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Epidermal growth factor (EGF) is known to be present in the alpha granules of human platelets; however the source of this EGF, ie, whether it is taken up by the platelets from the circulation, or whether it is packaged into the platelets from the megakaryocyte during thrombopoiesis, is unknown. To determine whether EGF is taken up by platelets, platelets for EGF receptors were assayed and it was attempted to detect uptake of EGF by the platelets from culture medium. Platelets were found to lack EGF receptors, and no uptake of EGF from the culture medium was detected. To assess whether EGF is packaged into platelets from the megakaryocyte, megakaryocytes in frozen section bone marrow cores were stained for EGF protein by immunohistochemistry, and it was demonstrated that EGF is present in megakaryocytes. In addition, staining of megakaryocytes by in situ hybridization for EGF mRNA demonstrated its presence in these cells. Therefore it is concluded that the source of EGF in human platelets is the megakaryocyte and that this EGF is synthesized in the megakaryocyte rather than being taken up from its environment.

Monocytoid B lymphocytes (MBLs), originally described as part of the histologic picture of toxoplasmic lymphadenitis, have been recognized as a reactive component in a variety of lymph node disorders. The authors now report 3 cases of non-Hodgkin's lymphoma in which a multidisciplinary approach allowed them to confirm the existence of a malignant lymphoma composed of the neoplastic counterpart of the MBLs found in nonneoplastic disorders. In all 3 cases, the lymphoma was composed of a relatively monomorphous infiltrate of atypical MBLs that had rather uniform-appearing nuclei and had well-defined, moderately abundant pale cytoplasm. The pattern of lymph node involvement in all 3 cases was predominantly sinusoidal and interfollicular. The neoplastic lymphoid cells were strongly positive for B-cell-restricted antigens; the light- and heavy-chain phenotypes were kappa-IgM (2 cases) and kappa-IgG (1 case). In all 3 cases, rearrangement of heavy- and/or light-chain genes was clearly identified by Southern blot hybridization. The name "monocytoid B-cell lymphoma" is proposed for this newly described malignant B-cell neoplasm.

Detection of immunoglobulin gene rearrangements by molecular hybridization is considered to be a highly sensitive approach to the evaluation of clonality of B-cell-derived neoplasms. Like monoclonal surface immunoglobulin in B cells, which serves as a reliable immunophenotypic marker for clonality, rearrangement of the genes encoding immunoglobulin light chains has been accepted as a reliable genotypic marker for the presence of a clonal expansion of B lymphocytes. The authors now report 3 cases of non-Hodgkin's lymphoma that were immunologically classified as having a T-cell phenotype and in which, in addition to rearrangements of the T-cell receptor beta-chain gene, a rearrangement of an immunoglobulin light-chain gene was clearly identified by Southern blot hybridization. The results demonstrate that the data obtained by molecular hybridization should be interpreted with caution when the immunogenetic findings do not correlate with immunophenotypic expression, and that the results of molecular genetics studies should be interpreted in conjunction with morphologic and immunologic findings.

The authors investigated the distribution of interleukin-2 receptors (TAC antigen) in the lymph nodes of 300 patients with lymphoproliferative disorders. They used fresh-frozen sections to evaluate a possible correlation between the immunophenotype of specific lymphoid disorders and the presence or absence of TAC expression and to determine whether the TAC positivity of lymphoid cells contributes to the characterization of lymphoproliferative processes. All of the cases had previously been studied with a large screening panel of monoclonal antibodies and polyclonal antisera. Among 85 patients with a variety of benign reactive processes, the lymph nodes from 47 contained TAC-bearing lymphocytes in various patterns of distribution. Of 41 patients with Hodgkin's disease, 37 had TAC-bearing lymphocytes. Of 26 B-cell, well-differentiated lymphocytic lymphomas (WDL), 14 were diffusely TAC-positive and one had TAC-bearing cells in random distribution. Six cases of intermediate lymphocytic lymphoma were also studied, and three showed randomly distributed TAC-bearing lymphocytes. Of 19 patients with follicular or follicular and diffuse, poorly differentiated lymphocytic (PDL) lymphoma, 14 were TAC-positive. All 3 diffuse PDL lymphomas studied were TAC-negative. Among 23 cases of B-cell and 5 cases of T-cell mixed cell lymphoma, 15 and three, respectively, had TAC-positive lymphocytes. Of 39 large cell lymphomas (B-cell, 33; T-cell, 6), 14 were TAC-positive. All 13 cases of hairy cell leukemia were diffusely positive. Of 23 T-lymphoblastic lymphomas, only 1 showed positive TAC reactivity, which was focal. Of 5 cases of cutaneous T-cell lymphoma, 2 had TAC-bearing lymphocytes. Our study indicates that the TAC antigen is not lineage-specific, and that it may be expressed by lymphoid cells regardless of their phenotype.

