non-Langerhans Cell Histiocytosis Research Articles

Isolated thoracic intramedullary Erdheim-Chester disease presenting with paraplegia: a case report and literature review

BackgroundErdheim-Chester disease (ECD) is a rare, idiopathic, systemic non-Langerhans cell histiocytosis involving long bone and visceral organs. Central nervous system (CNS) involvement is uncommon and most cases develop as a part of systemic disease. We present a rare case of variant ECD as an isolated intramedullary tumor.Case presentationA 75-year-old female patient with a medical history of diabetes and hypertension presented with sudden-onset flaccid paraparesis for 1 day. Neurological examination revealed grade 2–3 weakness in both legs, decreased deep tendon reflex, loss of anal tone, and numbness below T4. Leg weakness deteriorated to G1 before surgery. Preoperative magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed an intramedullary mass lesion at T2-T4 with no systemic lesion, which was heterogeneous enhancement pattern with cord swelling and edema from C7 to T6. Gross total removal was achieved for the white-gray-colored and soft-natured intramedullary mass lesion with an ill-defined boundary. Histological finding revealed benign histiocytic proliferation with foamy histiocytes and uniform nuclei. We concluded it as an isolated intramedullary ECD. The patient showed self-standing and walkable at 18-month with no evidence of recurrence and new lesion on spine MRI and whole-body FDG-PET/CT until sudden occurrence of unknown originated thoracic cord infarction.ConclusionsWe experienced an extremely rare case of isolated intramedullary ECD, which was controlled by surgical resection with no adjuvant therapy. Histological examination is the most important for final diagnosis, and careful serial follow-up after surgical resection is required to identify the recurrence and progression to systemic disease.

Case of BRAF mutant Erdheim-Chester disease presenting with multisystem involvement: A case report

Objective: Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis of unknown etiology. It is a multisystemic disease that can involve bones, skin, brain, retroperitoneum, cardiovascular system, endocrine system, and lungs. Diagnosis is made by clinical findings, imaging results, and histopathological examination. BRAFV600E (B-rapidly accelerated fibrosarcoma gene) mutation is found in more than half of the cases. When Erdheim-Chester disease is not considered the differential diagnosis, it is not possible to diagnose and treat. In this case report, an Erdheim-Chester case with symptomatic, multisystem involvement, BRAFV600E mutation, and initiated vemurafenib treatment is presented in the light of literature data.

An unusual presentation of cutaneous Rosai Dorfman Disease in a child

Introduction: Rosai-dorfman disease (RDD) is a self-limiting, non-Langerhans cell histiocytosis of unknown etiology. It was originally thought to involve only the lymph nodes, however recent literature suggests extranodal involvement as wel. Case Report: Herein we report a case of cutaneous RDD in a six year-old girl, presenting with multiple subcutaneous nodules. Discussion: Cutaneous RDD is an extremely rare entity and unlike classic RDD, it has a predilection for the age group above 40 years and is more common in females. It is extremely rare in children.

15120 Erdheim-Chester disease: Case report with multisystem manifestations

A 61-year-old man presented with a 3-year history of extensive yellow plaques on both eyelids. The patient also reported retro-orbital headache, lower limb pain, polydipsia-polyuria and progressive fatigue, since last year. Reflectance confocal microscopy showed clusters of multinucleated roundish structures, along with discoid-shaped structures, at superficial dermis. Histopathology examination proved them to be Touton cells and foamy histiocytes respectively. Immunohistochemically, foamy histiocytes were positive for CD68 and negative for S-100 and CD1a. Further investigation revealed retro-orbital masses, osteosclerosis of the distal long bones, pleural and pericardial effusion, diabetes insipidus and retroperitoneal fibrosis. Therefore, the patient was diagnosed with Erdheim-Chester disease. A BRAF V600E mutation was confirmed and vemurafenib (1920 mg/day) was initiated. However, three weeks later the patient developed DRESS syndrome and the treatment was stopped. After multidisciplinary discussion, it was decided to begin treatment with cobimetinib (40 mg/day). A clinically and radiographically (assessed with 18F-FDG PET) significant improvement was noted after three months of therapy. Erdheim-Chester disease is a non-Langerhans cell histiocytosis with possible cutaneous involvement. Diagnosis is challenging and should be suspected in the presence of xanthelasma-like lesions and signs of a multisystem disease. Since 2012 with discovery of BRAF mutations in about 50% of patients, BRAF inhibitors have become a first-line treatment. More recently, cobimetinib, a MEK inhibitor, has been used in patients with BRAF wild-type disease, or in who cannot tolerate or do not respond to vemurafenib. To the best of our knowledge, we report herein the first case of Erdheim-Chester disease evaluated by confocal microscopy.

