Twenty-seven patients treated with high-dose rTNF alpha, IFN gamma and melphalan by isolated limb perfusion were histologically documented. There were 20 cases of melanoma-in-transit metastases and 7 cases of high-grade soft-tissue sarcoma. Biopsies were taken before IFN gamma, after IFN gamma, before TNF alpha and between 2 hr and 60 days after the TNF alpha perfusion. Immunohistochemistry was performed for adhesion molecules ICAM-I, ELAM-I (E selectin), VCAM-I and PECAM. During the first hours after beginning perfusion, the endothelial cells of the tumour capillaries appeared swollen. Significant tumour necrosis was already observed 3 hours after the perfusion in melanoma cases. The overall predominant feature was coagulative necrosis associated or not with haemorrhagic necrosis. TNF alpha induced increased expression of ELAM-I and VCAM-I adhesion molecules on intratumoral endothelial cells. The activated tumour vessels were progressively destroyed. Significant intravascular recruitment of polymorphonuclear cells (PMNs) was observed 3 hr after starting TNF alpha; it was followed by diapedesis and tumour colonization 3 days later. T lymphocytes and macrophages were detected during the first 7 days and B lymphocytes during the second week. Melanoma in transit metastases treated with alkylating agent alone did not show significant necrosis and did not express high levels of adhesion molecules (ELAM-I, VCAM-I) nor infiltration by PMN.

Medullary carcinoma of the breast is an epithelial malignant proliferation that shares many characteristics (macroscopic, microscopic, epidemiologic, and prognostic) with lymphoepithelioma-like carcinomas of various sites. The authors hypothesized that they could also share the same etiologic agent, the Epstein-Barr virus (EBV). Epstein-Barr virus, a virus of the herpesvirus family, is to be associated with lymphoepithelioma-like carcinomas of the nasopharynx, stomach, lung, thymus, and salivary gland. Therefore, the authors looked for the virus in a series of 10 medullary carcinomas of the breast. Using immunohistochemistry, in situ hybridization and polymerase chain reaction, this investigation failed to show evidence of EBV. Similar negative results have been reported in lymphoepithelioma-like carcinomas arising in the skin and in the uterine cervix, which like the breast do not originate in the foregut. These results suggest that the pathogenesis of these tumors is not unique, implicating probably different etiopathogenic entities.

Non-suppressible insulin-like activity (NSILA) is a term used for a variety of substances in serum, excluding insulin, which promote glucose uptake of adipose tissue and diaphragm in vitro. NSILA-S is a peptide with a mole¬ cular weight of 7000 which is soluble in acid ethanol and which has been purified on a large scale from human serum. This study describes a simple Chromatographie one step procedure by which NSILA-S can be extracted and quantitatively measured in individual sera. Using Sephadex G-75 equilibrated with 1 M acetic acid, NSILA-S was detected only in one peak containing small molecular peptides. NSILA-S obtained with this one step Chromatographie procedure exerted all the effects of purified NSILA-S including sulphation activity on the rat cartilage. All Chromatographie fractions with NSILA-S also had sul¬ phation activity. Both, NSILA-S and sulphation activity were increased in acromegalics and decreased in pituitary dwarfs. It is suggested that one molecule in serum is responsible for both activities which are, at least in part, under the control of growth hormone.

Non-suppressible insulin-like activity (NSILA-S) was determined in 5 dogs before and after pancreatectomy and again during insulin therapy. All NSILA-S determinations were carried out on serum samples which were passed over Sephadex G-50 columns equilibrated with 1 m acetic acid. The levels of NSILA-S decreased drastically shortly after pancreatectomy and rose slowly after institution of insulin therapy, to normal levels. During the period of severe diabetes after pancreatectomy the concentration of growth hormone was elevated. These findings indicate that 1) the pancreas cannot be the site of synthesis and release of NSILA-S, 2) NSILA-S levels do not always parallel growth hormone levels and 3) the synthesis and secretion of NSILA-S among other factors is under the control of insulin.Insulin-like effects of non-suppressible insulin-like activity (NSILA-S) have been extensively studied in vitro and in vivo (for review see Oelz et al. (1972)).

The paper reports a re-evaluation--based on the Kiel classification for non-Hodgkin lymphomas--of a group of cases initially diagnosed as undifferentiated small cell carcinomas or primary lymphomas of the thyroid. Twelve such cases were found among the 155 cases of primary malignant tumours of the thyroid recorded at the Institut Jules Bordet between 1955 and 1975. The review of the clinical charts and the histology showed that all the cases were in fact malignant lymphomas fitting easily into one of the groups described in the Kiel classification. These findings support the growing opinion that undifferentiated small cell carcinoma of the thyroid does not exist as a distinctive clinicopathological entity. Furthermore, the Kiel classification proved to be an excellent prognostic indicator, since all the cases classified as highly malignant were indeed fatal, whereas the surviving cases--three of which had shown tumoral extension beyond the thyroid capsule--fell into the group of low malignancy. Lastly, this study acknowledges the frequently observed association of malignant lymphoma of the thyroid with stigmata of Hashimoto's disease, and thus supports the concept that the continuous antigenic stimulation observed in the latter could trigger the development of a malignant lymphoma.