Skin lesions characteristically regress spontaneously within 3-6 years. We describe an unusually aggressive cutaneous presentation requiring input from paediatric oncology. A 6 year old boy presented with extensive soft yellowish papules, plaques and nodules particularly around the eyes but also over the chest and leg. Biopsy confirmed the clinical diagnosis of JXG. The lesions enlarged progressively with new lesions appearing, causing significant distortion of the upper and lower eyelids with reduced ability to open the eyes, discomfort and distress. Treatment was started with topical steroids, progressing to intralesional and systemic steroids, but with minimal effect. In view of the severity, vinblastine and subsequently cytarabine were added, again with limited benefit. The periocular lesions were surgically debulked and he was commenced on Trametinib (a MEK inhibitor) with a good response. Now aged 9 years, and the patient displayed a favourable clinical response after 3 months of being on Trametinib. JXG rarely requires treatment, but there is no recognised therapy for the occasional problematic lesions. In this case trametinib was effective and well-tolerated. The efficacy of trametinib in histiocytosis has been attributed to the presence of activating BRAF and MAP2K1 mutations. Genetic analysis of JXG may guide future therapies.

Disseminated Xanthogranuloma with BRAF Gene Fusion and Profound Response to MEK Inhibitor Therapy

Background: Histiocytic neoplasms represent a diverse group of clonal hematopoietic disorders, varying in severity from xanthogranuloma to multisystemic Erdheim-Chester Disease (ECD). Both Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (nLCH) are characterized by activating mutations in the MAPK pathway, primarily involving BRAF point mutations. In this report, we present a compelling case of disseminated xanthogranuloma with a unique BRAF fusion, which exhibited a remarkable therapeutic response to MEK inhibition. This finding adds to our understanding of the molecular heterogeneity within histiocytic neoplasms and highlights the potential significance of targeted therapies in managing these rare but clinically significant disorders Clinical Observation: In this clinical observation, we present the case of a 71-year-old female who sought medical attention due to a 3-year history of progressive cutaneous lesions, accompanied by hoarseness and blurry vision. A biopsy of a lesion revealed characteristic features consistent with xanthogranuloma. Further examination through direct laryngoscopy unveiled lesions on the vocal cords and tracheal masses, which exhibited identical histologic findings as the skin biopsies. A comprehensive analysis involving massively parallel DNA sequencing revealed the presence of a GAB2-BRAF fusion, along with a tumor mutational burden of 1 mutation/megabase (Mb). Immunohistochemical testing of the endobronchial biopsy demonstrated a combined positive score of 10% for PDL-1 expression, suggesting the potential for immune checkpoint blockade. Given the implicated role of MAPK pathway activation due to the identified fusion, a therapeutic approach utilizing the MEK inhibitor Trametinib was initiated. Encouragingly, the patient exhibited a favorable response with a reduction in tumor burden, near-resolution of hoarseness, and improved vision. However, this treatment was accompanied by MEK inhibitor-associated cardiotoxicity, leading to the discontinuation of Trametinib. Regrettably, following the cessation of Trametinib, the patient's lesions rapidly progressed, and her disease worsened beyond the pre-treatment state. Taking into account the 10% PDL-1 positivity, immunotherapy with Pembrolizumab was commenced, resulting in partial improvement. Nonetheless, the patient developed immunotherapy-related cardiotoxicity. In light of the continued disease progression off therapy, the MEK inhibitor Cobimetinib was introduced. The patient responded rapidly to this therapeutic intervention; however, during a one-week break in Cobimetinib treatment, the disease worsened back to the baseline. Consequently, Cobimetinib was discontinued, and a continuously dosed MEK inhibitor, Binimetinib, was cautiously administered at a lower dose to mitigate the risk of cardiotoxicity. As of the time of this report, the patient remains on Binimetinib, achieving complete clinical remission, and there is no evidence of further cardiotoxicity. This clinical observation underscores the challenges and complexities in managing advanced xanthogranuloma with unique molecular alterations and highlights the importance of closely monitoring and tailoring therapies to optimize patient outcomes. Conclusion: To our knowledge, this is the first clinical trial documenting MEK inhibition for a patient with xanthoma disseminatum harboring a BRAF fusion. Seeking to target downstream of BRAF, MEK inhibition demonstrated a dramatic response, with rapid relapse upon cessation, supporting a central oncogenic role for BRAF fusion. Further studies should explore alterations in the RAS-BRAF-ERK pathway in nLCH and consider clinical trials with MEK inhibitors. Our clinical experience suggests continuous MEK inhibitor exposure may be necessary for effective disease control. These findings advance our understanding of therapeutic options in histiocytic neoplasms, paving the way for more precise and impactful treatments.

