histamine: pathological tissues 



Recently, however, two fresh mast-cell tumours in mice have been described. 

 The first (Dunn and Potter, 1957) has already been shown to be rich in histamine 

 (Sjoerdsma et al, 1957); the second, of which we were fortunate enough to obtain 

 an example, has been similarly investigated by Furth and his group (Furth 

 et al, 1957). In our hands (Cass et al, 1958), lyophilized samples of tumour 

 yielded no less than 1700 ng./g. histamine and 944 i.u./g. heparin. The mouse 

 mastocytomas are unique in that they also contain substantial amounts of a 

 second amine, 5-hydroxytryptamine. 



Discussion 



The significance of the earlier finding of a striking positive correlation 

 between the mast-cell and histamine contents of normal tissues is greatly 

 strengthened by the examination of pathological material abnormally rich in 

 mast cells. Urticaria pigmentosa in man, mast-cell tumours in dogs, cats, 

 cattle and mice, all demonstrate conclusively that an excessively high mast-cell 

 content in a tissue is associated with a correspondingly high histamine value. 

 In the case of the tumours, histamine assay of an organ proved to be as accurate 

 a method as histological examination for the detection of distant metastases. 



Curiously enough, it is now the heparin which, in certain species, shows 

 the poorer correlation with the mast-cell content. Whereas in dogs, the heparin 

 values are in general proportionate to the mast-cell content, the cat tumours 

 yielded surprisingly low values for heparin, despite the brilliant metachromatism 

 of the granules in tissue sections. This heightens the suspicion raised in the 

 Introduction that the estimation of heparin as an anticoagulant, may not truly 

 reflect the function of heparin in the organism. It would be of interest to 

 confirm the low potency of cat heparin on plasma of the same species. 



The pattern of spread and metastasis in all the above conditions is of 

 interest. The majority of the cases with localized tumours showed spread 

 to the regional lymph nodes : this supports the theory of a focal origin of the 

 tumour. However, in others there was involvement of distant organs, especially 

 the spleen. It will be recalled that the spleen is very rarely the site of metastasis 

 in cases of carcinoma and sarcoma, though it is frequently involved in the leuk- 

 aemias and reticuloses. Since there was nothing to suggest that these animals 

 were suffering from a basophilic leukaemia of myeloid origin the possibility 

 remains that their 'tumours' were local manifestations of a more generalized 

 'mast-cell reticulosis' (Cazal, 1942). Within the past few years evidence has 

 accumulated that the underlying pathology of urticaria pigmentosa in man 

 may perhaps rest on a similar basis (cf. Ellis, 1949; Nickel, 1957; Marshall 

 et al, 1957; Remy, 1957; Beare, 1958). 



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