Manifestations Of Erdheim-Chester Disease Research Articles

Erdheim-Chester Disease of the Breast: First Review and First Case of Isolated Severe Gynecomastia.

(1) Introduction: Erdheim-Chester disease (ECD) is a life-threatening condition and often a diagnostic challenge. It has recently been classified as a hematopoietic tumour, and the cases of ECD reported in the literature has dramatically increased during the last 15 years. (2) Methods: We describe the case of a 57-year-old male patient with severe gynecomastia, with a detailed description of his diagnostic iter and consequent surgical operation. We provide the first systematic review of the literature of breast involvement in ECD, following PRISMA guidelines, including 13 studies and 16 patients. (3) Results: Our report resulted to be the first case of gynecomastia as a single clinical and imaging feature of ECD described in English literature. A total of 81.3% of patients included were female. Among them, 76.9% had unilateral and nodular presentation, while male patients presented bilateral heterogeneous breast enlargement. Globally, 87.5% expressed breast alterations as their first manifestations of ECD. Only 50% presented skeletal involvement. (4) Conclusion: The reported case represents a unique addition to the literature. We found two different patterns in ECD-related breast involvement between male and female patients, an unusual M/F ratio, and a lower rate of bone involvement. Breast involvement is frequently the first clinical feature; therefore, breast caregivers should be aware of this dangerous and most likely underestimated condition.

Erdheim-Chester Disease Involving the Left Uterine Adnexa: Mimicking an Ovarian Carcinoma Clinically.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis (LCH) that results in multiorgan disease involving the skin, bones, lungs, and kidneys. Female reproductive system manifestation of ECD was rare. Herein, we report a case of ECD involving the left ovary and fallopian tube. A 69-year-old woman presented with abdominal pain for 20 days. Magnetic resonance imaging revealed a solid and cystic mass on the left pelvic cavity. Histological examination revealed ovarian and fallopian tube infiltration by abundant histiocytes, with single small nuclei and foamy cytoplasm, reactive small lymphocytes, and plasma cells. Based on histopathological and immunohistochemical findings of positivity for CD68, CD163, and BRAF V600E and negativity for CD1α and S100, the molecular finding of BRAF V600E mutation, the patient was diagnosed with ECD. Positron emission tomography examination did not reveal any other lesions. The patient recovered well 12 months after surgery without any treatment. ECD involving the left fallopian tube and ovary was rare and needed to be differentiated from LCH, Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), IgG4+-related disease (IgG4+RD), and metastatic signet ring cell carcinoma.

S2212 A Rare Systemic Illness Presenting With Fever and Abdomen Pain

Introduction: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytic disease. ECD can practically involve any organ system in the body with common organs involved being skeletal system, cardiovascular system and the central nervous system. Rarely, other organs like breast, liver, spleen, kidney, testis and thyroid glands were reported to be involved. Case Description/Methods: A 51-year-old female presented to our emergency with fever and left upper quadrant pain abdomen of 10 days. Historically, she was symptomatic for last 3 years with complaints of intermittent fever, knee joints pain, polyuria, nocturia and polydipsia. Contrast enhanced computer tomography (CECT) chest and abdomen showed bilateral pleural and pericardial effusion, thrombosis in splenic vein and right portal vein, splenic infarct, bilateral urothelial thickening with perinephric fat stranding, soft tissue thickening around the aorta and asymmetrical bulky adrenals. PET-CT revealed Flouro-deoxyglucose (FDG) avid ill-defined lesion in the pericardium which was extending into the inter-atrial and atrioventricular septum and FDG avid asymmetrical mural thickening of aorta extending from ascending thoracic aorta up to the infrarenal abdominal aorta. There was presence of bulky tail of pancreas, bulky left adrenal, lytic lesions involving left femoral head, right sacrum and mandible, FDG avid lesions involving meninges, sella and cranial venous sinuses. Tc-99m bone scan showed increased tracer uptake in maxilla, mandible, bilateral forearm bones, bilateral femurs and bilateral tibia. PET guided biopsy from the lytic bone lesion in the right sacrum showed presence of cluster of atypical histiocytes with occasional multinucleated Touton type giant cells. The cells also showed granular cytoplasmic positivity for BRAFV600E, confirming the diagnosis of Erdheim Chester disease (ECD). She was initiated on oral vemurafenib, BRAF inhibitor, at a dose of 240mg twice a day. Discussion: ECD presenting with splenic infarct has not been described previously. A thorough evaluation and targeted biopsy confirmed the diagnosis. BRAFV600E is the most common mutation noted in these patients, seen in nearly 60% of the patients and the patients with BRAF mutations respond well to vemurafenib, a kinase domain inhibitor of mutant BRAF. Here in, we report a patient of ECD who presented with multisite venous thrombosis and splenic infarct, a rare manifestation of ECD, who was treated successfully with vemurafenib.

