Chlamydia or Not Chlamydia , That Is the Question: Which Is the Microorganism Associated With MALT Lymphomas of the Ocular Adnexa?

Abstract

In the mid-1990s, the demonstration that Helicobacter pylori infection is a risk factor for gastric marginal-zone B-cell lymphoma of MALT type (MALT lymphoma) and the fi nding that eradication of these bacteria can result in histological lymphoma regression in most patients made this tumor a popular model of antigen-driven lymphomagenesis ( 1 ) . The association of H. pylori with gastric MALT lymphoma led to the hypothesis that the microorganism provides an antigenic stimulus that sustains the growth of the lymphoma in the stomach, and today it is generally accepted that administration of antibiotics to eradicate H. pylori should be the sole initial treatment of gastric MALT lymphoma that is confi ned to the gastric wall. This approach has been validated in more than 20 reported studies ( 2 ) . These advances in the understanding and treatment of gastric MALT lymphoma pro mpted a search for microorganisms responsible for the growth of MALT lymphomas outside the stomach. Although Borrelia burgdorferi and Campylobacter jejuni have been associated with marginal-zone lymphomas arising in the skin and small intestine, respectively ( 3 , 4 ) , results implicating particular infectious microorganisms in nongastric lymphomas have often been elusive. In 2004, Ferreri et al. ( 5 ) reported in this journal that Chlamydia psittaci DNA was detected in 87% of lymphomas arising in the ocular adnexa (orbital soft tissue, lachrymal glands, and conjunctiva), and therefore, it has been proposed that C. psittaci infection may be a cause of these lymphomas. Furthermore, a very recent epidemiologic paper has shown a possible real increase in the incidence of ocular adnexal lymphomas, suggesting C. psittaci or another microorganism as possible causative agents ( 6 ) . However, subsequent to the report of Ferreri et al., other groups analyzed the prevalence of C. psittaci in these lymphomas, and overall, the reported data did not confi rm a strong link between C. psittaci infection and ocular adnexal MALT lymphomas ( Table 1 ). Thus, our understanding of the role of C. psittaci is far from complete. In this issue of the Journal, Ferreri et al. ( 7 ) report the results of a prospective trial in which patients affected by marginal-zone B-cell lymphoma of the ocular adnexa were treated for 3 weeks with the oral antibiotic doxycycline, with the intent of eradicating C. psittaci. The endpoints of the study were the rate of objective lymphoma response to antibiotic treatment and the presence or absence of C. psittaci DNA in peripheral blood mononuclear cells, the latter endpoint serving as a measure of C. psittaci eradication. Twenty-seven patients were enrolled and evaluated for response to treatment, 15 of them were newly diagnosed with ocular adnexal lymphoma and 12 had relapsed after previous therapies. Three patients had lymphoma involving regional lymph nodes and fi ve had bilateral MALT lymphomas. Preliminary results in the fi rst nine cases of the study have previously been published ( 8 ). C. psittaci was detected, using, as in the previous studies, a touchdown enzyme time release polymerase chain reaction ( 5 , 7 – 8 ) in 11 of 27 or 41% of lymphoma biopsies, a percentage lower than in the fi rst report from the same investigators