Imaging in multicentric Castleman's disease.
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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PET-CT has recently been introduced into the clinical management algorithm for HIV-associated MCD. Results for seven HIV-seropositive patients with active MCD, either newly diagnosed or relapsed, showed that 36% of lymph node groups included radiologically enlarged nodes on CT scan, whilst 63% of lymph node groups showed enhanced FDG uptake on PET-CT scan (Figure 4). These findings suggest that FDG PET-CT may be more sensitive than CT alone in detecting MCD. In contrast, in two scans from patients in remission, there were no enlarged lymph nodes on CT scan but 11% of lymph nodes demonstrated enhanced FDG uptake, suggesting that FDG PET-CT may be less sensitive in monitoring disease activity than CT (results submitted for publication). These limitations of FDG PET-CT are well known in terms of uptake in reactive or infected nodes and this uptake in HIV-positive patients can be highly variable in persistent generalised lymphadenopathy . Nevertheless, these preliminary findings suggest that FDG PET-CT may assist in the monitoring of disease activity in MCD along with the familiar clinical and laboratory tools and the more recently introduced plasma HHV8 DNA viral load measurement [24,25].
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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 firstname.lastname@example.org
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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|Title Annotation:||LEADING ARTICLE|
|Author:||Barker, Robert; Kazmi, Fahrad; Bower, Mark|
|Publication:||Journal of HIV Therapy|
|Date:||Sep 1, 2008|
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