Prevalence of Hypothyroidism in Patients With Erdheim-Chester Disease

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis affecting multiple organs and commonly caused by somatic pathogenic variants in BRAF V600E and mitogen-activated protein kinase genes. Clinical features of ECD result from histiocytic involvement of various tissues; while endocrine involvement in ECD occurs frequently, the prevalence of central or primary hypothyroidism has not been thoroughly investigated. To assess hypothalamus-pituitary-thyroid (HPT) dysfunction in patients with ECD. This cross-sectional study included 61 patients with ECD who were enrolled in a natural history study at a tertiary care center between January 2011 and December 2018. ECD was diagnosed on the basis of clinical, genetic, and histopathological features. Data were analyzed in March 2020. Diagnosis of ECD. Main outcome was the prevalence of thyroid dysfunction in adults with ECD compared with community estimates. Patients underwent baseline evaluation with a thyroid function test, including thyrotropin, free thyroxine (fT4), and total thyroxine (T4), and sellar imaging with magnetic resonance imaging or computed tomography scan. The association of HPT dysfunction was assessed for differences in age, sex, body mass index, BRAF V600E status, high sensitivity C-reactive protein level, sellar imaging, and pituitary hormonal dysfunction. A total of 61 patients with ECD (46 [75%] men; mean [SD] age, 54.3 [10.9] years) were evaluated. Seventeen patients (28%) had hypothyroidism requiring levothyroxine therapy. The prevalence of both central and primary hypothyroidism were higher than community estimates (central hypothyroidism: 9.8% vs 0.1%; odds ratio, 109.0; 95% CI, 37.4-260.6; P < .001; primary hypothyroidism: 18.0% vs 4.7%; OR, 4.4; 95% CI, 2.1-8.7; P < .001). Patients with hypothyroidism (both primary and central), compared with patients with euthyroidism, had higher body mass index (median [interquartile range] 31.4 [28.3-38.3] vs 26.7 [24.4-31.9]; P = .004) and a higher prevalence of panhypopituitarism (7 [47%] vs 3 [7%]; P < .001). Among patients with hypothyroidism, those with central hypothyroidism, compared with patients with primary hypothyroidism, had a lower mean (SD) body mass index (28.3 [2.6] vs 36.3 [5.9]; P = .007) and higher frequencies of abnormal sellar imaging (5 [83%] vs 3 [27%]; P = .050) and panhypopituitarism (5 [83%] vs 3 [27%]; P = .050). In this cohort study, a higher prevalence of central and primary hypothyroidism was identified in patients with ECD compared with the community. There should be a low threshold for testing for hypothyroidism in patients with ECD, and treatment should follow standard guidelines.

A rare cutaneous lesion in the neonatal period: The non-Langerhans cell histiocytosis

The non-Langerhans cell histiocytosis (non-LCH) is a group of diseases characterized by cutaneous involvement in the neonatal&#x0D; period. The non-LCH affects less than 1 in 200,000 children born each year. A definitive diagnosis is important for the treatment of&#x0D; the disease. Therefore, skin biopsies should be performed in neonates with cutaneous lesions as early as possible. Only in the presence&#x0D; of cutaneous involvement without systemic involvement, it does not require any treatment, because the lesions can mostly self-heal.&#x0D; Here, we present a neonate diagnosed with non-LCH following a skin biopsy.&#x0D; Keywords: Histiocytic disorders, Neonatal, non-Langerhans cell histiocytosis

