Castleman Disease

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].

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].

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2. van Rhee F, Fayad L, Voorhees P, et al. Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman’s disease. J Clin Oncol. 2010;28: 3701–3708.
3. Chadburn A, Hyjek EM, Tam W, et al. Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD). Histopathology. 2008;53(5):513–524.
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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.
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11. Barker R, Kazmi F, Stebbing J, et al. FDG-PET/CT imaging in the management of HIV-associated multicentric Castleman's disease. Eur J Nucl Med Mol Imaging. 2009;36(4):648-652.