Multiple lymphoid nodules in bone marrow biopsy in immunocompetent patient with cytomegalovirus infection: an immunohistochemical analysis Múltiplos nódulos linfóides na medula óssea de paciente imunocompetente com infecção pelo citomegalovirus: uma análise imunohistoquímica

In Brazil, a high prevalence of cytomegalovirus (CMV) infection has been documented. In immunocompetent adults CMV infection is usually asymptomatic and therefore morphologic and immunophenotypic bone marrow changes have rarely been described. The authors report the case of a previously healthy patient who developed fever of undetermined origin. The diagnosis of acute CMV infection was based on serological testing. A computed tomographic scan showed mediastinal lymphadenopathy. A bone marrow biopsy revealed a hypercellular haematopoiesis with eosinophilia and large mixed Tand B-cell lymphoid aggregates. In spite of bcl-2 positivity, their reactive nature was demonstrated. Polymerase chain reaction (PCR) and immunohistochemistry were unable to detect CMV-DNA in paraffin-embedded bone marrow sections. Much like in other systemic disorders, the lymphoid nodules in this case seemed to be caused by immunological mechanisms, possibly due to cytokines released in response to the systemic infectious process. Key-words: Cytomegalovirus. Bone marrow. Lymphoid nodules. Resumo Uma elevada prevalência de infecção pelo citomegalovírus (CMV) está documentada no Brasil. Em adultos imunocompetentes a infecção pelo CMV é, em geral, assintomática e, portanto, as alterações morfológicas e imunohistoquímicas na medula óssea têm sido raramente descritas. Relatamos o caso de um paciente previamente assintomático que desenvolveu febre de origem obscura. O diagnóstico de infecção aguda pelo CMV foi baseado em estudo sorológico. A tomografia computadorizada do tórax mostrou linfadenopatia mediastinal. A biópsia óssea revelou medula hipercelular com eosinofilia e grandes agregados linfóides mistos de células B e T. Apesar da positividade para bcl-2, a sua natureza reacional foi demostrada. A reação em cadeia da polimerase (PCR) e a imunohistoquímica não detectaram DNA viral nos cortes de medula óssea em parafina. Assim como em outros distúrbios sistêmicos, os nódulos linfóides no nosso caso parecem ser causados por mecanismos imunológicos, possivelmente relacionados a citoquinas liberadas em resposta ao processo infeccioso sistêmico. Palavras-chaves: Citomegalovirus. Medula óssea. Nódulos linfóides. 1. Department of Clinical Medicine/HEMOCE, Federal University of Ceará, Fortaleza, CE. 2. Department of Pathology, State University of Campinas, Campinas, SP. 3. Department of Clinical Medicine/State University of Campinas, Campinas, SP Address to: Dra. Silvia Maria M. Magalhães. Centro de Hematologia e Hemoterapia do Ceará/HEMOCE/Universidade Federal do Ceará. Av. José Bastos 3390, 60436-160 Fortaleza,CE, Brasil Fax:55 85 433 4420 Recebido para publicação em 21/9/2000. Cytomegalovirus (CMV) is a common cause of viral infection and a major cause of morbidity and mor tality in immunocompromised patients. Both primary infection and reactivation of endogenous latent virus owing to acquired immunodeficiency or immunosuppress ive t reatment can cause disease. The infection is associated with nonspec i f i c bone mar row changes inc lud ing myelosuppression and a florid haemophagocytic syndrome, especially in severe immunodeficiency4. Nonimmunosuppressed patients rarely manifest clinical infection although CMV-induced thrombocytopenia and haemolysis have been reported1 14. CMV seroprevalence in adults ranges from 40% to 100% depending on geographical and socioeconomic conditions4. In Brazil, a high frequency of seropositivity has been reported5. Like other herpes virus, primary infection is followed by persistence of the virus in a latent form. It has been proposed that bone marrow progenitor cells and peripheral blood monocytes play a major role in the pathogenesis and latency of CMV15.