A RARE CASE OF PULMONARY NON-LANGERHANS CELL HISTIOCYTOSIS

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Histiocytic neoplasms are a rare group of heterogeneous disorders which may involve the lung. The most common, Langerhans cell histiocytosis (LCH), is often associated with smoking. Less common are the Non-Langerhans cell histiocytosis, Erdheim-Chester disease (ECD) and Rosai-Dorman disease (RDD). Diagnosis and treatment are often delayed due to lack of proper interpretation of clinical, radiological and histological findings. The following case poses as a diagnostic challenge as the patient is elderly, with no smoking history, and thus falls into an unsuspecting population vulnerable to prolonged invasive workup and missed diagnoses. CASE PRESENTATION: A 75-year-old male, non-smoker, was admitted for evaluation of persistent dyspnea and cough for several weeks despite outpatient treatment with antibiotics. Presented afebrile, and hypoxic requiring 4L/min via nasal cannula. History revealed recurrent pneumonias for several months and persistent infiltrates on CXR. Chest CT showed emphysematous changes with intralobular septae thickening, and bilateral pleural effusions. Thoracentesis was attempted but was unsuccessful due to the thick nature of the aspirate. Following an unyielding bronchoscopy, a subsequent right upper lobe wedge biopsy showed histological features diagnostic of pulmonary histiocytosis. Pleomorphic inflammatory infiltrates were seen with variably abundant pale staining cytoplasm and focal emperipolesis. There was fibrosis distributed in a lymphangitic pattern with diffuse involvement, and focal necrosis without granuloma formation. Immunohistochemical stains of the histiocytes were positive for CD163 and Factor XIIIa with focal staining of S100 and negative for cytokeratins (AE1/AEE3 and CAM5.2), calretinin, WT-1 and BRAF V600E. As a result, patient was not a candidate for targeted therapy; yet, improved with a course of tapered steroids. Planned for further genetic workup involving the MAPK signaling pathway in the future. DISCUSSION: This case illustrates the significant histological similarities seen in ECD and RDD including lymphangitic distribution, S100-positive histiocytes and emperipolesis. A positive BRAF V600E mutation can be seen in about 50% of ECD cases but not in RDD, giving both diagnostic and therapeutic value. Unfortunately for this patient, the mutation was negative and a definitive subclassification could not be made. However, given the patient’s lack of multisystem involvement including the classic long bone osteosclerosis, a diagnosis of RDD could be favored. CONCLUSIONS: Histiocytic lung disorders vary in clinical manifestations, making it difficult to establish a timely diagnosis. A disparity in identification and targeted treatment still exists, as illustrated in this case. It is prudent to raise awareness of these disorders and highlight the key clinical and histopathologic features which discern them for accurate diagnosis and medical therapy. Reference #1: Haroche J, Abla O; Uncommon histiocytic disorders: Rosai–Dorfman, juvenile xanthogranuloma, and Erdheim–Chester disease. Hematology Am Soc Hematol Educ Program 2015; 2015 (1): 571–578. doi: https://doi.org/10.1182/asheducation.V2015.1.571.3916289 Reference #2: DeMartino E et al. Langerhans Cell Histiocytosis and Other Histiocytic Diseases of the Lung. Clinics in Chest Medicine, Volume 37, Issue 3, 421 - 430 Reference #3: Goyal G, Young JR, Koster MJ, et al. The Mayo Clinic Histiocytosis Working Group Consensus Statement for the Diagnosis and Evaluation of Adult Patients With Histiocytic Neoplasms: Erdheim-Chester Disease, Langerhans Cell Histiocytosis, and Rosai-Dorfman Disease. Mayo Clin Proc. 2019;94(10):2054-2071. doi:10.1016/j.mayocp.2019.02.023 DISCLOSURES: No relevant relationships by Victoria Gonzalez, source=Web Response No relevant relationships by Kristen Hughes, source=Web Response No relevant relationships by Bernadette Schmidt, source=Web Response No relevant relationships by Emad Shehada, source=Web Response

Successful Salvage Treosulfan-Based Megachemotherapy With Allogeneic Stem Cell Transplantation in Nonsyndromic, Therapy-Resistant Disseminated Juvenile Xanthogranuloma: A Case Report

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder classified as non-Langerhans cell histiocytosis; although it is usually a benign and self-limiting disease, it can be fatal in some cases, especially with systemic dissemination. We present a case report of a boy with therapy-resistant disseminated JXG who was treated with systemic chemotherapy and received 3 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) from an unrelated donor. The post-transplant period was complicated by acute graft vs host disease and lymphoproliferative disease caused by Epstein-Barr virus. Currently, almost 7.5 years after the first transplantation, the boy is in complete remission with full donor chimerism and without symptoms of JXG. The presented data confirm rare observations that allo-HSCT can lead to durable remission of systemic JXG, which warrants its use in life-threatening, therapy-resistant subtypes of disease.

