Studies in the Osteopathic Sciences
Cells of the Blood: Volume 4
Louisa Burns, M.S., D.O., D.Sc.O.
    A satisfactory definition of leukemia has not yet been devised. Barker’sdefinition of the leukemic state as one “in which there is definite proliferation of leukopoietic tissues, either myeloid or lymphadenoid, and the appearance in the blood of immature white cells, usually in large numbers, the degree of whose immaturity is more pronounced the more acute the cases,” has much to commend it, but it seems to exclude those cases in which the blood picture is atypical. It is true that diagnosis is very difficult when the blood picture is atypical. There are many instances in which immature forms never are found in the blood, the white cell count is not found increased at any time, and yet at autopsy the pathological changes are definitely those of leukemia. It must be remembered that an aleukemic phase may occur during the course of the disease and also that in its initial stages the blood picture may remain unaltered for variable and sometimes for considerable periods of time.

    Hodgkins disease and other abnormal conditions of lymphoid and myeloid tissues included as pseudo-leukemias are properly excluded from the leukemias by the definition given. There is no rational basis for the attempt made by piney and others to change the terms employed in discussing these diseases because of their inaccuracy; if the names of diseases were changed with each advance in our knowledge of their nature great confusion would be inevitable. The term leukemia as applied to this group of diseases is certainly not more objectionable than is the term malaria, as applied to a disease with no real relationship to bad air. There are many other conditions in which a name has been given to a disease or to a symptom complex before correct understanding of its essential qualities, yet these names persist because their use is convenient.

    The relationship between hyperplasia of the bone marrow and the leukemias has not been adequately studied. That certain forms of leukemia develop after infections is certain; it is not certain that the infection is the sole cause of the hyperplasia of the bone marrow. That aleukemic leukemia follows an infectious process to which the system appears unable to make adequate response is also frequently the case. But it is not at all certain whether the inability of the bone marrow to make adequate response to the infections agent was or was not due to developmental imperfections or to some acquired etiological factor. The possibility that the inadequate response to the infection may be due to costal or vertebral lesions has received no investigation at all.

    Fox reported a case of leukemia in the opossum (Didelphys virginianus) in which the autopsy findings were typical, though the diagnosis had not been determined before death. Birds in captivity and ordinary barnyard fowls occasionally suffer from leukemia, and in these cases the disease seems to be infectious. Corson-White reported a case of chronic lymphatic leukemia in a monkey.

    Hyperplasia of the bone marrow occurs as a reaction to various infections and secondary anemias. Certain infectious agents arouse hyperplasia of the leucocytopoietic areas of bone marrow. Other infectious agents initiate hyperplasia of the lymphoid tissues. Very severe hemorrhages, repeated at intervals, lead to hyperplasia of the erythrocytopoietic areas. Hemolytic infections sometimes cause hyperplasia of the erythrocytopoietic tissues.

    Exhaustion and atrophy of the bone marrow occur in rare cases, when the condition known as aplastic anemia supervenes if the erythrocytopoietic tissues are affected. The rare monocytic leukemia is associated with atrophy of the leucocytopoietic tissues, though it is not known whether the atrophy is the cause of the failure of the neutrophilic reaction, or the overwhelming infection is the cause of the neutrophilic failure.

    The relations between the erythrocytopoietic and the leucocytopoietic tissues affected by disease are not yet well understood. In pernicious anemia the leucocytopoietic tissues seem to be inactive if they are not truly atrophied. Yet in occasional cases of pernicious anemia after several exacerbations the leucocytopoietic areas share in the hyperplasia and the condition called leukanemia is found. On the other hand in certain cases of leukemia the anemia becomes very severe, and in late cases t he high color index, the megaloblasts and other findings characteristic of pernicious anemia are found. When the patient is first examined late in the disease it is often impossible to determine whether the red cells or the white cells were first affected. The unsatisfactory diagnosis of leukanemia is then unavoidable.

    In all the leukemias there is a marked tendency for the cells characteristic of the disease to appear in exudates, transudates, pus, sputum and various abnormal secretions. Patients with leukemia fail to develop opsonins and agglutinins when they contract typhoid fever or when they receive typhoid vaccine. They are especially subject to pneumonia and to other acute infections. Immunity may still further be lowered as a r esult of ill-judged treatment of the leukemias by radium or by the X-ray. The leucopenia thus produced by unwise treatment seems to reduce several of the factors concerned in immunity to acute infections. If pneumonia occurs during the course of lymphatic leukemia, the small hyaline cells are abundant in the sputum. In cases of splenomedullary leukemia, when pneumonia or any other pulmonary infection occurs, the sputum contains great masses of myelocytes. Pus occurring anywhere in the body contains abundant small hyaline cells if the patient already suffers from lymphatic leukemia, abundant myelocytes if he has splenomedullary leukemia, large monocytes if he has monocytic leukemia. In cases in which the leukemia is chronic, mild and unrecognized at the time of the acute infection, diagnosis may be clouded by the finding of these unusual cells in secretions. Examination of the blood usually clears the diagnosis. (Plate XII)
    Extramyeloid masses of tissues resembling bone marrow may cause atypical symptoms. In lymphatic leukemia especially the growth of masses of lymphoid tissue within the central nervous system may complicate the diagnosis very seriously. Chloroma and splenomedullary leukemia sometimes cause symptoms of brain tumor by means of these invading masses of cells.

    The leukemias are classified according to the type of cell most abundant in the blood stream. Many intermediate and mixed forms are found, and in late cases it is very frequently impossible to determine the exact diagnosis.

(Splenomedullary leukemia; myeloid leukemia; splenic leucocythemia; leukemic myelosis.)
    Splenomyelogenous leukemia is a disease of the hematopoietic tissues characterized chiefly by marked enlargement of the spleen and by the presence of considerable numbers of immature granular blood cells; usually also by great increase in the white cell count. The symptoms are indefinite and usually include irregular feverish attacks, feelings of fatigue, various nervous symptoms and discomfort due to the increased size of the spleen. Irregular feverish attacks are very common. They seem to bear no relation to fatigue, constipation or infections. The temperature often remains below 101 degrees F. and rarely exceeds 103 degrees.

    Subcutaneous and submucous hemorrhages are very common. Occasionally death follows severe bleeding from the nose, intestines or uterus in cases which have not shown serious symptoms before.

    Prispism is a common symptom and is probably due to thrombosis. Ascites also is a common symptom; this is usually due to enlargement of the spleen. Visual disturbances due to the invasion of the retina by masses of leucocytes are not common, but may be an early symptom. Symptoms suggesting tumor of the brain may follow invasion of the brain by masses of leucocytes and myelocytes.

    The changes in the structure of the spleen and the bone marrow and the changes in the blood picture are the most interesting features of the disease. Two forms are recognized, the acute and the chronic; these differ chiefly in the time necessary for the progress of the disease.

    Lesions of the ninth thoracic vertebra and neighboring bones have been found in every human with chronic Splenomyelogenous leukemia. Every human subject with a lesion of the ninth thoracic vertebra has also some congestion of the spleen and the spleen is always palpable when such a lesion has been present for two years or more. These patients may not show any recognizable increase in the white cell count, but they always have a recognizable increase in immature and myelocytoid granular cells. Every laboratory animal with a lesion of the ninth thoracic vertebra has an enlarged spleen. Records of blood examinations of such animals are too scanty for any definite statements to be made as to the changes due to splenic enlargement or to the lesion itself.

    Correction of the lesion has resulted in marked improvement in every case of human subjects with Splenomyelogenous leukemia receiving regular and systematic osteopathic care.

    Other etiological factors are unknown. Malaria, syphilis and chronic pyogenic infections have been mentioned but none of these always causes the disease and all are absent in many cases. Only the ninth thoracic lesion is always present, and this lesion invariably causes some of the conditions characteristic of the disease. Not every patient with a ninth thoracic lesion develops typical symptoms or typical blood picture of leukemia, but all show some symptoms of the disease.

    Pathological changes in the spleen are those which might be expected to occur as a result of abnormal relaxation of the muscular fibers of the splenic capsule, together with those changes due to accumulation of leucocytes within the blood vessels. The Malpighian bodies show no evidence of being actively concerned in the pathological changes, but are affected by pressure changes and circulatory disturbances due to congestion and infarction.

