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American Journal of Hematology 72:216–219 (2003

)

HIV-Related Hodgkin’s Disease With Central Nervous
System Involvement and Association With
Epstein-Barr Virus
Suleiman Massarweh,1* Mark M. Udden,1 Imran Shahab,2 Michael Kroll,1 David A. Sears,1
Garrett R. Lynch,1 Bin S. Teh,3 and Hsin H. Lu3
1

Department of Medicine, Division of Oncology-Hematology, Ben Taub General Hospital, Baylor College of Medicine, Houston, Texas
2
Department of Pathology, Baylor College of Medicine, Houston, Texas
3
Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas

Central nervous system (CNS) involvement is a rare occurrence in the course of human
immunodeficiency virus (HIV)-related Hodgkin’s disease (HD). We report the clinical
course of a patient with HIV infection who developed systemic HD, mixed cellularity
subtype, later complicated by leptomeningeal involvement. The patient died from his
illness, and autopsy was performed. Examining the brain lesion, Epstein-Barr virus (EBV)
presence was demonstrated in Reed-Sternberg cells by immunohistochemistry using an
EBER probe for EBV RNA. This is the second case report in the English literature of HD
involving the CNS in an HIV-positive individual, and the first demonstrating EBV presence. Extranodal presence of Hodgkin’s disease in patients with HIV infection is probably
related to immunosuppression, and physicians treating this illness should be alert to the
potential of unusual sites of involvement. Am. J. Hematol. 72:216–219, 2003.
© 2003 Wiley-Liss, Inc.

Key words: human Immunodeficiency virus; Hodgkin’s disease; central nervous system;
Epstein-Barr virus; autopsy

INTRODUCTION

Hodgkin’s disease is increasing in frequency among
patients infected with human immunodeficiency virus
(HIV) [1,2]. Features of the disease in the HIV setting
include unfavorable histology, advanced stage at presentation, and aggressive clinical behavior [3,4]. Although
extranodal involvement is not common, cases of HD involving unusual sites are reported in the literature [5–7].
HIV-related HD involving the central nervous system is
an extremely rare occurrence [8]. We describe an HIVinfected patient with Hodgkin’s disease who developed
intracerebral involvement and demonstrate presence of
Epstein-Barr virus (EBV).
CASE REPORT

A 26-year-old homosexual man with HIV infection
(CD4 count, 140/mm3; viral load of 67,000 copies per
milliliter) was evaluated in July 1998 for increasing right
neck swelling. He had no systemic symptoms and no
previous history of opportunistic infections.
© 2003 Wiley-Liss, Inc.

Laboratory findings, including a complete blood
count, were within normal limits. Computerized tomography (CT) scan revealed diffuse enlargement of the right
submandibular gland and to a lesser extent the left
submandibular gland, along with extensive cervical adenopathy. Aside from a prominent spleen and increased
axillary lymph node number, there were no other significant CT scan findings. Incisional biopsy of the right submandibular mass revealed the presence of Hodgkin’s disease, mixed cellularity subtype. A gallium scan showed
marked uptake in the soft tissue of the right side of the
neck, with no other sites of activity. Bone marrow ex-

*Correspondence to: Suleiman Massarweh, M.D., Division of Oncology-Hematology, Smith Tower, Suite 1057, Houston, TX 77030.
E-mail: sam@bcm.tmc.edu
Received for publication 28 June 2002; Accepted 15 November 2002
Published online in Wiley InterScience (www.interscience.wiley.com).
DOI: 10.1002/ajh.10288

2B). and mantle field radiotherapy was started. consistent with a meningoencephalitic picture (Fig. On the basis of these clinical findings. Cerebrospinal fluid examination was normal. puted tomography (SPECT) study showed a focal area of increased thallium uptake corresponding to the CT and MRI findings. CT scan of the head showing prominent contrast enhancement in the right sylvian fissure with surrounding edema. MRI images showing a large hypointense area within the right insular cortex with marked enhancement after contrast administration (A) and on flare images (B). 1). vinblastine. Laboratory work revealed pancytopenia and abnormal liver function tests. his disease was staged as Ann Arbor stage IIa. ABVD chemotherapy (Adriamycin.Case Report: HIV-Related CNS Hodgkin’s Disease 217 Fig. He had hepatosplenomegaly and prominent retroperitoneal adenopathy on CT scans. 2A) and intense flare signal (Fig. bleomycin. and Crixivan. 2. lymphocytes. 1. Head CT showed marked enhancement in the right insular cortex with surrounding edema. Bone marrow biopsy showed replacement of normal marrow by a polymorphic cellular infiltrate of histiocytes. Brain single-photon emission com- Fig. He subsequently underwent a stereotactic brain biopsy of the lesion which re- . He had a good response to chemotherapy with complete disappearance of his symptoms and normalization of blood counts and liver function tests. with nearly complete disappearance of the neck mass. amination showed no evidence of Hodgkin’s disease. with the first dose reduced because of abnormal liver function. Brain magnetic resonance imaging (MRI) revealed a large hypointense area within the right insular cortex with contrast enhancement (Fig. He was maintained on antiretroviral therapy using Lamivudine. and DTIC) was given. Response to radiation therapy was good. In January 1999 he presented with abdominal pain and jaundice. Stavudine. and Reed-Sternberg cells. CNS Involvement While receiving ABVD he presented in April 1999 with new-onset seizures. suggestive of neoplasia.

