Burkitt ’ s lymphoma of the duodenum in a patient with AIDS

Non-Hodgkin’s lymphoma of B-cell type is the second most common neoplasm after Kaposi’s sarcoma, among patients with human immunodeficiency virus infection. Most non-Hodgkin’s lymphoma cases that are associated with acquired immunodeficiency syndrome involve extranodal sites, especially the digestive tract and the central nervous system. We report a case of primary lymphoma of the duodenum in a patient with AIDS. Upper gastrointestinal endoscopy revealed pseudopolypoid masses found in the second portion of the duodenum. A complete diagnostic study including histological, immunohistochemical and virological analyses showed high-grade B-cell Burkitt’s lymphoma. The Epstein-Barr virus genome was detected in biopsies by immunohistochemical and in situ hybridization. Key-words: Non-Hodgkin’s lymphoma. Duodenum. AIDS. Epstein-Barr virus.

Non-Hodgkin's lymphomas (NHL) are the second most frequent malignancies in acquired immunodeficiency syndrome (AIDS) patients.More than 9�% of HIV-associated NHL is derived from B cells and the majority is high-grade and extranodal.The digestive tract is one of the most common extranodal primary sites for NHL in AIDS patients, accounting for ��% of all primary extranodal lymphomas 11 .Burkitt's lymphoma (BL) has frequently been reported as a neoplasm in HIV-infected patients.These lymphomas are now better designated as AIDS-related BL 1 .
We report a case of primary BL of the duodenum in an AIDS patient.

CASE REPORT
A �5-year-old man infected with the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) was admitted to our unit for AIDS-related illness with fever (��°C -��.5°C), anorexia, upper abdominal pain, night sweats and weight loss of three months duration.He had no history of AIDS-defining illness and he had never received highly active antiretroviral therapy (HAART).�hysical examination revealed that he had lost approximately 15kg of weight during the last three months prior to admission.Lung and cardiac auscultation were normal.His abdomen was tender, with spontaneous epigastric and right hypochondrium pain that increased during palpation and hepatomegaly (2cm below the right costal margin).He did not present rebound tenderness.
A chest X-ray was normal.Abdominal ultrasound showed hepatomegaly with increased echogenicity, isoechoic periportal adenopathy and splenomegaly.Abdominal computed tomography (CT) scan showed the same signs as the ultrasonography.CT scan of the thorax and pelvis were normal.A bone marrow biopsy did not show atypical cells.
Upper digestive tract endoscopy was performed; the esophagus and stomach were normal, and inspection of the second portion of the duodenum revealed pseudopolypoid masses (Figure 1).Several samples for biopsy and microbiological cultures were taken.Histopathological examination of the duodenal biopsies showed a dense and diffuse infiltrate of lymphoid cells with large and multinucleated cells with prominent inclusion-like nucleoli.The atypical cells showed hyperchromatic central nuclei and one to three nucleoli near the basal membrane (Figures 2 and �).Immunostaining was performed on paraffin-embedded tissue by means of the avidin-biotin complex technique.Monoclonal antibodies demonstrated that the atypical cells showed reactivity to anti-CD2� (�AN B) and CD1�; the T-cell marker CD� was negative.All neoplastic cells showed intense staining with the Ki �7 antigen, consistent with a very high proliferation index (close to 1��%).The histopathological findings were consistent with   The patient died due to progressive disease one month after admission.His physical condition did not allow him to receive either chemotherapy or antiretroviral therapy.

