Multicentric Castleman’s disease, an uncommon cause of lymphadenopathy in HIV infection

Clinical History

A 27-year-old transsexual man with a 6-year history of Human Immunodeficiency Virus (HIV) infection, previously treated disseminated tuberculosis, and recent discontinuation of antiretroviral therapy, was hospitalized with diarrhoea, fever, and enlarged superficial lymph nodes.
Laboratory disclosed low serum electrolytes, haemoglobin (8.8 g/dl), white blood cell and platelet count.

Imaging Findings

Abdominal multidetector CT, initially performed to investigate clinical suspicion of opportunistic colitis or disseminated mycobacterial infection, showed homogeneously enhancing liver and spleen enlargement without focal lesions, absent pleural and peritoneal effusions. An extensive, non-confluent enlargement of mesenteric lymph nodes causing a “sandwich sign” appearance was noted, without appreciable nodal necrosis.
With markedly suppressed immune function (45 CD4 cells/mmc), clinical and laboratory worsening occurred during empiric antibiotic and anti-mycobacterial treatment.
Two weeks later, follow-up body CT showed mildly increased mesenterial adenopathies, a moderate, diffuse enlargement of submandibular, cervical, supraclavicular, axillary, and inguinal nodes, and persistent absence of nodal necrosis, effusions, lung and abdominal parenchymal lesions.
Cervical node surgical biopsy disclosed histologic findings consistent with Kaposi’s sarcoma Herpes virus (KHSV)-positive Castleman’s disease, confirmed by markedly elevated KHSV plasma titer. Coexisting infections were excluded by extensive serology investigations.
Chemotherapy with etoposide, plus antiretroviral drugs and growth factors allowed clinical and cytopaenia improvement.

Discussion

Castleman’s disease is a rare lymphoproliferative disease histologically characterized by angiofollicular hyperplasia. Exceptional in the general population, its disseminated variant termed multicentric Castleman’s disease (MCD) is increasingly reported in people infected with the Human Immunodeficiency Virus (HIV) in the highly active antiretroviral therapy era [1-3].
Recent research disclosed that the occurrence of HIV-related MCD is mediated by the Human Herpesvirus 8 (HHV8). Also known as Kaposi’s sarcoma herpesvirus (KHSV), HHV8 is highly prevalent in areas of the developing world, much less common in Europe. The pathogenesis involves proliferation of infected B cells and viral replication, secretion of KHSV-encoded viral interleukin 6, and cytokine dysregulation [4-7].
Most MCD cases are diagnosed in HIV-infected patients with intermediate degrees of immune suppression, without a clear relation with the CD4 cell count (median 206/mmc, range 60-432). Manifestations include systemic symptoms such as fever, malaise, weight loss, and respiratory complaints. Kaposi’s sarcoma is associated in more than half of patients. Anaemia is invariably present, usually with other laboratory abnormalities such as cytopaenias, elevated C-reactive protein, hypoalbuminaemia, and hyponatraemia. A high KHSV plasmatic viral load is usually detectable [2, 5, 7].
Lymph node enlargement involves multiple sites, such as the axillary, mediastinal, mesenteric and retroperitoneal, inguinal, and retrocrural sites in descending order of frequency. As this case exemplifies, bulky mesenteric adenopathies may envelop fat and vessels leading to a “sandwich sign” appearance. At CT, nodal enhancement is moderate and comparable to that of skeletal muscle, sometimes avid [8].
Splenomegaly is universally present, whereas ascites is absent and the liver is enlarged in most (75-85%) patients. Lung abnormalities such as consolidations, bronchovascular nodularity, or pleural effusions, may be sometimes associated [8].
Although not considered an AIDS-defining illness, until recently HIV-related MCD was associated with an aggressive course and a poor survival. Improved understanding of the disease and targeted treatment with anti-CD20 monoclonal antibody rituximab plus suppression of viral replication using valganciclovir led to improved outcomes and reduced need for cytotoxic chemotherapy [3, 7, 8].
In conclusion, multicentric non-necrotic lymphadenopathy with hepato-splenomegaly and absent ascites in a HIV-positive patient, particularly of non-European origin or with Kaposi’s sarcoma, is very suggestive of MCD. Due to the unspecific clinical and imaging features, laboratory and biopsy confirmation is needed to differentiate this uncommon disorder from other causes of lymphadenopathy in HIV such as non-Hodgkin lymphoma, atypical mycobacterial or tubercular infection [1, 8, 9].

Differential Diagnosis List

Final Diagnosis

Multicentric Castleman's disease in HIV infection

URL:	https://www.eurorad.org/case/10387
DOI:	10.1594/EURORAD/CASE.10387
ISSN:	1563-4086