Advances in Understanding and Management of Erdheim-Chester Disease.

Erdheim Chester Disease (ECD) is a rare histiocytic disorder marked by infiltration of organs with CD68+ histiocytes. ECD stems from mutations of BRAF and MAP2K1 in hematopoietic stem and progenitor cells (HSPCs), which further differentiate into monocytes and histiocytes. Histopathology reveals lipid-containing histiocytes, which test positive for CD68 and CD133 in immunohistochemistry. Signs and symptoms vary and depend on the organ/s of manifestation. Definitive radiological results associated with ECD include hairy kidney, coated aorta, and cardiac pseudotumor. Treatment options primarily include anti-cytokine therapy and inhibitors of BRAF and MEK signaling.

Erdheim-Chester disease as complex clinical presentation and diagnosis: A case report and concise review of literature.

RATIONALE: Erdheim-Chester disease (ECD) is a rare multisystemic disease characterized by the infiltration of multiple organs by foamy CD68 + CD1a-histiocytes. The genetic background consists of gain-of-function somatic mutations in the mitogen-activated protein kinase pathway. The purpose of the present paper is to make a contribution to the scientific literature on ECD by reporting our experience with a complex clinical case report, along with a concise review of the literature. We discussed the unusual clinical presentation, the complex diagnostic process and the comparison with other published cases. PATIENT CONCERNS: A 70-year-old man presented with arthralgia due to multiple bone areas of sclerosis, first diagnosed with metastases of a prostatic neoplasm. Sequential thorax-abdomen, femoral and homer contrast-enhanced computed tomography (CT) showed pericardial effusion, pulmonary fibrosis, and perirenal fibrous tissue as "hairy kidneys." He underwent. Three bone biopsies were unsuccessful to reach diagnosis. DIAGNOSES: A xanthelasma biopsy showed histopathological signs compatible with ECD; genetic analysis showed the mutation BRAFV600E. INTERVENTIONS: The patient underwent targeted therapy with vemurafenib (BRAF-inhibitor), discontinued 2 weeks later due to the onset of a diffuse erythematous papular rash on the trunk and limbs. OUTCOMES: At the 1-year follow-up, there was only progression of chronic kidney disease (CKD). LESSONS: The present case report describes how ECD diagnosis could represent a challenge for clinicians, owing to its heterogeneous clinical presentation. Early diagnosis followed by prompt therapy is essential for modifying the natural history of the disease.

[Xanthogranulomatous adrenalitis : A rare and difficult differential diagnosis of adrenal gland tumors]. / Xanthogranulomatöse Adrenalitis : Seltene und schwierige Differentialdiagnose von Nebennierentumoren.

A radiologically diagnosed tumor in a 29-year-old woman with a fever of around 39 °C was operated on under the suspicion of cholecystitis or a liver abscess. A solid tumor was found in the adrenal gland and resected. The frozen section findings did not reveal a clear diagnosis of entity and assignment. Histologically, the tumor was found to consist of densely clustered large histiocyte-like cells with expression of vimentin, CD68, and CD163 as well as negativity for keratin, langerin, and SMA. We diagnosed xanthogranulomatous adrenalitis and discussed the differential diagnoses (Langerhans cell histiocytosis, Rosai-Dorfman disease, malakoplakia, Erdheim-Chester disease).

Multisystem Erdheim-Chester disease presenting with pericardial effusion confirmed by the effusion cytology specimen.

Erdheim-Chester disease (ECD) is a rare histiocytosis characterized by the foamy CD68+CD1a- histiocytes infiltrating multiple organs and tissues. ECD might be asymptomatic or present with variable manifestations. The diagnosis of ECD requires characteristic radiological findings and pathological features. Herein, we described a 52-year-old female patient who was admitted to our hospital for recurrent pericardial effusion for two months. She has a medical history of papillary thyroid carcinoma (PTC) and underwent a total thyroidectomy two years before admission. The radiological findings suggested a potential diagnosis of ECD. Cytological analysis of the effusion cytology specimen revealed CD68+CD1a- histiocytes, confirming the ECD diagnosis. The BRAF V600E mutation was identified in the histiocytes, prompting the administration of vemurafenib, a BRAF inhibitor. After two months of standard-dose vemurafenib treatment, the disease was well controlled with pericardial effusion regression.

[Central nervous system disorders secondary to histiocytoses: neurodegeneration with potential for improvement].

