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Multinucleated giant cells resembling Reed-Sternberg (RS) cells are occasionally observed in high-grade lymphomas of the large-cell or immunoblastic type, but much less commonly in low-grade lymphomas. This study was conducted to determine whether RS-like cells found in seven B-cell low-grade lymphomas were immunologically similar to the neoplastic cells in the lymphoma or to the true RS cells seen in Hodgkin's disease, and whether they were therefore indicative of a composite lymphoma. Immunohistochemical studies were performed on paraffin sections of the seven low-grade (one small lymphocytic, one mantle zone, and five follicular) lymphomas with a panel of antibodies reactive with leukocyte common antigen (LCA), B-cell, T-cell, and Hodgkin's disease associated antigens. The RS-like cells were reactive with LCA (four of six), L26 (seven of seven), LN1 (five of six), LN2 (two of six), and MB2 (three of six). No positive staining was seen with either Leu-M1 or Ber-H2. The RS-like cells in the mantle zone lymphoma expressed L26, Leu-22, and kappa cytoplasmic light chains. This immunophenotype is similar to that of the neoplastic small lymphocytic cells. One of the low-grade follicular lymphomas progressed to an immunoblastic lymphoma with many RS-like cells. Paraffin immunohistochemistry on both lesions revealed a similar B-cell phenotype for the RS-like cells. Immunogenetic studies revealed B-cell and bcl-2 gene rearrangements in the immunoblastic lymphoma. These results indicate that RS-like cells in low-grade lymphomas are transformed neoplastic cells of B-cell lineage. With careful morphologic examination augmented by immunohistochemical studies, these lesions can be differentiated from Hodgkin's disease and from composite lymphomas of the combined Hodgkin's and non-Hodgkin's type.

Hodgkin's disease (HD) is characterized morphologically by a variable infiltration of tissues by eosinophilic granulocytes. The lesions also contain numerous T cells, predominantly of the CD4+ immunophenotype. To investigate whether the presence or absence of tissue eosinophilia is related to the immunophenotype of the T cells, we studied 43 cases of HD (28 nodular sclerosing, ten mixed cellularity, and five unclassifiable) for the relative numbers of lymphocytes positive for CD2, CD3, CD4, CD5, CD8, CD25, CD38, T9, TQ1, HLA-DR, and beta F1, and for the number of eosinophils in tissue sections. By univariate and multivariate analysis, we determined that there was an inverse relationship between the number of eosinophils and the presence of TQ1+ (P less than .0005) and CD25+ (P less than .0005) lymphocytes. In addition, we observed that TQ1 stained the Reed-Sternberg cells in these lesions. We also determined that the T cells expressed HLA-DR more frequently in the nodular sclerosis subtype than in other subtypes of HD (P less than or equal to .0001). We therefore conclude that the degree of tissue eosinophilia in the lymph nodes of patients with HD may be explained, at least in part, by the immunophenotype of the T cells present in the affected lymph nodes.

The immunohistochemical and ultrastructural characteristics of involved lymph nodes from four patients with typical clinical and histopathologic features of malignant histiocytosis are reported. The neoplastic cells in all four cases had numerous irregular surface projections and pseudopodia, as well as lobulated or biolobed nuclei with macronucleoli. The cytoplasm contained many lysosomes, mitochondria, and polyribosomes, and displayed evidence of phagocytosis. Langerhans' granules were not identified. The ultrastructural features in the four cases were similar, effectively excluded an epithelial origin in each instance, and delineated morphological characteristics common to neoplastic macrophages. Intracytoplasmic muramidase (CM), an enzyme marker essentially restricted to cells of myeloid and true histiocytic origin, was identified with the unlabeled immunocytochemical technique and was strongly positive in neoplastic histiocytes at all stages of differentiation. Thus, fine structural features and the presence of CM are useful confirmatory studies in the diagnosis of malignant histiocytosis.

Recent evidence suggests that immunofluorescence is superior to immunohistochemistry for the study of lymphomas, since the latter procedure often results in identification of polyclonal cytoplasmic immunoglobulins or negative immunostaining in non-Hodgkin's lymphomas marking monoclonal with immunofluorescence. However, immunohistochemical studies are usually applied to paraffin-embedded tissues. A modified direct immunoperoxidase procedure using fresh-frozen cryostat tissue sections, short incubation with peroxidase-labeled antikappa and antilambda antisera, and chromogens chemically unrelated to benzidine was developed. Non-Hodgkin's lymphomas previously characterized by direct immunofluorescence showed monoclonal surface membrane-associated light chains outlining each neoplastic cell. Follicular (nodular) lymphomas were characterized by monoclonal light chains in neoplastic nodules with compressed negative or polyclonal rims. Diffuse non-Hodgkin's lymphomas demonstrated diffuse individual cellular monoclonal staining. Five normal lymph nodes showed polyclonal immunostaining of follicular centers. The immunostained slides resulting from this procedure are permanent preparations amenable to counterstaining.

