348 LEUKEMIA 



ther de-velopment of the latter into a correspondingly greater number of poly- 

 nuclear cells. 



In the spleen and lymph-glands leukocytes are not produced, at least 

 not in noteworthy amounts (even in cases where they are much needed, as in 

 leukocytosis). On the other hand, the lymph-glands (the spleen only to a 

 slighter degree) are the points of origin for the formation of lymphocytes, 

 which, as is well known, represent one-fourth of the white blood cells in nor- 

 mal blood. Similarly to the myelocytes they are probably also formed in the 

 bone-marrow from large basophilic, mononuclear cells which are the early 

 stages of the leukocytes and generally do not enter the blood, or at most only 

 as " large lymphocytes " in children, and under pathologic conditions in 

 lymphatic leukemia (where they are met with in the blood in great numbers, 

 particularly in the acute form of the disease). Just as the myelocytes mature 

 ("age") into polymorphonuclear leukocytes, so does the nucleus of the 

 lymphocytes pass through this aging process in that it later undergoes lobula- 

 tion and fragmentation (Rieder's cells), without the protoplasm losing its 

 basophilic, non-granular character. 



The nuclear changes — lobulation and segmentation into several nuclei — 

 therefore, indicate the physiological age of the cells; just so may we assume, 

 in general, that a slighter staining quality (amblychromasia), especially of 

 the cell nuclei, characterizes the cells as incomplete, undeveloped, in contrast 

 to the intensely staining ( " trachychromatic " ) mature forms. 



As already mentioned, the tone-marrow is almost exclusively the organ of 

 production of the myelocytes and polynuclear cells, although typical myelo- 

 cytes are found in the spleen and lymph-glands (without having been carried 

 in by the blood stream). On the other hand, the lymph-glands are to le con- 

 sidered the seat of production of the small lymphocytes. Of course, we find 

 lymphocytes in scant numbers in the bone-marrow too ; of these it is probable 

 that a fair proportion have been carried in, a part, however, having been 

 formed in the marrow itself. 



The origin of the very small number of mast-cells, which, under normal 

 conditions, are found in the blood, has not yet been determined with certainty. 

 Most investigators assume that they originate in the connective tissue; others 

 believe that they develop from lymphocytes. 



SYMPTOMS AND BLOOD-CHANGES 



Let us now return to the discussion of leukemia. Marked cases are mani- 

 fest at the first glance by the extreme pallor of the patient's skin and mucous 

 membranes, and occasionally by the color of the blood as obtained by puncture 

 or incision of the finger tips which may be whitish red. [Cases are pale only 

 if anemia has developed, and this even in well-marked cases is often not nota- 

 ble. In the later stage of the disease, but not until then, anemia becomes 

 severe.^Eo.] The microscopic examination of the fresh blood in cases of 

 leukemia of high grade shows even without counting the abnormal increase 

 in the white blood-corpuscles. But a count and a comparison with the num- 

 ber of erythrocytes is absolutely necessary in the less marked cases. Whereas 