    In early cases the sole change in the spleen is a profound congestion with atony of the capsule. Later the accumulation of white cells causes thrombosis, infarction and degeneration of the pulp cells. In early cases t here is no marked change in the bone marrow. After the disease has assumed its classical form the bone marrow shows characteristic changes. The fatty areas of the bone marrow are replaced by cellular masses in which leucocytopoiesis is progressing rapidly. The bony spicules are frequently absorbed Grossly the marrow presents irregular areas of reddish, pinkish and whitish areas. Sometimes greenish areas are also present; the latter are due to degeneration of the red cells. After death this richly cellular ;material undergoes rapid digestion so that the marrow presents an appearance of being purulent. On microscopic examination it is seen that the cells are all myeloid in type and that no pus is present. Eosinophilic myelocytes are especially abundant, usually in definite areas, and associated with these eosinophilic areas are many Charcot-Leyden crystals (needle-like crystals, roughly octohedral, about 10 microns in length in this situation). Neutrophilic and basophilic myeloblastic cells are also abundant. Erythroblastic areas are scanty and may show atrophic changes.

    The blood picture is characteristic in typical cases. The white cell count varies very rapidly and may reach tremendous figures. In one of our cases the count dropped from 503,600 to 146,400 in twelve days, then increased to 546,000 in the next nine days. Counts of 250,000 per cubic millimeter are not rare, though those below 100,000 are more frequent. The increase is chiefly due to neutrophilic cells, and these include great numbers of myelocytes, myelocytoid forms and early myeloblastic types. Cells resembling neutrophiles but with very fine and feebly-staining eosinophilic, basophilic or amphophilic granules are abundant in some cases. These are not normally present in human blood or bone marrow at any age, and are found normally only in certain lower vertebrates. Similar cells containing no granules and with amblychromatic protoplasm are occasionally found, and these may account for almost the entire increase in leucocyte count. The neutrophiles vary greatly in size, and in the same slide cells may be found which are 30 microns in diameter, 20 microns, and even 4 microns in diameter. Nuclear variations are mostly in the direction of the embryonic or the atavistic types. Senile types are occasionally found in chronic cases which are of slow development. Myelocytic and myeloblastic forms frequently show karyokinesis. Eosinophiles and basophiles are often greatly increased, varying between 2,000 and 15,000 per cubic millimeter but they may remain relatively or even absolutely normal in number. Both eosinophiles and basophiles sometimes show atavistic qualities, and immature, myelocytoid and myeloblastic forms are common. Ehrlich considered absolute increase in basophiles essential to a diagnosis of this form of leukemia. Blood in which the eosinophiles are abundant often develops Charcot-Leyden crystals on standing for an hours or a few hours. Small hyaline cells include varying numbers which give the oxidase reaction and are, therefore, really myeloid. Small lymphocytes are usually relatively diminished and actually increased. Large hyaline cells include many hyaline myelocytes and many endothelial cells. The large hyaline cell with intensely basophilic nucleus and cytoplasm containing fibrillae is rather common; the protoplasm is either feebly acidophilic or feebly basophilic. These cells are not found in normal embryonic or adult human blood or marrow and are normally found only in lower vertebrates. (Plate XII)

    Examination of a blood slide alone may give the diagnosis in typical cases. Ewing considers the finding of eosinophilic myelocytes with granules of varying size, form and staining pathognomonic. The finding of any considerable numbers of myelocytoid forms, especially the finding of several basophiles within a comparatively small area, should lead to further study of the blood. In one of our patients receiving treatment for neurasthenic symptoms, the leukemia was not suspected until the examination of a smear of blood showed many myelocytes. A differential count alone usually gives more definite information in leukemia than the actual count alone. The actual count of white cells alone cannot be considered diagnostic, because the white cells reach such high counts in pyogenic infections and in pneumonia.

    Atypical counts are not rare in leukemia. The actual count may drop to normal or even to a very low number. Under such conditions the presence of immature forms and myelocytes, and an excess of basophiles and eosinophiles may cause leukemia to be suspected. The blood picture may become normal in every recognizable manner in some cases, and this condition may persist even until death. More frequently the low counts are followed by increasingly high counts which show the usual blood picture. Sometimes an intercurrent infection, such as influenza, typhoid fever or malaria, may lead to diminished actual count; in such cases the differential count usually remains indicative of leukemia. Occasionally the intercurrent disease is fatal, and in such cases the autopsy may show abundant evidences of leukemia, or may show no signs whatever that leukemia had ever been present.

    With exhaustion of the hematopoietic tissues the granules disappear from many cells. The erythrocytopoietic areas also may become exhausted and the red cell picture may be that of aplastic anemia, or they may share in the hyperplasia and anaplasia in which case the red cell picture is that of pernicious anemia. The leucocytic blood picture remains almost or quite unchanged by the development of the anemic phase of the disease.

    The red cell count usually remains fairly normal during the early stages of the disease, especially in the chronic types.  Later there seems to be some increased destruction of the red cells, and always there is some anemia as the disease progresses.  The hemoglobin may be as low as 30% of the normal for the age of the patient, but is commonly between 40% and 60% in chronic cases.  In acute cases the hemoglobin may be 10% of the normal, or even lower.  No doubt this is due to the effect of the abnormal leucocytopoietic areas upon the erythrocytopoietic areas in the bone marrow together with the effect of the toxic katabolites of the abnormal leucocytes.  The hemorrhages which are so common in this form of leukemia also tend to produce secondary anemia.  The seriousness of the anemia does not bear any secondary anemia.  The seriousness of the anemia does not bear any recognizable relation to the seriousness of the leukemia, nor to the progress of the disease.  Patients with quite low red counts and lower hemoglobin may feel very well and show considerable improvement in the white cell counts, while others with either normal or low red cell counts may be extremely weak and toxic and may die.  Perhaps in no other disease does the symptom-complex bear less definite relations to the actual progress of the disease.

    Blood fibrin is increased.  The threads appear on the warm stage at once or within two minutes at most.  Beaded and irregular threads are abundant.  Threads radiating in long strands from debris are frequently found.  Net-like arrangements of fibrin threads are less common.

    Fibrinolysis is absent in all cases examined in our laboratories.  The blood volume is increased.  Ten cases were studied by Rowntree.  In all polycythemic hypervolemia was present.  The mean values were 109 cubic centimeters of whole blood and 69 cubic centimeters of plasma per kilogram of body weight.  The findings varied between 92 cubic centimeters and 125 cubic centimeters of whole blood, and between 65 cubic centimeters and 78 cubic centimeters of plasma per kilogram of body weight.

    Monocytic leukemia is a form of splenomedullary leukemia in which monocytes are greatly increased in numbers.  Usually this is a temporary condition, and ordinary myelocytes soon cause the usual findings of splenomedullary leukemia.

    Eosinophilic leukemia is a form of splenomedullary leukemia in which many eosinophiles and eosinophilic myelocytes are present.

    Basophilic or mast-cell leukemia is very rare.  The large granular basophiles or mast cells are present in large numbers.  It is often a terminal stage in splenomedullary leukemia.

    Plasma cell leukemia seems to be related to lymphatic leukemia.  Many of the large hyaline cells are of the plasma cell type.

    Aleukemic leukemia is probably always a stage in the uneven progress of Splenomyelogenous leukemia.  It should not be confused with aleukemic lymphoma.

    The following cases were selected because they illustrate the place osteopathic treatment has in the handling of cases of Splenomyelogenous leukemia.  Our records are too few for any definite conclusions, but they are suggestive, and they may point the way to methods far more efficient than those which have been previously employed.  Perhaps we may find that many cases in the initial stages can be cured and that, after the disease has become advanced beyond a certain point, no treatment is of any avail.  Since it has been fairly well proved, by reports from many laboratories, that one function of the spleen is the maintenance of a correct relationship between leucocyte development and leucocyte destruction, it is easy to see the steps in pathogenesis from a lesion of the ninth thoracic vertebra, abnormal relaxation of the splenic capsule, disturbed nervous control of the splenic blood vessels, disturbed functions of the spleen and disturbances in the control of white-cell destruction and development, with the leucocytopoietic tissues left completely uncontrolled.
    Megalomyelocytes and micromyelocytes containing eosinophilic, basophilic and amphophilic granules showing great variations in size.  Blood taken from patient with splenomedullary leukemia of atypical nature, two days before death.  Cells show distinctly atavistic characteristics.
    The following case history is typical of what seems to be a very early case of splenomyelogenous leukemia.  We have no reports of very early stages in this disease among the publications accessible, and only a very few in our own records.