Molecular Findings on Plasma Cell-Free DNA Analysis Among Adults with Histiocytic Neoplasms

Introduction The discovery of MAPK/ERK pathway mutations has revolutionized the care for patients with histiocytic neoplasms. However, mutational analysis on biopsy specimens is often limited by low tumor cellularity leading to testing failure or disease involvement of difficult-to-reach sites (e.g., central nervous system). Recently, molecular analysis of cell-free DNA (cfDNA) has shown promise as a viable tool for discovering driver mutations in multiple cancers. A recent study of mainly BRAF-mutated non-Langerhans cell histiocytosis (LCH) showed 50% concordance between tumor and plasma cfDNA analysis for BRAF-V600E. However, it is unknown whether cfDNA has a role in the evaluation of cases that harbor mutations beyond BRAF-V600E. We conducted this study to address this unanswered question using a large cohort of individuals with diverse histiocytic neoplasms from a tertiary-care institution. Methods We included 40 cases with histiocytic neoplasms with stored plasma and germline DNA in this study. Tissue molecular analysis was conducted using a targeted next generation sequencing (NGS) using commercial assays or whole exome sequencing (WES) using an in-house assay. A custom panel of 226 genes, including exonic and intronic regions, was used for the cfDNA assay in this study. To avoid cfDNA false positives, germline mutations identified from normal DNA sequencing were filtered using a BostonGene ®-developed error reduction algorithm.The total length of the analyzed genomic regions was 1.56 MB. For samples with an input greater than 30 ng, a 0.2% variant allele frequency (VAF) limit of detection (LOD) was used; a 0.4% VAF LOD was used for samples less than 30 ng. Results The final analysis cohort included 38 patients with histiocytic neoplasms after exclusion of 2 cases (failure of germline DNA library preparation and mismatch of germline and somatic DNA, respectively). Disease types included Erdheim-Chester disease (ECD; n=13, 34%), Langerhans cell histiocytosis (LCH; n=13, 34%), and Rosai-Dorfman disease (RDD; n=12, 32%). 24 cases were multisystem (63%), and the remaining were single-system. Commonly involved organs included bone (n=25, 66%), kidney (n=12, 32%), skin (n=8, 21%), central nervous system (n=7, 18%), and pituitary (n=7, 18%). Most cases (n=31, 82%) underwent plasma collection pre-treatment, 5 cases underwent collection after histiocytosis-directed therapy, and 2 while on treatment. Tissue NGS/WES data were available for 28 (74%) cases; 5 cases (13%) had insufficient tissue cellularity, and 5 (13%) did not undergo any tissue sequencing. Among those who underwent successful tissue sequencing assays, the most common common driver alterations was BRAF V600E (n=5, 26%). Other alterations included those in MAP2K1 (n=4, 21%), BRAF-fusions (n=3, 10%; partners UBDT2, RNF11, and LMTK2, respectively), and single cases of KRAS, NRAS and BRAF indel, respectively. cfDNA analysis showed at least one variant in 23 cases (60%). Correlation between tissue and cfDNA for known driver mutations was poor and concordant findings were only seen in one case with ECD harboring BRAF V600E in tissue as well as plasma (VAF 0.5%). Among the 5 cases where tissue mutational analysis had failed, cfDNA showed mutations in MUTYH, PTCH2, NOTCH3SDHD, and TMEM127, respectively (Figure 1). Among the 5 cases where tissue molecular assessment could not be undertaken due to various reasons, cfDNA showed alterations in 4 cases, encompassing NOTCH1, TET2, BRCA1, MSH6, PIK3CD, and FUS genes. Conclusions In a large cohort of adults with diverse histiocytic neoplasms, we found poor correlation between tumor and plasma cfDNA molecular findings. The reason for the lack of correlation may be related to low tumor shedding especially among non- BRAF V600E cases. cfDNA analysis may have a role to identify potential drivers of pathogenesis among cases that are unable to successfully undergo tissue molecular analysis. Further studies are underway to characterize other novel alterations that were discovered in the cfDNA analysis.

