A NOTE ON “MULBERRY CELLS” AND CLUSTERS

OF EOSINOPHILE SPHERULES, PROBABLY A

FORM OF RUSSELL’S “FUCHSINE BODIES” I N
THE WALLS OF A CHRONIC CEREBRAL ABSCESS
AND I N A CASE OF MULTIPLE MYELOMA.
M.D.
WEBER,M.D., F.E.C.P. and R. BLENDINGER,
By F. PAHKES
(PLATE111.)
THEsubject of the chronic cerebral abscess was a married woman, at. 37,
admitted into the German Hospital on 13th October 1904. She had suffered
from occasional headaches (since Christmas 1903) and vomiting ; but, though
she felt weak, had been up and about until three weeks before admission.
No history of fits or convulsions. Some years previously she had suffered
from spasmodic abdominal pains, possibly connected with cholelithiasis. In
regard to family history, it may be noted that her father lived to an old age
and her mother died of consumption. The patient had five children living
and healthy ; two others had died, of diphtheria and some uncertain cause,
respectively.
I n the hospital the patient was found to have advanced double optic
neuritis. The pupils were rather large, and reacted sluggishly to light.
Though there was no objective disturbance in the movements of the eyeballs,
diplopia of some kind was mentioned by the patient. There was no para-
plegia, but without assistance she could not remain in the standing position,
even with her eyes open, and she had a tendency to fall to the right. NO
disturbance of cutaneous sensation was detected, but there was apparently
slight inco-ordination in the upper extremities, shown by asking her to make
the tips of her two forefingers meet rather quickly in front of her. She
answered even the simplest questions slowly. We have no note as to the
condition of the knee-jerks and other reflexes. Xothing abnormal was
observed on physical examination of the thorax and abdomen. There was
no fever. The pulse varied between 76 and 88 per minute. The urine was
free from albumin and sugar. The patient died suddenly in the night on
28nd October. Treatment by iodide of potassium had been commenced on the
chance of the disease being due to syphilis.
At the necropsy on 22nd October nothing abnormal (spinal cord not
examined) was discovered on naked-eye examination, beyond the presence of
gall stones in the gall bladder and a chronic abscess (f softening gumnia) in
the brain. It is to this latter condition we have now to devote our attention.
The abscess was of about the size of a large walnut, measuring nearly 4 crns.
in the sagittal direction and about 2 4 crns. in the coronal and vertical direc-
tions, and was situated in the left cerebral hemisphere, just above the corpus
callosum and quite close to the intercerebral fissure, so as to cause bulging
when the hemispheres were separated. There was a thrombosed blood vessel
60 I;: PARKES WEBER AND R. BLENDINGER.
in the cerebral cortex in the neighbourhood of the abscess. I n this macro-
scopic exnmiuation of the brain we had the advantage of Dr. F. E. Batten’s
kind assistance. The other portions appeared not to be diseased, and this
would account for the absence of localising symptoms during life. The
abscess contained a thick, creamy, greenish, purulent-looking fluid, which
under the microscope was found to consist of granular material and cells, the
latter relatively few and in process of degeneration. The abscess wall was
firm and rather irregular, and this irregularity rather favoured the view that
the disease was of syphilitic origin. It may he stated at once that sections
were specially stained for tubercle bacilli with a negative result.