    Mrs. J., aged 48 years, six years past the menopause, had been ordinarily well until an attack of influenza during July and early August of 1921.  She had received medical care during that attack and had been given an unusually severe course of drug therapy.  She was unable to learn the identity of the drugs given, but she attributed various gastric, nervous and cardiac symptoms to the medication received, and many of these symptoms disappeared very shortly after she refused further medication.  In November, 1921, she complained of insomnia, emotional instability and great weakness.  The following blood findings were reported on that date:
            Hemoglobin, 105 grams per liter; 89% of normal for age.
            Erythrocytes, 4,480,000; 80% of normal for age.
            Color index, .9
            Normoblasts about 10 per  Abnormal red cells few.
            Coagulation time 11 minutes; (normal for technique, 5 minutes).
            Leucocytes, 7,700 per
            Large hyaline                                                  12.8%              985 per
            Small hyaline                                                   28.4%              2187 per
            Mononuclear neutrophiles                                 3.4%                262 per
            Polymorphonuclear neutrophiles                      49.0%              3773 per
            Eosinophiles                                                      5.0%              385 per
            Basophiles                                                         1.4%              108 per
            Hyaline and granular myelocytes and endothelial cells, all present in small numbers.
            Neutrophile nuclear average 1.86 (normal, 2.45 to 2.55).
            Notes:  Atypical granules abundant in hyaline and granular cells.
            Immature and atavistic types abundant.
    Physical findings were negative except that the spleen was easily palpable.  A lesion of the ninth thoracic vertebra was present; no other definite spinal or costal lesions were found.  The lesion was corrected; symptoms disappeared.  During the next six years the blood remained normal.
    In such a case as this the ninth thoracic lesion should be corrected as the most important factor in therapy.  If the patient’s dietetic and other habits include any unhygienic factors these should also be corrected.

    Mrs. O., aged 43 years, history contains nothing of significance so far as the leukemia is concerned.  She appeared by the clinic of The Pacific College of Osteopathy complaining of weakness, insomnia, with “nervousness,” which seemed to mean emotional instability in her case.  A rather superficial flood examination was made Mar. 1, 1909, with the following findings:

            Hemoglobin, 57% (Dare).
            Erythrocytes, 4,920,000 per
            Leucocytes 20,000 per, with many myelocytes.

    April 2, 1909, the second blood examination was made and the findings were as follows:

            Hemoglobin, 50% (Dare).
            Erythrocytes, 4,296,000 per
            Leucocytes, 64,000 per
            Large hyaline                                                  3.6%               2,304 per
            Small hyaline                                                  16.4%              10,496 per
            Neutrophiles                                                    57.0%              36,480 per
            Eosinophiles                                                    12.4%              7.936 per
            Basophiles                                                         4.5%              2,880 per
            Basophilic myelocytes                                        2.5%                1,600 per
            Neutrophilic myelocytes                                      .8%                    512 per
            Eosinophilic myelocytes                                       .2%                    128 per
            Fractured and degenerated myelocytes                2.6%                1,664 per
            Unrecognizable forms, many.
    On physical examination the spleen was found enlarged to a point just below the umbilicus.  Color somewhat pasty, no jaundice.  Other findings negligible.  Lesion of eighth to tenth thoracic vertebrae with rigidity.  Many secondary lesions in which rigidity was not marked; the latter apparently secondary.  Diet and habits of living were found to be good and no change was advised.  Correction of the lesion was advised and this was the only treatment given.

    This treatment was carried on in the clinic for several weeks, during which time several blood examinations were made.  A gradual improvement in the insomnia and the weakness was noted within a week, then the spleen began to diminish in size and the leucocyte count diminished gradually, with diminishing numbers of myelocytes.  On May 11, 1909, the count was as follows:
            Hemoglobin                                                  56% (Dare).
            Erythrocytes                                                                4,464,000 per
            Leucocytes                                                                        11,520 per
            Large Lymphocytes                                       3.3%                380 per
            Small lymphocytes                                        15.7%             1809 per
            Mononuclear neutrophiles                              .6%                      69 per
            Polymorphonuclear neutrophiles                      75.0%              8640 per
            Eosinophiles                                                    2.1%                242 per
            Basophiles                                                       1.5%                173 per
            Myelocytes (all neutrophilic).                             1.8%                207 per

    At that time the spleen was just easily palpable. Symptoms were nearly gone except for some weakness due, no doubt, to the low hemoglobin.  The lesion had been corrected but it recurred after she had lifted some heavy articles at house-cleaning time.  Correction of the lesion the second time was easy and required only a few treatments.

    April 13, 1910, the blood count was as follows:

            Hemoglobin                                                   68%
            Erythrocytes                                                                 4,456,000 per
            Leucocytes                                                                          5,600 per
            Large hyaline                                                  3.8%               380 per
            Small hyaline                                                  30.8%              1725 per
            Neutrophiles                                                    62.2%              3483 per
            Eosinophiles                                                    1.2%                  67 per
            Myelocytes                                                      2.0%                 112 per
            Basophiles, very few (less than .1%)

    After this her history was uneventful until January, 1912, when she fell and broke both radius and ulna.  Feb. 26, 1912, her blood count was as follows:
            Hemoglobin                                                     53%
            Erythrocytes                                                                  3,576,000 per
            Leucocytes                                                                            7,100 per
            Large hyaline                                                  4.8%               3441 per
            Small hyaline                                                  35.0%              2385 per
            Mononuclear neutrophiles                                 .2%                      14 per
            Polymorphonuclear neutrophiles                        47.8%              4104 per
            Eosinophiles                                                       .9%                   64 per
            Basophiles                                                          .6%                   43 per
            Myelocytes (all neutrophilic)                                .7%                      50 per
    At this time the ninth thoracic lesion had not recurred, and the few myelocytes were attributed to the injury.  There was some general spinal rigidity.  The spleen was not palpable and the splenic dullness was normal in size.  Her diet had been somewhat deficient during the winter and she had been over-worked.  With rest, improved diet, and the relief of spinal rigidity during the months of March and April her condition improved again.

    May 10, 1912, the blood examination gave the following findings:

            Hemoglobin                                                  80% (Dare)
            Erythrocytes                                                                  4,476,000 per
            Leucocytes                                                                           9,100 per
            Large hyaline                                                  3.6%                328 per
            Small hyaline                                                  32.6%              2967 per
            Mononuclear neutrophiles                              1.2%                  109 per
            Polymorphonuclear neutrophiles                      62.0%              5642 per
            Eosinophiles                                                       .6%                  55 per
            Basophiles, very few
            Myelocytes, none

    During the years of 1912, 1913 and 1914 several blood examinations were made with about the same findings.  During 1914 she left the city and no further blood examinations were made.  In 1915 year health was not good, and no osteopathic attention was possible where she lived.  She had no blood examinations made.  She was able to be up, and helped with the housework and with house-cleaning on the last day of her life.  That night she died in her sleep.  After death hemorrhagic areas appeared upon the skin of the legs and arms, though no hemorrhages had even appeared during her lifetime.  The coroner signed a certificate of death from “heart disease.”

    Miss C.  Age 24 years.  History contains nothing significant; no definite symptoms.  While the diagnosis is not positive, the case is probably one of aleukemic leukemia.  Spleen and cervical lymph nodes enlarged moderately.  Four blood examinations made between June 30 and July 23.  These tests were made while the patient was on a uniform milk diet, resting in bed, and the blood was always taken at the same time of the day.  Red cell counts varied from 4,460,000 to 4,550,000, hemoglobin about 85%, with color index remaining at about .8 constantly  A few normoblasts and reticulated cells at each examination.

    Leucocyte counts varied from 3,600 to 4,400 per cubic centimeter not varying with red cell count.  The differential count presented only slight variations.  A typical report, based on the examination of 2,000 cells, is as follows:

            Leucocytes,                                                                           4,000 per
            Large hyaline                                                  4.4%               176 per
            Small hyaline                                                  24.6%              984 per
            Mononuclear neutrophiles,                    less than .1%
            Polymorphonuclear neutrophiles                  54.0%              2160 per
            Eosinophiles                                                       .8%                   32 per
            Basophiles                                                         .2%                      8 per
            Neutrophilic myelocytes                                   1.0%                     40 per
            Eosinophilic myelocytes, few
            Large hyaline myelocytes, including gigantoblasts  5.0%               200 per
            Small hyaline myelocytes                                   10.0%              400 per

    On examination the moderately enlarged spleen and cervical lymph nodes were found; also a lesion involving the ninth and tenth thoracic vertebrae associated with marked rigidity, and several other lesions in which the rigidity was much less pronounced.  The time when the lymphatic enlargement began was not known, nor was there any injury which might have caused the lesion definitely known.  The patient had had several falls while riding horseback, during the fifteenth to the seventeenth year of her life, and these might have caused the spinal condition.