Solitary long-bone epiphyseal lesions in children: radiologic-pathological correlation and epidemiology.

Solitary epiphyseal lesions are rare and present with nonspecific imaging features. Knowledge regarding etiologies of pediatric epiphyseal lesions is limited to small studies. The purpose of this study was to determine the relative incidence of pathologies affecting the pediatric epiphysis based on biopsy-proven cases with imaging. We conducted a retrospective review of imaging studies including the terms "biopsy" or "resection" and entities known to affect the epiphysis and cross-referenced these with pathology reports, recording the relevant clinical data. Two radiologists performed comprehensive imaging review and recorded relevant features. Forty-nine children and adolescents met inclusion criteria. The long-bone epiphyseal lesion etiologies included chondroblastoma (n=22, 45%), nonspecific nonmalignant pathology (n=11, 22%), osteomyelitis (n=9, 18%), lymphoma (n=2, 4%) and 1 case of each of aneurysmal bone cyst, chondrosarcoma, enchondroma, hemangioendothelioma, and non-Langerhans cell histiocytosis. Median age was 13.1years old (range 1.5-18.6years). We performed comparative analysis of the two most common lesions in our series, chondroblastoma and osteomyelitis. Chondroblastoma was significantly more likely to be peripherally located (94% vs. 33%, P=0.002) and to demonstrate a discrete T1-weighted hypointense rim (94% vs. 33%, P=0.002); there were no significant differences in enhancement or intrinsic signal properties. Children with chondroblastoma were older (15.1years vs. 7.3years, P=0.001), and chondroblastoma lesions were significantly larger, with mean maximum lesion diameter of 25mm (interquartile range [IQR] 20-30) vs. 12mm (IQR 11-18) (P=0.001) and lesion volumes of 4.4mL (IQR 2.4-7.9) vs. 0.4mL (IQR 0.2-1.4) (P=0.01). This study reports the relative frequency of pathology of pediatric solitary epiphyseal lesions and describes several features that might assist in differentiating between chondroblastoma and osteomyelitis.

Erdheim-Chester disease: a rapidly evolving disease model.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis with a putative neoplastic and inflammatory nature. The disease is driven by mutations in proto-oncogenes such as BRAF and MEK, while immune-mediated mechanisms contribute to disease development and progression. The clinical presentation of ECD is highly heterogeneous, ranging from smouldering unifocal forms to multiorgan life-threatening disease. Almost any organ can be involved, but the most common lesions include long-bone involvement, retroperitoneal fibrosis, interstitial lung disease, pericardial and myocardial infiltration, CNS, retro-orbital, and large-vessel involvement. These manifestations may mimic those of neoplastic and systemic immune-mediated diseases. Overlap with these conditions represents an emerging challenge for the clinician. A variety of treatments are efficacious for ECD, targeting both the MAPK-pathway and the immune-mediated pathomechanisms. The traditional approach is based on immunomodulatory agents (interferon-α), but recent alternatives-including anti-cytokine therapies (IL1- and TNFα-blockers) and immunosuppressants (mTOR-inhibitors)-showed promising results. However, since the detection of MAPK pathway activation in most patients and the dramatic efficacy of BRAF and MEK inhibitors, these targeted treatments represent the first-line approach in patients with severe disease forms. High rates of radiologic responses do not often mean clinical remission, especially for CNS involvement, which often results in chronic disability. This review will outline the main clinical features of ECD, with emphasis on the emerging challenges in pathogenesis and management, and on the role of recent targeted approaches.

Retroperitoneal Erdheim-Chester disease without skeletal bone involvement mimicking uterine sarcoma with multiple organ involvement.

Erdheim-Chester disease (ECD) is a rare type of non-Langerhans cell histiocytosis and is characterized by the diffuse histiocytic infiltration of multiple organs. Retroperitoneal ECD, especially with uterine involvement, is extremely rare. We report about a 73-year-old woman who presented with vaginal spotting for a month and experienced abdominal pain along with pus-like urine. Computed tomography revealed an irregular mass-like lesion in the uterus, possibly a uterine sarcoma, invading the ureter, rectosigmoid, and bladder. A tissue biopsy of the retroperitoneal mass revealed typical morphological and immunohistochemical features of ECD. However, clinical features, especially long bone involvement, did not coincide with ECD, and BRAF V600E gene mutation was not detected. We made a diagnosis of atypical retroperitoneal ECD mimicking uterine sarcoma with multiple organ involvement.

