L E UCOCYTH~~EMIA.

Bv JAMES CRAIG, M.D., F.R.C.P.; Physician to the Meath Hospital.

[Read in the l~edical Section, May 8, 1896.J

A BOr died in the M~eath Hospital on the 27th of January last, a victim to the comparatively rare but generally rapidly fatal form of leucocytha~mia, known as the lymphatic tvpe.

The pure]y splenic, or lymphatic, or medullary form of leukaemia is seldom met with; more usually mŸ t.ypes occur, in which two or perhaps all three varieties are com- bined, the commonest of all being the spleno-medullary, but still when you have examined the films of stained blood that ate placed under the microscope, I think you will agree with me in regarding this case as belonging to the purely lym- phatic type. In a paper read before the Medical Section of this Academy in 1891, Dr. Wallace Beatty recorded a case of the purely medullary form, and for the recognition of which, in the absence of external signs to prompt him, he deserves the greatest credit. Unfortunately, at that time but little had been done in the direction of distinguishing the different kinds of leucocytes to be found in the blood, so that although these cells were, asa whole, greatly increased, still the particular variety met with in that case has not been recorded.

The hoy, who was nineteen years of age, was an Italian by birth, ah image-maker by occupation, and his fatal illness, ~vhich was of ah acute nature, extended only over two months altogether.

On observing the photograph [exhibited] you will note par. ticularly the thickness of his neck, the swelling of the parotid region, the tumours in the axill~e--all of ]ymphatic origin--and the distension of bis abdomen; The enlargement of lymphatio

lt:

114 JLeucocyt]tcemia.

glands was universal. The spleen and liver were both in- creased in size, and the tonsils were swollen and painful.

The pallor of his skin was probably accentuated by a naturally sallow complexion peculiar to his countrymen. As the illness progressed, dyspncea became more marked. Profuse epistaxis occurred, and with this a diarrhoea so persistent that the treatment of the case was mainly directed to combating these two distressing symptoms. Severe epigastric pain was constant, which, with evident intestinal distension, as well as the persistent diarrhcea, suggested ah inflammation of the colon that was not verified by the post-mortem examination.

There was no tenderness.over the sternum. Priapism an occasional symptom in such cases was

observed. A venous hum was present in the neck, anda soft systolic murmur was audible over the mitral arca. About a w eek before his death the lower extremities became ~dematous, and the glandular swelling was considerably diminished. The temperature was variable, ranging from 99 ~ to 103 ~ F., andas death approached it fell to 97 ~ F.

The case on admission was thought to be one of Hodgkin's disease, or lymphadenoma, and undoubtedly many of the cases described as such were similar in nature to the present one; but if we take it that permanent increase of whŸ blood cells is cl~aracteristic of leucocyth~emia, while mete diminution of the cellular elements of the blood is a feature of the other, then we ate in a position to discriminate between these closely-allied affections--lymphatic leucocy-

thmmia, and lymphadenoma. I will not weary you with details of the repeated examina-

tions of the blood which were made; suffice to say that the red cells were reduced to at least one-third of their normal number--a condition for which the epistaxis was probably largely accountable, while the white ones were both abso- lutely and relatively increased, the proportion of white to red beiug about one to twenty instead of one to three hundred.

By DR. JA~IES CRAIG. 115

In the slides which are placed under the microscopes, an'~ for the staining of which [ am indebted to Dr. M:'Weeney, you will observe at a glance this increase of white cells, but in addition to the increase ir is possible also to distinguish between the different varieties of these corpuscles. One preparation is stained with acid h~ematoxylin and eosin, and the other with Ehrlich-Biondi triple stain of methyl green, acid fuschin, and orange.

You are aware that the leucocytes of human blood are not all of the same size, and that they differ also in other respects. In some the protopIasm is granular, in others it is without granules; in some the granules are large, in others, again, they are small. But, in addition to these peculiarities, it has been found that the granules in some cells stain with acid dyes, while in other cells they stain only with basic dyes. I may add that the latest Ÿ in this con- nection go to show that the granules of certain cells, which were supposed by Ehrlich to stain with neutral dyes alone, and hence called by hŸ neutrophiles, are now found to staia not with neutral but with acid dyes.

