Pathology and "molecular histology' of Hodgkin's disease and the border to non-Hodgkin's lymphomas.

HD is characterized by a small amount of tumour cells (the H- and RS-cells) in a background of many, probably reactive, lymphocytes and histiocytes. Lymphocyte predominant HD seems to be a distinct clinicopathological entity of germinal centre cell origin and has a relatively favourable prognosis. This type has to be differentiated from mixed cellularity and nodular sclerosis HD, which show a different marker profile of the H- and RS-cells and their variants. Differentiation of progressively transformed germinal centres from lymphocyte predominant HD may be problematical and is based on the detection of L&H-cells in the latter entity. Diffuse paragranuloma may be difficult to differentiate from classic HD as well as non-Hodgkin's lymphomas, especially T-cell-rich B-cell lymphomas and peripheral T-cell lymphomas. In rare cases a distinction between HD and non-Hodgkin's lymphomas may be impossible. Similar to lymphocyte predominant HD, lymphocyte depletion HD may provide difficulties in its differential diagnosis from non-Hodgkin's lymphomas. The border with anaplastic large cell lymphoma cannot be clearly drawn and may be blurred. The border between HD and non-Hodgkin lymphomas may be especially blurred in composite lymphomas, if single cell studies can demonstrate a common clonal origin of both parts of the lymphoma. Analysis of immunoglobulin or T-cell receptor variable region genes amplified by PCR from single cells picked from histological sections ("molecular histology') combines morphological characterization and identification of H- and RS-cells with a molecular analysis of those cells. This enables one not only to determine the nature of H- and RS-cells and their clonality but also to answer questions about the relationship between Hodgkin and non-Hodgkin's lymphomas.