Effects of cyclosporin A on the splenic tissue of rats: a histomorphometric analysis.

Histological studies demonstrated that long-term cyclosporin A treatment of nonantigenically challenged (untransplanted and unimmunized) Lewis rats markedly reduces the total percentage of splenic white pulp when compared to untreated control spleens (mean = 24 vs 34%, P less than 0.001). Direct measurements of periarteriolar sheaths and marginal zones demonstrated a marked reduction in size of these compartments in cyclosporin A-treated rats compared to untreated controls (P less than 0.001). In addition, there was a striking reduction in cellular density of the periarteriolar sheaths (P less than 0.001) and a minimal reduction in cellular density of the marginal zones (P less than 0.1) in the cyclosporin A-treated group when compared to untreated controls. There was no significant difference in total splenic size between the cyclosporin A-treated and the control groups, as indicated by total cross section measurements (mean = 33.3 vs 35.0, P less than 0.4). Qualitative observations of methyl green-pyroninophilic cells within and surrounding the marginal zones of the cyclosporin A-treated spleens revealed a much greater proportion of large pyroninophilic lymphocytes, which suggests that they are B immunoblasts. We conclude that long-term cyclosporin A treatment depletes splenic periarteriolar sheaths and marginal zones, compartments known to contain primary T lymphocytes, and induces an immunoblastic cell proliferation within the marginal zones and red pulp as well.

A human monoclonal antibody to cytokeratin intermediate filament antigens derived from a tumor draining lymph node.

Human lymphocytes derived from a lymph node draining a primary breast adenocarcinoma were fused with the mouse myeloma P3X63Ag8.653 to generate human-mouse hybridomas secreting human monoclonal antibodies (MAbs) to tumor associated antigens (TAAs). One of the resulting human MAbs, YBB 190 (IgM) is described. Enzyme-linked immunosorbent assays (ELISA) employing membrane and cytosol fractions of human tissues demonstrated YBB 190 reactivity against cytosol but not membrane components of malignant and normal epithelial tissues. When tested by an indirect immunoperoxidase staining method against fresh frozen human tissue sections, YBB 190 reacted with malignant cells in 26 of 28 epithelial cancers and with normal epithelia in 11 different benign tissues. Preliminary western blot antigen characterization indicated that YBB 190 recognizes cytokeratin intermediate filaments, or a protein that is closely associated with cytokeratins. These data indicate that B cells with specificity for intermediate filaments are present in tumor draining lymph nodes. Our findings provide insights into the nature of potential autoimmune responses in cancer patients and suggest that improved tumor directed sensitization procedures may be required to more effectively utilize lymphocytes from tumor draining lymph nodes to generate therapeutically useful human MAbs to TAAs.

Epidermal growth factor receptor expression in human lung carcinomas defined by a monoclonal antibody.

Acetone-fixed frozen tissue sections from 56 cases of human lung carcinoma were tested for reactivity by an indirect immunoperoxidase technique with a monoclonal antibody (MAb 528) specific for the external domain of the epidermal growth factor receptor (EGFR). MAb 528 reacted with all epidermoid (22/22) and large-cell (4/4) lung carcinomas evaluated. The antibody was also positive with a subset of lung adenocarcinomas (13/21) and did not react with small-cell lung cancers (SCLCs) (0/9). MAb 528 also stained normal bronchial epithelium identified within the tumor sections of 5 cases. Thus EGFR was expressed by all epidermoid and large-cell lung carcinomas examined, a subset of lung adenocarcinomas, and normal bronchial epithelium. EGFR expression was not identified in any of the SCLCs tested. These data imply that immunohistochemical detection of EGFR expression may find future application in distinguishing epidermoid, large-cell, and some adenocarcinomas of the lung from SCLCs.

A novel monoclonal antibody-defined antigen which distinguishes human non-small cell from small cell lung carcinomas.

Spleen cells from BALB/c mice hyperimmunized with the human epidermoid lung carcinoma cell line T222 were fused with NS-1 mouse myeloma cells to produce monoclonal antibodies to human lung cancer antigens. Hybridoma culture supernatants were tested by an enzyme-linked immunosorbent assay for reactivity against a panel of human lung tumor cell lines. Supernatant from hybridoma EA1 (immunoglobulin G1) displayed strong reactivity with four of four non-small cell lung carcinomas but did not react with three of three small cell lung carcinoma (SCLC) cell lines. This hybridoma was cloned by limiting dilution and utilized to generate ascites antibody for subsequent immunohistochemical and antigen characterization studies. Evaluation of fresh frozen tumor tissue sections by immunoperoxidase staining methods revealed EA1 reactivity with the vast majority of non-SCLCs tested (21 of 21 epidermoid, 17 of 18 adenocarcinomas, four of four large cell, two of two bronchioloalveolar) and no reactivity with nine of nine small cell lung carcinomas. EA1 also stained bronchial epithelium and other benign and malignant epithelial tissues. The EA1 antigen was determined to have a molecular weight of 75,000 by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of human non-SCLC tumor extracts. These data imply that EA1 recognizes a novel antigen expressed by non-SCLCs and other epithelial tissues. The absence of EA1 reactivity with SCLCs suggests that this monoclonal antibody may find future application in distinguishing non-SCLC from SCLC and prove useful in furthering our understanding of the histogenesis of lung carcinomas.