DISCUSSION
The lymphomas associated with HIV include high-grade Bcell lymphomas (the vast majority), BL, two subtypes of diffuse large B-cell lymphoma (centroblastic and immunoblastic) and, finally, two uncommon lymphomas that occur specifically in HIV-positive patients, called primary effusion lymphoma (�EL) and plasmablastic lymphoma of the oral cavity.There are two types of BL.The African or endemic type, which is frequent in children, presents with a jaw or retroperitoneal mass and is strongly associated with Epstein-Barr virus infection 1 1� .The other type, sporadic BL, especially affects the adult HIV-positive population, with identical histology but typically presenting as an intra-abdominal mass or intraluminal digestive tract lesion 1 1� , as could be seen in our patient.
The estimated relative risk of NHL-associated HIV infection is 1�� times greater than in the general population and this risk increases with the progressive immunosuppression related to the retrovirus 15 .The association with the CD� T cell count is higher for NHL than for Kaposi's sarcoma.Our patient presented a diagnosis of advanced HIV/AIDS disease with severe immunodepression and CD� T cell count lower than 1�� cell/µl 15 .
One of the major clinical characteristics of AIDS-associated NHL is the high frequency of extranodal involvement, including the gastrointestinal tract at initial presentation, as in our patient.The relationship between NHL and the digestive tract has been well established in the medical literature.The gastrointestinal tract is the second most common extranodal primary site of NHL in AIDS patients after the central nervous system.The stomach, distal ileum and cecum are the most commonly involved sites � .BL of the duodenum is rare and affects 2�% to ��% of the patients.Most of the tumors are found in the second portion of the duodenum, like in our patient.In a series of �5 consecutive necropsies on adults patients with AIDS, de Carvalho et al � encountered only seven (15.5%) neoplasias and only one gastric lymphoma.
In AIDS patients, the clinical presentation and histopathological findings are consistent, in most cases, with primary neoplasms of the digestive tract � .�atients usually present with mild and nonspecific gastrointestinal symptoms and "B" symptoms such as weight loss, unexplained fever and night sweats 2 .These symptoms are identical to those of numerous opportunistic infections and may delay the diagnosis of lymphoma.Consequently, a high suspicion rate is necessary when infectologists evaluate patients with HIV/ AIDS and chronic abdominal symptoms.In 11 consecutive AIDS patients with gastrointestinal lymphomas, Cappell et al 2 determined the frequencies of significant gastrointestinal complications such as bleeding and intestinal obstruction.
Early endoscopy followed by histopathological examination of biopsy smears helps to identify lymphomas of the digestive tract in AIDS patients.
Epstein-Barr virus is strongly associated with the pathogenesis of NHL in AIDS patients.Epstein-Barr virus genome is present in 25% to ��% of HIV-associated BL 5 1� .The presence of Epstein-Barr genome in atypical cells can be demonstrated by two techniques: immunohistochemistry and in situ hybridization � 9 .
The Medline, Embase and Cochrane databases were searched to identify articles on duodenal BL associated with AIDS.The search was performed using the following key words: Burkitt lymphoma, duodenum, HIV and AIDS.To our knowledge, BL of the duodenum in a patient with AIDS has not been previously reported in the medical literature.
With improved survival among AIDS patients, there may be an increased in AIDS-related malignancies 7 12 1� .The significant improvement in the survival of patients with HIV-NHL is associated with the positive impact of highly active antiretroviral therapy (HAART) on the survival of these patients with centroblastic and immunoblastic NHL.However, the prognosis for AIDS-associated BL remains poor, despite the use of HAART � .

Figure 1 -
Figure 1 -Upper gastrointestinal endoscopy showing pseudopolypoid masses in the second portion of the duodenum.

Figure 2 -
Figure 2 -Dense and atypical lymphoid infiltrate of the glands and stroma of the duodenum.

Figure 3 -
Figure 3 -Lymphoid infiltrate with large and multinucleated cells and prominent inclusions-like nucleoli.the diagnosis of BL.Epstein-Barr virus (EBV) in association with latent membrane protein-1 (LM�-1) was detected in tumor cells by immunohistochemical techniques, and EBV-encoded mRNA was also detected by in situ hybridization.The patient died due to progressive disease one month after admission.His physical condition did not allow him to receive either chemotherapy or antiretroviral therapy.