4). 3.interscience. HD shows a strong correlation between histologic subtype and EBV. In situ hybridization for EBV-encoded small ribonucleic acid (EBER) showed nuclear staining in the large cells (Fig. 4. suggesting that EBV has a role in pathogenesis [13.2–0. In this setting. Binucleated Reed-Sternberg cell with nuclear staining using an in situ probe for EBV-encoded small ribonucleic acid (EBER). in the non-HIV setting. including headache and cranial nerve palsies.com. there was perivascular and meningeal infiltration by large binucleated malignant cells characteristic of the classic Reed-Sternberg cells. recognized to have oncogenic capacity.5% of all advanced-stage cases [18.or B-cell malignancy. In August 1999 he presented with symptoms of increased intracranial pressure and obstructive hydrocephalus on imaging studies. night sweats.] vealed polymorphic cellular infiltrates involving the meningeal surface composed of large binucleated cells staining positive for CD30 and negative for T and B lymphocyte markers. and he was continued on systemic chemotherapy. patients present with symptoms of increased intracranial pressure. Immunohistochemical staining for CD30 was positive in these cells (Fig. Fig. Whether Hodgkin’s dis- Fig. Interestingly. Immunohistochemical staining for CD30 showing the classic binucleated Reed-Sternberg cells (original magnification 1000×). with the mixed cellularity subtype showing higher rates of EBV infection than the nodular sclerosing variety [15–17]. In the setting of systemic disease. reported by Hair et al. and fungal stains were all negative. which is available at www. He underwent palliative ventriculostomy placement but died shortly thereafter. Involvement of the CNS or meninges is a rare but well recognized complication of HD in the non-HIV setting. and weight loss). At the time of diagnosis. is indicative of latent infection and relates to the immunecompromised state. occurring in 0.] ease will be classified as an AIDS-defining illness or not. CD20. Typically.19] and less commonly as the sole site of involvement [19–22]. performed on paraffin-embedded tissue (original magnification 1000×). subsequent registry-linked data and prospective reports demonstrated a small but definite increased risk of Hodgkin’s disease in HIV-infected patients [9–12]. it is clear that the features and natural history of the disease are altered in the HIV setting. [Color figure can be viewed in the online issue. The English literature has one documented case report of CNS Hodgkin’s in the setting of HIV infection. Whole-brain radiation therapy was administered.wiley. There was no disease involvement of other organs. [8] in 1991. mycobacterial.com. The presence of EBERs. Autopsy Findings The brain was diffusely edematous with leptomeningeal thickening. which is available at www.14]. RS cells are characterized by a high frequency of EBV infection approaching 100%.218 Case Report: Massarweh et al. Findings were consistent with Hodgkin’s disease. Bacterial. DISCUSSION Despite the lack of an obvious association between Hodgkin’s disease and the acquired immunodeficiency syndrome epidemic in the early 1980s. HD in HIV-infected patients is commonly composed of the mixed cellularity and lymphocyte depletion varieties and is frequently rich in Reed-Sternberg (RS) cells [13]. [Color figure can be viewed in the online issue. CD15. CD45. 70–90% of patients with HIV-related Hodgkin’s have advanced stage and exhibit a similarly high frequency of B symptoms (fever. Histologically. Bone marrow involvement is seen in 40% of patients. and non-contiguous organ involvement is a well-described phenomenon [4]. The authors described the case of a 34-year-old HIV-infected intravenous drug user who presented with advanced mixed-cellularity HD .wiley. 3) and other markers including CD3.interscience. as well as ALK (anaplastic lymphoma kinase) were all negative. The morphologic and immunologic features were consistent with a diagnosis of Hodgkin’s disease and did not support a T. CNS involvement results from either hematogenous spread or direct meningeal infiltration from adjacent disease. Microscopically.

Epstein-Barr virus in the pathogenesis of Hodgkin’s disease. Chen Y. Boiocchi M. Freer C. Morava-Protzner I. Rates of non-AIDS defining cancers in people with AIDS. 19. Optimal approach for treatment of HIV-associated HD is not well defined. EBV-associated perianal Hodgkin’s disease in an HIVpositive individual. As part of the diagnostic evaluation of intracranial or leptomeningeal disease in an HIV patient with HD. This suggests that systemic chemotherapy should be used as the initial therapeutic modality. Sanchez H. Coates M. Law M. Bendszus M. biopsy would be imperative to establish a diagnosis and make subsequent treatment decisions. Vaccer E. Dolcetti R. Hodgkin’s disease and AIDS: twenty-three new cases and a review of the literature.83:481–485. response to treatment is typically far inferior and relapses are common. although CNS Hodgkin’s disease in the setting of HIV infection is quite unusual. 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