Castleman disease patients may be asymptomatic, especially if suffering from the unicentric (localized) type. When the disease is not clinically silent, patients complain about the presence of slow growing localized mass that may cause neighboring structures compression, depending on its location and size. The multicentric subtype is characterized by multiple lymphadenopathy. Both forms may be accompanied by systemic manifestations of the disease, consisting of fever, fatigue, abundant nocturnal sweating, inappetence, nausea, vomiting, cough, and dyspnea, as well as hepatomegaly, splenomegaly, peripheral edema, ascites, pleural effusions, and cutaneous signs, such as hemangiomata, rashes, or pemphigus [1] [2]. Symptoms may follow a bimodal pattern, with remissions and relapses. In patients with human immunodeficiency virus infection, Kaposi sarcoma or primary effusion lymphoma may also be noticed [3].

Amyloidosis, a complication of this illness, causes symptoms that sometimes overlap with those of multicentric Castleman disease, making the diagnosis more difficult. Castleman disease treatment improves amyloidosis manifestations, as well. If the treatment is delayed, multicentric Castleman disease associated with human herpesvirus 8 is fatal within two years by multiorgan failure, infections, or immunoblastic lymphoma development [4] [5].

Idiopathic multiple Castleman disease is more frequent in men in their fourth or fifth decade of life [6]. Different ethnic groups have various clinical traits. For example, Asian individuals frequently have interstitial pneumonitis and large violaceous skin lesions [7], while Polynesian individuals usually have a mild form of the disease [8].

• Splenomegaly

  Facing a patient with fever, peripheral lymphadenopathy, splenomegaly, and the biochemical and immunological picture depicted above, the physician may find it difficult to pinpoint the exact diagnosis. [symptoma.com]

  In further analysis of the MCD subgroup, a multivariate analysis using a Cox regression model revealed that age, splenomegaly and pretreatment serum albumin level were independent prognostic factors for OS. [ncbi.nlm.nih.gov]

  The size of the lymph nodes also decreased, but the splenomegaly persisted. [mct.aacrjournals.org]

• Generalized Lymphadenopathy

  HHV-8–Positive MCD HHV-8–positive MCD presents with generalized lymphadenopathy and constitutional symptoms, and can progress to multi-organ failure leading to death. [hematology.org]

  Case Report: We present a case of a 63-year-old woman with multicentric CD who was admitted with weight loss, night sweat, fever, and generalized lymphadenopathy. [karger.com]

  Physical examination will mainly demonstrate presence of either localized or generalized lymphadenopathy. [cancertherapyadvisor.com]

  In contrast, the multicentric form is found in older adults and is usually associated with the plasma cell variant, a systemic disease with generalized lymphadenopathy, hepatosplenomegaly, fever, and night sweats; in addition, it is frequently associated [revespcardiol.org]

  For multicentric disease: multi-region CT bilateral hilar and mediastinal lymphadenopathy centrilobular nodules diffuse abdominal lymphadenopathy hepatosplenomegaly ascites MRI General signal characteristics include: T1: iso to hyperintense relative to [radiopaedia.org]

• Cervical Lymphadenopathy

  In this case report, we discuss the case of a 7-year-old boy with multicentric plasma cell variant of CD, who presented with cervical lymphadenopathies, autoimmune hemolytic anemia, bone marrow insufficiency, pulmonary, renal, hepatic, and gastrointestinal [ncbi.nlm.nih.gov]

  […] nodes) Cervical lymphadenopathy Cervical lymphadenopathy (large neck lymph nodes) Diffuse lymphadenopathy Diffuse lymphadenopathy (large lymph nodes) Focal lymphadenopathy Focal lymphadenopathy (large lymph nodes) Generalized enlarged lymph nodes Inguinal [icd9data.com]

  All patients, except in case 4, had systemic symptoms, including fatigue and weight loss; the patient in case 4 was essentially asymptomatic, with extensive cervical lymphadenopathy and some retroperitoneal lymphadenopathy noted on a routine follow-up [ajcp.oxfordjournals.org]

  Symptoms are usually related to the area of lymph node enlargement which includes, in a classic case, a large mediastinal mass with pulmonary symptoms or palpable cervical lymphadenopathy. [cancertherapyadvisor.com]

