Tumors of lymphoid tissue
Lymphoid infiltrates of the conjunctiva and orbit are common and it has been long recognized that the differentiation of benign infiltrates from malignant lymphomas can be challenging not only for the clinician but also for the pathologist (63). The introduction of immunohistochemistry, flow cytometry, and molecular methods has progressively improved our ability to differentiate between benign lymphoid infiltrates and lymphomas in the past two decades. It is also widely recognized that the outcome of different types of lymphomas in the same location can be diverse and therefore an accurate subclassification of the lymphoma is equally crucial. The current classification of lymphomas is based to a large extent on our understanding of the development of the immune system and the molecular and cellular biology of processes controlling cell cycle progression, cell division, and cell death. The demonstration of specific cytogenetic abnormalities associated with specific lymphomas and leukemia spurred further this study. More recently the molecules involved in these chromosomal events have been defined in detail, revealing a fascinating picture of complex molecular interactions, often converging on a few key molecules that control cell division and cell death, leading ultimately to an uncontrolled proliferation and accumulation of a clone of lymphoid cells. In an important departure from a purely morphologically based classification systems, the current World Health Organization (WHO) classification (52) and its forerunner the Revised European American Lymphoma (REAL) classification (43), define the various types of lymphomas as different diseases with unique clinical behavior (122). This behavior is predicated on the putative cell of origin and the aberration of cellular processes brought about by specific cytogenetic abnormalities. The use of gene chips, which allow the simultaneous examination of the expression of hundreds of genes, has led to further subclassification of certain common categories of lymphomas based on reproducible patterns of expression of gene cohorts. Rather unexpectedly, these studies have also emphasized the importance of the host immune system in determining the ultimate outcome of the lymphoma in a particular patient. A related development of major significance in our understanding of the biology of lymphomas is the role of viruses and bacteria in their causation.