It was shown recently that monocytoid cells express B-cell-restricted antigens and polyclonal surface immunoglobulins, and the term monocytoid B lymphocytes (MBL) has thus been offered as a more appropriate designation. Although most commonly seen in toxoplasmic lymphadenitis, MBL have been observed in a variety of reactive and neoplastic conditions involving lymph nodes. In the present study MBL were found in 17 of 22 lymph nodes from 20 patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related lymphadenopathy. In all 17 samples, the MBL were found in lymph nodes with florid reactive follicular hyperplasia, and they were geographically close to the hyperplastic lymphoid follicles. However, MBL were not detected in lymph nodes showing involuted follicles or lymphocyte depletion. The disappearance of MBL apparently parallels the progressive involution of secondary follicles. Leu-3+/Leu-2+ (T-helper/T-suppressor) ratios were studied in 14 lymph node cell suspension samples and ten peripheral blood samples. The lymph node Leu-3+/Leu-2+ ratios were significantly lower in AIDS-related lymphadenopathy than in non-AIDS-related reactive follicular hyperplasia (P less than 0.001); the peripheral blood ratios were decreased in nine of the ten cases. The diminished T-helper status in patients with AIDS and AIDS-related lymphadenopathy may be relevant to the immunopathogenesis of follicular involution and, indirectly, to the disappearance of MBL.

Cytogenetic studies were performed on 12 involved lymph nodes from Hodgkin's disease patients utilizing conditioned medium from 12-O-tetradecanoylphorbol-13-acetate-staphylococcus enterotoxin A induced mononuclear cells. The majority of cells analyzed had a normal karyotype. An unusually high rate of nonclonal karyotypic abnormalities was noted in most cultures. Clonal abnormalities involving chromosomes 3 and 21 were noted in two patients. Cytogenetic analysis of cultures stimulated with conditioned medium or specific growth factors may lead to a better understanding of the genetic mechanisms involved in Hodgkin's disease.

Some human malignant lymphomas of the B-cell type have morphologic and immunologic similarities to follicles seen in nonneoplastic reactive lymph nodes. In contrast, a peculiar, vaguely nodular pattern of growth called "pseudonodules" or "pseudofollicular proliferation centers," which is morphologically distinguishable from "true" follicles, is seen in malignant lymphoma, well-differentiated (small) lymphocytic type (WDL). To characterize the cellular components of "pseudofollicles," we undertook a detailed, comparative immunohistologic study of the architectural relationship and distribution of T cells, B cells, and follicular dendritic reticulum cells (DRCs) in reactive follicles, neoplastic follicles, and pseudofollicles. We report several observations on the presence of DRCs and T-cell subset topography in pseudofollicles. Immunohistologic staining for the C3d complement receptor on DRCs revealed that DRC networks associated with "true" follicles were present in all cases of reactive follicular hyperplasia (RFH) and malignant lymphoma, nodular, poorly differentiated lymphocytic type (PDL) studied. Surprisingly, DRC networks were also identified in 8 of 23 cases of WDL. Although the size distribution of DRC network diameters was nearly identical in RFH and PDL, the sizes were markedly diminished in WDL. Immunohistologic staining for Leu 3+ and Leu 2+ T-cell subsets confirmed cellular arrangements in RFH and PDL reported by others. In only 2 of 23 cases of WDL could T cells localized to "pseudofollicles" in frozen tissue sections be identified in a nonrandom arrangement.

We recently received in consultation a lymph node involved by metastatic malignant melanoma with unusual and previously undescribed morphologic features. The neoplastic cells had a striking signet-ring appearance, similar to the signet-ring cells normally seen in mucin-producing adenocarcinoma and signet-ring cell lymphoma. Review of our consultation files of malignant melanomas revealed an additional case in which the neoplastic cells had a signet-ring cell appearance. Electron microscopic studies revealed that formation of signet-ring cells is caused by the presence of abundant vimentin filaments in the cytoplasm of neoplastic cells. Immunologic studies using a series of monoclonal and polyclonal antibodies, including S-100 protein, HMB-45, vimentin, cytokeratin, leukocyte common antigen, and Leu-M1, on both cases clearly established the diagnosis of this morphologically unusual variant of malignant melanoma for which we propose the term "signet-ring cell melanoma."