Erdheim-Chester Disease with Isolated CNS Involvement: A Systematic Review of the Literature.

Erdheim–Chester disease (ECD) is a rare, sporadic, non-Langerhans cell histiocytosis that can have various presentations and higher mortality in patients presenting with neurological symptoms. We performed a systematic review to investigate and chronicle the frequency of neurological manifestations, imaging findings, treatments, and outcomes in published ECD patients presenting with neurological symptoms. A PubMed literature search was conducted for articles (published between January 1980 and June 2021) on ECD cases presenting with neurological manifestations. We analyzed the data of 40 patients, including our patient. Cranial neuropathies and ataxia were the most frequent clinical manifestations. A total of 50% of the symptomatic ECD CNS lesions were intraparenchymal and nearly 33% of patients died due to the disease itself or complications. CNS involvement may be the only manifestation of ECD and sometimes may require a repeat biopsy with IHC testing for excellent treatment outcomes.

Erdheim–Chester disease and vemurafenib: a review of ophthalmic presentations and clinical outcomes

ABSTRACT Purpose To provide a comprehensive review of ocular and orbital manifestations of Erdheim–Chester Disease (ECD) and compare clinical outcomes with vemurafenib (INN) to historical treatments (HT). Primary outcomes are ophthalmic findings on presentation, changes in visual acuity, and mortality rate. Secondary outcomes include the progression of ocular findings, systemic involvements, and treatment modalities. Methods All published literature from January 1983 to March 2021 was searched for ophthalmic manifestations of ECD. Clinical outcomes following HT were collected and compared with INN. Results Forty-seven patients with ECD and ophthalmic presentations were identified. The mean age was 49.6 years (SD = 15.0). Proptosis (65.6%) and extraocular muscle restrictions (42.5%) were the most common presenting signs. Of 41 (87.2%) patients with orbital masses on radiologic examination, 90.2% were bilateral, and 53.7% were located in the intraconal space. Ophthalmic examination was significant for xanthelasma (27.2%), optic disc edema (34.0%), and subretinal changes (21.3%). Common treatments were systemic steroids (76.6%), interferon-α (17.0%), and cyclophosphamide (14.9%). INN was less commonly used (12.8%). The mean change in logMAR visual acuity declined with HT (29.9%) but improved with INN (79.1%) (p > 0.05). The proportion of eyes with complete vision loss increased after HT (p < 0.05). The overall mortality rate was 27.7% and notably higher in the HT group (29.3%) when compared to the INN group (16.7%) (p > 0.05). Conclusion ECD presents with many ophthalmic manifestations. Although the intraocular treatments remain controversial, INN should be highly considered in treating orbital ECD patients with BRAF-V600E mutations to prevent and reverse vision loss.

Medullary Lesions in Erdheim Chester Disease: A Case Report

ERDHEIM CHESTER disease (ECD) called also non-Langerhans Histiocytosis, is a rare illness, which can present various unusual clinical aspects. It is a Histiocytosis characterized by an infiltration of various tissues and organs, bones, retroperitoneum, pleuro-pulmonary sites, skin, and central nervous system. The most frequent central nervous system manifestations of ECD are diabetes insipidus, cerebellar syndromes, orbital lesions, and extra-axial masses involving the dura and here we report a rare case with spinal cord compression on the context of ERDHEIM CHESTER disease. Our work highlights another different clinical, radiological and pathological manifestation associated with ECD that should be considered.