    She did not receive osteopathic treatments and her further history is not known.

    In the later stages of Splenomyelogenous leukemia the myelocytes become so fragile that satisfactory counts of the white cells are very difficult and may be impossible.  Fragments which are the remains of myelocytes undergoing degeneration within the blood vessels, and even more rapidly as the blood is withdrawn for counting, obscure other elements in the smear, and irregular nuclear masses as well as protoplasmic fragments obscure the fields in the counting chamber.  Myelocytes cannot be satisfactorily classified because the hematopoietic tissues seem to become unable to develop granules; occasionally a very few, feebly staining granules may be found in cells with feebly staining, ragged protoplasm and with nuclei which present atypical forms and atypical staining reactions.  Nearly all of the cells show scanty protoplasm of somewhat irregular consistency and staining surrounding roundish, rather large, feebly staining nuclei.  Megakaryocytes are occasionally found and these are easily recognizable.  Normoblasts, megaloblasts, poikiloblasts, microblasts and erythroblasts are abundant, and the predominance of megalocytes and megaloblasts with the abundant fragmentation may strongly suggest the terminal stages of pernicious anemia.  In one of our cases, seen the first time only a few days before death, it was impossible to secure either a white cell count or a red cell count because of the abundant debris.  The examination of the smears gave findings equally suggestive of pernicious anemia, lymphatic leukemia and Splenomyelogenous leukemia.  A diagnosis of splenomyelogenous leukemia was made on the history of the case and the physical findings, together with the fact that the blood examination did not eliminate this disease.
         Lymphatic leukemia may be either chronic or acute.  Both forms are characterized by the great abundance of hyaline mononuclear cells in the blood stream.  Many of them really are lymphocytes.  Others are myelocytes of atypical of atypical form while still others are reversionary types.  Usually one certain type of cell predominates in each case.  The most common form is a small hyaline cell with a round nucleus in which there is often a wheel-like arrangement of chromatin.  The protoplasm of this cell is scanty, feebly or intensely basophilic and the edges of the cytoplasm are often ragged or frayed.  While this cell predominates, in the most common form of lymphatic leukemia, it is by no means the sole abnormal cell.  Other cells usually associated with this include many myelocytoid forms.  A peculiar, large, hyaline cell with scanty protoplasm and feebly staining, round, or oval nucleus eccentrically located is frequently present.  The protoplasm of this very large cell sometimes presents a rather granular appearance but no true granules are present.  The cytoplasm may be feebly basophilic or feebly eosinophilic.  In other cases a medium sized hyaline cell may predominate; in still others the most abundant cell is very large, round and of the endothelial type.  (Plate XIII)

    The leucocyte counts are not generally so high as in the splenomyelogenous type of leukemia, but they may exceed 200,000 per cubic millimeter.  Usually they vary around 100,000 cells, of which from 80% to 99% may be small hyaline cells.

    The neutrophilic granular cells are usually greatly diminished.  Eosinophiles may be absent altogether.  Myelocytes are not present in the blood in typical cases.

    In lymphatic leukemia the blood volume is normal or increased.  The findings varied between 87 cubic centimeters and 114 cubic centimeters of whole blood, and between 33 cubic centimeters and 46 cubic centimeters of plasma for each kilogram of body weight in four cases studied at the Mayo Clinic by Rowntree.

    Periods of ten occur during which the white cell count drops to normal or very near normal.  During these periods the differential count usually shows some relations suggesting the disease.

    An intercurrent infectious disease may cause neutrophilic reaction on the part of the red bone marrow and the leukemia disappear.  When death occurs during the intercurrent infection, there may be no post mortem evidence of the characteristic findings of the leukemia.  When pregnancy occurs during chronic leukemia the blood may return to normal.  Within a few weeks after labor the leukemia recurs.  If death occurs during pregnancy or labor the necropsy may show no evidence of leukemia.

    The bone marrow shows about the same changes on gross examination in lymphatic and in splenomyelogenous leukemia.  In the lymphatic form, however, the cells found on microscopic examination are chiefly small hyaline cells, mostly lymph cells.  These apparently have invaded the bone marrow.  However, the normal bone marrow contains small areas of true lymphoid tissue, and the hyperplasia of these areas may be the source of the cells found so abundantly in the bone marrow.

    The lymph nodes in lymphatic leukemia are usually considerably enlarged.  The increase in size is due to an overwhelming abundance of the cells predominant in the blood (usually small hyaline) there is no associated hyperplasia of connective tissue.  Occasionally none of the lymph nodes is recognizably enlarged and the sole site of lymphoid hyperplasia is in the bone marrow.

    The spleen may or may not be greatly enlarged in lymphatic leukemia.  In one of our cases the spleen extended into the pelvis on the left side, and beyond the umbilicus on the right; its dull area extended to the liver dullness.  On X-ray examination the diaphragm was found to be pushed upward by the enlarged spleen, so that the lungs were subjected to considerable pressure.  In other cases there is no recognizable enlargement of the spleen on physical or X-ray examination, though usually some slight enlargement is found at autopsy.  The enlargement of the spleen, when this is present, is due to the same pathological changes as those found in the enlarged lymph nodes.

    The pathogenesis of lymphatic leukemia is unknown.  In fowls there is an infectious disease which causes either lymphatic or myeloid leukemia, and both these forms seem very much like the leukemias of human beings.  There is no evidence that lymphatic leukemia is infectious in the human form.  No vertebral lesions have been identified with the disease, and there is no evidence that the correction of such lesions as may be found present in the cases so far reported has exerted any effect upon the progress of the disease. As in other incurable diseases, very often the correction of such lesions as may be found on examination gives considerable relief to the patient and improves the health in general. Symptoms due to the disease itself are often relieved by correction of local tension of the tissues and other palliative manipulations.

    According to Fox, the lymphatic adenopathies may be classified according to the  reaction of neutrophiles to radiation treatments.  The leukemic group, including chronic lymphatic leukemia, sublymphemic adenosis and leukosarcoma, is characterized by a neutrophile count both relatively and absolutely low, and which decreases as a result of radiation.  The sarcoma group, including aleukemia adenosis (aleukemic leukemia) and lymphosarcoma, is characterized by a neutrophile count which does not vary greatly from normal, and in which the neutrophiles are diminished only slightly or not at all by radiation.  In the first group unwise radiation may so reduce the neutrophiles as to diminish immunity and prevent neutrophilic reaction to infections.

    Since the publication of Fox’s report our cases have all had radiation and other methods of treatment before our first counts, or have been unsuitable for study for some other reason.

    This is rather a rare disease.  It occurs especially in children and is occasionally associated with tumors of the thymus gland.  The disease usually begins with sore throat.  Enlarged tonsils, moderate or high fever, pharyngeal ulcers, stomatitis, nausea, diarrhea, vomiting, subcutaneous and submucous hemorrhages, dyspnea, anemia, all follow in order within a few days.  The serious nature of the disease is usually manifest at once.  Very rarely improvement occurs and the disease becomes chronic.

    The disease progresses very rapidly and death may occur within a few days of the first appearance of symptoms.  Small hyaline cells may make up 99% of a total count of 20,000 to 1,000,000 cells per cubic millimeter.  The red cells are greatly diminished, and often the red cell count is less than the white cell count.  Nucleated red cells are abundant.  Falling white cell counts precede death.  No cases under osteopathic treatment have been reported.

    Death usually occurs within three months at most after the first symptoms.

    Recoveries have been reported for cases of acute lymphatic leukemia occurring in adults.  Treatment has included many drugs.  Spontaneous recoveries have been reported; also recoveries following acute infectious processes.  Since the diagnosis is usually not made until the patient seeks medical attention it is not possible to say how many cases recover without such treatment.
    N, this abnormal cell is of the same size as normal small lymphocytes.
    N.L.  This abnormal cell is of the same size as normal large lymphocytes.
    Note the great variations in size and in nuclear positions.  This blood was taken ten days before death from gastric hemorrhage.