• Fever

  A 46-year-old male patient presented with fever for over 5 months. An FDG PET/CT was acquired to evaluate the source of the fever. [ncbi.nlm.nih.gov]

  Facing a patient with fever, peripheral lymphadenopathy, splenomegaly, and the biochemical and immunological picture depicted above, the physician may find it difficult to pinpoint the exact diagnosis. [symptoma.com]

  However, occasional fever peaks indicated that control of the disease was possibly incomplete. Figure 1. [mct.aacrjournals.org]

• Anemia

  Chronic, iron-refractory, microcytic anemia can be a diagnostic and therapeutic challenge. [ncbi.nlm.nih.gov]

  Unicentric CD in patients with microcytic anemia is rarely described in the English literature. [dx.doi.org]

• Weight Loss

  The disease is characterized by fever, weight loss, anemia, polyclonal hyperglobulinemia, splenomegaly, thrombocytosis and peripheral lymphadenopathy. [ncbi.nlm.nih.gov]

  The patient reported an episode of self-limiting haemoptysis one month previously, weight loss that she related with anxiety, occasional retrosternal oppression accompanied by paraesthesia in the left arm and episodes of bronchospasm. [archbronconeumol.org]

  Symptoms include: High fever Anemia Weight loss Loss of appetite Low white blood cell counts Castleman’s disease can also be defined as hyaline vascular or plasma cell type. This is based on the appearance of the lymph node tissue. [uamshealth.com]

  Other symptoms include unexplained weight loss, fever, fatigue, or a sense of fullness in the chest or abdomen. [disabilitybenefitscenter.org]

• Lymphadenopathy

  The remaining 6 referral cases showed morphologic features consistent with reactive lymphadenopathy. [ncbi.nlm.nih.gov]

  lymphadenopathy Inguinal lymphadenopathy (large groin lymph nodes) Lymphadenopathy Lymphadenopathy (enlarged lymph nodes) Lymphadenopathy (large lymph nodes) Lymphadenopathy, axillary Lymphadenopathy, axillary (large armpit lymph nodes) Lymphadenopathy [icd9data.com]

• Fatigue

  We describe herein the case of an adolescent girl with anemia non-responsive to oral iron, associated with low-grade fever, diminished appetite and fatigue. A palpable mass below the xiphoid was noted. [ncbi.nlm.nih.gov]

  In my experience, patients experience debilitating fatigue, oftentimes leading them to be disabled, not able to work, not able to enjoy their activities of daily living and being with their families. [targetedonc.com]

  weight loss, splenomegaly, anemia and hypergammaglobulinemia Multicentric Castleman disease is multifocal and is associated with systemic symptoms, such as fever, night sweats, fatigue, cachexia, lymphadenopathy, splenomegaly, cytopenia and hypoalbuminemia [pathologyoutlines.com]

• Cough

  CD evolving into intrabronchial, extramedullary plasmacytoma.Intrabronchial mass with consequential obstruction of the left main bronchus, left lung atelectasis and mediastinal lymphadenomegaly was detected by chest CT in our patient suffering from cough [ncbi.nlm.nih.gov]

  Both forms may be accompanied by systemic manifestations of the disease, consisting of fever, fatigue, abundant nocturnal sweating, inappetence, nausea, vomiting, cough, and dyspnea, as well as hepatomegaly, splenomegaly, peripheral edema, ascites, pleural [symptoma.com]

• Dyspnea

  A 36-year-old woman suffering from oral ulcerations, skin rash, and dyspnea was suspected of having paraneoplastic pemphigus. [ncbi.nlm.nih.gov]

  Both forms may be accompanied by systemic manifestations of the disease, consisting of fever, fatigue, abundant nocturnal sweating, inappetence, nausea, vomiting, cough, and dyspnea, as well as hepatomegaly, splenomegaly, peripheral edema, ascites, pleural [symptoma.com]

• Nausea

  Both forms may be accompanied by systemic manifestations of the disease, consisting of fever, fatigue, abundant nocturnal sweating, inappetence, nausea, vomiting, cough, and dyspnea, as well as hepatomegaly, splenomegaly, peripheral edema, ascites, pleural [symptoma.com]