Erdheim-Chester Disease in a Patient after Double Lung Transplantation for Pulmonary Langerhans Cell Histiocytosis

Introduction Both, Langerhans cell histiocytosis (LCH) and Erdheim-Chester Disease (ECD) belong to the heterogeneous group of histiocytoses. Their association is exceptional and thought to be linked to the BRAF mutation. Both diseases express with different radiographic and histopathologic phenotypes. Radiological features of pulmonary LCH include cystic and fibrotic changes sparing the costophrenic angles. On histology, positive staining with CD1a and Langerin is characteristic. Lung transplantation is the only therapeutical option in end-stage LCH. Radiologic manifestations of ECD include sclerotic bone lesions, retroperitoneal fibrosis, and cardiovascular involvement with infiltration of tissues by foamy histiocytes negative for CD1a. Case Report With an end-stage pulmonary LCH, a 38 years old man received a double lung transplantation (DLuTX). The explanted lungs revealed on histology clusters of Langerhans cells histiocytes positive for CD1a. Nine years after DLuTX and continuous immunosuppression, a PET-CT presented sclerotic changes in the scapula and 3rd thoracic vertebra, soft-tissue infiltration of the right atrium and circumferentially surrounding aorta and right coronary artery (“coated” aspect) and edematous thickening of the renal capsule (”hairy kidney“). The imaging findings were thus compatible with ECD. Bone biopsy showed fibrosis of the bone marrow. Biopsy of the retroperitoneum revealed fibrosis, cells inconsistent with Langerhans cells, immune-histochemically lacking CD1a expression. The mediastinal changes slowly progressed over years, requiring biopsy, which also yielded fibrotic tissue. Additionally, the patient developed a massive jaundice and anorexia. The abdominal CT showed intra- and extrahepatic cholangiectasis with circumferential soft tissue sheathing of the common bile duct (CBD). An ERCP with biopsy of the CBD revealed cells positive for langerin and CD1a. Further cranial CT showed symmetric sclerotic bone lesions. Patient died 12 years after DLuTx due to cardiovascular complications. He had never developed any dysfunction of his lung allografts. Summary Distinctive histopathologic results of various tissues at different time points and the extensive radiologic features in the same patient indicate the concomitant occurrence of two distinct histiocytoses, LCH and ECD after DLuTX.

Chapter 10 - Neuroendocrine manifestations of Erdheim–Chester disease

Neuroendocrine manifestations are common in Erdheim-Chester disease (ECD) patients. ECD is a rare non-Langerhans form of histiocytosis with multisystemic infiltration. The involvement of the hypothalamo-pituitary axis is common and central diabetes insipidus (CDI) is one of the most common endocrine manifestations in ECD patients. CDI is the first manifestation of ECD in 25%-48% of the cases. Suprasellar region extension, due to the infiltration of ECD lesions, can cause neurologic manifestations by mass effects, such as headache, visual disturbance, and cranial nerve palsies. Recent studies have revealed that disorders affecting anterior pituitary hormones are common in ECD patients. Secondary adrenal insufficiency, secondary hypothyroidism, (adult) growth hormone deficiency, hypogonadotropic hypogonadism, hyperprolactinemia, and hypoprolactinemia can develop as the neuroendocrine manifestations of ECD. Since the symptoms of anterior pituitary hormone deficiencies tend to be nonspecific, the diagnosis of anterior pituitary hormone dysfunctions can be delayed. Some anterior pituitary dysfunctions such as adrenocorticotropic hormone and/or thyroid-stimulating hormone deficiencies can be life-threatening without adequate hormone supplementation therapies. An endocrinological evaluation of the function of the pituitary gland should be performed at the initial diagnosis of ECD. It is important to recognize that endocrine dysfunctions can develop later during the follow-up of ECD.