    Chronic lymphatic leukemia is a disease of the blood characterized by insidious onset, vague and indeterminate symptoms, enlarged lymphatic glands and the presence of greatly increased numbers of lymphocytes in the circulating blood.  Pigmentation, urticaria and attacks of severe itching often occur.  Irregular fevers and a tendency to neurotic symptoms are frequent.

    One noticeable feature which appears after the disease has become well-established is the presence of miliary tumors which arise from the enlargement of the subcutaneous lymphoid masses, normally only microscopic in size.  These may break down into ulcers.  The tonsils are usually enlarged and are frequently inflamed.  In the later stages anemia may become severe.  Hemorrhages, usually ecchymotic, may be submucous or subcutaneous.

    In the few cases which have been treated by osteopathic physicians the bony lesions and the reflex muscular contractions are so varied that no structural etiological factors can be given at this time.  The cause of lymphatic leukemia is unknown.

    The symptoms are rather vague and mild in the beginning of the disease.  Sometimes the enlargement of the glands of the neck, axilla or groin is first noticed.  Weakness, short breath or insomnia, pain in the limbs like sciatica, muscular rheumatism or brachial neuralgia are common early symptoms.  This pain is localized according to vertebral lesions affecting the spinal segments from which the painful areas are innervated.  The correction of these maladjustments exercises a palliative effect upon the pain.

    The nausea, diarrhea and other gastro-intestinal symptoms bear little or no relation to the time of eating or the variety of food which is taken.

    Lesions involving the mid-thoracic area are present when digestive symptoms are marked and the correction of the lesions as found relieves the symptoms.  Permanent relief is not secured, however, and the patient returns with the same or other symptoms because of the progress of the disease itself.

    The physical examination shows the enlarged lymphatics, sometimes pallor, rarely a slightly weakened heart-action.  After anemia has been well advanced hemic murmurs may appear.  A dull area over the sternum may be due to the presence of a persistent thymus, or to enlarged bronchial lymphatics.  The spleen is usually slightly enlarged.  The muscles of the abdomen are often flabby and intestinal atony is then present.  Gastro-enteroptosis often is found early in the disease when lesions of the sixth to the tenth thoracic vertebrae are present.

    The urine shows an increase in the uric acid in relation to the urea, sometimes slightly excessive indican.  In the later stages albumin, casts, and kidney cells may appear.  The blood contains high uric acid and creatinin.

    The blood in the early stages shows normal hemoglobin and erythrocyte count.  The color index is likely to be low, even in the early stage, and normoblast may often abe found while there is still no sign of anemia.  The small lymphocytes are at first relatively increased; later the increase is absolute and it may reach a total of more than a million small lymphocytes in a cubic millimeter of blood in the later stages.  After the disease has become well-established the lymphocyte percentage is very high.  A few cases are on record of 99% of lymphocytes.  Even from the beginning there is a tendency to a return to immature types in the blood cells.  This is shown by basophilic reticulation of the erythrocytes, various nucleated forms and somewhat more than the usual variations in size and shape of erythrocytes.  A slightly increased number of mononuclear neutrophiles is present.  The nuclear average of the polymorphonuclear neutrophiles is low.  The eosinophiles include more than the usual number of mononuclear forms.  Rarely true myelocytes may appear.  (Plate XIII)

    Fibrinolysis is absent.  The fibrin forms normally on the warm slide.

    The blood in the later stages of chronic lymphatic leukemia greatly resembles that of acute lymphatic leukemia.  The hemoglobin and erythrocyte count are greatly diminished, sometimes to below 20% of the normal findings.  The color index is always low, sometimes below 0.5.  The white cell count is very high, often surpassing the red cell count, though the number of white cells is usually less than the number found in spleno-medullary leukemia.  Great numbers of large hyaline, basophilic myelocytes are present as in the acute form of the disease.

    The disease is rarely recognized in the early stages because blood examinations are not often made in general practice for patients suffering from the symptoms given above.  In clinics and hospitals where the blood examination is made as a routine procedure the earlier stages of the disease often evade recognition because patients are not likely to come under care until the disease is well-established.  A lymphocyte count of 5,000 per cubic millimeter or more, occurring in an adult, should arouse suspicion of beginning lymphatic leukemia.  The blood should be watched in all such cases and the condition of the lymphatic glands investigated in order to make as early a diagnosis as possible.  After the disease is well-established, with a high lymphocyte percentage and a high leucocyte count, the enlarged lymphatic glands and the progressing weakness, pain and gastro-intestinal symptoms usually make the diagnosis very easy.  It is distinguished from Hodgkin’s disease by the lymphocyte count; from splenomedullary leukemia by the high lymphocyte percentage, from the anemias by the lack of the pathognomonic erythrocyte changes and the presence of the lymphocytic increase; from acute lymphatic leukemia by the slow and insidious onset and milder symptoms.

    No rational treatment for the disease can yet be given.  The symptoms can be relieved by the treatment adapted to each as it occurs.  The correction of the vertebral lesions usually relieves the pain.  Very gentle massage of the affected areas and rest of the painful joints may be helpful. For the gastro-intestinal symptoms the correction of the lesions is usually efficient, sometimes temporarily, sometimes permanently.

    There is no one diet that is particularly suitable for these cases but every patient is a law to himself.  Generally speaking it is better to limit the purins considerably.  The rapid growth and destruction of the white cells fills the blood with nuclear derivatives, as is apparent from the increase in the uric acid and other purin bodies in the blood and urine.  The pressure of clothing or other factors of irritation to the affected glands must be avoided.  Generally speaking, the hygienic conditions should be good and the surroundings pleasant, wholesome and comfortable in every way.

    The insomnia is best met by osteopathic treatment for the relief of cerebral congestion.  Baths of suitable temperatures, plenty of fresh air and such educational measures as are necessary to keep the mental state of the patient normal, are helpful.  It is perhaps needless to insist that drugs are absolutely to be forbidden in the treatment of these diseases.

    The use of the X-ray and of radium have been advised in the treatment of this as of other leukemias.  A few recorded cases seem to indicate that these treatments are of some value; in others the progress of the disease seems to be more rapid under their influence than before the treatment was begun.  Since the progress of the disease varies irregularly it is difficult to determine the usefulness of such treatments.

    It is not yet possible to make any absolute statement as to prognosis under the osteopathic treatment.  A few cases which have been recognized by osteopaths while the disease is yet in its early stages have seemed to improve as the result of the treatment as outlined above.  None has been under observation long enough to warrant any conclusions.  From the medical standpoint such cases are hopeless from the beginning.  Nothing can exercise more than temporary delay in the progress of the disease.  Surgically no help is to be expected  The removal of the spleen or of the enlarged glands in the neck, axilla and groin is usually followed by a more rapid hypertrophy of other glands in the body.

    The disease is frequently complicated by kidney and cardiac diseases and by various pulmonary infections.  Death often occurs from pneumonia, nephritis or some other intercurrent disease.  The chronic form sometimes passes suddenly into acute type and death occurs within a few days to a few months.

    The relation between chronic and acute lymphatic leukemia is probably of the same nature as that between fibroma and sarcoma or between adenoma and carcinoma.  So long as the blood cells include only somewhat increased numbers of lymphocytes of the adult type no immediate danger is to be feared.  But when the lymphocytes increase rapidly and when cells of the fetal or the myeloid type appear the terminal stages are imminent.

    The following patient with chronic lymphatic leukemia terminating in the fulminating form had a fairly typical blood count.  Mr. H., a man of sixty-three years, first noted that the glands of the neck were enlarged several years ago; the exact date was not remembered.  The swellings appeared, then diminished, then reappeared; finally they persisted and increased.  In December, 19221, the neck was not very noticeably enlarged though the glands were hard and easily palpable.  X-ray examination showed the thoracic lymphatic nodes all enlarged.  Small nodules were present all over the body in irregular masses.  The spleen covered more than one-third the surface area of the abdomen.  Feverish attacks occurred at very irregular intervals, so that some suspicion of atypical malaria had arisen.  Except for these feverish attacks and some slight sense of weakness there were no subjective symptoms.  The history was negative except as stated.  The first blood examination was made Dec., 27, 1921, with findings as follows:

            Hemoglobin, 77.3 gms. Per liter, 72% of normal for age.
            Erythrocytes,  3,600,000 per, 56% of normal for age.
            Color index .78
            Poikilocytes, abundant
            Microcytes present
            Megalocytes, few
            Normoblasts, 800 per
            Poikiloblasts, few
            Microblasts, few
            Megaloblasts, 700 per
            Hemoconien, increased considerably.
            Leucocytes, 400,000 per
            Large hyaline cells                                            .8%                  3,200 per
            Small hyaline cells                                          45. %               180,000 per
            Mononuclear neutrophiles                                 .1%                         400 per
            Polymorphonuclear neutrophiles                  3.8%                 15,200 per
            Eosinophiles                                                       .2%                      800 per
            Basophiles                                                          .1%                      400 per
            Myelocytoid forms, protoplasm degenerated            50. %               200,000 per
            Fibrinolysis absent.  Warm stage examination difficult because the small hyaline cells and myelocytes obstruct vision of the more active cells.

