A clinicopathological study of non-Hodgkin's malignant lymphomas in terms of the Kiel classification.

A group of 25 patients with non-Hodgkin's lymphoma was investigated. Patients diagnosed earlier were reclassified according to the Kiel system. A correlation between age distribution and histological malignancy was found. The time between the onset of symptoms and diagnosis was 1 year on an average. The majority of the patients belonged to stage IV. The survival rate was higher in the low-grade malignancy group than in the high-grade group. When assessing the prognosis, the histological classification as well as the clinical staging ought to be considered. The bone marrow was the most frequent extranodal site of involvement in stage IV. Cytopenic changes were almost invariably accompanied by bone marrow infiltration. All the 7 cases analysed for lymphocyte surface markers proved to be B cell type. No significant difference was seen between the results of single agent and combined chemotherapy.     

Cell growth and death in malignant lymphomas. A quantitative analysis

OBJECTIVE: To review the value of biopathologic factors in single lymphomatous patients across the boundaries of histologic classification. STUDY DESIGN: In a series of previous studies, based on a large collection of biopsy samples, the value of the above biopathologic characteristics in individual lymphomatous patients was quantitatively evaluated. RESULTS: The relationships between apoptotic index and growth fraction, in light of the expression of oncogenes, which regulate cell birth and death, were of particular value in determining the growth pattern of different lymphoma cases across the boundaries of histologic classification. CONCLUSION: The study of mechanisms that regulate cell proliferation and death might have therapeutic implications as the proper therapeutic approach should be based on detailed knowledge of the kinetic and molecular characteristics of each tumor.     

BCG in the immunotherapy of malignant lymphomas

Summary The effectiveness of a nonspecific immunostimulation in related human or animal diseases incited us to do a study of nonspecific immunotherapy by BCG in Hodgkin's disease, and then in other malignant lymphomas. Seventy patients, each one fulfilling at least 2 criteria of poor prognosis, were initially put in complete remission by a combination of radio-chemotherapy, followed by a reinforcing chemotherapy. These patients were then randomized into two groups. The first group received no further treatment; the second received BCG in weekly cutaneous scarifications. Eight patients were excluded from the study. The rate of relapses is significantly lower in the treated group. The results are discussed. Other therapeutic studies are necessary to fix the indications and modalities of this immunotherapy.Communication to the Medical Oncology Society, Nice, December 7, 1976     

The significance of fine needle aspiration cytology for the diagnosis and treatment of malignant lymphomas

Fine needle aspiration biopsy of a laesion, thought to be a lymph node, is a minor procedure, which provides quick and valuable information. It should be performed with a fine needle (0.6 mM outer diameter = 23 Gauge) and a special syringe, which needs only one hand during the aspiration itself. From the experience obtained in over 6000 own patients a f.n.a.b. gives the first place information whether the laesion actually is a lymph node, or a cyst, a salivary gland, a chemodectoma or any other lesion which can mimic a lymph node, In 3000 cases a benign lymph node was found and this finding often is as important as reporting malignancy. In 2000 cases metastatic malignancy was found. In 90% of these the primary tumour could be ascertained by coupling the clinical and the cytological data. False-negatives and false-positives practically do not occur with our technique. In 1023 patients primary lymphoma was found; 523 of them being Hodgkin's disease and 500 non-Hodgkin's lymphoma. In fresh cases of lymphoma surgical biopsies should always be done. In relapses cytology alone will as a rule be sufficient. In case of doubt repeat the f.n.a.b. after one week and do not immediately proceed to histological biopsy.     

A method of synchronization of normal and malignant human cells in culture.

A method is described for providing reproducible S phase parasynchrony in both normal mesenchyme and transformed epithelia. Cells were seeded at low density in medium containing 10% serum. 24 h later the serum concentration was reduced to 0.5%. After 110th the cells were collected at the G1/S boundary in fresh medium containing 10% serum plus 2.5mM hydroxyurea over 20h. After removal of hydroxyurea and trypsinization the re-plated cells entered the S phase with a high degree of synchrony, as judged by autoradiography, pulse-labelling with 3H-thymidine, cell growth and time lapse cinematography. By 6h after synchronization 80% of the population had entered the S phase and between 10-13h 70% went through mitosis.     