Clinical and diagnostic imaging manifestations of Erdheim-Chester disease

Introduction: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans-cell histiocytosis which typically presents with bilateral masses due to retro-orbital deposition, xanthelasma of the eyelids, cardiopulmonary manifestations, along with sclerosis and cortical thickening of the long bones, particularly in the lower extremities. Case Report: We present the case of a 58-year-old male who presented to a local emergency department with a one day history of severe dizziness, diaphoresis, dyspnea, and intermittent diplopia. Imaging demonstrated bilateral symmetric retrobulbar masses. Subsequent imaging as well as orbital and bone marrow biopsies lead to the diagnosis of ECD. Conclusion: Erdheim-Chester disease is a rare form of non-Langerhans-cell histiocytosis. This case demonstrates classic clinical and imaging findings representative of ECD. Diagnostic imaging and pathologic findings play a vital role in the diagnosis and choice of therapy in patients with ECD. Although interferon is currently considered to be first-line therapy, targeted BRAF and MEK inhibitors hold promise for future direction.

Enfermedad de Erdheim-Chester. Serie de diecinueve casos y un diagnóstico diferencial de relevancia

Erdheim-Chester disease (ECD) is a non-Langerhans histiocytosis, protein manifestations at start and little known. We included 19 patients from June 2012 to June of 2019. Inclusion criteria: clinical features, histopathology and immunostaining compatible with ECD. We excluded patients with undefined features. Results: Bones were the most frequent affected, half of them were asymptomatic. Seventy per cent of the patients were women, and 7 of them developed a nodule breast as first manifestation of ECD. The patients were treated with corticosteroids associated or not with immunosuppressants. The mortality rate was 16%. Conclusion: we reported a series of patients with ECD, enhancing the most frequent features. It is striking the number of patients with breast involvement; we propose to include the Erdheim-Chester disease in differential diagnosis of breast tumor.

MON-605 Hypothyroidism in Erdheim-Chester Disease: Experience from a Tertiary Care National Referral Center

Background: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis affecting multiple organs, including the endocrine system. While endocrine involvement in ECD is well characterized, infiltration of the hypothalamic-pituitary-thyroid axis may cause either primary or central hypothyroidism that is often underdiagnosed. The prevalence of hypothyroidism and the occurrence of isolated central hypothyroidism in ECD has not been thoroughly investigated. Methods: A prospective cohort study of biopsy-confirmed cases of ECD was conducted at the National Institutes of Health. Clinical, radiographic, and biochemical characteristics were assessed. All subjects underwent baseline evaluation with a thyroid function test, including TSH, free thyroxine (fT4) and total thyroxine (T4).Results: Sixty-one subjects with ECD (46 males, 54.3 ± 10.8 years) were evaluated. Sixteen subjects (26%) hadprimary hypothyroidism and were receiving thyroid hormone supplementation before enrollment, with a mean TSH 2.00 ±1.63 mcIU/mL (normal 0.27-4.20 mcIU/mL), fT4 1.52 ±1.51 ng/dL (normal 0.9-1.7 ng/dL), and T4 7.42 ±2.15 mcg/dL (normal 4.5-11.7 mcg/dL). The prevalence of primary hypothyroidism was higher than general population estimates (26% vs. 3.7%, P<0.05). No subject presented with myxedema coma or thyrotoxicosis. One subject (1.6%), a 61-year-old Caucasian female with ECD-related cerebellar dysfunction, retroperitoneal fibrosis, and osteosclerosis, harbored the BRAF V600E pathogenic variant and had a biochemical pattern suggestive of isolated central hypothyroidism: TSH 0.16 mcIU/mL, fT4 1.2 ng/dL and a normal baseline pituitary function test. She did not report symptoms suggestive of clinical thyroid disease and her physical examination was unremarkable. Pituitary MRI showed a small hypoenhancing lesion in the posterior aspect of the pituitary gland that is clinically insignificant. Dynamic TSH-secretion testing with a thyrotropin releasing hormone (200 μg IV synthetic TRH with serial TSH testing) demonstrated a blunted response in keeping with central hypothyroidism; baseline TSH 0.35 mcIU/mL, peak 2.90 mcIU/mL (ΔTSH <7 mcIU/mL). Conclusion: The prevalence of hypothyroidism (1 in 4) is high in subjects with ECD. Clinicians should have a low threshold to screen for hypothyroidism in this at-risk population. Central hypothyroidism is a rare manifestation of ECD and should be suspected in the setting of pituitary disease with a fT4 level below the laboratory reference range or low-normal levels in conjunction with a low, normal, or mildly elevated TSH.