    The second blood examination, Jan. 18, 1922, gave the following findings:

            Hemoglobin 85.6 grams per liter; 75% of normal for age.
            Erythrocytes 3,776,000 per, 62% of normal for age.
            Color index .83
            All abnormal red cells less abundant than before.
            Leucocytes                                                                              370,000 per
            Large hyaline                                                  3.0%               11,100 per
            Small hyaline                                                  70.0%              259,000 per
            Mononuclear neutrophiles                                  .2%                         740 per
            Polymorphonuclear neutrophiles                  6.5%               24,050 per
            Eosinophiles                                                       .3%                 1,110 per
            Basophiles, very few
            Myelocytoid and atypical                         20. %               74,000 per
            General appearance of the cells improved; less evidences of toxicity and a larger proportion of normal forms among both red and white cells.

    Chemical tests made Jan. 18, 1922, were as follows:
            Total non-protein nitrogen,                       40  mgs. per 100 c.c.                   35
            Urea                                                     20 mgs. per 100 c.c.                  18
            Creatinine                                             1.9 mgs. per 100 c.c.                           1.9
            Uric acid                                          10. mgs per 100 c.c.                  3-4
            Sugar                                                 130. mgs. per 100 c.c.                        100
            Carbon dioxid combining power  69. mgs per 100 c.c.                  70-75
    The third blood examination was made April 12, 1922, as follows:

            Hemoglobin 77.0 grams per liter; 71% of normal for age.
            Erythrocytes 3,552,000, 56% of normal for age.
            Color index .8
            Poikilocytes, microcytes, megalocytes, normoblasts, microblasts, poikiloblasts, megaloblasts, all present; megalocytes more abundant than microcytes; megaloblasts more abundant than normoblasts.
            Leucocytes, 500,000 per  Differential count difficult on account of the abundant reversionary and atypical forms, and on account of atypical staining reactions and the speedy degeneration of many forms of cells.  Fragmented cells and naked nuclear masses were abundant.  The following figures were secured with difficulty:
            Large hyaline                                                    .34%                1,700 per
            Small hyaline                                                  80.0%              400,000 per
            Mononuclear neutrophiles                                 .06%                       300 per
            Eosinophiles                                                      .78%                  3,900 per
            Basophiles, very few
            Myelocytoid and atypical                         18.8%              94,000 per

    The cells degenerated very rapidly on the warm slide, but smears fixed immediately as the blood left the capillaries showed also a great abundance of degenerated cells, so that the processes of degeneration were evidently occurring within the blood vessels.  In May, 1922, Mr. H. left the city.  His death was reported in July of that year.

    In this case no definite bony lesions were present. No adequate etiological factors could be found, either in the structural relations, the hygiene, or the clinical history of the patient to account for the condition.  So far as history could be secured and so far as any laboratory diagnosis or physical examination could determine, there was only an ordinary history of the life of an ordinary farmer in good circumstances.  His work had not been exhausting and his diet and his habits were wholesome.

    Some few areas of slight rigidity were found on examination and the treatments were devoted to relieving these.  Some slight dietetic changes were advised.  These methods were followed by the slight general improvement noted at the second blood test.  The inadequacy of these methods so far as affecting the progress of the disease was concerned was recognized by the osteopathic physician in charge of the case, and only symptomatic good results anticipated.

    Until further study has clarified our understanding of the nature of such cases as this, palliative measures only can be employed.

    This disease remains essentially unexplained.  It presents the characteristics of a granuloma involving lymphoid tissues almost or quite exclusively.  The cornybacterium Hodgkini was at one time supposed to be the etiological agent.  Several other etiological agents have been described.  It has been reported in young children, even in babies three months of age.  These cases are acute and death is rarely delayed for more than a few weeks after the first symptoms appear.  It has been supposed to be an aberrant form of tuberculosis of the lymph glands.  Several authors have considered it to be really a neoplasm.  None of these hypotheses has been verified.

    Usually the lymph nodes of the neck are first enlarged, then other lymphoid tissues are affected in turn.  Sometimes the enlargement appears first in other lymph nodes of the body, and occasionally several widely separated areas may be affected at the time.  Always the lymphoid tissues are affected; metastases in tissues not containing lymphoid tissue are extremely rare, and usually the disease follows some chain of lymph nodes in its extension.  Symptoms are indeterminate.  There is no pain in the affected lymph nodes unless adjacent nerve trunks or sensitive tissues are subjected to the pressure of the enlarged lymph nodes.  Weight is not usually affected.  There is some weakness and late in the disease toxic symptoms occur.  Remissions are common but death from the disease is inevitable unless life is terminated by some intercurrent acute disease or by accident.

    Hodgkins disease may begin insidiously with no recognizable symptoms before the glandular enlargement is noticed.  Often an attack of pharyngitis or tonsillitis or some other acute infection seems to initiate the disease.  Itching of the skin is often very distressing.  Bronzing suggesting Addison’s disease often occurs.  Cough and dyspnea may be due to intrathoracic lymphatic enlargement.

    Acute Hodgkins disease may cause death within a few weeks.  Chronic Hodgkins disease with atypical symptoms may not be recognized during life, and death be due to intercurrent disease.  At autopsy the condition is recognized.

    More commonly the disease is moderately chronic and death results from it within two to five years.

    The changes in the lymph nodes are characteristic, and in many cases only a biopsy of an enlarged lymph node determines the diagnosis.  The microscopic picture varies with the progress of the disease in any given node, and if several nodes in different stages of involvement are examined the various stages of the disease can be recognized.

    In the earliest stage the only change in the lymph node is an increase in the number of small hyaline cells.  This stage does not indicate the nature of the disease since the same changes might be found in any chronic infection involving lymphoid tissue.

    Next there occurs a great hyperplasia of the reticulo-endothelial cells with the development of masses of large round cells, very feebly basophilic, with large rounded vesicular nuclei.  These cells are pathognomic.  They are not found so abundantly in any other disease.  Associated with these are the multinuclear and very large cells called “Dorothy Reed” cells.  These contain four to a dozen or more roundish nuclei crowded together; the nuclei are intensely basophilic.  At this stage there are usually many mononuclear and polymorphonuclear eosinophiles.  In no other disease of lymphoid tissue are the eosinophiles of the lymph nodes so abundant and so immature in structure.

    The connective tissue cells of the trabeculae of the lymphoid tissue show increasing hyperplasia.  In the later stages of the disease the connective tissue crowds out the other cells so that only a small mass of scar-like tissue remains at the site of the lymph node.

    The spleen is rarely affected early in the disease.  In later cases the spleen shows rather a patchy involvement so that on microscopic examination the cut spleen shows areas of a suet-like or fatty appearance in which the changes found in the lymph nodes are recognizable on microscopic examination.

    The thymus, bone marrow, mesentery and other parts of the body in which lymphoid tissue is normally present may become involved in the disease.

    The blood picture is not distinct, but by repeated and careful examinations it is often possible to determine the diagnosis without biopsy of a lymph node.  Eosinophiles are usually increased moderately and they may reach remarkably high numbers; hyaline cells are relatively increased; large hyaline mononuclears are considerably increased; endothelial cells are present in varying numbers and these are often of abnormal type, being derived from the cells of the affected lymphoid tissues.  It is not often possible to find these abnormal cells in a differential count of the ordinary type, but on making a differential count of two thousand to four thousand cells the abnormal cells are apt to be found in sufficient numbers to warrant at least a tentative diagnosis of Hodgkins disease.  The blood platelets are usually increased, sometimes to five hundred thousand per cubic millimeter.