  Some known complementary treatment methods include: Medication to reduce stress Acupuncture to decrease pain Peppermint tea for nausea Some of these methods have been helpful, while the others have not been so effective. [dovemed.com]

  Symptoms and signs of MCD include fever, night sweats, loss of appetite, nausea/vomiting, weight loss, cough, shortness of breath, weakness or fatigue from anemia, enlarged lymph nodes (around the neck, collarbone, underarm, and groin area), enlarged [secure.ssa.gov]

  Signs and symptoms of Castleman disease occur most often with the multicentric form and can include fever, night sweats, loss of appetite, nausea, vomiting, and fatigue. [medicinenet.com]

  Symptoms and laboratory tests associated with MCD are general but can include the following: fever unexpected tiredness unexpected weight loss night sweats nausea vomiting loss of appetite rash swollen legs less-than-normal levels of red blood cells If [catie.ca]

• Vomiting

  Both forms may be accompanied by systemic manifestations of the disease, consisting of fever, fatigue, abundant nocturnal sweating, inappetence, nausea, vomiting, cough, and dyspnea, as well as hepatomegaly, splenomegaly, peripheral edema, ascites, pleural [symptoma.com]

  Symptoms and signs of MCD include fever, night sweats, loss of appetite, nausea/vomiting, weight loss, cough, shortness of breath, weakness or fatigue from anemia, enlarged lymph nodes (around the neck, collarbone, underarm, and groin area), enlarged [secure.ssa.gov]

  Signs and symptoms of Castleman disease occur most often with the multicentric form and can include fever, night sweats, loss of appetite, nausea, vomiting, and fatigue. [medicinenet.com]

  Symptoms and laboratory tests associated with MCD are general but can include the following: fever unexpected tiredness unexpected weight loss night sweats nausea vomiting loss of appetite rash swollen legs less-than-normal levels of red blood cells If [catie.ca]

  Symptoms for MCD can include Fever and night sweats Nausea and vomiting Loss of appetite Weight loss A buildup of fluid in your belly Bruising and easy bleeding Cherry-like spots on your skin Numbness in your hands and feet Anemia -- having too few red [webmd.com]

• Loss of Appetite

  Symptoms include: High fever Anemia Weight loss Loss of appetite Low white blood cell counts Castleman’s disease can also be defined as hyaline vascular or plasma cell type. This is based on the appearance of the lymph node tissue. [uamshealth.com]

  Symptoms and signs of MCD include fever, night sweats, loss of appetite, nausea/vomiting, weight loss, cough, shortness of breath, weakness or fatigue from anemia, enlarged lymph nodes (around the neck, collarbone, underarm, and groin area), enlarged [secure.ssa.gov]

  Signs and symptoms of Castleman disease occur most often with the multicentric form and can include fever, night sweats, loss of appetite, nausea, vomiting, and fatigue. [medicinenet.com]

  Symptoms and laboratory tests associated with MCD are general but can include the following: fever unexpected tiredness unexpected weight loss night sweats nausea vomiting loss of appetite rash swollen legs less-than-normal levels of red blood cells If [catie.ca]

  Symptoms for MCD can include Fever and night sweats Nausea and vomiting Loss of appetite Weight loss A buildup of fluid in your belly Bruising and easy bleeding Cherry-like spots on your skin Numbness in your hands and feet Anemia -- having too few red [webmd.com]

• Abdominal Pain

  Discussion Our patient presented with vague abdominal pain secondary to nephrolithiasis. [acgcasereports.gi.org]

  It occasionally causes symptoms of compression, such as chest or abdominal pain. Peripheral lymphadenopathies are rare and laboratory tests show abnormalities in only 25% of cases. [archbronconeumol.org]

  At admission the patient reported paroxysmal abdominal pain, mostly in the area of the left hypogastrium, similar to intestinal colic, occurring for 4-5 years, and dyspareunia. [termedia.pl]

  At the age of 13.5 years, the patient was hospitalized as a consequence of fatigue, diffuse abdominal pain, and elevated biologic inflammatory markers. [mct.aacrjournals.org]

  Of the 23 patients, 17 (74%) had isolated lymphadenopathy or mass lesions without symptoms, and the remaining 6 (26%) had symptoms or complaints related to regional compression by the massive enlargement of internal lymph nodes (abdominal pain in a case [ajcp.oxfordjournals.org]