Rosai-Dorfman Disease in a Pediatric Patient: Imaging Findings and Pathology with a brief review of the Literature

Rosai-Dorfman Disease, otherwise known as sinus histiocytosis with massive lymphadenopathy, is a rare form of non-Langerhans cell histiocytosis with an estimated incidence of 100 cases per year in the United States. Due to its variable presentation and nonspecific clinical findings, it is particularly difficult to diagnose in pediatric patients. We report a case of an 11-month-old male who presented with a 4-day history of a right groin mass. Ultrasound of the groin and pelvis demonstrated, and MRI of the abdomen and pelvis confirmed an inguinal mass with surrounding lymphadenopathy. Pathology confirmed Rosai-Dorfman Disease and the patient improved after starting oral steroid therapy. To the best of our knowledge, this is the first case of Rosai-Dorfman Disease involving the inguinal region in an infant under 1 year of age reported in the literature. In this case report, we discuss the imaging and histology findings as well as provide a brief literature review for this diagnosis.

The clinical spectrum and prognostic factors of Erdheim-Chester disease and mixed Langerhans cell histiocytosis and Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare and probably fatal multisystemic non-Langerhans cell histiocytosis (LCH). To comprehensively investigate the clinical features, genomic analysis, treatments, and prognostic factors of ECD, we retrospectively analyzed the clinical data of 75 ECD patients and 10 mixed LCH and ECD patients in our center. The median age at diagnosis was 46years (range, 5-70). ECD patients were older at diagnosis (p = 0.006) and had more cardiac involvement (p = 0.011) as well as vascular (p = 0.031) involvement compared to mixed LCH and ECD patients. 64.8% of ECD patients and 87.5% of mixed LCH and ECD patients carried BRAFV600E mutation. The BRAFV600E mutation correlated with a greater number of affected organs (p = 0.030) and was associated with lung involvement (p = 0.033) as well as pleural involvement (p = 0.002). The median follow-up time was 38months (range, 1-174). The estimated 5-year progression-free survival (PFS) and overall survival (OS) were 48.9% and 84.7%, respectively. In a multivariate analysis, right atrial pseudotumor (p = 0.013) and pancreatic involvement (p = 0.005) predicted worse OS, while pleural (p = 0.042) and central nervous system (CNS) involvement (p = 0.043) predicted worse PFS. Our study described the clinical spectrum of ECD and mixed LCH and ECD, while also revealed the prognostic value of right atrial pseudotumor and pancreatic, pleural, and CNS involvement for worse survival.

Erdheim-Chester Disease Presenting as Bilateral Facial Masses

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis with unknown etiology. It is recently recognized to be neoplastic with genetic mutations affecting the mitogen-activating protein kinase (MAPK) pathway. We here present a case of a 49-year-old female who initially presented in 2012 with bilateral facial masses to a tertiary care center. These were removed but later recurred over a period of ten years. She then presented with xanthelasmas, bone lesions, secondary infertility due to hypothalamic hypogonadism, diabetes insipidus, and Hashimoto’s hypothyroidism. The facial masses were biopsied, and they showed classic morphological features in the form of diffuse infiltration by foamy histiocytes, with scattered Touton type of giant cells, patchy lymphocytic infiltrates, and dense fibrosis. The presented ECD case is particularly interesting due to the recurrent bilateral facial masses. To the best of our knowledge, this is the first documented case in Oman. The patient is stable and is being followed up in the clinic.
 Keywords: Erdheim-Chester disease, Langerhans cell histiocytosis.

Recurrent petit mal seizures in Erdheim-Chester disease mimicking an intra-axial brain tumor: illustrative case.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized histologically by foamy histiocytes and Touton giant cells in a background of fibrosis. Bone pain with long bone osteosclerosis is highly specific for ECD. Central nervous system involvement is rare, although dural, hypothalamic, cerebellar, brainstem, and sellar region involvement has been described. A 59-year-old man with a history of ureteral obstruction, medically managed petit mal seizures, and a left temporal lesion followed with serial magnetic resonance imaging (MRI) presented with worsening seizure control. Repeat MRI identified bilateral amygdala region lesions. Gradual growth of the left temporal lesion over 1 year with increasing seizure frequency prompted resection. A non-Langerhans cell histiocytosis with a BRAF V600E mutation was identified on pathology. Imaging findings demonstrated retroperitoneal fibrosis and long bone osteosclerosis with increased fluorodeoxyglucose uptake that, together with the neuropathologic findings, were diagnostic of ECD. This case of biopsy-proven ECD is unique in that the singular symptom was seizures well controlled with medical management in the presence of similarly located bilateral anterior mesial temporal lobe lesions. Although ECD is rare intracranially, its variable imaging presentation, including the potential to mimic seizure-associated medial temporal lobe tumors, emphasizes the need for a wide differential diagnosis.