    Anemia occurs after the disease has been present for some weeks or months.  This is usually secondary in type, but occasionally the anemia may resemble the chlorotic or the pernicious form.

    Leukemia often follows or is associated with the later stages of Hodgkins disease.

    Miss A., late stage with leukemic symptoms.  Death in October.  Blood count in March with a differential count based on examination of 3,000 cells.

            Hemoglobin 87 grams per liter; 60% of normal
            Erythrocytes 4,000,000 per cubic millimeter, 80% of normal
            Color index  .6
            Poikilocytes abundant
            Microcytes, abundant
            Megalocytes, none
            Normoblasts, 20 per cubic millimeter
            Other abnormal red cells, none
            Leucocytes                                                                              13,000 per
            Large hyaline                                                  4.0%                    960 per
            Small hyaline                                                  6.0%               1,440 per
            Mononuclear neutrophiles                              3.3%                    792 per
            Polymorphonuclear neutrophiles                  77.0%              18,480 per
            Eosinophiles                                                    9.7%                 2,328 per
            Basophiles and Amphophiles, very few
            Hyaline myelocytes and reticular cells, abundant
            Granular myelocytes, very abundant
            Endothelial cells, many
            Degenerated forms, unrecognizable, few
            Neutrophile nuclear average 1.47
            Leucocytes began to move after three minutes on the warm slide.
            Neutrophiles moved very feebly.  Hyaline cells showed no activity.
            Eosinophiles showed greater activity than normal.
            Immature and reversionary forms abundant.
            Fibrin threads long, heavy, formed completely at once.
            Fibrinolysis absent
            Serum tinged with a pigment which does not give reaction for bile and is probably a derivative of hemoglobin.
            Gregariousness marked.

    There are several conditions which show atypical symptoms or atypical blood findings.  In some instances these may be merely symptom-groups, in others the same disease has probably received different names by different authors.  No satisfactory pathogenesis is known.  Studies made of these diseases in our laboratories have not resulted in any satisfactory understanding of the conditions.  Very much more study is necessary in order that these various symptom-groups may be classified and their etiological and pathological relations explained.
    Occasionally the blood picture in leukemia includes many small hyaline cells and also many myelocytes and myeloblasts.  Basophilic and eosinophilic myelocytes are also present, but less abundantly than in typical splenomyelogenous leukemia.  This form of leukemia has been found in early cases.  Many myelocytes are frequently found in the late stages of lymphatic leukemia, and a diagnosis of mixed leukemia should not be made when the first examinations are made for a patient apparently near death, or in whom anemia is very profound.  In late cases of splenomyelogenous leukemia many very small hyaline myelocytes are present.  These are to be differentiated from lymphocytes only by the oxidase reaction; even when this test is employed there may be errors due to the fact that in exhaustion of the bone marrow the oxidizing ferment may be absent from many cells and especially from the immature forms.  So a diagnosis of mixed leukemia should not be made in any case unless the first blood examinations are made before any evidences of marked anemia or of exhaustion of the bone marrow appear.

    In children very acute leukemias are characterized by many hyaline and many myelocytic forms, so that it may not be possible, even at necropsy, to differentiate between the lymphatic and the splenomedullary types.

    Leukanemia is a disease usually secondary to some very severe infection such as severe malaria or pyogenic infections; or to some severe cachectic disorder, such as cancer of rapid growth; or to repeated injuries or hemorrhages which make great demands upon the hematopoietic tissues.

    In late stages of either lymphatic or splenic leukemia there may occur an anemia of the pernicious type.  In late stages of pernicious anemia there may be marked leucocytosis with abundant myelocytes.  When the patient is first seen after the development of the conditions, a diagnosis of leukanemia may be the only one possible.

    The reed blood cells show the changes characteristic of pernicious anemia.  The white blood cells show the changes typical of either lymphatic, splenomyelogenous or mixed leukemia.

    Status lymphaticus is a congenital anomaly in which there is some developmental defect of the autonomic nervous system, certain ductless glands, the bones and the circulatory system.  The thymus fails to atrophy and the child is seriously injured by relatively insignificant poisoning, injury or nervous shock.  Sudden deaths during anesthesia or as a result of comparatively trivial injuries are common among these children.  The administration of serums is especially dangerous to them.

    The blood shows relative and often absolute lymphocytosis, with increase in the number of large hyaline cells and endothelial cells.  The hyaline cells reached 70% of the total leucocyte count in several of our cases.  Red cells, hemoglobin and fibrin are normal in uncomplicated cases.

    This is a form of leukemia in which there are metastases in bones, most commonly of the skull of the orbital region.  Exophthalmos is a common symptom.  The tumors produced by these metastases present a greenish tint, hence the name.

    The blood shows the characteristics of splenomedullary leukemia.  Cases with the findings of lymphatic leukemia have been reported, but these were probably late splenomedullary leukemia with a large number of hyaline myelocytes of immature type.  The leucocyte count may be only moderately increased, or may reach 500,000 or more.  The myeloblasts are more common than myelocytes in typical cases.

    A peculiar tendency associated with the tumors of chloroma is an associated hyperplasia of the tissues invaded by metastases.  The invasion of the skull by metastases may produce pressure on the brain with symptoms referable to the area affected. Metastases in the long bones may be associated with spontaneous fractures of the weakened bones.

    The disease is usually acute and death occurs within a few months from the time of the first noticeable symptoms.  No treatment has any satisfactory effect.

    Aleukia is a peculiar condition associated with aplasia or atrophy of the red bone marrow.  The granular leucocytes are greatly diminished.  The red cells present the usual findings noted in aplastic anemia, with no evidence of regeneration.  Blood platelets are greatly diminished.  Subcutaneous and submucous hemorrhages are abundant and death often occurs from gastric or nasal hemorrhage.  Death usually occurs within a few days after the first hemorrhage.  No treatment has any good permanent effects.  Transfusion of blood sometimes delays the inevitably fatal outcome.
    Occasionally there is enlargement of the lymph nodes with symptoms of lymphatic leukemia, but the blood itself shows no lymphemia.  In such cases a careful study of many slides usually finds a few abnormal large hyaline cells.

    Anemia of the secondary type is usually present. Fibrinolysis is absent.

    Aleukemia lymphoma may be an early stage or an intermission in lymphatic leukemia, or it may be unassociated with leukemia at any time.  Anemia of secondary type is usually present. Rarely the blood seems normal.  The nature of the disorder is unknown.

    This is a disease which is most common in children.  It is characterized by irregular attacks of fever or feverishness, with swelling of the lymph nodes.  The disease itself is chronic but the separate attacks are acute and may be quite severe.

    The blood shows typical findings.  The hyaline cells are considerably increased, both actually and relatively, and many atypical forms are present.  These include—

    Immature lymphocytes in which the chromatin is arranged in fine masses with a delicate network between them.  Sometimes one to three nucleoli are present.

    Abnormally large lymphocytes which are apparently derived from the germinal centers of the lymph nodes and the spleen.

    Monocytes of atypical staining, containing azure granules in scanty protoplasm which is either very deeply or very feebly basophilic.

    Hyaline myelocytes which sometimes contain a very few small, feebly eosinophilic granules and which give the oxidase reaction.

    The red cells are normal.  Hemoglobin may be slightly diminished.  Fibrin is scanty.  The coagulation time is somewhat prolonged.

    The attack usually begins with a mild degree of malaise and feverishness.  The lymph nodes of the neck may enlarge slightly.  Other lymph nodes rarely increase in size.  Moderate splenic enlargement occasionally can be found.  The thymus often persists in children subject to glandular fever, sometimes into adolescence.

    No vertebral lesions are found of etiological importance, except that such lesions lower resistance generally.  The children subject to glandular fever usually do have vertebral lesions, but these vary from week to week.  There is an associated weakness of the ligaments of the entire body, in many cases.

    Osteopathic treatment devoted to such structural abnormalities as can be found often relives the attack and hastens the ultimate disappearance of the attacks.

    During adolescence the attacks diminish in severity and in frequency until they do not occur at all.

    This is a disease of early or late middle life, and is most common among women.

    The disease is initiated by a high fever and the development of ulcers, resembling those of diphtheria, in the throat.  Rarely the vagina, intestines, skin and cheek show the ulcers.

