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"Si

ON HiEMORKHAGIC CYSTS OF THE THYROID

GLAND.

By W. I. BRADLEY. B. A., M. D., M. R. C. S.

(From the Pathological Laboratory of the Royal Victoria Hospital, and the
Molaon Pathological Laboratory, McOill University, Montreal.)

Plate XV.

It is generally taught that the most frequent form of enlargement
of the thyroid gland is the parenchymatous goitre, or bronchocele,
a form in which, by the overproduction or retention of colloid mate-
rial within the vesicles in general, there is brought about a very
considerable increase in the size of one lobe or in that of the
whole organ. There is, however, another form of cystic enlargement,
not generalized, but localized, in which the enlargement is due not
to multiple retention cysts, but to the development of large isolated,
cystic swellings, either solitary or not exceeding three or four in num-
ber. The size of these cysts greatly exceeds that of the individual
distended follicles in the most extreme cases of parenchymatous goitre,
and the walls as well as the contents are of a wholly different nature.

Judging from the material which I have had the opportunity of
studying, this in Canada constitutes quite the most frequent form of
unilateral and considerable enlargement of the thyroid presenting
itself for operation. Out of eighteen cases of bronchocele operated
upon by Dr. Shepherd at the General Hospital in Montreal, the mate-
rial from eight of which came into my hands, no less than nine, if
not ten, were of this nature,* a proportion much larger than I had
been prepared to encounter. A study of the literature bearing upon
the morbid histology of the gland has convinced me that, relatively,
very little attention has been paid to the nature and characters of these

* Of these eighteen, one was a case of generalised parenchymatous goitre,
four were definitely " colloid cysts " (adenomatous nodules with retention),
nine were definitely of the type here described, the remaining four being of
doubtful nature.

COPTRIOHT, 1896, BY D. APPLETON AND COJfPANT.

On lioBmorrhctgio CyiiU of the Thyroid Gland

large cysts; and, though it may be true that elsewhere they do not
form 80 large a percentage of the cases of goitre operated upon as they
do here in Dr. Shepherd's practice, nevertheless since surgical litera-
ture shows that they are very common, and now that operative inter-
ference with the thyroid is becoming increasingly frequent and in-
creasingly successful, it may be opportune to draw more attention to
their structure and characters than has hitherto been accorded to
them.

Dr. Shepherd has described the surgical features of his cases in
detail in the Annals of Surgery * It will, therefore, be only neces-
sary to append here a table of the cases, giving a brief epitome of the
main points in connection with each.

Case.

Mrs. S.

II.
III.

IV.

VI.

VII.

Name.

Mrs. 0.

Miss L.

Miss C.

Age.

Mrs.
Miss
Miss

McL.f

McP.f

Size, poBition, and contents of tumour.

Duration.

Two cysts in the right lobe— one the
size of n Tangierine orange, the
other that of a walnut. Contents :
a thick, reddish-brown material.

Two cysts in right lobe, the larger
more superficial. Contents: a
thick, greenish-brown fluid.

Solitary cyst the size of a lemon
in the right lobe. Contents:
grumous, containing cholesterine
crystals ; extensive papillomatous
projections into cyst.

Solitary cyst the size of a hen's egg
in the left lobe. Contents: dark,
yellowish- brown fluid with clots
of blood.

Solitary cyst the size of a small
orange in the left lobe. Contents :
straw-coloured fluid.

Single enormous cyst the size of a
turnip in the left lobe. Contents :
dark brown, thickish fluid.

Large solitary cysit the size of a
grape-fruit in the right lobe, ex-
tending beneath the sternum.
Contents: dark-yellow fluid.

Ten years ago, when crossing the
Atlantic, she was violently sea-
siiik. Lump on right side of
neck was noticed shortly after-
ward. This continued to 'now
steadily, and had increasr in
size considerably during the last
thirteen months.

Noticed for six years. Growth at
flrst small, slowly increased
until a year before operation ;
then grew rapidly, the position
becoming somewhat altered.

Present for three years; very
slow enlargement until a year
before operation, when there
was a sudden increase in size.

Gradual enlargement noticed for
a year; then sudden increase
in size three months before op-
eration.

Noticed for twelve years.

Present for six years ; more rapid
enlargement a few months be-
fore operation.

Two years ; had enlarged rapidly
during the six months preced-
ing operation.

* F. J. Shepherd, Annals of Surgery, September, 1896.

f Cases VI and VII were operated upon shortly after Dr. Shepherd's article in the
Annals of Surgtry had gone to press, and consequently are not referred to in that article.