Adult leukoencephalopathies with prominent infratentorial involvement can be caused by Erdheim-Chester disease.

Leukoencephalopathies with prominent involvement of cerebellum and brainstem, henceforward called prominent infratentorial leukoencephalopathies (PILs), encompass a variety of inherited and acquired white matter diseases. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis likely under-diagnosed as cause of adult PIL. We reviewed the clinical and laboratory information of ten consecutive sporadic adult patients with PIL of unknown origin, who were investigated for ECD. There were seven males and three females; mean age at clinical onset was 49.6years (range 38-59); cerebellar ataxia with or without other neurological symptoms was the only or the main clinical manifestation; diabetes insipidus was present in three individuals. Eight patients had white matter focal supratentorial abnormalities, in addition to the infratentorial white matter changes. Six out of eight patients had spinal cord lesions. Thoraco-abdominal CT showed periaortic sheathing in two patients, whole-body FDG-PET revealed increased glucose uptake in the long bones of the legs in five patients, brain FDG-PET showed overt infratentorial hypermetabolism in one patient. In eight patients, ECD was confirmed by bone scintigraphy, pathological data, or both. Two ECD patients treated with vemurafenib showed a marked improvement of neurological symptoms and brain MRI abnormalities at 1 year follow-up. Symptoms of PIL can be the only clinical manifestation of ECD. Adult patients with PIL of unknown origin should undergo investigations aimed at unveiling ECD, including bone scintigraphy and whole-body FDG-PET. The early diagnosis allows starting disease-modifying therapies of an otherwise life-threatening disease.

Three Cases of Erdheim-Chester Disease With Intraocular Manifestations: Imaging and Histopathology Findings of a Rare Entity

To report intraocular manifestations of Erdheim-Chester Disease (ECD) with multimodal imaging. A retrospective observational case series. This was a multicenter case series of 3 patients with confirmed tissue diagnosis of ECD that showed intraocular manifestations and were imaged at baseline and follow-up visits. Intraocular manifestations are rarely observed in association with ECD. Intraocular manifestations of ECD seen on multimodal imaging include histiocytic choroidal infiltration causing choroidal lesions, complicated by recurrent serous retinal detachment (SRD). Short-term resolution of SRD was observed with ocular therapies including intravitreal injections ofanti-vascular endothelial growth factor or verteporfin photodynamic therapy in combination with systemic chemotherapy therapies and oral corticosteroids; however, recurrences were common. Chorioretinal biopsy confirmed the diagnosis of ECD in 1 case, with the presence of histiocytic infiltration, fibrosis, and characteristic immunohistologic staining. In another case, with a novel ARAF positive mutation, treatment with sorafenib showed regression of the choroidal lesions and resolution of the SRD on multimodal imaging. These lesions were previously resistant to other forms of therapy. Rare intraocular manifestations of ECD confirmed on histopathology can be imaged with multimodal imaging. We report 3 cases, including 1 case diagnosed through histology from chorioretinal biopsy and another case associated with a novel ARAF mutation responsive to targeted therapy with sorafenib. The identification of novel somatic mutation associated with ECD enabled treatment with a new-targeted systemic agent. Multimodal imaging in these cases can also be used to monitor response to therapy.

Diagnosis and Treatment of Erdheim-Chester Disease -Review

Erdheim-Chester Disease (ECD) is a rare form of non Langerhans' cell histiocytosis. The etiology of ECD is unknown yet. The disease is characterized by the infiltration of lipid-laden histiocytes with foamy to bones and various organs. The heterogeneous manifestations of ECD vary among different individuals. This results in a presentation that may vary from an indolent focal disease to a life threatening organ failure. This review focuses on the etiology, clinical presentation, diagnostic criteria and treatment of Erdheim-Chester disease (ECD).

Erdheim-Chester Disease: A Case of Cardiac and Hypophyseal Involvement Showing Positive Response with High Dose Pegylated Interferon-Α

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis, with multifaceted clinical presentations. There are currently fewer than 550 cases reported in the literature. This case illustrates the protean manifestations of ECD with multisystem involvement, including skeletal and extra skeletal (cutaneous, cardiac, pituitary, retroperitoneal, and pulmonary) manifestations. It reports on the complexity in making the diagnosis and subsequent positive response of ECD to pegylated interferon α.

