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We describe 35 peripheral lymph nodes classified as mantle cell/marginal zone B-cell hyperplasia with clear cells using morphologic and immunologic findings. For the purpose of this study, we obtained clinical follow-up information and performed immunoglobulin gene rearrangement studies on paraffin sections by polymerase chain reaction. Architecturally, the nodes were suggestive of a benign process: no pericapsular infiltration, sinuses readily identified, scattered reactive follicles present, and paracortical nodular hyperplasia present. No monocytoid B cells were present. Focally, small lymphoid cells with round nuclei and clear cytoplasm (clear cells) formed monomorphic nodular, inverse follicular, and/or marginal zone patterns. Flow cytometry and immunohistochemical analysis revealed neither light chain restriction nor an aberrant B-cell phenotype. Immunoglobulin gene rearrangement studies showed a clonal band in 1 of 26 cases in which DNA was amplified. To ascertain the clinical relevance of this positive case, follow-up information was obtained 30 months after the initial biopsy; the 83-year-old woman was alive without treatment but had splenomegaly and bone marrow involvement by marginal zone B-cell lymphoma. The morphologic and immunologic criteria used for diagnosis of mantle cell/marginal zone B-cell hyperplasia with clear cytoplasm are valid; however, to rule out the possibility of occult lymphoma, immunoglobulin gene rearrangement studies and clinical follow-up are necessary.

We investigated the clonal relationship between follicular center cell and monocytoid B-cell components of non-Hodgkin lymphoma by isolating the components and comparing the nucleotide sequences of the complementarity-determining region (CDR)3 of the rearranged immunoglobulin heavy chain (IgH) gene. Paraffin blocks from 4 cases with amplifiable DNA using the polymerase chain reaction (PCR) were identified. Multiple representative cell clusters of the 2 components were obtained by microdissection, and the IgH CDR3 was amplified using a seminested PCR. Most of the PCR products obtained from both tumor components in each case had identical lengths when analyzed with polyacrylamide gel electrophoresis (PAGE) and identical migratory patterns on denaturing gradient gel electrophoresis (DGGE). These findings indicate sequence identity of the IgH CDR3 of both tumor components. Sequence analysis showed that point mutations were responsible for bands from the same case that had nonidentical migratory patterns by DGGE. The components in each of the 4 cases studied have the same clonal origin. Intraclonal sequence variations in the IgH gene were observed in 2 cases, consistent with the presence of continued somatic hypermutation after establishment of the clone. The expression of CD10 and bcl-2, as well as the detection of bcl-2 rearrangements in 2 cases, indicate that these lymphomas are of follicular center cell origin.

The authors report three cases of Hodgkin's disease (HD) occurring in monocytoid B-cell (MBC) clusters within lymph nodes, a finding heretofore not published. MBC clusters were found mainly in a perisinusoidal and perifollicular distribution in all three cases. Within some of the MBC clusters of each case, small foci of overt necrosis were evident. Sternberg-Reed cells or their variants were found adjacent to all of these foci, as well as within some MBC clusters that were free of necrosis. These findings suggest that the presence of necrosis within MBC clusters has diagnostic utility. In two cases, evidence of HD was detected only within MBC clusters and nowhere else. In the third case, HD was found primarily within MBC clusters. These observations imply that HD arose within MBC clusters. Minimal involvement of lymph node by HD can occur within MBC clusters and should be recognized as such on the basis of morphologic features. The earlier a diagnosis of HD can be made, the better is the patient's outlook for survival.

The large cell lymphoma (LCL) that occurs in patients with chronic lymphocytic leukemia (Richter's syndrome) has generally been shown to be of the same light chain type as the original chronic lymphocytic leukemia (CLL). The authors now report on a patient with diffuse well-differentiated lymphocytic lymphoma (WDL) of the kappa light chain type who in the course of his illness first had the blood picture of CLL and then developed malignant lymphoma of large cell ("histiocytic") type, which expressed lambda light chains. Despite an extensive multiparameter investigation, we could not determine with certainty whether the presence of two morphologically and immunologically different lymphomas represented proliferation of two distinctly separate clones or whether it represented clonal evolution of the disease with an alteration in immunoglobulin light chain associated genes. The results of the study, however, suggest that the development of lymphoma with expression of a different immunoglobulin light chain may not necessarily indicate the occurrence of a second primary. This study also illustrates the necessity for sequential lymph node biopsies to document progression of disease in patients with low-grade lymphoproliferative disorders and indicates that the immunologic phenotype of a B-cell neoplasm in a given patient should not be assumed to remain constant.

Terminal deoxynucleotidyl transferase activity was investigated by enzyme assay and (or) an indirect immunofluorescence method with specimens from 151 patients who had a variety of neoplastic and nonneoplastic conditions: leukemia, 62; non-Hodgkin's lymphoma, 36; Hodgkin's disease, seven; lymph nodes without neoplasms, 21; normal peripheral blood, 15; normal bone marrow, ten. Immunologic studies were done on samples from 82 of these patients. Increased terminal deoxynucleotidyl transferase activity was found by both methods in patients who had acute lymphoblastic leukemia and the lymphoid blast crisis of chronic myelocytic leukemia and by the immunofluorescence method in patients who had lymphoblastic lymphoma. A single patient with acute monoblastic leukemia was found by both technics to have increased enzyme activity. Three B-cell proliferations were positive by the enzyme assay; none was positive with the immunofluorescence method. In the remaining 42 B-cell proliferations, the levels of terminal deoxynucleotidyl transferase activity were found to be normal by both the enzyme assay and the immunofluorescence method. Cytoplasmic positivity was observed in as much as 10% of the cells in 13 specimens that were otherwise negative and in eight samples in association with nuclear positivity. A comparison of terminal deoxynucleotidyl transferase activity in microunits/mg protein (enzyme assay) with the percentage of positive cells (immunofluorescence method) yielded a correlation coefficient of 0.62 (P less than 0.01).

The diagnosis of mantle zone lymphoma is sometimes difficult to make solely on the basis of morphology because the mantle zone pattern may be present in other disorders such as benign mantle zone hyperplasia, follicular center cell (FCC) lymphomas, and Castleman disease. To distinguish mantle zone lymphoma from the other disorders mentioned previously, the authors performed immunoperoxidase studies on B-5-fixed, paraffin-embedded sections or cryostat sections of lymph nodes from nine patients with a diagnosis of mantle zone lymphoma. The results then were compared with the immunostaining pattern seen in FCC lymphomas and various benign lymphoid hyperplasias. A monoclonal proliferation of mantle zone cells, as shown by staining for immunoglobulin light chains, was noted in the mantle zones and interfollicular areas in all six cases from which cryostat sections were available. The cells in the residual follicular centers uniformly had a polyclonal light chain marking pattern. Two novel monoclonal antibodies (LN-1 and LN-2) that identify FCCs and B-cells in B-5-fixed, paraffin-embedded tissues also were used in this study. Of the six cases in which the monoclonal antibodies could be used, the cells in the residual follicles were uniformly LN-1 positive, LN-2 positive, while the mantle zone and interfollicular cells were almost completely LN-1 negative, LN-2 positive. The data suggest that mantle zone lymphomas are a distinctive neoplasm of monoclonal B-cells of non-FCC origin. The authors conclude that immunostaining is a sensitive technic for identifying a malignant neoplasm of B-cells in the mantle zone and interfollicular areas. In addition, the method is relatively specific and useful for distinguishing mantle zone lymphoma from similar-appearing disorders such as benign mantle zone hyperplasias and certain FCC lymphomas.