Juvenile xanthogranulomas: Examining single, multiple, and extracutaneous presentations

Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis characterized by yellowish papules in the skin. JXGs most often occur in infancy or early childhood and are typically solitary and asymptomatic, often regressing after several years. While JXGs predominantly occur on the skin, extracutaneous JXGs also exist. In this paper, we review the literature on single, multiple, and visceral JXGs and provide recommendations on monitoring and work-up. A literature review was conducted with the PubMed database using selective search terms for single, multiple, ocular, and visceral lesions as well as NF1/JMML. JXG is typically a self-limited disorder if lesions are cutaneous and singular. While rare, JXGs may manifest as multiple and extracutaneous lesions. Further screening and referral to specialists may be warranted in these cases based on age and extent of involvement. Our review demonstrates common presentations of single, multiple, and extracutaneous lesions in addition to those that occur with NF1 and JMML. We suggest patients be evaluated on a case-by-case basis by a dermatologist and referred to specialists as appropriate.

Long‐term outcomes of children with extracutaneous juvenile xanthogranulomas in Japan

Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytosis in children. The mortality and morbidity of JXG with extracutaneous lesions remain unclear. Data of patients aged<18 years who were diagnosed with JXG between 2001 and 2010 were retrospectively collected through a nationwide survey. Twenty patients (11 male and nine female) had extracutaneous lesions. The median observation time was 10 years (range, 0-17). Six patients presented with symptoms at birth. The median age at diagnosis was 8.5 months (range, 0 month-13 years). Fifteen patients underwent treatment for JXG, including chemotherapy (n=11), and five did not receive treatment. All patients except one survived; 17 were disease-free and two survived with disease. One newborn-onset patient with liver, spleen, and bone marrow involvement died of the disease. Permanent sequelae included central diabetes insipidus, growth hormone deficiency, and panhypopituitarism detected at diagnosis in three, one, and two patients, respectively. Four patients had visual impairment (optic nerve compression and intraocular invasion in two each), three had epilepsy, one had mental retardation, and one had a skin scar. Eight patients who had intracranial lesions were older at diagnosis, and had a higher frequency of disease-related comorbidities and permanent sequelae than those without intracranial involvement. Patients with extracutaneous JXG had good outcomes, although those with intracranial lesions had serious permanent sequelae. Effective and safe treatment regimens for patients with intracranial JXG need to be developed.

Erdheim-Chester Disease: An Unusual Etiology of Recurrent Massive Pericardial Effusion

Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis, involves multiple systems and may display pericardial effusion. Herein, we report a 60-year-old man who presented with refractory pericardial effusion of "unknown" etiology. As in this patient, ECD should be considered when rapidly recurrent pericardial effusion is accompanied by a pseudotumoral lesion of the right atrium and other systemic manifestations.

Rosai-Dorfman Disease—Utility of 18F-FDG PET/CT for Initial Evaluation and Follow-up

The role of imaging in the management of Rosai-Dorfman disease (RDD), a rare non-Langerhans cell histiocytosis, is not clearly defined. We present an analysis of FDG PET/CT findings obtained for initial disease characterization, follow-up evaluation, and treatment planning for this disease. From an institutional pathology database (2001-2018), we identified RDD patients who underwent FDG PET/CT scans either as part of clinical care or when done as part of clinical trials. For all scans, sites of abnormal FDG uptake were assessed, and SUVmax was measured. Comparison of PET/CT findings was made with anatomic (CT/MRI-based) imaging, where available. Instances of changing treatment based on PET/CT were recorded. We reviewed 109 FDG PET/CT scans in 27 patients with RDD. Five of 27 patients had only nodal/cutaneous disease, whereas 22 patients had extranodal disease, most commonly in bone (n = 9) and central nervous system (n = 7). PET/CT identified sites of active disease in 24 of 27 patients. All identified bone and extraskeletal lesions, except for a brain lesion in 1 patient, were FDG-avid. In 6 of 20 patients (30%) with available prior CT or MRI, PET/CT demonstrated additional RDD lesions (bones: n = 5, pleura: n = 1) that were not apparent on anatomic imaging; 3 of these lesions were outside the CT field of view, and 3 were not recognized on CT. Overall, 13 of 109 PET/CT scans led to a change in management, affecting 41% (11/27) of patients. FDG PET/CT was valuable in defining disease extent and optimizing treatment strategy in patients with RDD.

