Both classifications, Kiel and IWF, have their advantages and disadvantages, страница 4

Plasmacytic Lymphoma (Plasmacytoma)

Plasmacytes represent the end stage of differentiation of B cells after antigenic stimulation. From this point of view Plasmacytoma must be considered as a kind of lymphoma. Here we mainly discuss the extramedullary Plasmacytoma [66], which more frequently involve the upper respiratory tract. However, Plasmacytoma of the gastrointestinal tract, the testes and the lungs, among other organs, are no curiosities. Primary lymph node Plasmacytoma represents about 0.8% of non-Hodgkin lymphomas. The neoplastic plasma cells display Immunohistochemically monoclonal CIg, usually of the IgA, less frequently of the IgG and rarely of the IgM class [66]. Their immunophenotype corresponds to CD19-, CD20-' CD22- and PCA1/CD38+ [67,68]. Not infrequently, however, they express one or more haematopoietic and non-haematopoietic antigens, thus complicating the differential diagnosis [69]. Basically there is no histogenetic difference between extramedullary Plasmacytoma and multiple myelomas. Moreover, solitary Plasmacytoma of the bone occur [70,71] and extramedullary Plasmacytoma may develop typical multiple myelomas. Extramedullary Plasmacytoma do not often display paraproteinaemia. Their prognosis is much better than that of multiple myelomas.

Mantle Cell Lymphoma

This type, formally called centrocytic lymphoma [72], corresponds to intermediate lymphocytic lymphoma of the Rappaport group [73,74]. It has been proved that it derives from mantle cells of the follicles and has nothing to do with the centrocyte of the follicular (germinal) centers [75,76]. Histologically, the neoplasm consists of small to medium-sized centrocyte-like cells (Fig. 5a) with irregular, cleaved nuclei [72,74]. By definition no neoplastic cells with blastic appearance are found among the cleaved cells. Instead, a small number of T cells can be found. Very often the vessel wall, mostly of the capillaries, is thickened and hyalinized. The growth pattern is rather diffuse, but not infrequently a modularity is seen. in early stages of growth a mantle-like neoplastic infiltration around reactive germinal centers is observed. Immunophenotypically they are strongly and simultaneously positive for surface IgM and IgD [75-77]. Their phenotype corresponds to a subtype of cells of the follicular mantle zone being CD19+, CD20+, CD22+ and especially CD5+ and CD23-. The phenotypes of the various categories of centrocyte-like cells are given in Table 3. The mean number of mitoses and Ki67-positive neoplastic cells is much higher than that found in B-CLL, LP-immunocytoma and centroblastic/ centrocytic malignant lymphoma. Mantle cell lymphoma can also be distinguished from the latter on the basis of molecular genetic differences. It shows the translocation t(11;14) (q13;q32) causing bcl-1 gene rearrangement, while very often centroblastic/centrocytic lymphoma (especially the nodular type) shows the translocation t(14;18) causing bcl-2 gene rearrangement [75,78]. Mantle cell lymphoma has a much worse prognosis than B-CLL, LP-immunocytoma and centroblastic/centrocytic lymphomas [79]. It has been shown that t(11 ;14) chromosomal translocation occurring in mantle cell lymphoma results in overexpression of a cyclin gene, PRAD1 [80]. The median survival time is less than 4 years. Mantle cell lymphomas represent 10% of non-Hodgkin lymphomas and the great majority occur at ages over 20.

According to the IWF classification most of the cases of mantle cell lymphoma can be categorized as either "diffuse small cleaved cell" or "diffuse large cleaved cell" lymphoma, although the reverse does not apply.

Centroblastic/centrocytic Lymphoma

This neoplasm derives from follicular (germinal) centers. The neoplastic population consists of variable numbers of centroblasts and centrocyte. Among these histiocytes and especially follicular dendritic cells are found. The latter are more easily recognized after appropriate immunohistochemical staining (anti-DRC antibodies, CD21) [81]. Three histological subtypes are distinguished: a) a type with small centrocytes and low numbers of centroblasts; b) a type with small centrocytes and numerous centroblasts; c) a type with large centrocytes and numerous centroblasts. In over 60% of the cases a complete or partial nodular (follicular) pattern (Figs. 5b and 6) of the neoplastic tissue is observed [82-85]. Among and within the neoplastic nodular structures substantial numbers of T cells are found. CD4-positive helper cells predominate [3,86]. Sclerosis may also be present [87] and is considered an indicator of good prognosis. Neoplastic cells show SIgs and not infrequently CIgs which mostly belong to the IgM and IgD classes [86,88]. Those with follicular distribution are consistently positive for CD19, CD20, CD22 and CD10 (CALLA). Neoplastic cells within diffuse patterns of growth show negativity for CD10 and positivity for CD23. Centrocytes are CDS negative. Immunohistochemically the bcl-2 oncoprotein is expressed in follicular centroblastic-centrocytic lymphoma because of bcl-2 gene rearrangement due to the translocation t(14;18) which frequently occurs in this type of lymphoma [89-91]. The bcl-2 oncoprotein inhibits cell apoptosis and is normally present in the small lymphocytes of the follicle mantle while it is absent from reactive germinal centers. Although bcl-2 oncoprotein expression is not exclusively related to t(14;18) and may occur in non-lymphoid tissues as well, its presence is considered to be helpful in distinguishing reactive follicles from neoplastic follicular structures [89,90,92,93]. Centroblastic-centrocytic lymphoma is rare in young persons and very rare in childhood [94]. Paraproteinaemia is rare while a leukemia picture is observed in over 30% of cases. In peripheral blood smears the characteristic cleaved cells can be recognized. Centroblastic/centrocytic lymphoma has the most favorable prognosis after B-CLL. Prognosis is much better in nodular (follicular) subtypes and especially in those with very many centrocytes and very few centroblasts [95,96]. Survival drops significantly when transformation to high-grade centroblastic lymphoma occurs, irrespectively of the nodular or diffuse pattern of growth.