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].

• 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]

• 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]

• Lymphadenopathy

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

  The multicentric subtype is characterized by multiple lymphadenopathy. [symptoma.com]

• 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]

• 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]

  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]

  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]

• Splenomegaly

  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]

  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]

• 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]

  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]

• 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]

  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 lymphadenopathy [icd9data.com]

  However, in case 1, subsequent flow cytometric analysis at the time of recurrent cervical lymphadenopathy detected a monoclonal B-cell population with CD10 coexpression. [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]

• 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]

  Skin rashes, weakness, nausea and vomiting, and a loss of appetite, are common side effects with radiation therapy Corticosteroid drugs: These drugs inhibit the immune system, thus decreasing the abnormal proliferation of lymphocytes. [dovemed.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]

  Skin rashes, weakness, nausea and vomiting, and a loss of appetite, are common side effects with radiation therapy Corticosteroid drugs: These drugs inhibit the immune system, thus decreasing the abnormal proliferation of lymphocytes. [dovemed.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]

  […] 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]

  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]

• 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]

  The recurrent high fevers, night sweats, sky-high inflammatory markers—like C-reactive protein or erythrocyte sedimentation rate—are attributable to IL-6 overexpression. [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]

• 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]

• Xanthoma

  Murray-Lyon, Reversible plane xanthoma, vasculitis, and peliosis hepatis in giant lymph node hyperplasia (Castleman's disease): A case report and review of the cutaneous manifestations of giant lymph node hyperplasia, Journal of the American Academy of [dx.doi.org]

• Polyradiculoneuropathy

  The cause and pathogenesis of the four subtypes of CD (unicentric CD; human herpesvirus-8-associated multicentric CD; polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes [POEMS]-associated multicentric [ncbi.nlm.nih.gov]

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]

• Human Herpesvirus 8

  In human herpesvirus 8 associated multicentric Castelman disease (HHV-8-associated MCD), enlarged lymph nodes are present in multiple lymph node regions and infection with human herpesvirus 8 is present. [en.wikipedia.org]

  Hepatitis B, human immunodeficiency virus, and human herpesvirus 8 serologies are parts of the workup. [symptoma.com]

  The cause and pathogenesis of the four subtypes of CD (unicentric CD; human herpesvirus-8-associated multicentric CD; polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes [POEMS]-associated multicentric [ncbi.nlm.nih.gov]

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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.
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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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