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From fhe Medical Department and the Central Laboratory of the Frederiksborg County Hospital, Denmark. (Chiefs: Torben Andersen, M.D., and Gregers Serensen.) OSTEOMYELOSCLEROSIS COMBINED WITH SPLENOGENIC INHIBITION OF THE BONE MARROW BY Torben Andersen and Gregers Serensen. In 1947 EngeZZ(1)published from this department a report of a patient who had died of progressive myelosclerosis. Four years earlier the patient had had a very large spleen removed under the diagnosis splenogenic inhibition of the bone marrow. As was to be expected according to the considerations which caused the splenectomy to be made, a marked improvement of the patient's general health took place after the operation. The improvement was, however, transient only, and during the last period before his death he was again increasingly debilitated and anaemic. When he was admitted here it was realized that he was suffering from osteomyelosclerosis, which diagnosis was corroborated iby the histological examination post mortem. The clinical picture gave rise to a number of interesting pathogenetic (sonsiderations by Engell, which, however, will not be dealt with in detail here. But we were reminded of the clinical picture when another patient with osteomyelosclerosis was admitted to our department :- Case record No. B 673/1945.-A 25-year-old station worker was admitted on October 16th, 1950, under the diagnosis osteomyelosclerosis. As a stretcher-bearer at the hospital he had been admitted to the Medical Depart- ment on a few occasions earlier (in 1945) for trifling disorders, but had otherwise chiefly been in good health until, on September 3rd, 1949, he was admitted to another hospital because of pain below the left costal margin and in the left shoulder. The diagnosis osteomyelosclerosis was established there on the basis of thorough examinations. The case was reported by Raaschou (2) in the Dansk selskab for intern medicin (the Danish Society for Internal Medicine) on Nov. 12th, 1949. When he was admitted here a few years later, he was anaemic, fatigued and in poor general health. The results of the examinations of the blood are shown in Table 1. It was realized that his prognosis was extremely bad, and it was therefore decided to advise extirpation of the spleen, bearing in mind that the func- ~~~ ~ Submitted for publication June 13, 1951. 12' 179

OSTEOMYELOSCLEROSIS COMBINED WITH SPLENOGENIC INHIBITION OF THE BONE MARROW

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Page 1: OSTEOMYELOSCLEROSIS COMBINED WITH SPLENOGENIC INHIBITION OF THE BONE MARROW

From fhe Medical Department and the Central Laboratory of the Frederiksborg County Hospital, Denmark.

(Chiefs: Torben Andersen, M.D., and Gregers Serensen.)

OSTEOMYELOSCLEROSIS COMBINED WITH SPLENOGENIC INHIBITION OF THE BONE MARROW

BY Torben Andersen and Gregers Serensen.

In 1947 EngeZZ(1) published from this department a report of a patient who had died of progressive myelosclerosis. Four years earlier the patient had had a very large spleen removed under the diagnosis splenogenic inhibition of the bone marrow. As was to be expected according to the considerations which caused the splenectomy to be made, a marked improvement of the patient's general health took place after the operation. The improvement was, however, transient only, and during the last period before his death he was again increasingly debilitated and anaemic. When he was admitted here it was realized that he was suffering from osteomyelosclerosis, which diagnosis was corroborated iby the histological examination post mortem. The clinical picture gave rise to a number of interesting pathogenetic (sonsiderations by Engell, which, however, will not be dealt with in detail here. But we were reminded of the clinical picture when another patient with osteomyelosclerosis was admitted to our department :-

Case record No. B 673/1945.-A 25-year-old station worker was admitted on October 16th, 1950, under the diagnosis osteomyelosclerosis. As a stretcher-bearer at the hospital he had been admitted to the Medical Depart- ment on a few occasions earlier (in 1945) for trifling disorders, but had otherwise chiefly been in good health until, on September 3rd, 1949, he was admitted to another hospital because of pain below the left costal margin and in the left shoulder. The diagnosis osteomyelosclerosis was established there on the basis of thorough examinations. The case was reported by Raaschou ( 2 ) in the Dansk selskab for intern medicin (the Danish Society for Internal Medicine) on Nov. 12th, 1949. When he was admitted here a few years later, he was anaemic, fatigued and in poor general health. The results of the examinations of the blood are shown in Table 1.