An effective treatment in Erdheim Chester disease: vemurafenib: a case report

BackgroundErdheim Chester disease (ECD) is a rare disease with multisystemic involvement in the group of non-langerhans cell histiocytosis. Although nearly 100 years have passed since its definition, the number of cases reported all over the world is below 1000. In addition to the rarity of the disease, low awareness seems to play a role in this.Case presentation47-year-old white caucasian women patient who presented to our clinic with symptoms of weakness-fatigue as well as increasing pain in the knees and ptosis in the left eye. Result of the patient's bone biopsy, ECD was considered pathologically and BRAF V600E mutation was shown molecularly. After presenting the clinical, laboratory and other examination results of the case, the dramatic response seen with targeted therapy will be discussed.ConclusionsBRAF V600E mutation is frequently seen in ECD. Vemurafenib plays an active role in targeted therapy.

Therapy of necrobiotic xanthogranuloma - case series and review of the literature.

Necrobiotic xanthogranuloma is a rare disease that is part of the non-Langerhans cell histiocytoses. It is characterized by yellowish skin lesions, which are typically periorbitally localized. Extracutaneous manifestations of all organs are possible and can cause potentially life-threatening complications. The disease also belongs to the facultative paraneoplasias and is often associated with paraproteinemia. These aspects should be considered regarding further diagnostics. Due to the rarity of the disease, there are no standardized guidelines for therapy so far. The combination of prednisolone and chlorambucil as well as intravenous immunoglobulins seem to be effective therapeutic options. We present four cases from our clinic as well as the current results of the literature in this mini-review and would like to highlight the therapeutic challenge as well as the need for the development of guidelines.

Juvenile xanthogranuloma as a differential diagnosis for sellar and suprasellar lesions in child: Case report and review of literature

Juvenile xanthogranuloma (JXG) is a rare type of non-Langerhans cell histiocytosis. Its systemic form affects 4% of patients. Lesions in the Central Nervous System (CNS) occur in 2% of systemic cases. Sellar JXG should be one of the differential diagnoses for sellar lesions in young. This is a 15-year-old patient with non-specific headache, progressive visual loss and magnetic resonance imaging showing sellar lesion with suprasellar extension. The patient underwent microsurgery by pterional craniotomy with partial resection of the tumor. Pathology evidenced JXG. It progressively evolved with impairment of neuroendocrine functions, new lesions in different CNS locations and death two years after diagnosis. Sellar JXG without cutaneous manifestations is rare. There are no specific findings of the disease. Diagnosis requires additional tests, being defined by pathological analysis. Total resection presents a greater potential control comparing to partial resection. Even so, some patients may have progressive disease with poor clinical outcome.