MICROSCOPICAL OF THE ABSCESS

EXAMINATION WALL.
Sections cut from paraffin blocks were stained in various ways. By the
mode of preparation all fat was of course necessarily got rid of. The tissue
was fibroid, with inflammatory cellular infiltration, merging on the outer side
into normal brain tissue. Besides lymphocytes there were a good many rather
large cells of an oval shape, which evidently, as the result of a degeneration
process, had an extremely small nucleus and a relatively large amount of
swollen-looking protoplasm, staining poorly with hmmatoxylin. It is, how-
eveq to a third kind of cells, representing, doubtless, a special form of
degeneration, to which we particularly wish to draw attention. These cells,
scattered here and there in the abscess wall, were of large size, with a single
relatively small nucleus, and contained spherical globules (Plate 111. Figs. 2
and 3) in their protoplasm, up to fifteen or twenty in number.
The spherules attracted attention owing to their retaining the
fuchsine colour in preparations which were stained with carbol-fuchsine
for tubercle bacilli, but they were likewise picked out by the eosine
in the ordinary haematoxylin-eosine staining, and could be well defined
by several other methods. On account of their peculiar appearance
we have called the cells containing the globules “ mulberry cells.” It
seems a~ if after a time the protoplasm becomes quite used up in the
formation and growth of these globules, so that the cells come to
consist of nothing but a small irregularly shaped nucleus and n mass
of spherules apparently held together by a kind of cement substance or
by a thin cell wall (Plate 111. Fig. 3). Then, as far as we can judge,
the nucleus disappears, and nothing but a cluster of spherules remains
(Plate 111. Fig. l), or the cell breaks and the sphernles are set free in the
tissue ; but even after this their arrangement in a group or cluster, and
the appearance of adherence of some of the spherules to each other,
often still suggest that they have been derived from the breaking up of
a single mulberry cell. I n the lowest of the three clusters represented
in Plate 111. Fig. 1, a emall body, stained deep blue, is to be noted
between the spherules, and appears to be the atrophied remnant of a
nucleus, as if the cluster in question had been derived from a,
mulberry cell similar to that represented in Fig. 3.
The diameter of the spherules in the mulberry cells and clusters is mostly
from one-sixth to rather more than the whole diameter of an ordinary red-
blood corpuscle. That is to say, that in diameter the spherules mostly vary
between 1.5 and 9 or 10p, but are sometimes decidedly larger, especially whelk
 A NOTE O N “MULBERRY CELLS.” 61
only one or two are contained in a single cell. Some of the spherules at first
sight appearing to be free in the tissue are, on careful examination, found to
be single globules, replacing, practically, the whole of the cell protoplasm,
though a remnant of the nucleus is left. When many spherules are, as is
usually the case, contained in the same cell, they often vary considerably in
size. The spherules seem all ta be perfectly homogeneous, and we can make
out no vestige of structure in any of them. The larger ones stain, if any-
thing, more deeply with eosine than the smaller ones.
We may note incidentally that in some preparations the large
spherules apparently lying free in the tissue are a more striking
feature than in other preparations, and we have a suspicion that the
method of preparation may sometimes break up the cells, setting the
spherules free, or may cause smaller globules to coalesce to form
single large globules, either within cells or free in the tissue.
I n regard to the staining reactipns of the spherules, the following
are our results from the use of a variety of stains:-
1. Hsmatoxylin and eosine-the globules are stained red.
2. Methylene-blue and eosine-red.
3. Jenner’s methylene-blue and eosine combination ‘-faint red.
4. Mann’s long method of staining by his methyl-blue and eosine com-
bination 2-red.
5. Ehrlich’s triacid blood stain-crimson.
6. Methyl-violet-violet (i.c. not the pink staining of amyloid substance).
7. Carbol-fuchsine-red.
8. Puchsine and methylene-blue-purple.
9. Russell’s fuchsine and iodine-green method 3--red, often with a bluish
tinge ; sometimes, probably owing to faulty technique-blue.
It must be added that the spleen and a kidney from the eanie
case were examined microscopically. Nothing abnormal was seen in
the section of the kidney, but an interesting fact is that a few
clusters of spherules, similar to those found in the walls of the
cerebral abscess, were discovered in sections of the spleen. The
latter organ showed no amyloid change, but a hyaline-like degenera-
tion in the walls of some of the smaller blood vessels.
The mulberry cells and spherule clusters in the present case are
obviously very similar to those found in greater abundance in the
myelomatous bone marrow of a case described by one of us (F.P. W.)
and illustrated in the Medko-C‘hiruTgkal Tvamactwns, vol. lxxxvi?
Professor R. Muir of Glasgow, who kindly examined the tissue in that
case, reported :-
“ I n the protoplasm, moreover, there can be shown a larger number of
granules which vary considerably in size, but the smallest and most abundant
of which are distinctly larger than the neutrophile granules. With hrsmat-
1 Louis Jenuer, h a n u t , London, 1899, vol. i. p. 3iO.
G. Y a m , “Physiological Histology,” 1902, p. 216.
W. Russell, “An Address on a Characteristic Orgauism of Cancer,”Bd. Med. Jam.,
London, 1890, vol. ii. p. 1366.
F. Parkes Weber, ‘‘A Case of Multiple Myeloma,” bled.-Chir. Trans., London, 1903,
vol. lxxxvi. pp. 395 et q.
62 E PARKES WE3ER AND R. BLENDINGER.
oxylin and eosine these smallest granules are practically unstained By the
eosine ; with Ehrlich’s triacid they are coloured, but have not quita the same
tints as the neutrophiles, the staining being of a dirty brown colour; with
Mann’s eosine-methyl-blue combination they are stained bright red with a
slightly violet tint (whereas the neutrophiles are not stained) ; with Unna’s
polychrome methylene-blue the granularity is faintly visible, but the granules
are not really stained. ... I n addition, however, to these smnll granules,
many larger ones are present, and all intermediate sizes can be found up to
large rounded bodies as large as, or even larger than, ordinary red corpuscles.
I thought at first that these rounded bodies were included red corpuscles. . . .
Some of them also are seen lying free. They are more distinctly oxyphile
than the smaller granules, and stain with eosine by the ordinary methods. ...
They always seem to be perfectly spherical in form.” I n the account of the
case Dr. Weber added that some of the larger globules were two or three times
a8 large as ordinary red corpuscles. The globules of about the same size as red
corpuscles were, however, more numerous, and were moetly enclosed in cells
(Plate 111. Fig. 4) or arranged in clusters as if those of each cluster had been
formed in a single cell and were still held together in some way. Such
clusters often consisted of a dozen or more globules, and sometimes resembled
muZbt?rries (Plate 111. Fig. 6 ) or bunches of grapes.
Unfortunately, when we recently endeavoured to try fresh stains
on sections of a piece of the myelomatous bone marrow which had
been preserved in glycerin and formalin, we found that the tissue had
undergone some change, so that the globules could no longer be
properly stained. However, we believe it is clear that the globules,
whether enclosed in mulberry cells or lying free in the tissue, were
similar, if not quite identical, in their chemical nature in the two wees.
Mulberry-like cells, similar in form if not in their staining
reactions, have been described and figured by Gulland and Goodall in
their elaborate paper on pernicious ancmia. I n their cases of per-
nicious ansmia they found basophile cells with very large (‘dropsical-
looking granules ” in the intestinal submucosa. “ Every intermediate
stage,” they said, “ from the cell with ordinary granules t o those with
granules larger than erythrocytes, could be seen.”
Mr. S. G. Shattock kindly suggested to one of us that the spherules
in our cerebral abscess case might be allied to the so-called fuchsine
bodies originally described by W. Russell as cancer organisms. Buffer
and Walkers say :-
(‘By means of a special stain he (W. Russell) showed that these fuchsine
bodies occurred in little clusters of one UP to twenty or more. They formed
perfect spheres, nnd varied in size from 4 t o 12 p. They appeared to be
perfectly homogeneous and structureless, and the larger clumps were held
together by a delicate cementing substance, which stained faintly.”
So much does this description tally with what we have observed
in regard to the epherules and mulberry cells of our cerebral abscess
Path. and Bacterial, Edin. and London. 1905, vol. x. pp. 125 et seq.
1 Joum.
W. Russell, “ An Address on a Characteristic Organism of Cancer,” Brit. Meed. Jam.,
London, 1890, vol. ii. p. 1366.
a M. A. Ruffer aud J. H. Walker, “On some Parasitic Protozoa found in Cancerolls
Tumours,” Journ. Path. a d Baeteriol., Edin. and London, 1893, 701. i. p. ZOO.
 A NOTE O N “MULBERRY CELLS.” 63