■

AC'

I •

W. I. Bradley 8

Before speaking generally upon the subject of these cysts, it will
be advisable to record briefly the results of the microscopical examina-
tion in each case:

Case I. — In this there were t)vo cysts in the right lobe, whose con-
tents were reported by Dr. Shepherd to be of the nature of a reddish-
brown fluid. The cyst wall did not come into my possession, the mate-
rial supplied to me being an ingrowth into the cyst. It presented the
characters of somewhat modified glandular tissue; the average diameter
of the vesicles appeared to be 15 fi, the largest measuring 60 /n.

Owing to the great variation in the size of the follicles, it is only
possible to give a rough approximate statement of the average size of
the vesicles. Although these figures have been reached by estimating
the diameters of fifty or more neighbouring follicles, it is not pretended
that they represent more than a general approximation to the average
sizp.

The majority of the collections of gland cells had no lumen, and were
4=imply clumps of nucleated cells. Some of the vesicles contained a dense
colloid material, deeply stained as though by blood pigment, and here
nnd there the colloid masses showed a definite concentric appearance.
In some, in the middle of the colloid, it was possible to recognise one or
more clear transparent crystals, varying in shape from a square to an
oblong, and in longitudinal diameter from 10 /x to 55 /it (Plate XV,
Fig. 1). As to the exact nature of these crystals, I am not in a position
to make any statement; they were unaffected by all the ordinary media
employed in hardening and fixation, such as alcohol, MUller't; fluid, and
the essential oils. It must be added that the crystals were .ijiy present
where there was surrounding interstitial haemorrhage, with a degenerated
condition of the epithelium.

Corresponding with the irregularity in the size and contents of the
vesicles, their epithelium showed great variation in depth. There was
periarteritis and also extravesicular (interstitial) haemorrhages; the capil-
laries were dilated, and the vesicles widely separated. This presence of
dilated capillaries and of hsemorrhages is worthy of note in connection
with the reddish-brown character of the fluid contained in the cyst.

The above case is unsatisfactory to this extent, that the relation-
ship of this intracystic growth to the cyst wall could not be made out,

# On IloiinorrKagic Cyait of the Thyroid Gland

and because the absence of the cyst wall prevented a fuller study of
the case. In the remaining cases the material sent fortunately in-
cluded the cyst walls, and thus gave a far more satisfactory insight
into the nature of the cysts themselves.

Case II. — (Two cysts of the right lobe, the second removed through
the posterior wall of the cavity left by removal of the first.)

The cyst wall in this case consisted of several irregular overlapping
and not perfectly concentric layers of dense fibrous tissue, with inter-
spersed occasional short imperfect layers, characterized by the presence
of numerous small nuclei. Some of the outermost of these imperfect
nucleated layers appeared to merge into more perfect gland tissue; they
represented evidently the remains of atrophied lobules or collections of
vesicles. Upon the inner surface of the cyst, section showed here and
there accumulations of well-developed vesicles 50 /* to JJOO /a in diame-
ter, possessing a somewhat flattened epithelium; here and there several
vesicles appeared to have run together into a common chamber.

There were, in addition, small areas of fibrosis and of calcareous de-
posits. The fluid filling the main cyst contained cholesterine crystals
and large, round cells filled with fatty globules. The fluid had a glairy,
yellowish-brown appearance.

Case III. — (Single cyst of right lobe.)

As in the case last mentioned, the cyst wall was formed of several
layers of fibrous tissue, with intermediate partial layers of atrophied
gland tissue. From the wall there projected inward large, firm masses
of gland tissue, with vesicles varying in diameter between 50 ^ and
400 fi, having a thin, low epithelium and very little tissue between the
individual vesicles. The fluid contents of the cyst were grumous, and
contained cholesterine crystals.

<:U'

Case IV. — (Single cyst of left lobe, the size of a hen's egg.)
The cyst wall possessed the same features as those in the last two
cases, except that it was not quite so dense, and that here and there in
it could be observed flattened masses of colloid. Greatly elongated vesi-
cles could also be seen gradually losing their epithelium, and passing
into what might possibly be lymph channels (vide Plate XV, Fig. 4).
Both on the outer and on the inner side of the cyst wall there was typi-
cal gland tissue, the diameter of the vesicles varying between 40 ji and
125 It.. In these masses of gland tissue protruding into the lumen of the

1 ^-

W. 1. Bradley •

cyst were unmistakable signs of old hsemorrhages (deposits of pigment
and cells containing pigment granules). The contents of this cyst were
reported by Dr. Shepherd to consist of a yellowish-brown fluid, with
blood clots.