The biology of head and neck cancer. Detection and control by parallel histologic sections.

Microscopic fingers of epidermoid cancer can extend submucosally 1 to 3 cm from grossly discernible borders of upper aerodigestive tract cancers. These fingers are best detected by sectioning all surgical margins parallel to the margins. Microscopic disease was found at the original excisional margins in 75% of 70 cases. Using this principle for frozen-section evaluation, and reexcising further tissue as indicated, local disease was completely controlled in all 24 patients eligible for two-year follow-up.

Effectiveness of curettage and electrodesiccation in the removal of basal cell carcinoma.

Basal cell carcinomas are slow-growing malignant skin tumors which have traditionally been successfully treated by curettage and electrodesiccation. Curettage and electrodesiccation is traditionally repeated two or three times, but there are no previous studies documenting the value for the repetitions. This study compares the efficacy of curettage and desiccation once and three times in removing basal cell tumors. The results suggest that these neoplasms have two distinct growth patterns. One is more invasive and incompletely removed by curettage-desiccation. The second pattern is removed by a single cycle of curettage and desiccation. It is hypothesized, based on a review of pertinent literature, that these growth patterns are related to immunologic interaction with tumor cells.

Concurrent primary parathyroid hyperplasia and parathyroid carcinoma.

We noted the association of parathyroid carcinoma and primary parathyroid hyperplasia in a 53-year-old woman who had a clinical and laboratory profile of primary hyperparathyroidism. At surgery, three hyperplastic parathyroid glands were excised, one of which also demonstrated parathyroid carcinoma. Postoperatively, she was treated for persistent hypercalcemia and died of congestive cardiac failure. At autopsy, there was evidence of metastatic parathyroid carcinoma, and a further hyperplastic parathyroid gland was identified. The association of parathyroid hyperplasia and carcinoma is rare.

Angiosarcoma of the lung with fatal pulmonary hemorrhage.

A patient with fatal pulmonary hemorrhage was found to have angiosarcoma of the lung at postmortem examination. This case, occurring in a man with a prior history of industrial exposure in South African copper mines, is the third well-described primary occurrence of this tumor in the lung.

Bronchogenic carcinoma presenting as an endobronchial mass.

The purpose of this study was to determine the optimal number of biopsy specimens which should be taken of an endobronchial mass lesion to assure the diagnosis of bronchogenic carcinoma. Five biopsies were performed on each of 18 consecutive mass lesions. Before biopsy, the tumor was well visualized, cleared of blood if possible, and the forceps carefully placed on the mass. Each biopsy specimen was placed in a separate coded container so that the pathologic interpretation was blind to the order in which the samples were taken. Ten out of a total of 90 biopsy specimens were negative for tumor and all of the tumors were diagnosed within the first three biopsy samples. The totals of negative diagnoses for each of the five biopsy specimens were not significantly different by the approximate Cochran Q test (p = 0.441) or by the exact test (p = 0.360), and no evidence was found for dependence of successive biopsies (p = 0.106) or for a patient effect (p = 0.325). The estimated probability of obtaining a diagnosis of malignancy after one biopsy was .889; after two biopsies, .9877; and after three, .9986. The yield is not meaningfully increased with more biopsies being done. We suggest performing three biopsies of endobronchial mass lesions to achieve an optimal diagnostic yield with minimal risk of bleeding.

Orbital and adnexal lymphomas. A multiparameter approach.

The application of immunologic, cytochemical, and electron-microscopic technics to the study of lymphoid lesions of the orbit and adnexa was found to enhance the accuracy of diagnoses of malignant lymphoma in five challenging referral cases. Although careful specimen collection, ideal fixation, and processing constitute the cornerstone of the morphologic diagnosis of nodal and extranodal lymphomas, the immunologic characterization of these lymphoproliferative disorders is emphasized as an especially useful diagnostic parameter. The occurrence of false-negative diagnoses of pseudolymphoma of the orbital region may be partially explained by a failure to recognize the relatively frequent plasma-cytoid lymphocytic lymphoma, a distinctive entity that may mimic a reactive inflammatory process. All of the cases of malignant lymphoma reported represented stage I or stage II disease, suggesting that primary lymphoma of the orbital region may be a disease with a favorable prognosis.

Association of an isomeric species of carcinoembryonic antigen with neoplasia of the gastrointestinal tract.

We studied the association between serum levels of an isomeric species of carcinoembryonic antigen and neoplasia of the gastrointestinal tract in 993 patients. With use of an empirically determined threshold, the antigen was found to be elevated in 80.4 per cent of 138 patients with neof other tumors, predominantly lung and breast tumors. Serum levels were elevated in 0.23 per cent of random patients and 0.41 per cent of 725 patients without neoplasia, including those with liver diseases, inflammatory bowel disease and chronic renal disease. The results of this study suggest that this species of carcinoembryonic antigen, and that assay for it offers an improved approach to the diagnosis and management of neoplasia of the gastroinetestinal tract.