The bone-marrow may be replaced by typical lymphatic tissue, as well as by the substance of malignant tumours. The former occurs constantly in lymphatic leukæmia according to the well-known results of Neumann, which have since been generally confirmed. In these cases extensive tracts of bone-marrow are replaced not by masses of malignant growth but by an indifferent tissue, so to speak, a tissue which is unable to exercise the above-described stimulating influence upon the remaining bone-marrow. It is owing to this circumstance that we are able to observe in the cases of lymphatic degeneration of the bone-marrow the phenomena due to its exclusion, in their most uncomplicated form[19].
The most convincing results are obtained from cases of acute (lymphatic) leukæmia, the pretty frequent occurrence of which was first noticed by Epstein, and which has lately been very thoroughly studied by A. Fränkel. For the purpose in question, acute leukæmia is specially suited, since the abnormal growth of the lymphatic tissue takes place very rapidly, and for this reason brings about a quick and uncomplicated exclusion of the bone-marrow tissue; as it were, experimentally. Under its influence the neutrophil elements of the bone-marrow vanish rapidly, and in many cases so completely that it needs some trouble to find a single myelocyte, as for example in a case of Ehrlich's. The polynuclear leucocytes are produced in the bone-marrow, consequently where the bone-marrow is destroyed, as in this case, it is clear that their numbers must be absolutely very much diminished in the blood.
Dock has also arrived at similar results, as we see from a preliminary report; and he similarly explains the absence of neutrophil cells in lymphatic leukæmia by the replacement of the myeloid by lymphatic tissue.
Thus lymphatic leukæmia affords a striking proof that the lymphocytes are cells of a peculiar kind, and which are quite independent of the polynuclear cells. It is therefore exceedingly surprising that Fränkel, after accurately examining and analysing eight cases of acute lymphatic leukæmia, believes he has found in them imperative reasons for the assumption that the lymphocytes are transformed to polynuclear cells. This can only be explained by the confusion which Uskoff's doctrine of "young cells" has brought about.
We define lymphocytosis as an increase of the lymphocytes of the blood; Fränkel like Uskoff regards it as the emigration of the young forms of the white blood corpuscles into the blood. He concludes logically from the diminution of the polynuclear cells in this form of disease "that the conditions of the transformation of the young forms have undergone a disturbance." But if one assumes that the lymphocytes are young forms, and the polynuclears their older stages, it is much nearer to the facts to speak, not of a disturbance in lymphatic leukæmia, but of an absolute hinderance to the ripening process. It is easy to conceive any particular stimulus or injury bringing about an acceleration of the normal process, that is, a premature old age, but it is equally difficult to represent clearly to oneself conditions which retard or completely prevent the normal ageing of the elements. The discovery of such conditions would be really epoch-making, both for general biology, and for therapeutics. The only escape from this dilemma would be the assumption of a very premature death of the lymphocytes, for which however not the smallest evidence is to be found, even in Fränkel's monograph. Fränkel distinguishes the acute from the chronic forms of leukæmia by the fact, "that in the former the newly formed elements emigrate from their places of formation into the blood-stream with extraordinary rapidity. Hence there is not time for further local metamorphosis. In chronic leukæmia the emigration takes place very probably much more slowly." This distinction is contradicted by the facts; for there are chronic forms of lymphatic leukæmia whose microscopic picture is identical with that of acute leukæmia. And hence the starting-point of all Fränkel's deductions is rendered insecure.
FOOTNOTES:
[14] C. S. Engel has recently proposed to call acute leucocytosis "lienal leucocytosis," in analogy with the clinical idea of a lienal leukæmia. This terminology should only be used if the polynuclear cells did in fact arise from the spleen, an assumption which Engel himself does not once appear to make, since he expressly warns against drawing any conclusions from this name as to their origin. Since, however, the acute leucocytoses, as we shall shew in the next section, are exclusively to be referred to the bone-marrow, the term lienal leucocytosis seems to us quite mistaken, for it must logically lead to a conception of the origin of the leucocytes, exactly opposed to their actual relationships.
[15] Many authors, e.g. Arnold, explain this double staining of the eosinophil cells by the presence of eosinophil and mast cell granulation side by side. That this is certainly not the case is shewn by the fact that the "basophil" granulation of the eosinophil cells does not in metachromatic staining shew the metachromasia characteristic for the mast cells.
[16] A. Fränkel has recently reported histological investigations in which he could demonstrate in one case true myelocytes in inflamed lymph glands. He says (xv. Congress f. innere Medecin): "For some time past I have had systematic examinations carried out by my assistant, Dr Japha, on the granulations of the leucocytes contained in these glands in a large number of infectious diseases, which are accompanied by acute swelling of the lymphatic glands, such as scarlet fever, diphtheria, typhoid. They were performed in the following way: dry cover-slip preparations were made from the juice of the glands removed shortly after death, and were stained in the usual way by Ehrlich's triacid mixture. Amongst a large number of cases thus examined, it was possible in only one case of scarlet fever—but in this beyond all doubt—to demonstrate the presence of mononuclear cells with neutrophil granulation." The extreme rarity of this condition supports our opinion that the formation of neutrophil mononuclear elements cannot be regarded as a normal function of the lymphatic glands. Polynuclear neutrophil cells are nearly always naturally present in inflamed lymph glands, as a product of the inflammation which has immigrated there. Every pus preparation shews that the polynuclear neutrophil leucocytes can change in the tissues to mononuclear, and the isolated observations of Japha should be explained in this manner.
[17] Moreover the investigations of Roietzky are quite without foundation, inasmuch as the tibia of the dog, upon which this author performed his experiments, contains in all races of dogs—according to the information very kindly given us by Prof. Schütz—no red marrow, but fatty marrow only, which as is well known is incapable of the smallest hæmatopoietic function.