Case V. — (Single cyst of left lobe, the size of a small orange.)
The wall of the cyst in this was much thicker than in the preceding
case, and was almost entirely fibrous, though there were evidences of
contained atrophied gland tissue. Externally, the gland tissue showed u
chronic interstitial thyroiditis, and in places merged imperceptibly inio
the cyst wall. In addition, the capsule exhibited patches of calcareous de>
generation; in the middle of one such patch the remains of an artery
showing obliterating endarteritis could be distinguished. The papilloma-
like ingrowths into the cyst showed dilated vesicles tilled with a clear
homogeneous colloid material; the vesicular epithelium was greatly flat-
tened, and exhibited areas of atrophy with communication between the
vesicles. There were the remains of old hsamorrhages with pigment de>
posits, and more recent haemorrhages causing rupture of the vesicular
epithelium, so that the blood was both intravesicular and extravesicular.
The contents of the cyst were reported by Dr. Shepherd to consist of a
straw-coloured fluid.

Case VI. — (Single enormous cyst of the left lobe of the siie of a
turnip.)

The wall of this cyst, which had of late grown rapidly, was compara>
tively thin, and in its immediate neighbourhood was found nonnal thy>
roid tissue, the vesicles averaging about 25 fi in diameter. All around
the inner aspect of the wall was similar tissue in fair quantities form-
ing an inner lining, and showing here and there a hemorrhagic focus.
At one place a large papillomatous mass projecting inward showed thy-
roid tissue of a similar nature, with, however, much fibrous tissue and
great compression of the vesicles. According to Dr. Shepherd's report,
the contents consisted of a dark-brown, thickish fluid, and from the pos-
terior wall there projected several papilloma-like patches the size of
walnuts.

Case VII. — (Large soft cyst of right lobe, extending beneath the
sternum over the vessels arising from the arch of the aorta; the cyst in
consequence could not be shelled out in its entirety.)

The wall of the cyst was very similar to that of the preceding case.
From the inner aspect there was thyroid tissue projecting, with vesi-

$ On Ilmmorrhagio Cyats qf' the Thyroid Gland

cles generally large, varying from 40 ^ to 250 /i, the average diameter
being calculated to be about 75 ft,. Here the interHtitial fibrous tissue
was much increased, the colloid in the follicles was shrunken, and there
were marked evidences of multiple haemorrhages, both intravesicular and
extravesicular. The contents of the cyst were reported by Dr. Shepherd

Case VIII.-^The eighth specimen receiVed from Dr. Shepherd was -;„ ^^ . ^^^^
of a different nature. While at the operation the case appeared to be c|^^;i;^''.$.4;>i ■
one of multiple large cysts with colloid contents affecting both lobeij
upon microscopic examination ox the dense colloid material enucleate^;
it was found that this was made up of thyroid tissue, with vesicles rangi-t^iv
ing from 25 /i up to 030 /* in diameter, the average being about 50 /*.
The vesicular epithelium was greatly flattened, and consisted of little
more than small rounded nuclei. Thus the case was one of multiple
nodular or lobular overgrowths, or, more correctly, aberrant growths of
the gland tissue. I have since received a similar specimen removed by
Dr. J. Bell from a patient in this hospital. • /;w>;^>ii , vfi,., ;>;-;: ..

Taking into consideration all of the varioiiis featurbs presented
by these large fluid cysts, it will be seen that the contents differ mark-
edly from those of the ordinary vesicles of the thyroid gland. They
are fluid, and in general present evidences of containing blood or
derivatives from the blood; they vary from a straw-coloured fluid
(as in Case V), through greenish brown (Case I), to a dark-brown,
grumous fluid (as in Case VI); or, again (as in Case IV), actual
blood clots may be present. It is of importance to note that when,
as in Case VI, the growth immediately before the operation had been
rapid and the cyst wall was thin, there was found the most abundant
evidence of recent effusion of blood; when, on the other hand, as in
Case V, the wall was thick and, judging from the calcareous deposits
within it, the cyst was of long standing and quiescent, the contents
showed least evidence of admixture with blood, consisting simply of
a thin straw-coloured fluid.

