Growth fraction in centrocytic and follicular center cell lymphomas: assessment in paraffin sections with a proliferating cell nuclear antigen antibody and morphometric correlates.

Measurement of growth fraction is an important way to provide an objective assessment of non-Hodgkin's lymphomas; however, many of the techniques used require fresh tissue and/or special instrumentation. Recently, antibodies to the proliferating cell nuclear antigen (PCNA)/cyclin reactive in paraffin-embedded sections have become available. To investigate the utility of one such antibody in the study of follicular center cell (FCC) lymphomas and cleaved cell lymphomas of centrocytic type (CC), paraffin sections from 40 cases that had been characterized in two previous morphometric studies were stained with a PCNA antibody. Strong correlations were found between PCNA staining in formalin- and B5-fixed tissues, between the overall proportion of PCNA-positive cells and the proportion in the area of greatest staining, and between strong and total staining. Proliferating cell nuclear antigen staining was significantly stronger in the noncleaved FCC lymphomas than in the cleaved cell lymphomas. The FCC lymphomas showed moderate to strong correlations between PCNA staining and morphometric features of transformation, but only nuclear area correlated with PCNA staining in the CC group. Proliferating cell nuclear antigen staining was not significantly different between CC lymphomas with and without the characteristic bcl-1/PRAD 1 gene rearrangement. In summary, PCNA staining of either B5- or formalin-fixed, paraffin-embedded tissue sections is a simple aid in the objective categorization of FCC lymphomas and may offer additional potentially prognostic information in some FCC subsets and in CC lymphomas. The findings further support the distinction between CC and true FCC lymphomas.

Multilobated lymphoma of B cell type: a multiparameter investigation.

Multilobated lymphomas were originally described as T-cell neoplasms, but many of B-cell type have subsequently been reported. A case of B-cell origin is reported in which both immunophenotypic and genotypic studies performed on a cell suspension of the lymphoma gave inconclusive and potentially misleading information, while paraffin and frozen section immunohistologic studies, as well as genotypic studies performed on DNA obtained from snap-frozen tissue, were definitive. Thus, this case illustrates some of the problems that may be encountered using cell suspensions as a source for immunophenotypic, and even the much more sensitive genotypic, studies.

Genotypic characterization of centrocytic lymphoma: frequent rearrangement of the chromosome 11 bcl-1 locus.

Centrocytic lymphomas are defined in the Kiel classification as B-cell lymphomas composed exclusively of cells resembling cleaved follicular center cells (FCC). These lymphomas have been shown to be histologically, immunophenotypically, and clinically distinct from other cleaved FCC lymphomas. DNA from 18 centrocytic lymphomas (14 patients) was analyzed using Southern blotting and probes for immunoglobulin heavy (JH) and kappa light chain (JK) joining gene, T-cell receptor beta chain constant gene (CB), bcl-1, bcl-2, and c-myc gene rearrangements. All of the lymphomas had JH and JK rearrangements, confirming their B-cell origin. None of the specimens had detectable CB, bcl-2, or c-myc rearrangements. However, 4 of 14 patients (28.6%) had rearrangement of the chromosome 11 bcl-1 locus. Therefore, centrocytic lymphomas are genotypically distinguishable from the majority of other small cleaved FCC lymphomas by their lack of demonstrable bcl-2 rearrangements. This supports the distinct nature of centrocytic lymphomas and suggests the lack of importance for the putative oncogene bcl-2 in these cases. Furthermore, the frequent rearrangement of bcl-1 suggests a possible role for this locus in the pathogenesis of at least some centrocytic lymphomas.

Comparison of histologic nodal reactive patterns, cell suspension immunophenotypic data, and HIV status.

While cell suspension immunophenotypic studies are widely used as an aid in the diagnosis and classification of lymphomas and leukemias, much less attention has been directed toward interpretation of the results in reactive lymphoid proliferations. Cell suspension immunophenotypic data were therefore analyzed for 119 lymph nodes with reactive lymphoid proliferations which were divided into five major histologic categories: follicular hyperplasia, marked (FH,M), or moderate (FH); dermatopathic lymphadenopathy (DL); diffuse hyperplasia (DH); or "other." With the aid of a computer-assisted morphometer, the following were also measured and calculated: proportion of node occupied by follicles, mean relative follicle size, and mean follicle shape factor. Finally, in 57 cases, the influence of human immunodeficiency (HIV) status on the findings was analyzed. Although individual cases varied widely, cases of DL had significantly more CD3+ (T) cells, higher CD4:CD8 ratios, and fewer CD19+ (B) cells than other categories. Cases of FH,M had significantly lower CD4:CD8 ratios and more CD19+, CD10+, and transferrin receptor positive cells. Cases of FH,M and FH known to be HIV-negative had higher CD4:CD8 ratios than the HIV-positive cases. Peripheral blood CD4:CD8 ratios performed in 38 patients showed a strong correlation with nodal ratios. Morphometric data supported the correlation between follicular hyperplasia and increased proportions of CD19+, CD10+, and transferrin receptor-positive cells. Rare cases had CD5:CD2 or CD3 ratios of greater than 1 or "monoclonal" kappa to lambda ratios. CD4:CD8 ratios varied widely, but aberrant T cell phenotypes were not identified. These studies demonstrate that, although great variation exists, there are certain associations between types of reactive lymphoid hyperplasia and cell suspension immunophenotypic findings.(ABSTRACT TRUNCATED AT 250 WORDS)