Marcelo CortiI; María Florencia VillafañeI; Liliana SoutoI; Ricardo SchtirbuI; Marina NarbaitzII; Marcela de Dios SolerII
IDivision of HIV/AIDS disease, F. J. Muñiz Infectious Diseases Hospital, Buenos Aires, Argentina IIHistopathological Laboratory, National Academy of Medicine, Buenos Aires, Argentina
ABSTRACT
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.
RESUMO
O linfoma não-Hodgkin de células B é a segunda neoplasia mais comum em pacientes com infecção pelo vírus da imunodeficiência humana depois do sarcoma de Kaposi. A maioria dos casos de linfoma não-Hodgkin associados com a síndrome da imunodeficiência adquirida envolve locais extraganglionares, especialmente o trato digestivo e o sistema nervoso central. Nós relatamos um caso de linfoma primário do duodeno em um paciente com AIDS. Uma endoscopia digestiva alta mostrou massas pseudopolipóides encontradas na segunda porção do duodeno. Um estudo diagnóstico completo incluindo exames histológicos, imunohistoquímicos e virológicos mostrou um linfoma de células B tipo Burkitt. Detectou-se genoma do vírus Epstein-Barr em biópsias por hibridização in situ e imuno-histoquímica.
Palavras-chaves: Linfoma não-Hodgkin. Duodeno. AIDS. Vírus de Epstein-Barr.
Non-Hodgkin’s lymphomas (NHL) are the second most frequent malignancies in acquired immunodeficiency syndrome (AIDS) patients. More than 90% 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 40% of all primary extranodal lymphomas11. Burkitt’s lymphoma (BL) has frequently been reported as a neoplasm in HIV-infected patients. These lymphomas are now better designated as AIDS-related BL1.
We report a case of primary BL of the duodenum in an AIDS patient.
CASE REPORT
A 45-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 (38°C – 38.5°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). Physical 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.
The relevant laboratory findings were: hemoglobin 10.2g/dl; hematocrit 36%; leukocytes 5,600/mm3; platelets 156,000/mm3; lactate dehydrogenase 1,585U/l and alkaline phosphatase 2,445U/l. Liver function, transaminase level, kidney function and coagulation tests were normal. The CD4 T cell count was 87 cell/ul and the plasma viral load was 86,120 copies/ml (log10 4.8). Multiple blood, urine and sputum cultures were all negative.
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 3). 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-CD20 (PAN B) and CD10; the T-cell marker CD3 was negative. All neoplastic cells showed intense staining with the Ki 67 antigen, consistent with a very high proliferation index (close to 100%). The histopathological findings were consistent with the diagnosis of BL. Epstein-Barr virus (EBV) in association with latent membrane protein-1 (LMP-1) was detected in tumor cells by immunohistochemical techniques, and EBV-encoded mRNA was also detected by in situhybridization.
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 B-cell 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 (PEL) 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 infection1 13. 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 lesion1 13, as could be seen in our patient.
The estimated relative risk of NHL-associated HIV infection is 100 times greater than in the general population and this risk increases with the progressive immunosuppression related to the retrovirus15. The association with the CD4 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 CD4 T cell count lower than 100 cell/µl15.
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 sites8. BL of the duodenum is rare and affects 20% to 30% of the patients. Most of the tumors are found in the second portion of the duodenum, like in our patient. In a series of 45 consecutive necropsies on adults patients with AIDS, de Carvalho et al3 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 tract8. Patients usually present with mild and nonspecific gastrointestinal symptoms and “B” symptoms such as weight loss, unexplained fever and night sweats2. 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 al2 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 40% of HIV-associated BL5 10. The presence of Epstein-Barr genome in atypical cells can be demonstrated by two techniques: immunohistochemistry and in situ hybridization4 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 malignancies7 12 14. 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 HAART6.
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Address to:
Dr. Marcelo Corti
HIV/AIDS Division
Puán 381 2º C 1406CQG, Buenos Aires, Argentina
Tel: 54 11 4432-3762
e-mail: marcelocorti@fibertel.com.ar
Recebido em 26/4/2006
Aceito em 2/5/2007
