Imaging in multicentric Castleman's disease.
HIV infection (Complications and side effects)
Lymphoproliferative disorders (Risk factors)
Lymphoproliferative disorders (Diagnosis)
Lymphoproliferative disorders (Care and treatment)
|Publication:||Name: Journal of HIV Therapy Publisher: Mediscript Ltd. Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2008 Mediscript Ltd. ISSN: 1462-0308|
|Issue:||Date: Sept, 2008 Source Volume: 13 Source Issue: 3|
|Geographic:||Geographic Scope: United Kingdom Geographic Code: 4EUUK United Kingdom|
Multicentric Castleman's disease (MCD) is an uncommon
lymphoproliferative disorder that presents with fevers, anaemia and
multifocal lymphadenopathy, and nowadays it is most commonly diagnosed
in individuals infected with human immunodeficiency virus type-1 (HIV).
The first description of Castleman's disease appeared as a case
record of the Massachusetts General Hospital in the New England Journal
of Medicine in 1954 . Benjamin Castleman, the pathologist at
Massachusetts General Hospital, subsequently described 13 cases of
asymptomatic localised mediastinal masses demonstrating lymph node
hyperplasia resembling thymoma in 1956 . The localised form usually
presents in young adults with isolated masses in the mediastinum, neck
or abdomen and systemic manifestations are rare. In contrast,
HIV-associated MCD presents with polylymphadenopathy and frequently
multi-organ involvement, is associated with systemic features, and
follows a more aggressive natural history. Patients often present with
generalised malaise, night sweats, rigors, fever, anorexia and weight
loss but occasionally may present with pancytopenia and organ failure
(particularly respiratory and renal), as well as shock requiring
admission into intensive care units.
On examination, patients have diffuse lymphadenopathy, hepatosplenomegaly, and may have ascites, oedema and effusions both pulmonary and pericardial. The clinical manifestations include an acute interstitial pneumonitis [3,4] and haemophagocytic syndrome , and less frequently neuropathic problems including polyneuropathies, leptomeningeal and CNS infiltration, as well as myasthenia gravis . Laboratory investigations may reveal thrombocytopenia, anaemia, hypoalbuminaemia and hypergammaglobulinaemia.
MCD is a relapsing and remitting disease and the definition of an 'attack' has been proposed as a combination of fever and a raised serum C-reactive protein in the absence of other aetiology, plus three of the following symptoms: peripheral lymphadenopathy, splenomegaly, oedema, pleural effusion, ascites, cough, nasal obstruction, xerostomia, rash, central neurological symptoms, jaundice or autoimmune haemolytic anaemia .
There is an association between MCD and AIDS-associated Kaposi's sarcoma (KS) caused by human herpesvirus 8 (HHV8) or Kaposi's sarcoma herpesvirus (KSHV). This virus is also present in all cases of HIV-associated MCD  and many of the features of this condition can be explained by its presence. The diagnosis of MCD is established histologically by lymph node biopsy or if necessary splenectomy. The characteristic features are interfollicular plasmablasts that express the HHV8 latent nuclear antigen (LANA). These plasmablasts also express high levels of light-chain restricted IgM, but are polyclonal and do not contain somatic mutations in their IgV genes, suggesting that they arise from naive B-lymphocytes . Occasionally, these plasmablasts join together to form clusters or 'microlymphomas' and may progress to monoclonal plasmablastic lymphomas .
The radiological features of HIV-associated MCD have been described in a small series of nine patients, using predominantly the CT scan findings , and the extent of organ involvement may be derived from the larger clinical studies of HIV-associated MCD [7,12,13]. The common features include generalised lymph node enlargement (Figure 1), which is present in very nearly all cases, and splenomegaly (Figure 2), which was present in all patients who had a spleen in situ, whilst hepatomegaly was a less universal finding present in 75-85% of patients [11,13]. In general, following the administration of intravenous contrast medium, the enlarged lymph nodes enhanced avidly. Pulmonary radiological abnormalities, usually interstitial pneumonitis, were found in 45-65% (Figure 3) [11,13]. In a separate clinical series the pulmonary manifestations of HIV-associated MCD have been addressed in 12 patients, and the most common finding was an acute reticulo-nodular interstitial pneumonitis; pleural effusions were also frequently present . Table 1 gives an updated review of the CT radiology findings in 42 patients with newly diagnosed, histologically confirmed HIV-associated MCD.
Despite these observations, CT scan findings are not sufficiently reliable to establish a diagnosis of MCD, which requires histological confirmation. The differential diagnosis in people with HIV who present with these clinical findings includes many opportunistic infections, persistent generalised lymphadenopathy and lymphoma. HIV-associated MCD may also be complicated by the co-existence or subsequent development of non-Hodgkin's lymphoma, follicular dendritic cell sarcoma, Hodgkin's disease, and another KSHV-driven neoplasm, primary effusion lymphoma [14-17]. Newer imaging techniques have therefore been studied in patients with HIV-associated MCD in an attempt to improve diagnostic accuracy. Positron emission tomography (PET) uses the glucose analogue 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG), which is taken up and retained by metabolically active cells. It produces a metabolic body map demonstrating increased activity of normal glycolytic pathway-using tissues but also hypermetabolic pathological processes. PET scanning produces limited anatomical localisation which is significantly improved by using combined PET-CT imaging to anatomically localise the functional information. A few studies have investigated the role of FDG-PET in the diagnosis of Castleman's disease although the majority of these very small studies are either in unifocal Castleman's disease or in HIV-negative MCD [18-22].
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[19.] Kunishima S, Taniguchi H, Koh T et al. F-18 fluorodeoxyglucose positron emission tomography in mesenterial Castleman's lymphoma. Clin Nucl Med, 2001, 26, 789-790.
[20.] Blockmans D, Maes A, Stroobants S et al. FDG positron emission tomographic scintigraphy can reveal Castleman's disease as a cause of inflammation. Clin Nucl Med, 2001, 26, 975-976.
[21.] Reddy MP, Graham MM. FDG positron emission tomographic imaging of thoracic Castleman's disease. Clin Nucl Med, 2003, 28, 325-326.
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[23.] O'Doherty MJ, Barrington SF, Campbell M et al. PET scanning and the human immunodeficiency virus-positive patient. J Nucl Med, 1997, 38, 1575-1583.
[24.] Stebbing J, Pantanowitz L, Dayyani F et al. HIV-associated multicentric Castleman's disease. Am J Hematol, 2008, 83, 498-503.
[25.] Dieval C, Bonnet F, Mauclere S et al. Multicentric Castleman disease: use of HHV8 viral load monitoring and positron emission tomography during follow-up. Leuk Lymphoma, 2007, 48, 1881-1883.
Correspondence to: Professor Mark Bower, Department of Oncology, Imperial College School of Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK Email email@example.com
Table 1: CT scan findings in 42 HIV-seropositive patients with newly diagnosed histologically confirmed MCD. Number Percentage (%) Lymphadenopathy 42/42 10 Hepatomegaly 28/42 67 Splenomegaly 39/41 * 95 Pulmonary involvement 17/42 40 Pulmonary infiltrates 11/42 26 Bilateral pleural effusion 6/42 14 * One patient had undergone a splenectomy for ITP prior to developing MCD.
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