Histiocytoses, including Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD), are inflammatory myeloid tumors in which monocyte lineage cells aggregate in various organs, causing tissue damage. Most of these tumors harbor oncogenic mutations in mitogen-activated protein kinase (MAPK) pathway genes, typified by BRAFV600E. Some patients with LCH develop bilateral symmetrical cerebellar lesions and brain atrophy several years after diagnosis when the initial symptoms disappear, leading to cerebellar ataxia and higher cerebral dysfunction. A similar neurological disorder has also been reported in ECD. This neurological disorder can be improved with MAPK inhibitors. When patients with this neurological disorder are identified among neurodegeneration of unknown etiology or histiocytosis patients and treated early with MAPK inhibitors, the disorder can be reversible.

Erdheim-Chester Disease with Renal Mass Presentation: Report of the First Case From Palestine and a Review of the Literature.

BACKGROUND Erdheim-Chester disease (ECD), a form of non-Langerhans-cell histiocytosis, is extremely rare. The mean age of individuals with ECD is in their 50s. Histiocytic infiltration of vital organ systems is a potential cause of substantial morbidity, which is associated with the multisystemic form of ECD. This report presents the first case of ECD with renal abnormalities in Palestine. CASE REPORT A 54-year-old woman with no medical or surgical history presented with 6 months of bilateral flank pain with no radiation or fever. A physical examination revealed only bilateral flank pain. Urine tests showed microhematuria. Laboratory test results showed increased serum creatinine levels (1.21 mg/dL) and microcytic anemia. A CT scan revealed significant multi-organ abnormalities, including renal abnormalities with a hairy kidney sign, pericardial effusion, and an osteolytic lesion of the spine. The hairy kidney sign is pathognomonic for ECD, so the renal mass was biopsied to confirm the diagnosis. The biopsy showed foamy histiocytes, lymphocytes, and plasma cells. Foamy histiocytes were CD68-positive and negative for S100, CD1a, and HMB45. PAx5 and CD3 immunostaining showed T-predominant B-lymphocyte mixtures. CONCLUSIONS In the setting of systemic symptoms and imaging abnormalities such as presence of the hairy kidney sign, pericardial effusion, and osteolytic lesion of the spine, it is necessary to examine the possibility of ECD and proceed with a biopsy for confirmation. This is the first case in Palestine to be reported and the second case worldwide with a renal mass as an atypical presentation.

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

BACKGROUND: Erdheim 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 PRESENTATION: 47-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. CONCLUSIONS: BRAF V600E mutation is frequently seen in ECD. Vemurafenib plays an active role in targeted therapy.

A new phenotype of myorhythmia: Oculofacial myorhythmia in a patient with Erdheim Chester disease.

Oculofacial myorhythmia (OFM) is a movement disorder characterized by slow, rhythmic, and repetitive movement that affects the periorbital and perioral muscles. This abnormal movement is classified as a tremor and is highly suggestive of brainstem lesions. Unlike the oculomasticastory myorhythmia, the oculofacial pattern has rarely been reported to date. We present a patient diagnosed with Erdheim Chester disease who two years after the diagnosis developed an oculofacial myorhythmia. We additionally provide a pathological framework based on evolutionary changes on neuroimaging which could explain the appearance of this very rare movement disorder. No cases of OFM have been described in patients with ECD to date. To our knowledge we are reporting the first case of oculofacial myorhythmia secondary to Erdheim Chester disease. To conclude, oculofacial myorhytmia could be a late-onset clinical manifestation of ECD with brainstem involvement.

Novel paraneoplastic mechanism for cerebellar ataxia in Erdheim-Chester disease.

We report a case of BRAF-mutation positive Erdheim-Chester disease presenting with a cerebellar ataxia. This is the first such case to be reported without structural MRI abnormalities but with a single intrathecally produced oligoclonal band. Now that the histiocytoses have been recharacterised as neoplastic, we speculate that the mechanism of the ataxia in our case is paraneoplastic. We highlight the importance of searching for BRAF mutations in this disease, as their presence leads to effective personalised treatments.

Erdheim-Chester disease misdiagnosed as meningioma of the pontocerebellar angle: A case report and review of literature.