IL-6 mRNA expression in CD25 positive malignant lymphomas.

We recently demonstrated that IL-2 is produced by reactive T cells in CD25-positive malignant lymphomas (ML). Using in situ hybridization, we investigated IL-6 mRNA expression in these CD25-positive ML. The ML tested included 9 anaplastic large cell lymphomas and 3 B-diffuse large cell lymphomas. Five CD25-negative ML were studied as controls. We show that IL-6 producing cells are present in all these ML. The density of positive cells was heterogeneous from case to case. However 3 cases of CD25-positive ML showed a dramatically higher density of IL-6 producing cells (70, 50, 43 producing cells per 10,000 cells, respectively) as compared to the other 9 cases of CD25-positive ML (mean 6.03 +/- 2.1 per 10,000). Morphological and topographical data suggested that several types of cells including fibroblasts, lymphocytes, macrophages and endothelial cells may synthesize IL-6. A combination of immunohistochemistry and in situ hybridization showed that reactive T cells and endothelial cells express the IL-6 gene whereas CD30-positive ML cells do not express this gene. Previous studies showed that IL-6 was capable to induce IL-2 receptor expression as well as production of IL-2 and stimulation of lymphomatous cells growth. Our present results indicate that the paracrine production of this cytokine may play a role in the proliferation of malignant lymphomas.     

The clinical effect study on malignant tumors with chronoradiotherapy

Like normal cells, tumor cells are also rhythmic. Chronochemotherapy has been proven to be effective in clinic, yet there are still some controversies about the efficacy and radiotherapy-related toxicity of chronoradiotherapy. This study was designed to investigate the therapy-related toxicity and short-term effect of four types of malignant tumor patients who were treated with radiotherapy at two different times. 121 cases of malignant tumor patients with radiotherapy indications were randomly divided into morning radiotherapy (MR) group and evening radiotherapy (ER) group, who received an identical procedure of radiotherapy at 9?am or 9 pm, respectively. The effects of radiotherapy were evaluated by short-term effect and therapy-related toxicity in this study. The efficacy rates of radiotherapy of lung cancer and nasopharyngeal carcinoma in ER groups were higher than those in MR groups, but the difference was not statistically significant (P > 0.05); the efficacy rates of radiotherapy of cervical and esophageal cancers in ER groups were significantly higher than those in MR groups (P < 0.05). The incidences of radiotherapy-related toxicity in these 4 types of malignant tumor patients were significantly lower in ER groups (P < 0.05), compared with MR groups. It suggests that irradiation in the evening could increase the efficacy in cervical and esophageal cancer patients and reduce the incidence of radiotherapy-related toxicity in these four malignant tumor patients.     

Studies of human malignant lymphomas after treatment with endoxan. I. Cytochemical studies in the respiratory enzymes succinic dehydrogenase and cytochrome oxidase.

The respiratory enzymes succinic dehydrogenase and cytochrome oxidase were studied in normal lymph node and malignant lymphoma cells under the effect of endoxan treatment. It is concluded that the decrease in the respiratory enzymes in lymphoma cells may be taken as one of the outstanding differences between the neoplastic and normal tissues.     

Morphology and index of nucleoli in malignant lymphomas

The significance of morphology and the number of lymphocyte nucleoli was evaluated by electronmicroscopic sections of malignant lymphomas. It was not only the number and the size of nucleoli which characterized malignant lymphomas differing in histological respect, but above all the different morphology of the nucleoli. The prognostic significance of the nucleolus can be illustrated, if malignant lymphomas of a low grade malignancy with a preponderance of micronucleoli and a low nucleolar index are compared with a significantly higher nucleolar index and markedly increased macronucleoli. These differences are further supplemented by additional morphological properties of nucleoli in malignant lymphomas.