It was realized that his prognosis was extremely bad, and it was therefore decided to advise extirpation of the spleen, bearing in mind that the func-

~~~ ~

Submitted for publication June 13, 1951.

12' 179

Page 2: OSTEOMYELOSCLEROSIS COMBINED WITH SPLENOGENIC INHIBITION OF THE BONE MARROW

Tuble 1.

Haemoglohin % Erythrocytes mill/mmJ Leucocytes/mm3 Neutrophilic stabs

Eosinophilic - Lymphocytes Monocytes

- polymorphonuclears

Before splenectomy

After splenectomy

17/10 50. There were 8 polychromatophil and 9 orthochromatophil erythrohlasts pr. 100 leucocytes. The red blood picture disclosed aniso-, macro-, micro-, poikilocytosis and nolschromasia.

3013 51. The r e d blood picture disclosed macrocytosis, anisocytosis, polychromasia and a few nucleated rcd cells.

Thrombocytes. 6/12 50: 314000. 23/2 51: 297000.

Hone marrow: 17/10 50: The sternum was punctured in two places and the crista ilei in two places, but it was impossible to withdraw any marrow.

30111 50: A small amount of bone marrow was withdrawn from the 0s ileum. The number of nucleated cells was very small. Erythro- blasts and lymphocytes were normal. The precursors of the mye- loid cells were very abnormal with coarse granules and vacuoliza- tion of the cytoplasm. The reticulum cells were numerous with coarse granulation.

2312 51: A small amount of bone marrow was withdrawn from the sternum by vigorous suction - too little for counting the number of nueleat- ed cells, but the examination of the bone marrow smear disclosed a rather normal amount of nucleated cells and normal erythro- and granulocytopoiesis. Coarsely granulated endothelial cells we- re numerous.

Differential count of the bone marrow:

Basophilic erythroblasts Polychromatic - Orthochromatic - Haemocytohlasts Neutrophilic myelocytes

- met amyelocyt es - stabs - polymorphonuclears

Immature eosinophilic leucoeytes Eosinophilic polymorphonuclears Small lymphocytes Large - Monocyt es Plasmacells Megacaryocytes Reticulumcells

30111 50 1.0 % 14.0 ,, 0.5 ,, 0.5 ,, 13.0 ,, 12.0 ,, 6.5 ,, 16.0 ,,

3.5 ,, 7.5 ,, 11.0 ,, 3.5 ,, 0.5 ,,

10.5 ,,

23312 51 6.5 70 19.5 ,,

21.5 ,, 18.5 ,, 7.5 ,, 4.5 I ,

2.0 , I

1.5 ,, 13.5 ,,

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tion of his bone marrow which was inhibited in advance might be further deteriorated because of splenogenic inhibition of the marrow (cf. Engell's case).

This was, of course, a hazardous undertaking, and it was a little difficult to make the patient understand the timeliness of this interference, as he was fully familiar with the view that his spleen "substituted" his bone mar- row, and that he would possibly die if the spleen was removed.

Before deciding definitively on the operation we wanted to make surc by means of renewed puncture of the spleen ( i t had been made a year before in another department) that no additional myeloid metaplasia of the spleen

Occrm I Oktober. I Mvembri

1950

had occurred in the meantime. The findings in the first puncture of the spleen were as follows : "Moderate amounts of erythropoietic and granul- opoietic elements without any abnormalities, number of lymphocytes decreased. Numerous pathological cells, probably reticulum cells and fibroblasts". However, after the puncture of the spleen we had no oppor- tunity to consider the advisability of extirpation of the spleen again, as a vigorous splenic haeniorrhage rendered iminediate extirpation of the organ necessary. The operation was without any complications. Histological examination of the spleen showed : Pronounced proliferation of reticulum cells, fibroblast-formation, fibrosis and moderate extramedullary haema- topoiesis. After a postoperative course without any complications he was discharged on Dec. 2nd, 1950, and a follow-up examination, last on March 30th, 1951, showed that his general health was good, and his only com- plaints were a slight feeling of fatigue and palpitation coming on in attacks. With regard to the haemoglobin percentage, see Figure 1.

There is no docbt whatever that extirpation of the spleen in osteo- myelosclerosis must be considered a hazardous interference, and numerous