    On blood examination the neutrophiles are found absent or present only in very small numbers.  A high percentage of large mononuclear cells with finely granular, feebly basophilic or feebly eosinophilic protoplasm is found.  The total leucocyte count rarely exceeds 4,000 cells per cubic millimeters of blood and counts of less than 1,000 cells are common.  Lymphocytes are present in normal numbers absolutely but are relatively increased because of the low total count.  The red blood cells are not perceptibly affected.

    No cases have been reported under osteopathic care.

    Death is to be expected within a few days after the onset of the symptoms.

    By several authors this is not considered an independent disease.  It has been considered identical with the glandular fever of children, with infectious mononucleosis and with monocytic leukemia of fulminating type.

    It occasionally occurs that the red bone marrow fails to meet the demands made by any very severe infections.  Instead of neutrophilic leucocytosis the neutrophiles diminish or even disappear; and there is a marked increase in the mononuclear cells of the blood.  These cells are myelocytoid, have large, round, vesicular nuclei, and their protoplasm presents a peculiarly granular appearance though no true granules are present.  The protoplasm is feebly basophilic or feebly eosinophilic, and in many slides it is possible to find both tints present in adjacent cells.  The origin of the cells is not known.  The disease has been identified with agranulocytic angina by several authors.

    Ulcers are not always present but some very severe infection is invariably the circumstance which initiates the abnormal state of the blood.

    No cases have been reported in osteopathic practice.

    Recovery is not to be expected.  Death usually occurs within a few days or a few weeks, at most.

    Myeloma (Kahler’s disease) is a tumor of bone marrow, very malignant, with abundant metastases.  It usually begins in the vertebrae or the ribs and extends rapidly to other parts of the skeleton.  Aching is the first symptom in most cases.  Cachexia, severe pains, paralysis and death follow during a few months.

    The blood shows secondary anemia with changes in the cells which seem to depend upon the character of the tumor.  The blood may show the picture of pernicious anemia, of splenomedullary leukemia or of secondary anemia with only a few nucleated red cells and a few myelocytes.  Eosinophiles are usually increased, as in any disease of the red bone marrow.  The presence of the Bence-Jones albumose in the urine is an important factor in diagnosis.

    Any malignant neoplasm may invade the red bone marrow and produce similar symptoms including the presence of the Bence-Jones albumose in the urine.  In such cases the blood shows the picture associated with the malignant neoplasms plus an unusual number of myelocytes, eosinophiles and nucleated red cells.

    Multiple Myeloma has been reported for a gopher (Citellus grammurus) by Fox.

    Sarcoma may arise in any lymph node.  The cells show abundant and often irregular karyokinesis.  The capsule of the node is invaded and the cells escape into surrounding tissues, as in any other malignant neoplasm.  Metastases are abundant, and they tend to invade other lymphoid tissues rather than non-lymphoid areas.

    When the cells are small, resembling small lymphocytes, the tumor is called malignant lymphocytoma, or small round cell lymphocytoma.

    When the cells are large and have arisen from endothelial cells of the lymph node the tumor is called a reticulum-cell sarcoma or a large round-cell sarcoma.

    A small round cell sarcoma, such as may occur in other tissues, sometimes arises from the connective tissue cells, usually of the trabeculae of the lymph node or the adventitia of its vessels.

    The possibility that a lymphocytoma may arise from an aleukemic lymphoma has been shown by several pathologists.

    In all these cases the blood may show only a secondary anemia with toxemia.  Fibrinolysis was absent in all the cases so far examined in our laboratories.

    When the lymphocytoma has arisen in the intestinal lymphatics the blood often shows lymphemia.  In other cases it is usually possible to find abnormal hyaline cells in the blood smears.  In cases of malignant lymphoma the cells may be differentiated from ordinary lymphocytes with difficulty.  The finding of dividing small hyaline cells in the circulating blood, especially if the karyokinesis is irregular in type, should suggest the diagnosis rather definitely.

    Endothelioma of the lymph nodes occurs rarely, and most commonly follows some chronic infection and granuloma.  The blood shows secondary anemia but it is rarely possible to find typical endothelioma cells in the circulating blood.

    Mrs. P.  Childhood history and heredity present no unusual factors.  An attack of acute nephritis at the age of sixteen years followed severe cold.  The nephritis became chronic and persisted for three years.  Treatment given for this disorder was chiefly dietetic.  Within a few months after the symptoms of nephritis disappeared the lymph nodes of the neck enlarged.  These soon disappeared.  At the age of twenty a lump appeared on the shoulder, beneath the muscles.  The location could not be definitely described.  The tumor disappeared within a few weeks after several X-ray treatments.  Tumors appeared in nearly the same region, over the left scapula, between the tip of the shoulder and the back of the neck and in adjacent areas during the years between the twentieth and the twenty-fourth years.  Various methods of radium and X-ray treatment were employed, with relief of the pain and pressure symptoms and diminution in the size of the tumor.  Her health was excellent during the twenty-sixth and twenty-seventh years and she married.  No pregnancy occurred.  Two years later the tumors recurred around the shoulder, and extended around the neck to the right side.  Other small tumors appeared in the neck and within the abdomen.  During the next year an attack of influenza was followed by rapid growth of the tumors and by increasing weakness, toxic symptoms, great pain apparently due to pressure, and by increasing nervousness and insomnia.  The tumors vary in size from week to week with no recognizable cause therefore.  The pain varies greatly, and is not always worse when the tumors are largest.

    Wassermann reaction negative; five tests had been made during the progress of the disease.

            Blood chemistry.  Tests made after 12 hours fast.
            Non-protein nitrogen                         45.9 mgs. per 100 c.c. of blood
            Urea nitrogen                                    23.0 mgs. per 100 c.c. of blood
            Uric acid                                             4.0 mgs. per 100 c.c. of blood
            Creatinin                                              1.2 mgs. per 100 c.c. of blood
            Sugar                                                 97.0 mgs. per 100 c.c. of blood
            Uranalysis same date showed usual findings in mild chronic nephritis.  Urea, Sulphates, chlorides, phosphates, uric acid, creatinin all corresponded to the reported diet for two days before the collection of the urine and the day during which the urine was being collected.

    Blood cell examination made the same day showed the following picture:

            Hemoglobin, 91.0 grams per liter; 66% of normal for age and sex
            Red cells, 3,300,000 per, 73% of normal
            Color index  .9
            Poikilocytes, microcytes, normoblasts, few
            Other abnormal red cells, none
            Hemoconien, increased
            Platelets, 350,000 per
            Specific gravity, diminished slightly
            Osmotic tension increased slightly
            Coagulation time, ten minutes (normal for method employed, five minutes)
            Leucocytes                                                                  29,400 per
            Large hyaline                                      4.6%                1,352 per
            Small hyaline                                      8.0%                2,352 per
            Monocytes                                             .6%                   177 per
            Polymorphonuclear neutrophiles            86.0%              25,284
            Eosinophiles                                            .8%                 236 per
            Hyaline myelocytes, abundant
            Granular myelocytes, abundant
            Endothelial cells, abundant
            Neutrophile nuclear average 2.04
            Iodophilic cells and iodophilic granules, abundant
            Malarial and other parasites, none

    On the warm stage the leucocytes began to move at once very rapidly.  They grouped themselves into fours to nines, usually each type of cell together.  They are dead within twenty minuets (should live more than an hour).  Red cells inelastic, fragile.  They were arranged in groups of twenty to one hundred cells, irregularly, with slight tendency to normal rouleaux arrangement.

    Leucocytes included many reversionary forms.  Anaplasia marked.  Fibrin formed at once, very abundantly.  Fibrinolysis absent.

    During the next week seven X-ray treatments of unknown type were given with slight change in the size of the tumors and with moderate relief of the pain.  The blood examination twelve days after the last X-ray treatment gave the following findings:

            Hemoglobin 83 grams per liter
            Red cells 3,520,000 per
            Color index .77
            Abnormal red cells and other general findings as before
            Platelets, 100,000 per
            Leucocytes 14,400 per
            Large hyaline                                                  6.0%                 864 per
            Monocytes                                                      7.5%               1,080 per
            Polymorphonuclear neutrophiles                  83.0%              11,952 per
            Eosinophiles                                                    3.2%`                461 per
            Neutrophile nuclear average 2.0
            Anaplasia and reversionary forms more abundant than before.
            Fibrin threads formed at once, more abundant than before.
            Fibrinolysis masked by undifferentiated proteolysis.
    Notes.  In this case a diagnosis of sarcoma is indicated.  The leucocytosis is due to extension of the metastases to the peritoneal cavity.