CPC10 An unusual case of bilateral periorbital lesions

Abstract A 45-year-old man was referred to the dermatology department for a 5–10-year history of enlarging periorbital xanthelasma-like lesions with a non-significant lipid profile. The periorbital lesions episodically and spontaneously became swollen and were associated with a throbbing sensation. After exercise and minimal motion, haemorrhage into the lesions occurred. Clinical examination revealed multiple coalescing, symmetrical, thick, yellow plaques and nodules with red–brown areas of discoloration associated with eyelid telangiectasia. His past medical history included hiatus hernia, lipoma and Osgood-Schlatter disease of the knee. The differential diagnosis included adult-onset xanthelasma, necrobiotic xanthogranuloma and amyloidosis. Punch biopsy of the lesions showed histological features consistent with a xanthogranuloma. Owing to the association of this entity with underlying haematological malignancy, computed tomography was performed, which revealed a subtle 33 × 70 mm low-attenuating mass within the posterolateral aspect of the right iliacus muscle. On further radiological investigation, including magnetic resonance imaging (MRI) and positron emission tomography, an avid, nonaggressive right iliac bone lesion and nonavid bilateral, symmetrical metaphyseal and diaphyseal sclerosis involving both distal femur and proximal tibia were seen. Previous MRI of his knee, performed 3 years earlier following a fall, was reviewed and found to show an incidental signal abnormality in his distal femur. Tissue from the periocular xanthogranuloma was positive for the BRAF V600E mutation and tissue from biopsy of the right iliac crest was consistent with focal osteosclerosis. Owing to the histopathological, clinical and radiological features, a diagnosis of Erdheim–Chester disease (ECD) was established. As a result, the haematology team initiated the patient on a reducing dose of oral prednisolone with long-term methotrexate (15 mg weekly). This led to an improvement in appearance of the periorbital lesions. The differential diagnosis for periocular xanthogranuloma includes adult-onset xanthogranulomas and adult-onset asthma with periocular xanthogranuloma, necrobiotic xanthogranuloma and ECD. ECD is a rare form of non-Langerhans cell histiocytosis that is highly associated with BRAF V600E and other mitogen-activated protein kinase pathway mutations (Diamond EL, Durham BH, Haroche J et al. Diverse and targetable kinase alterations drive histiocytic neoplasms. Cancer Discov 2016; 6:154–65). The clinical course of ECD is generally aggressive, but it can vary from indolent disease to fatal multiorgan failure. Although ECD can have multiorgan involvement, approximately 25% of these patients have cutaneous manifestations (Kobic A, Shah KK, Schmitt AR et al. Erdheim-Chester disease: expanding the spectrum of cutaneous manifestations. Br J Dermatol 2020; 182:405–9). This case highlights the importance of considering ECD when faced with atypical periorbital lesions as these lesions can mimic common benign xanthelasma.

Longitudinal assessment of cardiac involvement in Erdheim-Chester disease using cardiac magnetic resonance imaging.

7067 Background: Erdheim-Chester disease (ECD) is a rare multi-systemic non-Langerhans cell histiocytosis that affects the heart in nearly half of patients. Atrial infiltration and pericardial effusion are the hallmarks of cardiac involvement and can lead to clinical complications (conduction disorders, coronary artery stenosis, tamponade, constrictive pericarditis). Evolution under treatment is poorly studied. We aimed to investigate the evolution of cardiac involvement in ECD using cardiac magnetic resonance (CMR) imaging. Methods: All ECD patients with a CMR imaging disclosing a cardiac involvement and who underwent at least one follow-up CMR imaging between 2005 and 2020 at a French tertiary center were retrospectively included. First and last CMR imaging were compared. Multivariable analysis was performed to search for independent predictors of cardiac involvement resolution. Variables were included in the model if their P-value was < 0.1 on univariable analysis. Results: Overall, 46 patients were included. Median age at first imaging was 63 years [53-69]. Median delay between the first and the last imaging was 4 years [2-7]. BRAFV600E mutation was present in 43 patients (94%). Patients received a median of 2 [1-3] treatments. All patients (100%) had cardiac involvement at baseline. Right atrio-ventricular sulcus (RAVS) was infiltrated in 38 patients (83%) and was the main cardiac feature.Overall, complete regression was observed in 6 patients (13%), partial regression in 26 patients (56%), stable imaging in 12 patients (26%), and worsening in 2 patients (5%). In patients with RAVS infiltration, complete regression was observed in 5 patients (16%) and partial regression was seen 22 patients (58%) regression. On univariable analysis, patients with regression of their infiltration had a lower rate of death (16% versus 64%, P= 0.002), a higher rate of atrial infiltration late gadolinium enhancement (LGE) (97% versus 71%, P= 0.01), a higher rate of hydronephrosis (50% versus 14%, P= 0.03) and a lower rate of interferon prescription (69% versus 100%, P= 0.02). A similar rate of vemurafenib use was observed in both groups (69% versus 54%, P= 0.3). On multivariable analysis, death remained significantly associated with follow-up imaging status (ß = -2.3 P= 0.01), while atrial infiltration LGE (ß = 2.7, P= 0.06), hydronephrosis (ß = 1.6, P= 0.1) and treatment with interferon (ß = -16, P= 1) were no longer significantly associated with imaging status. Conclusions: Partial or complete resolution of cardiac involvement was observed in 69% of patients with ECD and was significantly associated with a lower rate of death on multivariable analysis.