ABSTRACT
Monoclonal proliferations of uncertain significance 416 Malignant lymphomas developing within the context 418
of a chronic infective inflammation Hepatitis C virus chronic infection-related lymphomas 418 Hepatitis C virus infection and lymphoproliferation 418 Chronic bacterial infection and extranodal marginal zone 419
lymphoma
Epstein-Barr virus infection-related lymphomas 421 Kaposi sarcoma herpes virus/human herpes virus 423
8-related lymphoproliferations Malignant lymphomas and autoimmune diseases 424 Key points 425 References 425
Malignant lymphomas can develop within the context of a preexisting chronic inflammatory disorder that may or may not sustain autoimmune phenomena. Basically, the preexisting disorder causes long-lasting reactive lymphoid proliferation with possible emergence of clones carrying chromosomal or genetic aberrations that confer them an advantage over the others in terms of cell proliferation and/or resistance to apoptosis, but are insufficient to carry a tumoral growth. Such aberrations can be facilitated, for instance, by high oxidative levels that generate genomic instability. Defects of the immune surveillance and/or DNA repair mechanisms may further contribute to the survival of the aberrant cells. One of these clones may then develop further abnormalities leading to neoplastic transformation with disconnection from the microenvironment, progressive substitution of the inflammatory milieu, and possible spread through the body. This model of lymphomagenesis (reactive population : clonal selection : malignant transformation) was first demonstrated in human immunodeficiency virus (HIV)-positive patients developing aggressive B cell lymphomas.1 During the last few decades, it has been extended to a series of lymphoid tumors/clonal lymphoid proliferations ensuing from a chronic inflammation more often sustained by an infective agent. In the following text, the main categories of clonal
within this setting will be discussed in the light of the terminology and concepts introduced first by the Revised European-American Lymphoma (REAL) classification2 and more recently adopted by the World Health Organization (WHO).3 They will be divided into three groups depending on their biological significance and correlation with infectious agents and/or an autoimmune background, although the latter two factors are often simultaneously at work. It should be noted that an autoimmune disease will be considered only when it actually represents a favoring condition, but not as a lymphoma-related manifestation. In addition, the term ‘atypical lymphoproliferative disorder’ 4-6 will be intentionally avoided as it often refers to conditions – like Kikuki lymphadenitis7 – that can mimic the clinical presentation and/or morphologic features of malignant lymphomas, but do not actually represent lymphoid tumors.