With regard to the nature of the cyst wall, this is of a somewhat
peculiar character. Although very definitely fibrous in composition,
its nature is not sharply defined. The layers composing it are not

.-m

^*-:

v^M^'^^'il

Ml.".. ' ■!. ' > -•.' . >< /

W.I. Bradley •• 7

tnily coiu'cntric; hero niul there between them occur masses of small
cells, which, by comparison with the tissue immediately outside the
wall, are soon to Iw clearly the atrophied remains of gland tissue (vide
Plato XV, Fig. 4). These features explain why it is that in enuclea-
tion the cysts are found not to bo sharply defined from their sur-
roundings, and permit successive irregular layers to be partially peeled
off. The wall, in fact, passes gradually into the bands of interstitial

' • •., ..... tissue running between the surrounding collections of vesicles, and

■k

" vv.-Xr.-A-'^-r-

.^t..

, ■ 5 -4.

Portion of the capsule of the thyroid cyst removed from Case V. x 10. * ' "

E, external aspect; I, internal aspect; W, W, cyst wall of varying thickness. 1, Fine
layer of thyroid tissue oovering inner wall of cyst; 2, 2, naass of thyroid tissue pro-
jecting into lumen of cyst; 8, 3, large and healthy thyroid vesicles; 4, dense fibroid
mass (atheromatous) with some calcification; S, 6, small areas of haemorrhage with
pigmentation ; 6, atrophied glandular tissue included between the layers of the cyst wall ;
7, fibrons band or layer passing from the cyst wall to partially cover the projecting mass
of thyroid tissue.

evidently represents not so much a new formation of fibrous tissue
around the cyst as a compression of the surrounding thyroid tissue.
In the older cysts, judging from the thickness of the wall, it would
appear that there had been a certain amount of new fibrous tissue j^*vv
formation.

Upon its inner aspect also the wall differs ^videly from that of

i>f

-■r"

On HcBrnorrhagic Cysts of the Thyroid Gland

an ordinary retention cyst; it is not lined either with well-developed
epithelium or with the remains of ;l tch tissue, while between the
contained fluid and the fibrous envelope is to be found irregularly
distributed a greater or less amount of intact gland tissue.

The appearances here presented differ widely from what is to be
observed in the ordinary parenchymatous goitre. In the latter the
cysts are gener<illy distributed through the substance, and, while
individual cysts are often clearly recognisable with the naked eye,
they do not attain to any great size. It is easy to follow the stages in
their formation — that is to say, an examination of sections taken
from cases of parenchymatous or colloid goitre reveals a series of
modifications of the vesicles which can not but represent successive
stages of the process. In the first place, the vei=»icles in general may
be enlarged and distended with colloid material; later, as is well
shown in Wolfler's figures of injected thyroids, where two distended
vesicles are in close apposition, the vessels in between become com-
pressed, and become atrophied — a result which is followed by atrophy
of the neighbouring epithelium and of the interstitial substance. The
next change is in all respects comparable with what obtains in the
emphysematous lung under similar conditions. The atrophied tissue
becomes completely absorbed, and the two vesicles fuse into one, small
projections being left jutting into the common cavity, and indicating
the site of the previous partition. This process of fusion may con-
tinue so that finally numerous vesicles may thus form one common

r* chamber. The characters of such cysts are constant; they have a
clear, sharply cut wall, covered by a continuous layer of epithelium,
which is more or less flattened in different cases, according to the
amount of pressure exerted by the contents. The walls of the cysts
outside the epithelium are thin and indefinite. They are comparable,
on the one hand, with the retention cysts to be met with in the various
acinous glands — in the kidney, the mamma, the pancreas, and the
liver — and, on the other, as above stated, with areas in the emphyse-
matous lung. As with other retention cysts, in these there may occur

. secondary papillomatous ingrowths.

The whole appearance of the large cysts heve referred to is that

W. I. Bradley

."■ s-^l

of an accumulation in a lobule of the thyroid, the accumulation
being associated with some destruction of gland tissue; not all the
gland tissue of the lobule has been destroyed; some is left, and it is
this that forms the characteristic irregular coating of the internal wall
of the cyst. In support of this opinion is the fact that the large masses
frequently found projecting into the cysts most commonly spring from
the inner or medial aspect of the cyst, from the region where the
lobules are not sharply cut off the one from the other.

It must be remembered that the thyroid is an imperfectly lobu-
lated organ; toward the periphery the gland substance is seen to be
partitioned off by fibrous septa, running in somewhat irregularly from
the surface. These septa, however, become broken up and indefinite
in the more central and deeper areas of the organ. But, apart from
the character of the lobulation of the gland, it is to be noticed that in
any case of accumulation of fluid in the interstices of the thyroid the
tendency would evidently obtain for destruction and rupture of the
tissue to occur in an outward direction — in the direction of least re-
sistance. Thus, any advancing destruction of thyroid tissue would
be most marked toward the exterior.