case, that we think the spheriiles in the latter case may certainly be
regarded as a form of Russell’s fuchsine bodies. We say advisedly
‘‘ a form of,” because it is possible that Russell’s “ fuchsine bodies ” are
not all exactly identical with each other.
It follows from all this that the spherules found in Weber’s
multiple myeloma case, to which we have already alluded, though
present in extraordinary abundance both in clumps within the cells
(sometimes in the form of mulberry cells) and scattered free in the
tissues, must likewise be regarded as probably forms of Russell’s
fuchsine bodies, in spite of the fact that they were never tested by
Russell’s fuchsine and iodine-green method of staining.
The importance of this conclusion lies partly, we believe, in the
fact that, since fuchsine bodies are now regarded by almost all
observers merely as products of cell degeneration,’ they are not likely
to possess any special pathological diagnostic significance in regard to
multiple myeloma, and it is unlikely that they are more closely con-
nected with multiple myeloma (and Bence-Jones’ albumosuria) than
with other conditions in which they have been found present. This
is confirmed by the fact that their presence has not been recorded in
most other published cases of multiple myeloma.

DESCRIPTION OF PLATE 111.

FIG. 1.-Part of the wall of the chronic cerebral abscess showing clusters of the spherules
stained red. Mann’s long method of staining by his eosine and methyl-blue
combination. (High magnification.)
FIG.?,.-From another section of the abscess wall. Two cells containing a great number
of relatively emall spherules stained purple by Russell’s fuchsine and iodine-
green method. (High magnification.)
FIG.3.-From another section of the abaceas wall. A mulberry cell in which the proto-
plasm has been apparently entirely rephced by the spherules. Eosine and
haematoxylin stain.
FIG.*.-From the multiple myeloma case. A granulated cell containing spherules of
various sizes stained red by Mann’s eosin and methyl-blue combination.
A somewhat diagrammatic representation, reproduced from the died.-Chir.
Tram., London, vol. lxxxvi.; but the blue colour of the nucleus in the
present illustration is more correct than that in the original figure.
FIG.5.-From the multiple myeloma case. A mulberry cell in which the protoplasm has
been apparently entirely replaced by spherdes of various sizes. The
nucleus is still visible. Mann’e eosine and methyl-blue stain with
haematoxglin. Figure reproduced lrom the Med.-Chir. Trans., London,
vol. Ixxxvi.

Vide Shattock and Ballance, Brit. dfrd. J o ~ n t . London,

, 1891, vol. i. p. 565, and
many later observers. Recent workers in Germany, we believo, regard Russell’s fuchsine
bodica as representing a form of hyaline degeneration.
JOURNAL OF PATHOLOGY.-VOL 11 PLATE 111