Anti-Leu M1 generally does not stain the lymphocytic and histiocytic (L&H) variants of Reed-Sternberg cells in the lymphocyte predominant type of Hodgkin's disease. However, the authors found that after neuraminidase treatment for removal of sialic acid, the L&H cells in more than half of the cases studied could be stained by anti-Leu M1. This result strongly suggests that L&H cells differ from the Reed-Sternberg cells in other types of Hodgkin's disease in their unique capacity to sialylate the 150-kd Leu M1 antigen.

Documenting focal mycosis fungoides in lymph node biopsies that exhibit dermatopathic lymphadenopathy is morphologically difficult. Since mycosis fungoides is a lymphoma with the phenotype of mature T cells, usually of the T-helper class, the authors investigated whether there are alterations in the ratio of Leu 3a (T-helper):Leu 2a (T-suppressor) cells in dermatopathic lymphadenopathy in order to determine the significance of immunologic markers as a possible solution to the problem. Ten lymph node biopsy specimens with diagnostic evidence of dermatopathic lymphadenopathy, but not of mycosis fungoides, were studied with the use of fresh-frozen section immunohistochemistry (FS), cell suspensions (CS), or both; five of the specimens came from patients with known cutaneous mycosis fungoides, and the other five came from patients without mycosis fungoides. The mean Leu 3a/Leu 2a ratio was 7.0 +/- 1.06 (SE) in all 10 cases of dermatopathic lymphadenopathy studied by FS and 6.9 +/- 1.14 in the 6 cases studied by CS. These ratios were significantly higher (P less than 0.001) than the mean Leu 3a/Leu 2a ratios of 2.9 +/- 0.29 (FS) and 2.4 +/- 0.22 (CS) in control lymph nodes exhibiting nonspecific reactive follicular hyperplasia, but were comparable to the mean Leu 3a/Leu 2a ratio of 5.9 obtained in two lymph node biopsies with unequivocal involvement by mycosis fungoides. Despite the increase in Leu 3a staining cells in dermatopathic lymphadenopathy, however, there were no essential differences in the Leu 3a/Leu 2a ratios between patients with and those without known mycosis fungoides. The use of other antibodies reactive with T cells, such as anti-Leu 8, anti-Leu 9, and anti-Tac also did not aid in this discrimination. The results indicate that determination of the Leu 3a/Leu 2a ratio and use of other conventional T-cell monoclonal antibodies do not provide conclusive evidence in support of a presumptive or early diagnosis of mycosis fungoides in a lymph node which fails to show histologic evidence of the disease.

To evaluate the usefulness of an immunohistologic approach to the differential diagnosis of mesothelioma and pulmonary adenocarcinoma, the authors studied paraffin-embedded, fixed tissue sections from 50 primary adenocarcinomas of the lung and 28 mesotheliomas of the pleura by using a panel of monoclonal antikeratin, antihuman milk fat globule (HMFG-2), anti-Leu M1, and monoclonal anticarcinoembryonic antigen (CEA) antibody; we also used a conventional heterologous anti-CEA antiserum with and without prior absorption with spleen powder to remove antibodies to nonspecific cross-reacting antigen (NCA). Keratin was present in both mesotheliomas and adenocarcinomas and did not help in distinguishing between these two neoplasms. HMFG-2 was detected in 48 (96%), and Leu M1 was positive in 47 (94%) of the adenocarcinomas, but not in any of the mesotheliomas. By using conventional rabbit antiserum, the authors detected CEA in the majority of adenocarcinomas (96%), but also in two cases of mesothelioma. When the anti-CEA antiserum was absorbed with NCA, the number of positively reacting adenocarcinomas decreased considerably to 76%; however, after this treatment, none of the mesotheliomas gave positive reactions. The monoclonal anti-CEA antibody was reactive in 36 of the adenocarcinomas (72%), but in none of the mesotheliomas. Our results indicate that, in addition to HMFG-2 and CEA, the expression of Leu M1 antigen by most primary pulmonary adenocarcinoma (94%) and its absence in mesothelioma could be used as a valuable marker for primary adenocarcinoma of the lung that involves the pleura and permits its differentiation from mesothelioma.