Association of BRAF V600E with Hypothalamic-Pituitary-Adrenal Axis Involvement in Erdheim-Chester Disease

• Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by uncontrolled inflammation resulting in fibro-inflammatory damage of multiple organs, including the hypothalamic-pituitary-adrenal (HPA) axis. • Glucocorticoid insufficiency may occur and is associated with an increased burden of disease and an increased risk of adrenal crisis. • HPA axis in ECD tends to involve the adrenal glands in BRAF V600E-positive individuals, without influencing the rates of low cortisol levels, although there is a poor biochemical-radiological concordance in ECD. • In this cohort, most subjects with HPA axis involvement did not require glucocorticoid or mineralocorticoid therapy. • This study systematically demonstrates an association between the somatic activating BRAF V600E variant and the presence of radiographic and biochemical HPA axis involvement in ECD subjects. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by uncontrolled inflammation resulting in fibro-inflammatory damage of multiple organs, including the hypothalamic-pituitary-adrenal (HPA) axis. Glucocorticoid insufficiency may occur and is associated with an increased burden of disease and an increased risk of adrenal crisis. Sixty-one ECD subjects (46 males, age 54.3 ± 10.8 years) were evaluated; 56.1% (32/57) harbored a somatic activating BRAF V600E variant. Adrenal gland and sellar or suprasellar involvement was present in 18/57 (31.6%) and 9/57 (15.8%) subjects on computed tomography or magnetic resonance imaging, respectively. The BRAF -positive group was more likely to have adrenal gland involvement (56.2% vs. 20.0%; odds ratio (OR) 5.8, 95% confidence interval (CI) 1.5-17.1, P=0.008), with comparable rates for sellar or suprasellar involvement (28.1% vs. 20.0%; OR 1.6, 95% CI 0.5-5.4, P=0.5) and low random morning cortisol values (37.5% vs. 32.0%; OR 1.3, 95% CI 0.4-3.8, P=0.7). High-sensitivity C-reactive protein was significantly higher in the BRAF V600E-positive group with adrenal involvement when compared to the BRAF V600E-negative group without adrenal involvement (mean concentration: 40 mg/dL vs. 5 mg/dL, P=0.046). HPA axis in ECD tends to involve the adrenal glands in BRAF V600E-positive individuals, without influencing the rates of low cortisol levels, although there is a poor biochemical-radiological concordance in ECD. In this cohort, most subjects with HPA axis involvement did not require glucocorticoid or mineralocorticoid therapy. This study systematically demonstrates an association between the somatic activating BRAF V600E variant and the presence of radiographic and biochemical HPA axis involvement in ECD subjects. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01417520

Uncommon cutaneous non-Langerhans cell histiocytosis arising from dermal dendritic cells in adults: a clinicopathological study of five cases.

Non-Langerhans cell histiocytosis (non-LCH) is a collective term that encompasses a long list of rare "histiocytosis" that do not meet the criteria for Langerhans cell histiocytosis (LCH). Among cutaneous non-LCH, the xanthogranuloma (XG) family represents a distinct group of disorders derived from dermal dendritic cells (DDCs) at different stages of differentiation. To investigate the clinicopathological characteristics of the XG family in adults and review the relevant literature. We performed a retrospective clinicopathological study of five adult cases with a previous diagnosis of non-LCH. Clinicopathological features, immunophenotypes, genetic alterations and ultrastructural characteristics were analysed. Skin biopsies revealed that all five cases were characterized by diffuse infiltration of polymorphic cells, which were immunoreactive to factor XIIIa but negative for Langerin, CD1a, and S100. None of the cases harboured the BRAF V600E mutation. Electron microscopy of two cases exhibited abundant cytoplasmic processes with numerous lysosome-like dense bodies and electron-lucent vesicles in the cytoplasm and extracellular matrix. The overall features suggested that DDCs are the cellular origin, and these cases fulfilled the criteria for the XG family. The XG family represents a spectrum of rare diseases with different clinical presentations, a wide range of morphological appearances, and a shared common origin (DDCs). This group of disorders has been proposed as a unique entity with diagnostic challenges that should not be underestimated.