• Abdominal Mass in the Right Lower Quadrant

  A 50-year-old woman was found with a hypervascular abdominal mass in the right lower quadrant in contrast-enhanced CT. [ncbi.nlm.nih.gov]

• Hepatosplenomegaly

  Multicentric Castleman disease has an exuberant clinical presentation due to the systemic inflammation, with symptoms such as fevers, night sweats, fatigue, and weight loss, and clinical signs of generalized lymphadenopathy, hepatosplenomegaly, and fluid [radiopaedia.org]

  Plasmacytic or plasmablastic Yes Positive for HHV-8 by QPCR May be positive for HIV Rituximab ± etoposide Optional valganciclovir maintenance Multicentric HHV-8-Negative (Idiopathic) Generalized ± hepatosplenomegaly Mostly plasmacytic, but can be hyaline [hematology.org]

  […] pressure or discomfort causing difficulty with eating or swallowing Presence of a lump in the groin, neck, or armpit Unintentional loss of weight In some cases fever and weakness Easy fatigue Appetite loss or extremely poor appetite Lymph node enlargement Hepatosplenomegaly [epainassist.com]

• Hepatomegaly

  Examination revealed pallor; generalized edema; axillary, cervical, and inguinal lymphadenopathy; hypertension; and hepatomegaly. [ncbi.nlm.nih.gov]

  Both forms may be accompanied by systemic manifestations of the disease, consisting of fever, fatigue, abundant nocturnal sweating, inappetence, nausea, vomiting, cough, and dyspnea, as well as hepatomegaly, splenomegaly, peripheral edema, ascites, pleural [symptoma.com]

  […] concentric sheets of plasma cells surround germinal centers 1 Histologic characteristics: hyalinization and hypervascularity in germinal centers 1 Associated with an array of systemic symptoms, including 3,4 : Fever, night sweats Anorexia/weight loss Hepatomegaly [castlemansconnect.com]

  The main systemic symptoms of the disease are fever, fatigue, splenomegaly, and hepatomegaly, skin rash, and severe growth retardation. [mct.aacrjournals.org]

• Night Sweats

  Herein we present the case of a 49-year-old female with a 3-year history of progressively worsening lymphadenopathy associated with fevers, chills and night sweats. Laboratory studies showed anemia and mildly elevated sedimentation rate. [ncbi.nlm.nih.gov]

  night sweats, and more severely, multi-organ system failure and progression to lymphoma. [targetedonc.com]

  sweats, fatigue, weight loss, splenomegaly, anemia and hypergammaglobulinemia Multicentric Castleman disease is multifocal and is associated with systemic symptoms, such as fever, night sweats, fatigue, cachexia, lymphadenopathy, splenomegaly, cytopenia [pathologyoutlines.com]

  Symptoms and signs of MCD include fever, night sweats, loss of appetite, nausea/vomiting, weight loss, cough, shortness of breath, weakness or fatigue from anemia, enlarged lymph nodes (around the neck, collarbone, underarm, and groin area), enlarged [secure.ssa.gov]

  sweats Anorexia/weight loss Hepatomegaly/splenomegaly Pericardial/pleural effusions Localized symptoms associated with compression in affected area—systemic symptoms are uncommon 3 CD is not considered a malignant disease; however, affected patients [castlemansconnect.com]

• Skin Rash

  A 36-year-old woman suffering from oral ulcerations, skin rash, and dyspnea was suspected of having paraneoplastic pemphigus. [ncbi.nlm.nih.gov]

  The patient returned 5 years later with abdominal distension, weight loss, cervical and inguinal lymphadenopathy, hepatoslenomegaly and vescicobullous skin rashes for 3 months. [jcp.bmj.com]

  […] felt as masses under either side of the rib cage Fever Weakness and tiredness (fatigue) Night sweats (that soak the sheets) Unintentional weight loss Loss of appetite Nausea and vomiting Numbness and tingling (neuropathy) Leg swelling (edema) Skin rashes [sylvant.com]