Erdheim-Chester Disease (ECD) is a rare non-Langerhans form of systemic histiocytosis of unknown etiology with multiple organ involvement. It most commonly affects the long bones, lungs, heart, retroperitoneum, eyes, and kidneys and less commonly the brain and spinal cord. Although there are very few cases of supratentorial ECD mimicking intracranial meningioma reported in literature, to the best of our knowledge, there are no reports on ECD mimicking infratentorial pontocerebellar angle meningioma. The present study reports a case of ECD mimicking pontocerebellar angle meningioma. This study aimed to emphasize the importance of systemic evaluation using a multidisciplinary approach as well as the need for considering ECD as a differential diagnosis of xanthomatous meningioma.

An Unusual Case of Erdheim Chester Disease (ECD) with Knee Pain: A Case Report.

Background: Erdheim Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis of unknown etiology that occurs in multiple organs. The clinical characteristics of ECD are unknown, making it difficult to diagnose. Case presentation: A 61-year-old woman presented with left knee pain and contracture. She had recent medical problems such as recurrent urinary tract infection, pericardial effusion, and pleural effusion. Simple radiography and magnetic resonance imaging of the knee revealed an osteosclerotic lesion. Under suspicion of malignancy, other radiologic modalities were performed, but there were no significant results showing malignancy. A bone biopsy of the knee lesion led to a final diagnosis of ECD. The patient was treated with systemic steroids and was ultimately tried on PEG-interferon. Conclusion: This report describes an unusual presentation of ECD involving the skeletal system and multiple extraskeletal organs. Owing to its non-specific nature, ECD was notably difficult to diagnose. Therefore, if a patient has knee pain and other multiorgan presentations without malignancy, clinicians should suspect ECD.

Erdheim-Chester disease with bilateral orbital masses and multi-systemic symptoms: two case reports.

BACKGROUND: Erdheim-Chester disease (ECD) is a rare histiocytic disorder characterized by multisystem xanthogranulomatous infiltration by lipid-laden histiocytes. We report two cases of ECD involving the orbit and describe their clinicopathologic factors, treatments, and prognosis. One was a rare case of ECD complicated with primary thrombocytosis. CASE PRESENTATION: This study describes two patients with bilateral orbital ECD. Both presented with proptosis and visual loss; imaging findings showed bilateral intraorbital masses. Both had different degrees of systemic symptoms (pleural effusion, pericardial effusion, ascites, and heart failure) before the ocular symptoms and did not find the cause before ophthalmic tumor resection and pathological biopsy. The diagnosis of ECD was confirmed after pathological biopsy and detection of BRAFV600E mutation. Patient 2 also with primary thrombocytosis and had a CALR mutation as well as the BRAFV600E mutation. Both patients were recommended to receive targeted therapy. Patient 1 refused targeted therapy for financial reasons and was discharged after local radiotherapy only. The patient had no light perception in either eye and no improvement in systemic symptoms. Patient 2 began targeted treatment after diagnosis and reached the discharge criteria 2 weeks later. He is in good condition at present, but unfortunately, his eyesight has not improved because of the irreversible damage to his visual function. CONCLUSION: ECD is easily misdiagnosed and missed because of its rarity and diverse clinical manifestations. Orbital involvement is common in ECD, and surgery is the most frequently employed approach. Despite the surgical resection is not curative, its significance lies in biopsy to establish diagnosis and/or surgical debulking to relieve mass effect, minimizing further impairment of visual function. Targeted therapy is the most effective treatment for patients with a positive BRAF mutation gene. Evaluation of a concomitant myeloid neoplasm is also critical before initiating targeted therapies for refractory ECD.

Erdheim-Chester Disease: A Case Report of BRAF V600E-Negative, MAP2K1-Positive ECD Diagnosed by Blood Next-Generation Sequencing Assay and a Brief Literature Review.

Erdheim-Chester disease (ECD) is a rare type of non-Langerhans cell histiocytosis. However, its prevalence has increased significantly the past few years due to increased awareness about the disorder, and 1500 cases have been reported worldwide. It is often a multisystemic disease with skeletal, cardiovascular, urologic, renal, retroperitoneal, pulmonary, endocrine, cutaneous, and neurologic involvement. MAPK pathway mutations, such as BRAF activating and MAP2K1 mutations, play a key role in its pathogenesis. In addition to the characteristic clinical, radiological, and histopathological findings, identifying underlying mutations helps diagnose and treat patients with highly effective targeted therapies such as BRAF and MEK inhibitors. We report a case of a man, aged 55 years, with an extensive and prolonged course of an unexplained multisystemic disease, later diagnosed with BRAF V600E-negative and MAP2K1-positive ECD on cell-free DNA testing. Additionally, we review common clinical manifestations, mutations, diagnoses, and targeted therapies for ECD.