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warnings have been given against the operation (3, 4 ) . We consider, how- ever, that the surgeon should not in all cases adhere to doctrines and remain passively expecting with regard to the inexorable progress of the disease: he should in the individual case consider the possibility of giving the patient a good-though transient-period by removing an enlarged spleen the in- hibitory effect of which on the bone marrow must be estimated as greater than its haematopoietic effect.

In contrast with the case record mentioned above another example may be given of a favourable effect of extirpation of the spleen, where the in- dication as to this operation is universally recognized, but where the problem here was to improve the patient’s condition so as to render opera- tion justifiable.

Case record No. 612/50.-A 69-year-old gardener was first admitted to the department on March 17th, 1950. For about 10 years he had had un- characteristic dyspeptic complaints, and these in connection with the fact that from November, 1949, he had felt increasingly tired and poorly with fever caused him to be admitted, in January, 1950, to another hospital. Among other findings an infiltration in one of his lungs was demonstrated there, for which reason he was transferred to this hospital under the diagnosis observation for pulmonary tumour.

The examinations here showed changes of the blood and the ‘bone mar- row (see Table 2 ) which together with the finding of a considerably en- larged spleen allowed us to diagnose splenogenic inhibition of the marrow. He was advised splenectomy after the infiltration in the lung had subsided under treatment with chemotherapeutics, but he refused to be operated on.

During the next 2 months he was, however, readmitted 3 times to the hospital with relapsing pneumonia and as he also felt extremely poorly during his short stays at home between those in hospital, he at last agreed to be operated on.

On July 4th, 1950, the spleen was removed in the Surgical Department here, and the postoperative course was without any complications.

The findings in the blood and the bone marrow before and after opera- tion are shown in Table 2.

Since the operation he has been feeling subjectively well. There have been no renewed pulmonary infections, his dyspeptic symptoms have subsided, and his weight increased.

In contrast wit,h the former patient the indication was quite clear in this case. Before the splenectomy this patient could only be kept alive by means of intensive use of blood transfusions and antibiotics, whereas after the operation he seems to be in completely good health. Whether he will later develop symptoms of osteomyelosclerosis like Engell’s patient, remains an open question-considering the fact that he will soon be 70 years he may perhaps not experience this.

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Table 2.

Haemoglobin % Erythrocytes mill/mm3 Leucocytes/mm3 Neutrophilic stabs

Eosinophilic - Lymphocytes Monocytes Thrombocytes

- polymorphonuclears

Bone marrow: Basophilic erythroblasts Polychromic - Orthochromic - Erythroblasts in mitosis Haemocytoblasts Neutrophilic promyelocytes

- myelocytes - metamyelocytes - stabs - polymorphonuclears

Immature eosinophilic leucocytes Eosinophilic leucocytes Small lymphocytes Large - Monocytes Plasmacells Reticulumcells Megacaryocytes Number of cells/mm3

Before splenectomy

2% 50 56

3.10 1440

22 7 0

2 9 9 1 )

66 ,, 10 11

215000

ARer splenectomg

11/10 50 108

4.92 6520

11 % 33 1,

2 ,, 35 ,, 19 I,

248000

5.5 % 9.0 I,

0.5 w

0.5 ,,

14.0 ,, 15.5 ,, 12.0 ,, 12.5 ,,

2.0 ,, 1.0 I,

7.6 ,, 10.5 ,, 6.0 ,, 1.0 ,,

0.6 ,,

0-5 1,

1.5 ,,

84400

SUMMARY The paper reports on favourable effect of extirpation of the spleen in

two patients with splenogenic inhibition of the bone marrow. One of the patients also had osteomyelosclerosis, but our supposition that the inhibitory effect of the spleen on the bone marrow was greater than its erythropoietic effect was confirmed by the postoperative course.

REFERENCES 1. Engell, H. C.: Acta med. Scand. 129: 371, 1947. 2. Raaschou, F.: Nord. Med. 43: 722, 1950. 3. Johannesen, A. S.: Nord. Med. 45: 17, 1951. 4. Lancet 257: 757, 1949.

1) The nucleus of the polymorphonuclears had two segments only. 2) The bone marrow did not contain mature neutrophilic polymorphonuclears.

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