• Xanthelasma

  Scholar Curciarello J, Castelleto R, Bardero R, Belloni P, Gelemur M, Castelleto E, Barbero R, Belloni P, Jmelnitzky AC: Hepatic sinusoidal dilatatiion associated to giant lymph node hyperplasia (Castleman's): a new case in a patient with periorbital xanthelasmas [wjso.com]

• Pruritic Rash

  Other symptoms included a diffuse pruritic rash later defined as lichen simplex chronicus. Figure 1. CT scan of the abdomen showing a calcified homogeneous mass measuring 3.7 cm between the pancreatic and gastric body (arrow). [acgcasereports.gi.org]

Blood workup in Castleman disease should include a complete blood count which will highlight the presence of hemolytic anemia, most often of a mild or moderate level, and that of thrombocytosis, but thrombocytopenia is also possible. High platelet numbers, together with an increase of acute phase reactants such as the fibrinogen, erythrocyte sedimentation rate, and C-reactive protein are caused by high circulating levels of interleukin 6 [2] [9]. Vascular endothelial growth factor and other cytokines were also found to be elevated [10]. Other characteristic findings are the presence of hypoalbuminemia and hypergammaglobulinemia. Hepatitis B, human immunodeficiency virus, and human herpesvirus 8 serologies are parts of the workup.

Facing a patient with fever, peripheral lymphadenopathy, splenomegaly, and the biochemical and immunological picture depicted above, the physician may find it difficult to pinpoint the exact diagnosis. In this case, a computed tomography guided lymph node biopsy should be performed. The material obtained should be examined from a histopathological point of view, given that the hyaline vascular type usually has a favorable outcome, as opposed to the plasmablastic type. The plasma cell type is likely to have multiple locations, whereas the mixed subtype was seldom described. Genetic studies, as well as fluorescent in situ hybridization, should be performed in order to exclude lymphoma or other clonal disorders.

Imaging studies are used to determine the extent of the disease. A thoracic radiography can show a wide mediastinum or pleural effusions. More detailed information is offered by computed tomography or positron emission tomography studies of the thorax, abdomen, pelvis, and neck [11].

• Microcytic Anemia

  Chronic, iron-refractory, microcytic anemia can be a diagnostic and therapeutic challenge. [ncbi.nlm.nih.gov]

  Unicentric CD in patients with microcytic anemia is rarely described in the English literature. [dx.doi.org]

  anemia For disease progression of multicentric disease, some clinicians follow an IL-6 level and/or a HHV-8 viral load E. [clinicaladvisor.com]

  View Article PubMed Google Scholar De Heer-Groen TA, Prakken ABJ, Bax NMA, Van Dijken PJ: Iron therapy resistant microcytic anemia in a 13-year-old girl with Castleman disease. Eur J Pediatr. 1996, 155: 1015-1017. 10.1007/s004310050524. [wjso.com]

• Hyperglobulinemia

  The disease is characterized by fever, weight loss, anemia, polyclonal hyperglobulinemia, splenomegaly, thrombocytosis and peripheral lymphadenopathy. [ncbi.nlm.nih.gov]

  The most common of these are anemia, fever, diaphoresis, weight loss, night sweating and fatigue. 1,2,9 Patients with M-PCV may have an elevated erythrocyte sedimentation rate, hyperglobulinemia, hypoalbuminemia, polyclonal hypergammaglobulinemia, leukocytosis [scielo.br]

  View Article PubMed Google Scholar Neerhout RC, Larson W, Mansur P: Mesenteric lymphoid hamartoma associated with hypoferremia, anaemia, growth failure and hyperglobulinemia. N Engl J Med. 1969, 280: 922-925. [wjso.com]

• Bicytopenia

  Investigations showed bicytopenia, nephrotic range proteinuria with hypoalbuminemia, hypogammaglobulinemia, and features of hyaline-vascular type Castleman disease in a lymph node biopsy. [ncbi.nlm.nih.gov]

Patients had symptomatic MCD and were HIV negative and HHV-8 negative.[1] Treatment of MCD tumors and related symptoms is an important treatment goal for these patients. [jnj.com]

Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. [doi.org]

We aimed to characterise clinical features of, treatments for, and outcomes of idiopathic multicentric Castleman's disease. [ncbi.nlm.nih.gov]