The most recent work on the subject is a paper by Kanthack and Hardy. varieties, as follow: Acidophfles,

or Oxyphiles, granules

stain with Eosin

Basophile, granules ]

stain with I Methylene

blue

They classify these cells into tire

1. Coarsely granular, polynuclear or horseshoe-shaped nucleus (Ehr- lich's eosinophiles) 2-3 per cen~. 10"0 ~~ in dia.

2. •inely granular, irregular-branch- ing nucleus (Ehrlich's neutro- philes)--62 per een~. - - 8-9"0 p~�91 ,,

3. F inely granular, trilobed nucleus - 0"7 per cent. - - - 7"0 ~ ,,

4. Hyal ine cells, free frorr�91 granules, mononuclear, and generally sphe r i ca l - - l l per cent. -

5. Lymphocytes with single nucleus, a very little protoplasm--24 per C e n t . . . - , , .-

8"5-10"0 , 7

6"0 pp ,~

116 Zeucocytlt~raia.

The percentages here represent the proportion of each variety found in the blood in heaIth.

All of these cells occur in normal blood, and, roughly speak- ing, in splenic leukmmia No. 1 are greatly increased, in the ]ymphatic form the increase is in No. 5, while in the medullary form other cells are observed that are not present in health, namely, mononuclear cells, larger than No. 4, but unlike them in containing granules which stain only with neutral dyes. These are called myelocytes, from their sllpposed origin in the bone marrow.

Now, in these films, prepared from the Italian boy's blood, you wilI notice that, practically speaking, the small lympho- cytes only are increased, although a few of at least 1, 2 and 4 can be seen as well, but the total increase of leucocytes in the lymphatic forro is never found to be so great as in the

�9 splenomedullary forro. So much for the blood. The main facts revealed by the autopsy were these :--The

organs generally were pale and bloodless, all the subcutaneous ]ymphatic glands were enlarged, some not larger than a marble, others the size of a walnut. About a quart of serous transudation lay in the pleural sacs anda few ounces in the pericardium. A mass of lymphoid tissue lay in front of the ]ower end of the trachea, and a larger mass surrounded the right bronchus. The lymphatic glands along the whole course of the intestinal tube were much enlarged, the liver

.and spleen were considerably increased in size, the pancreas was white and bloodless, the stomach and intestines were distended with gas, and the mucous membrane of the latter was paje, while Peyer's patches and the solitary follicles were enlarged and sharp]y defined. Under the microscole the liver and spleeff were found to be impacted with lymphocytes, which accounted for their increased bulk.

The case is of interest in several particulars. In the first place this lymphatic variety is rare, and where it does occur

By DR. JA~~s CRAm. 117

is generally, as in the present instance, found in young sub- jects, and ir usually runs through a rapid and fatal course.

In the splenic or splenomedullary forms the insidious and slowly progressive nature of the affection, as ir is com- monly met with, affords ah opportunity for treatment, so that cases of improvement or recovery are not infrequent. I have several such patients whose blood has improved and whose spleens have returned almost, if not quite, to their normal dimensions under the free administration of arsenic, so that they are able, a f t e r a number of years, still to follow Ÿ heir daily avocations. In this case, however, I was obliged to drop the arsenic on account of the diarrhcea, and to treat symptoms instead.

In the next place, the acute nature of the symptoms pointed to an infective cause, and ir is highly probable that before long we may have the presence of a micro-organism, or its poisonous products, demonstrated in the blood to account for the grave changes that are present in leucocy- th~emia.

And last]y, the advances that have been made withia recent years in the study of the white-cell elements of the blood render it a fairly easy matter now to distinguish in stained preparations the particular form of the affection under observation, although ir is true that much has yet to be added before our knowledge becomes at all perfect.

Da. W. G. SmTa asked if arsenic had been administered in this case, or if the treatment by marrow fat had been tried. He laid stress on the great advance that had been made in the micros- copie examination of the blood in these cases, and thought that it should more generally be carried out in hospital practice, as the process was not a difficult one; he thought that the specifie significance clinically of the various leucocytes was still very doubtful. He stated that the continuou8 use of arsenie in chronie

118 Zeucocytheemia.

cases was not devoid of danger, as peripheral neuritis might follow asa result. He mentioned the great chemical changes that occurred in the urine in this disease. The uric acid increased and xanthiae bodies also increased. The normal oxidizing power of the body was not seriously affected.

Da. Bo~D mentioned that he had treated a case of the lymphatic form~ in which there was marked tenderness of tibim, sternum, and ribs. Under arsenic there was distinct improvement (proportion of leucocytes 1-300). The patient was then put on bone-marrow, but distinct relapse occurred (leucocytes 1-20). On returning to the arsenic treatment improvement again took place, and the p~tient returned to the country, where, however~ he relapsed again, and died in three or four months.

DR. CRAIO, in reply, said that he had tried arsenic, but as it caused diarrhcea and pain in the stomach~ he had to cease ad- ministering it. He had thought of using marrow fat, but had to content himself with trying to keep his patient alive.