[Histiocytosis]. / Histiocitosis.

Histiocytosis is a group of rare diseases characterized by inflammation and accumulation of cells derived from monocytes and macrophages in different tissues. The symptoms are highly variable, from mild forms with involvement of a single organ to severe multisystem forms that can be life compromising. The diagnosis of histiocytosis is based on the clinic, radiological findings and pathological anatomy. A biopsy of the affected tissue is recommended in all cases as it may have therapeutic implications. During the last decade, some mutations have been identified in the affected tissue that condition activation of the MAPK/ERK and PI3K/AKT pathway, in a variable proportion depending on the type of histiocytosis. In this review we mainly focus on Langerhans Cell Histiocytosis, Erdheim-Chester Disease and Rosai-Dorfman Disease.

Case report of a patient with Erdheim-Chester disease presenting with neuro-endocrine symptoms and negative for BRAF mutation.

RATIONALE: Erdheim-Chester disease (ECD) is a rare progressive disease affecting multiple systems. It has recently been recognized as a neoplastic disease following the discovery of activating mutations in the MAPK pathway. There are several striking signs of ECD, such as the long bone involvement, as well as the hairy kidney appearance on computed tomography scan. It is rare for ECD to manifest neurological symptoms. Central nervous system involvement is a strong prognostic factor and independent predictor of death. ECD is characterized by the overproduction and accumulation of foamy histiocytes and Touton's giant cells in various tissues and organs. ECD is a multisystem disorder in which any organ may be affected. PATIENT CONCERNS: This case report describes a 57-year-old woman with headaches and ataxia as the first clinical manifestation, without characteristic bone pain, but with delayed enuresis. In addition to the renal involvement, this patient had rarer splenic involvement. DIAGNOSES: The imaging presentation of this patient was similar to that of a "multiple meningiomas". A combination of clinical, imaging and pathology for the diagnosis of ECD. INTERVENTIONS: Patients were given INF-α therapy. OUTCOMES: Fortunately, the patient responded well to INF-α treatment. LESSONS: ECD patient with neuro-endocrine symptoms.

Neurological Manifestations of Histiocytic Disorders.

PURPOSE OF REVIEW: Histiocytic disorders, including Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman disease (RDD), are rare neoplasms that may present with a spectrum of neurologic involvement. Diagnostic delay is common due to heterogeneity in presentation and challenging pathology. RECENT FINDINGS: Recent advances in the treatment of these diseases targeted towards mutations in the MAP kinase pathway have led to an improved prognosis in these patients with neurologic involvement. It is critical for clinicians to have a high index of suspicion to allow for early targeted treatment and optimize neurologic outcomes. A systematic approach to diagnosis is presented in this article to allow for accurate diagnosis of these rare diseases.

Ophthalmologic Findings in Pediatric Erdheim-Chester Disease: A Literature Review With a Novel Case Report.

PURPOSE: The authors aim to describe the ophthalmologic manifestations of pediatric Erdheim-Chester disease (ECD). METHODS: The authors describe a novel case of ECD presenting as isolated bilateral proptosis in a child and provide a comprehensive review of the documented pediatric cases to observe overall trends and ophthalmic manifestations of disease. Twenty pediatric cases were identified in the literature. RESULTS: The mean age at presentation was 9.6 years (1.8-17 years) with a mean time of symptom presentation to diagnosis of 1.6 years (0-6 years). Nine patients (45%) had ophthalmic involvement at diagnosis, 4 who presented with ophthalmic complaints: 3 with observable proptosis and 1 with diplopia. Other ophthalmic abnormalities included eyelid findings of a maculopapular rash with central atrophy on the eyelids and bilateral xanthelasmas, neuro-ophthalmologic findings of a right hemifacial palsy accompanied by bilateral optic atrophy and diplopia, and imaging findings of orbital bone and enhancing chiasmal lesions. No intraocular involvement was described, and visual acuity was not reported in most cases. CONCLUSIONS: Ophthalmic involvement occurs in almost half of documented pediatric cases. Typically presenting with other symptoms, the case highlights that isolated exophthalmos may be the only clinical sign, and ECD should be included in the differential diagnosis of bilateral exophthalmos in children. Ophthalmologists may be the first to evaluate these patients, and a high index of suspicion and an understanding of the varied clinical, radiographic, pathologic, and molecular findings are critical for prompt diagnosis and treatment of this unusual disease.