Patients with ocular adnexal lymphoma had a high prevalence of C. psittaci infection in both tumor tissue and PBMCs. Persistent C. psittaci infection may contribute to the development of these lymphomas, as was also supported by the clinical responses observed in this study with C. psittaci-eradicating antibiotic therapy.

Microsatellite instability (MSI) characterizes colorectal carcinomas (CRCs) in hereditary nonpolyposis colorectal cancer (HNPCC) syndrome and a proportion of sporadic CRCs. These MSI+ CRCs share several clinicopathological features, including a reputation for better survival rates than MSI- cases and a pronounced stromal inflammatory reaction of still undefined nature. In the present study, the presence, spatial distribution, and activation status of infiltrating cytotoxic effectors were investigated comparatively in 18 MSI+ and 37 MSI- CRCs by immunohistochemistry. The frequency of apoptosis was also evaluated by morphology and in situ end-labeling. MSI+ cases carried significantly higher numbers of cytotoxic lymphocytes infiltrating within neoplastic epithelial structures, as shown by immunostaining for CD3 (15.1 +/- 6.2 versus 4.6 +/- 4.1, P < 0.001), CD8 (13 +/- 6.4 versus 3.7 +/- 3.8, P < 0.001), and TIA-1 (11.2 +/- 6.5 versus 1.9 +/- 1.7, P < 0.001). These cytotoxic effectors were globally more activated in MSI+ than in MSI- tumors, as revealed by the expression of granzyme B (5.3 +/- 4.5 versus 0.6 +/- 1.3, P < 0.001). In MSI+ CRCs, the number of intraepithelial activated cytotoxic lymphocytes was significantly correlated with the proximal location of the tumor, a poorly differentiated phenotype, and the presence of peritumor lymphoid nodules. Multivariate analysis revealed that MSI was the major determinant of the presence of activated cytotoxic intraepithelial lymphocytes. Moreover, MSI+ CRCs also showed a significantly higher percentage of tumor cells undergoing apoptotic cell death (4.1 +/- 2.1 versus 2.6 +/- 1.1, P < 0.0001, by the TUNEL method), often located in close proximity of activated cytotoxic lymphocytes. These results are consistent with the presence of anti-tumor cytotoxic immune responses in most of MSI+ CRCs, a phenomenon that may at least in part contribute to the survival advantage ascribed to these patients.

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Colorectal cancers with high-frequency microsatellite instability show peculiar clinicopathological features and a favorable clinical outcome. We investigated whether the improved prognosis for these cancers is related to the content of activated cytotoxic intraepithelial T lymphocytes. Microsatellite instability and the amount of activated cytotoxic lymphocytes were analyzed according to clinicopathological features, survival, and disease recurrence in 109 right-sided colon carcinomas from 245 consecutive patients with stage II/III colon cancer that underwent radical surgery. High-frequency microsatellite instability was found in 43% of stage II/III proximal colon cancers and was associated with significantly higher numbers of activated cytotoxic lymphocytes. High-frequency microsatellite instability, as well as the content of intratumoral-activated cytotoxic T lymphocytes correlated with improved overall and disease-free survival, particularly in patients with stage III tumors. Multivariate analysis revealed that patients with both features had a risk of death and relapse markedly lower than that associated with microsatellite status or intratumoral cytotoxic lymphocytes separately. The presence of local cytotoxic immune responses is probably the major determinant of the good clinical course of patients with microsatellite unstable colon cancer. Furthermore, high-frequency microsatellite instability coupled with a high content of intratumoral cytotoxic lymphocytes may identify a subset of colon cancer patients with a favorable clinical outcome, particularly in stage III disease.

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A high prevalence of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma (B-NHL) has been reported in some, but not all, studies, and the association showed a strong regional variation. We conducted a systematic review of the prevalence of HCV infection in case series of B-NHL and, when an appropriate control group was available, of the odds ratio of B-NHL associated with HCV infection. A high HCV prevalence in B-NHL was found in southern and eastern Europe, Japan and the southern United States, but not in central and northern Europe, Canada, northern United States, or a few Asian countries. Possible sources of heterogeneity and bias are discussed. The odds ratio of B-NHL for HCV infection was relatively weak, ranging from 2 to 4 in most studies. Thus, even if the observed association were causal, the percentage of cases of B-NHL attributable to HCV infection would be relatively low (10%) also in countries with a high prevalence of HCV infection in the general population, and extremely low in other countries. This may explain apparent inconsistencies between studies. Potential mechanisms of action are also discussed. © 2004 Wiley-Liss, Inc. Key words: hepatitis C virus; non-Hodgkin's lymphoma; Hodgkin's lymphoma; multiple myeloma; chronic lymphocytic leukemiaHepatitis C virus (HCV) is an RNA virus that belongs to the family of flaviviruses. It is hepatotrophic and causes hepatitis, liver cirrhosis and hepatocellular carcinoma. 1 HCV infection is sometimes accompanied by autoimmune manifestations, most notably essential mixed cryoglobulinemia (EMC), which is characterized by cutaneous vasculitis, nephritis, peripheral neuropathy and clonal B-cell lymphoproliferations. 2 HCV infection has also been involved in a subset of non-Hodgkin's lymphomas (NHLs), even in the absence of EMC. Higher than expected HCV prevalence among NHL patients has emerged, however, chiefly from studies in Italy 3,4 and Japan, 5,6 where intermediate to high prevalence of HCV (2-10%) can be found in the general population.Elucidating the causes of NHL is of great importance, since the disease is one of the few neoplasms showing unexplained upward trends in incidence and mortality rates in the last decades. 7,8 We therefore conducted a systematic review of published studies on HCV infection and NHL. MATERIAL AND METHODSWe identified peer-reviewed articles on HCV and NHL through a MEDLINE and EMBASE search, personal knowledge of the authors and the references of the retrieved articles. Key search words included the terms "hepatitis" and "lymphoma." No language or age limitation was imposed. We included articles published up to June 2003. Our primary aim was to identify all articles that presented the prevalence of HCV infection in case series of B-cell NHL patients and, if possible, in some appropriate control group. To avoid multiple inclusions of the same data, whenever the same author appeared in more than one article, we checked the place and time of recruitment of cases and, in case of overlapping, included th...

C psittaci-eradicating antibiotic therapy with doxycycline is followed by objective response in patients with ocular adnexal lymphoma, even after multiple relapses of the disease. A confirmatory, large, phase II trial is warranted to confirm whether this fast, cheap, and well-tolerated therapy could replace other more aggressive strategies as first-line treatment against ocular adnexal lymphomas.