4. The absolute increase of the mast cells. The mast cells are always increased in myelogenic leukæmia. They may be counted in leukæmic blood with the aid of the triacid or eosine-methylene blue stain. As shewn by the former they appear as polynuclear cells free from granules, since their granulation takes on no dye of the triacid mixture.
In all cases of myelogenic leukæmia the increase of mast cells is absolute and considerable. Generally they are equally or half as numerous as the eosinophils, occasionally they may exceed the latter in number. Hence it follows that the mast cells undergo an increase in number relatively greater than the eosinophil cells, for they normally amount only to some 0.28%. They are perhaps of greater diagnostic value than the eosinophils, because up to the present time we know of no other condition (in contradistinction to eosinophil leucocytosis) in which a marked increase of the mast cells occurs.
5. Atypical forms of the white corpuscles. Amongst these are to be mentioned: (a) dwarf forms of the polynuclear neutrophils and of the eosinophil elements respectively. As a rule they resemble normal polynuclear cells on a small scale. (b) Dwarf forms of the mononuclear neutrophil and eosinophil leucocytes, which correspond to the pseudo-lymphocytes described elsewhere (see p. 78). The importance of these dwarf forms for leukæmia is as yet insufficiently explained; and it is difficult to decide whether they are already small forms on reaching the blood-stream, or whether they are there produced by division of a large cell. (c)Cells with mitoses. Formerly particular weight was laid on the observation of mitoses, for they were regarded as evidence that the increase of white blood corpuscles was brought about in the circulating blood itself, an assumption specially supported by Löwit.
A large number of authors (H. F. Müller, Wertheim, Rieder) have demonstrated mitoses, particularly of the myelocytes, in the circulating blood in leukæmia. No diagnostic importance of any kind can however be ascribed to them. They are found in all cases only in very small numbers. Thus Müller says that he generally must look through many thousands of white cells before meeting one mitosis. Only in one case did he find the figures of nuclear division somewhat more abundant, where there was one mitosis only to several hundreds of leucocytes.
These really negative observations shew that the mitoses play a completely negligeable part in the increase of the cells in the blood itself. For the diagnosis of leukæmia they are valueless.
6. Nucleated red corpuscles form a constant constituent of leukæmic blood. In different cases their number is very varying; in one case they occur extremely sparingly, in another every field contains very many. The normoblastic type is found most frequently, but side by side with it, megaloblasts and forms transitional between the two are occasionally found. Mitoses within the red blood discs have been described by different authors, but possess no theoretic or clinical importance. The appearance of erythroblasts in leukæmia may be either a specific phenomenon, or merely the expression of an anæmia accompanying the leukæmia. We are inclined to the first supposition, since the occurrence in such numbers of nucleated red cells is hardly ever observed in other anæmias of the same severity.
So much for the characteristics of leukæmic blood, upon which the diagnosis of the disease is made. We must add that although in any case of medullary leukæmia each particular factor described is to be recognised, yet the manner of its appearance, its numerical relation to the others and to the total blood varies extremely. Apart from the degree of increase of the leucocytes, no one case is the same as another with regard to the other anomalies. In one case the blood bears a large-celled, mononuclear neutrophil character; in another the increase of the eosinophil cells predominates; in a third the nucleated red blood corpuscles preponderate; in a fourth we see a flooding of the blood with mast cells. And hence results a multiplicity of combinations, and each single case has its own individual features[34].
It is of special importance to study the changes due to certain intercurrent diseases in the blood picture of medullary leukæmia. This point has recently been the object of detailed investigation, in particular by A. Fraenkel, Lichtheim and others[35]. According to these authors, under the influence of febrile diseases the total number of leucocytes may be enormously decreased. The blood moreover is altered, so that the myelæmic characteristics become less marked, and the polynuclear neutrophil elements largely preponderate. The latter may attain the percentage numbers of common leucocytosis up to 90% and over.
We will here mention a few rare cases, demanding special attention, shewing the alterations leukæmic blood may undergo, and occasionally presenting almost insuperable difficulties in diagnosis. We find but a single case of this kind mentioned in the literature. Zappert reported a patient, who in February, 1892, had shewn the typical signs of myelogenic leukæmia. Amongst others the relation of white to red cells was found to be 1:4.92, and 1400 eosinophil cells per mm.3 (3.4%) were counted. At the end of September of the same year the patient was brought in a miserable condition to the hospital, where she soon died with gradually failing strength. During this period of observation the proportion of white to red was 1:1.5; the percentage of eosinophils, 0.43; the mononuclears, most of which had no neutrophil granulation, amounted to 70% of the leucocytes. Zappert expressly mentions that these mononuclear cells were in no way similar to the lymphocytes in general appearance. At the autopsy Zappert found the bone-marrow studded with non-granulated mononuclear cells, and the eosinophil cells were much more scanty than is usually the case in leukæmic bone-marrow. Blachstein, under Ehrlich's direction, investigated a second case of this kind. This patient had also been the subject of exact clinical investigations for some time on account of a myelogenic leukæmia. During the time he was last in hospital the blood could only be examined a day before the fatal termination, the direct consequence of a septic complication. With a markedly leukæmic constitution of the blood there were found 62% polynuclear cells, 17.5% mononuclear about the size of the ordinary myelocyte, 0.75% eosinophil cells, nucleated red blood corpuscles in moderate amount. The preponderance of polynuclear and the small number of eosinophil cells is readily explainable from the septic infection; on the other hand the absence of granules in the mononuclear cells is most surprising.