Erdheim Chester Hastalığı Olan Dört Olgunun Nükleer Tıp Görüntüleme Yöntemlerindeki Heterojen Bulguları

Erdheim-Chester disease (ECD) is an uncommon, sporadic, non-Langerhans cell histiocytosis characterized by xanthomatous or xanthogranulomatous histiocyte infiltration of affecting both bone and soft tissue systems. Herein we report the imaging features of four cases of ECD who had different multiorgan manifestations. The nuclear medicine imaging modalities consisting of technetium-99m methylene-diphosphonate (Tc-99m MDP) scintigraphy, Fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography (F-18 FDG PET/CT) and Ga-68 DOTA-octreotate (DOTA-TATE) PET/CT are useful methods to determine the ordinarily and extraordinarily heterogeneous clinical manifestations of ECD.

Endocrine Manifestations in a Monocentric Cohort of 64 Patients With Erdheim-Chester Disease.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by infiltration of foamy histiocytes in multiple organs. Endocrine involvement has mostly been described in case reports. We performed systematic endocrine evaluation in a large cohort of patients with ECD. This was a single-center observational study conducted between October 2007 and May 2013. The evaluation was conducted in Pitié-Salpêtrière Hospital (Paris, France), a tertiary care hospital. Sixty-four consecutive patients with ECD (sex ratio, 3.6; mean age, 57.6 years [range, 20-80 years]). Thirty-six patients had follow-up assessments. There were no interventions. Clinical, biological, and morphological evaluations of pituitary, gonadal, adrenal, and thyroid functions, as well as metabolic evaluation, were performed. Diabetes insipidus was found in 33.3% of patients, frequently as the first manifestation of ECD. Anterior pituitary dysfunction was found in 91.3% of patients with full anterior pituitary evaluation, including somatotropic deficiency (78.6%), hyperprolactinemia (44.1%), gonadotropic deficiency (22.2%), thyrotropic deficiency (9.5%), and corticotropic deficiency (3.1%). Thirty-five patients (54.7%) had ≥2 anterior pituitary dysfunctional axes, rising to 69.6% (16 of 23) when only patients with complete evaluations were considered. Two patients had panhypopituitarism. Infiltration of the pituitary and stalk was found with magnetic resonance imaging in 24.4% of patients. Testicular insufficiency was found in 53.1% of patients, with sonographic testicular infiltration in 29% of men, mostly bilateral. Computed tomography adrenal infiltration was found in 39.1% of patients, and 1 case of adrenal insufficiency was observed. No patient was free of endocrine hormonal or morphological involvement. Endocrine dysfunctions were most often permanent, and new deficits appeared during follow-up. Endocrine involvement is very frequent in ECD and should be evaluated carefully at diagnosis and during follow-up.

Contribution of MRI in neurological manifestations of Erdheim-Chester disease

Contribution of MRI in neurological manifestations of Erdheim-Chester disease

Fever of unknown origin as the first manifestation of Erdheim-Chester disease

Erdheim-Chester disease (ECD) is an uncommon non-Langerhans cell histiocytosis that affects multiple body systems and can present clinically in a myriad of ways. We report the case of a 29-year-old man presented with fever and diffuse bone pain. Physical examination showed bilateral and symmetrical long bone pain, especially the knees. Radiographs showed multiple mixed bone lesions with sclerotic and lytic areas of the femora, tibiae, and fibula. Biopsy of the tibial area displayed foamy lipid-laden histiocytes, confirming the diagnosis of ECD.

Retroperitoneal infiltration as the first sign of Erdheim‐Chester disease

We report a case of an elderly man with bladder cancer, in whom the first manifestation of Erdheim-Chester disease was retroperitoneal infiltration detected during routine follow-up. The disease was diagnosed on the basis of histology and immunochemistry findings (presence of histiocytes) and of imaging findings (plain radiography, computed tomography, magnetic resonance imaging, and bone scintigraphy). The differential diagnosis with respect to other causes of retroperitoneal infiltration is discussed.