In 2018, the first treatment guidelines for iMCD were established.World Castleman Disease Day was established in 2018 and is held every year on July 23. [en.wikipedia.org]

Multicentric CD is classically associated with systemic symptoms and poorer prognosis. [ncbi.nlm.nih.gov]

Treatment and prognosis For unicentric Castleman disease treatment is surgical, with good prognosis (can be curative). Multicentric Castleman disease may be treated with any combination of surgery, chemotherapy and prednisolone 6. [radiopaedia.org]

Unicentric CD has the best overall prognosis. Among the three categories of multicentric CD, the one with the osteosclerotic variant of POEMS syndrome has the best prognosis. 3 The management of Castleman's disease depends on its presentation. [jco.ascopubs.org]

Prognosis: For localized Castleman's, the prognosis is actually quite good. However, there may be a recurrence of the condition. For multicentric Castleman's, the prognosis is not so good. [lymphedemapeople.com]

Castleman disease is a rare lymphoproliferative disorder of unknown etiology. The localized form, which usually presents as a slow-growing mass, is most commonly located in the mediastinum. [ncbi.nlm.nih.gov]

Etiology The etiologies differ between the three subtypes of Castleman disease. The etiology of UCD is unknown, but a subset of UCD cases may be the result of somatic mutations in monoclonal cell populations, likely lymph node stromal cells. [emedicine.medscape.com]

Improved definitions should improve understanding of the epidemiology of Castleman disease and its subtypes. Copyright © 2017 Elsevier Inc. All rights reserved. [ncbi.nlm.nih.gov]

[…] and mixed hyaline vascular plasma cell Essential features Polyclonal proliferation of B lymphocytes Unicentric or multicentric types Hyaline vascular or plasma cell morphology types Terminology Angiofollicular hyperplasia Giant lymph node hyperplasia Epidemiology [pathologyoutlines.com]

Epidemiology The epidemiology of CD is difficult to characterize accurately due to its rarity and clinical heterogeneity. [atlasgeneticsoncology.org]

Epidemiology Castleman disease is rare. [emedicine.medscape.com]

The purpose of this article is to review the clinical, immunologic, and pathologic findings associated with both unicentric Castleman disease and MCD and discuss how the imaging findings correlate with the pathophysiology of the disease. [ncbi.nlm.nih.gov]

Pathophysiology The pathophysiology of Castleman disease (CD) varies between subtypes. Unicentric CD (UCD) pathophysiology is poorly understood. [emedicine.medscape.com]

The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care. Br J Haematol. 2005;129(1):3-17. Roca B. Castleman’s disease: a condition with protean manifestations. Onkologie. 2011;34(8-9):412-414. [castlemansconnect.com]

Right hemihepatectomy and hilar lymph node dissection was performed and preventative transcatheter arterial chemoembolization therapy was given after the surgery. The case had multiple systemic metastasis due to tumor progression. [ncbi.nlm.nih.gov]

Click here to view the NCCN Guidelines Panel Members individual disclosures NCCN Guidelines for Treatment of Cancer by Site NCCN Guidelines for Detection, Prevention, & Risk Reduction NCCN Guidelines for Supportive Care NCCN Guidelines for Age Related [nccn.org]

To prevent the need for a disability appeal, you should consider retaining the services of a qualified Social Security Disability attorney or advocate. [disabilitybenefitscenter.org]

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5. Mylona EE, Baraboutis IG, Lekakis LJ, et al. Multicentric Castleman's disease in HIV infection: a systematic review of the literature. AIDS Rev. 2008;10(1):25–35.
6. Nishimoto N, Kanakura Y, Aozasa K, et al. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. Blood 2005;106(8):2627-2632.
7. Ahmed B, Tschen JA, Cohen PR, et al. Cutaneous Castleman’s disease responds to anti interleukin-6 treatment. Mol Cancer Ther 2007;6(9):2386-2390.
8. Zhai S. Polynesian variant of idiopathic multicentric Castleman disease [abstract]. Blood. 2013;122(21). Abstract 5127.
9. Kishimoto T. IL-6: from its discovery to clinical applications. Intern Immunol. 2010;22:347–352
10. Nakahara H, Song J, Sugimoto M, et al. Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. Arthr Rheumat. 2003; 48:1521–1529.
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