The original diagnostic tumor slides were reviewed for those but 1.5% of cases, for whom the written results of the primary morphologic and immunohistochemical investigation were evaluated.17 All instances in both countries were classified according to the current World Health Organization classification of hematopoietic and lymphoid tumors.19 Info on lymphoma topography and location (nodal/extranodal) was acquired through LYFO in Denmark and 6 regional lymphoma registries in Sweden. Exposure assessment Exposure to illness was assessed in 2 ways. 1.0; 95% confidence interval: 0.9-1.1), illness (OR = 1.3 [0.96-1.8]) or the presence of anti-antibodies (OR = 1.3 [0.9-2.0]). However, in analyses of NHL subtypes, self-reported history of illness (OR = 2.5 [1.2-5.1]) and seropositivity for anti-antibodies (OR = 3.6 [1.8-7.4]) were both associated with risk of mantle cell lymphoma. Notably, this specific association was also observed in individuals who did not recall infection yet tested positive for anti-antibodies (OR = 4.2 [2.0-8.9]). Our observations suggest a previously unreported association between illness and risk of mantle cell lymphoma. Introduction RBM45 In recent years, a growing number of infectious providers have been linked to non-Hodgkin lymphoma (NHL), including, for example, display characteristic manifestations that may include pores and skin rash, arthritis, and neurologic deficits, a medical picture generally referred to as Lyme disease or borreliosis. 5 In some cases, illness may also entail chronic swelling of the skin with dense lymphocytic infiltration followed by atrophy, known as acrodermatitis chronica atrophicans (ACA).6 This chronic inflammatory state of the skin resembles the setting in which chronic infection may induce mucosa-associated lymphoid cells (MALT) lymphomas in the belly.7 Interestingly, several instances of cutaneous B-cell lymphomas have been reported to develop in the context of ACA.8 The suspicion of a causal association between and cutaneous lymphomas offers gained further trustworthiness by serologic evidence of infection in lymphoma individuals,9,10 and in particular from the demonstration of DNA inside a proportion of lymphoma skin lesions.11C13 Moreover, regression of lymphomas upon treatment of the infection has also been reported.13,14 IDO/TDO-IN-1 While the evidence that may be implicated in development of cutaneous B-cell lymphomas is considerable, the query remains if the association may also pertain to noncutaneous lymphomas. Illness with is indeed not limited to the pores and skin, but, as reflected by its wide range of medical manifestations, also disseminates to additional areas IDO/TDO-IN-1 including, presumably, the lymphoid cells.15 It is, therefore, of interest that we recently demonstrated the presence of DNA within the malignant lesions of 2 patients with nodal B-cell lymphoma.16 Inspired by this body of evidence, we investigated the hypothesis that infection is associated with an increased risk of NHL overall or specific subtypes of NHL, reflecting correspondingly increased risks of cutaneous andto a lesser extentnoncutaneous lymphomas. Methods Study populace The study was based on data and biologic materials collected inside a nationwide Danish-Swedish case-control study (Scandinavian Lymphoma Etiology study or Level) from 1999 to 2002 as previously explained.17 It encompassed residents 18 to 74 years old, living in either Denmark from June 1, 2000, to August 30, 2002, or Sweden from October 1, 1999, to April 15, 2002. Participants inside a Danish regional pilot study that began November 1, 1999, and gradually expanded to protect the entire country were also included. Eligible instances in SCALE were those with a primary, incident, and morphologically verified analysis of NHL. Participants were required to speak Danish or Swedish and to have no history of organ transplantation, HIV infection, or prior hematopoietic malignancy. Case patients were identified through a rapid case ascertainment network including all hospital departments where malignant lymphomas are diagnosed and treated in Denmark and Sweden. Continuous collaboration with the 6 regional malignancy registries in Sweden and the Danish National Pathology Registry ensured total reporting through the network. Settings were randomly IDO/TDO-IN-1 sampled from the entire Danish and Swedish populations using continually updated, computerized populace registers. Thus, a subset of settings was sampled every 6 months during the study period, frequency-matched within each country to the expected distribution of instances of NHL, by sex and age (in 10-12 months intervals). The study was authorized by regional ethics committees in both countries. Informed consent was from each participant before interview and blood sampling in accordance with the Declaration of Helsinki. Histopathologic classification In Denmark, review of tumor material from instances was performed within the Danish Lymphoma Group Registry (LYFO),18 where 10% of all incident instances in the country are continuously randomly chosen and examined by expert hematopathologists. In addition, LYFO-approved older hematopathologists performed the primary evaluation of the diagnostic tumor specimens.