Studies in the Osteopathic
Cells of the Blood: Volume
Louisa Burns, M.S., D.O., D.Sc.O.
LEUKEMIAS AND RELATED DISEASES
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
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
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;
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
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.
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
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
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
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.
MYELOCYTES IN LEUKEMIA
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
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:
EARLY SPLENOMYELOGENOUS LEUKEMIA
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 cu.mm. Abnormal red cells few.
Coagulation time 11 minutes; (normal for technique, 5 minutes).
Leucocytes, 7,700 per cu.mm.
985 per cu.mm.
2187 per cu.mm.
262 per cu.mm.
3773 per cu.mm.
385 per cu.mm.
108 per acu.mm.
Hyaline and granular myelocytes and endothelial cells, all present in small
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:
Erythrocytes, 4,920,000 per cu.mm.
Leucocytes 20,000 per cu.mm., with many myelocytes.
April 2, 1909, the second blood examination was made
and the findings were as follows:
Erythrocytes, 4,296,000 per cu.mm.
Leucocytes, 64,000 per cu.mm.
2,304 per cu.mm.
10,496 per cu.mm.
36,480 per cu.mm.
7.936 per cu.mm.
2,880 per cu.mm.
1,600 per cu.mm.
512 per cu.mm.
128 per cu.mm.
Fractured and degenerated myelocytes
1,664 per cu.mm.
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:
4,464,000 per cu.mm.
11,520 per cu.mm.
380 per cu.mm.
1809 per cu.mm.
69 per cu.mm.
8640 per cu.mm.
242 per cu.mm.
173 per cu.mm.
Myelocytes (all neutrophilic).
207 per cu.mm.
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:
4,456,000 per cu.mm.
5,600 per cu.mm.
380 per cu.mm.
1725 per cu.mm.
3483 per cu.mm.
67 per cu.mm.
112 per cu.mm.
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:
3,576,000 per cu.mm.
7,100 per cu.mm.
3441 per cu.mm.
2385 per cu.mm.
14 per cu.mm.
4104 per cu.mm.
64 per cu.mm.
43 per cu.mm.
Myelocytes (all neutrophilic)
50 per cu.mm.
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
4,476,000 per cu.mm.
9,100 per cu.mm.
328 per cu.mm.
2967 per cu.mm.
109 per cu.mm.
5642 per cu.mm.
55 per cu.mm.
Basophiles, very few
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.”
SPLENOMYELOGENOUS LEUKEMIA; ALEUKEMIC STAGE
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:
4,000 per cu.mm.
176 per cu.mm.
984 per cu.mm.
less than .1%
2160 per cu.mm.
32 per cu.mm.
8 per cu.mm.
40 per cu.mm.
Eosinophilic myelocytes, few
Large hyaline myelocytes, including gigantoblasts 5.0%
200 per cu.mm.
Small hyaline myelocytes
400 per cu.mm.
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.
LATE STAGES, SPLENOMYELOGENOUS LEUKEMIA
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
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.
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.
PATHOLOGY OF LYMPHATIC 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.
ACUTE LYMPHATIC LEUKEMIA
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
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.
CHRONIC LYMPHATIC LEUKEMIA
LATE LYMPHATIC LEUKEMIA
N, this abnormal cell is of the same size as normal
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
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
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
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
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
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:
77.3 gms. Per liter, 72% of normal for age.
Erythrocytes, 3,600,000 per cu.mm., 56% of normal for age.
Color index .78
Normoblasts, 800 per cu.mm.
Megaloblasts, 700 per cu.mm.
Hemoconien, increased considerably.
Leucocytes, 400,000 per cu.mm.
Large hyaline cells
3,200 per cu.mm.
Small hyaline cells
180,000 per cu.mm.
400 per cu.mm.
15,200 per cu.mm.
800 per cu.mm.
400 per cu.mm.
Myelocytoid forms, protoplasm degenerated
200,000 per cu.mm.
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:
85.6 grams per liter; 75% of normal for age.
Erythrocytes 3,776,000 per cu.mm., 62% of normal for age.
Color index .83
All abnormal red cells less abundant than before.
370,000 per cu.mm.
11,100 per cu.mm.
259,000 per cu.mm.
740 per cu.mm.
24,050 per cu.mm.
1,110 per cu.mm.
Basophiles, very few
Myelocytoid and atypical
74,000 per cu.mm.
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.
20 mgs. per 100 c.c.
1.9 mgs. per 100 c.c.
10. mgs per 100 c.c.
130. mgs. per 100 c.c.
Carbon dioxid combining power 69. mgs per 100 c.c.
The third blood examination was made April 12, 1922,
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 cu.mm. 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:
1,700 per cu.mm.
400,000 per cu.mm.
300 per cu.mm.
3,900 per cu.mm.
Basophiles, very few
Myelocytoid and atypical
94,000 per cu.mm.
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
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.
ILLUSTRATIVE CASE 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.
87 grams per liter; 60% of normal
ATYPICAL AND UNUSUAL CONDITIONS
Erythrocytes 4,000,000 per cubic millimeter, 80% of normal
Color index .6
Normoblasts, 20 per cubic millimeter
Other abnormal red cells, none
13,000 per cu.mm.
960 per cu.mm.
1,440 per cu.mm.
792 per cu.mm.
18,480 per cu.mm.
2,328 per cu.mm.
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.
Serum tinged with a pigment which does not give reaction for bile and is
probably a derivative of hemoglobin.
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
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
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
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
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
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
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.
chemistry. Tests made after 12 hours fast.
45.9 mgs. per 100 c.c. of blood
23.0 mgs. per 100 c.c. of blood
4.0 mgs. per 100 c.c. of blood
1.2 mgs. per 100 c.c. of blood
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
91.0 grams per liter; 66% of normal for age and sex
Red cells, 3,300,000 per cu.mm., 73% of normal
Color index .9
Poikilocytes, microcytes, normoblasts, few
Other abnormal red cells, none
Platelets, 350,000 per cu.mm.
Specific gravity, diminished slightly
Osmotic tension increased slightly
Coagulation time, ten minutes (normal for method employed, five minutes)
29,400 per cu.mm.
1,352 per cu.mm.
2,352 per cu.mm.
177 per cu.mm.
236 per cu.mm.
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
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:
83 grams per liter
3,520,000 per cu.mm.
red cells and other general findings as before
100,000 per cu.mm.
14,400 per cu.mm.
864 per cu.mm.
1,080 per cu.mm.
11,952 per cu.mm.
461 per cu.mm.
nuclear average 2.0
and reversionary forms more abundant than before.
formed at once, more abundant than before.
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.