P37 Erdheim-Chester disease: an ultra-rare mimic of IgG4-related disease

Abstract Background A 56 year old female was hospitalised in July 2019 with abdominal pain and significant weight loss, but little in the way of bone pain. Examination showed no evidence of xanthelasma. A large pericardial effusion was detected, requiring pericardiocentesis. The pericardial fluid contained numerous macrophages staining with CD68. Methods CT scans were reported as consistent with metastatic carcinoma. There were multiple sclerotic bone lesions in the manubrium, T7, T11, L2 and L4. She also had a periaortitis with soft tissue infiltrate around the ascending aorta and aortic arch, in the mediastinum, posterior paravertebral region, and in the retroperitoneum, obscuring both adrenal glands and surrounding both kidneys. Bone marrow aspirate and trephine demonstrated reactive appearances only. Results She required re-admission with breathlessness due to recurrence of the pericardial effusion. Biopsy from the left perinephric region was performed. Histopathology revealed a fibroinflammatory disorder. Some histiocytes were seen. There was no evidence of the typical features of IgG4-RD such as storiform fibrosis or obliterative phlebitis, which had been the working diagnosis thus far. Serum IgG4 level was normal. The classical histological features of Erdheim-Chester disease (ECD, an ultra-rare non-Langerhans cell Histiocytosis) in terms of foamy macrophages and Touton cells, were not obvious, but in the literature, it is not uncommon for the typical histological appearances of ECD to be absent. Further investigation demonstrated the classical radiographic findings of ECD with symmetrical sclerotic lesions in the long bones of the lower limbs. Radionuclide bone scan showed multifocal symmetrical increase in isotope uptake, predominately in the distal femora, proximal and distal tibiae, mandible and maxillae with multiple lesions in the thoracic and lumbar spine. Endocrine failure is frequently seen in ECD. Fortunately, our patient had neither pituitary disease nor hypoadrenalism. Furthermore, CNS involvement, ataxia and retro-orbital disease have all been reported in ECD. Our patient has experienced daily episodes of right retro-orbital pain, dizziness on upward gaze without diplopia, and occasional staggering. An MRI of brain, orbits and whole spine is scheduled, as are a whole body FDG-PET scan and cardiac MRI (to exclude myocardial infiltration). BRAF V600E mutation analysis is in progress since around 50% of ECD patients with this mutation may respond to vemurafenib treatment. Conclusion In this illustrative case, the combination of a fibroinflammatory disorder surrounding both kidneys, along with recurrent pericardial effusion and sclerotic bone lesions, was clinically and radiologically diagnostic of Erdheim-Chester disease. ECD is a recognised mimic of IgG4-RD, which itself is a mimic of multiple other conditions, including metastatic carcinoma. We present this case to highlight this little-known condition. Rheumatologists and Physicians should consider ECD in the differential diagnosis of IgG4-RD, periaortitis, pericardial effusion, symmetrical sclerotic bone lesions, endocrine failure and neurological features. Disclosures J.S. McLaren None. V. Campbell None. M. Rahilly None. J.M. Rehman None. R. Cargill None.

ERDHEIM-CHESTER DISEASE (ECD): A RARE DISEASE PRESENTING AS CARDIAC TAMPONADE

ECD is a very rare multisystem disease with ~500 cases reported. It is a non-Langerhans cell histiocytosis in which foamy histiocytes infiltrate the skeleton, nervous system, kidneys, skin and cardiovascular system (57% of cases). We describe a unique case of ECD presenting as cardiac tamponade. A

Non-Langerhans cell histiocytosis with peripheral joint destruction and mediastinal lymph node invasion: The continuous feature spectrum of clinical multicentric reticulohistiocytosis and microscopical xanthoma disseminatum

The non-Langerhans cell histiocytoses (non-LCH) are rare and benign histiocytic disorders. We present a 61-year-old female with progressive skin-colored nodules on the face and extremities. The skin biopsy showed dermal infiltration of foamy histiocytes. Further imaging study showed erosive arthritis and lymphadenopathy. The microscopical feature of anterior mediastinal lymph node was similar to that in the skin. Thus, the diagnosis is non-LCH with joints and lymph nodes involvement. This patient presented both the clinical manifestations of multicentric reticulohistiocytosis (MRH) and histologic findings of xanthoma disseminatum (XD), indicating the plausible association and the shared disease spectrum of MRH and XD.