If this be so, and if these cysts be due primarily to destruction
of thyroid tissue and accumulation of fluid in a space bordered by
destroyed or partially destroyed vesicles, what is the cause at work
leading to sucu destruction?

According to Wolfler, the main cause is an oversecretion of col-
loid in the vesicles, with consequent rupture of these, infiltration of
the interstitial substance with colloid material, atrophy of the infil-
trated tissue, and subsequent continued excretion of colloid from such
of the epithelial cells of the ruptured vesicles as remain undestroyed.
He devotes two pages to a consideration of the successive steps in such
a process.*

So far as I have been able to determine, this view has been gen-
erally accepted, and no other explanation has been brought forward
by more recent workers to explain the development of these cysts.

* Wolfler, Ueber die Entwickelung und den Bau des Kropfes, Berlin, 1883,
p. 192.

On UdBmorrhagio Cyatts of the ITiyroid Oland

Among recent French writers, Kiviere,* in a treatise of one hundred
and fifty pages, while discussing various diseases of the gland and
pointing out that heemorrhage into the vesicles may lead to a true
heematocele, has nothing further to say with regard to the relation-
ship hetween such hsemorrhages and cyst formation beyond the bare
notice of the occurrence of heemorrhagic cysts, and of the liability
on the part of intra-acinous papillary growths to give rise to intra-
cystic haemorrhage. . In English and American literature, descriptions
of the removal of gross solitary cysts of the gland, evidently similar
to those about to be described, are not infrequent, but the surgical
features are in general dwelt upon to the entire exclusion of the his-
tological characters. The only full and exact description that I have
met with in English or American literature is in an article by Dal-
ziel upon a case described as one of cystic adenoma.f His description
tallies entirely with that given by me, and he is careful to draw
attention to the very extensive haemorrhages both into and around
the vesicles, and to the evidence that in part, at least, these are of old
itanding.

But it would seem that against the theory of Wolfler there is not
a little to be said. Rupture of a secreting organ or of the follicles
of a secreting organ as a result of overactivity is most rare, even in
the acini of glands which possess efferent ducts. When these ducts
are obstructed, and retention cysts developed, the (at times) enormous
expansion of the secreting surface in the cysts does not lead to spon-
taneous rupture. This certainly may be laid down as a rule to which
there exist only peculiarly rare exceptions. Wolfler states that, in the
thyroid, areas of such bursting of the vesicles can be recognised.
While I am most ready to admit that he has examined a very much
larger number of thyroids than has come into my hands, I feel it
right to say that in more than twenty-five separate specimens of this
organ which I have recently studied, the majority presenting one or
other morbid condition, I have not seen any sign of this bursting of
dilated vesicles, although I have carefully sought for it; or, to state

* Kiviere, Contribution a I'etude anatomique du corps thyroide et des
goitres, Lyons, 1893.

+ Dalziel, Olasgow Medical Journal, xli, 1894, p. 227.

W. I. Bradley

the case more exacth here I have found heemorrhage in the thy-
roid, with associated .^)ture of the vesicles, I have been tinable to
determine that this rupture was at the same time primary and spon-
taneous, associated with extreme distention.

Again, the nature of the contents of these cysts furnishes a strong
argument in opposition to the above theory. If these were essentially
the specific secretion from such of the epithelial cells of ruptured vesi-
cles as remain undestroyed, we should expect to find them charac-
teristically thick and colloid. But this is not the case. The peculiar-
ity of the contents consists in the presence of cholesterine, of leuco-
cytes loaded with fatty globules, and of a colour ranging from pale
brownish yellow to the pronounced purple of hsemorrhagic effusion.
The contents, it is true, are in general glairy, viscid, and albumin-
ous, and contain, in all probability, some colloidal material; but this
is greatly diluted, and altogether the specific secretion contained in
the fluid appears to be of secondary importance. The so-called col-
loid cysts of the thyroid, from which upon enucleation thick, clear,
semisolid matter is removed, are of a totally different nature from the
cases to which here I would draw attention.. According to my own
observations upon two such " colloid cysts " (to one of which I have
already referred), and the notes of a third case recently occurring
under Dr. Bell at the Koyal Victoria Hospital and reported to me
by Dr. Adami, hardening and section of such enucleated colloid mate-
rial show that it is not homogeneous, but is composed of numerous
greatly distended vesicles with very thin walls. The material is, in
fact, modified thyroid tissue,, and the condition is one of cyst-ade-
noma, with localized overgrowth and retention of the colloid within
the vesicles.

The examination of a series of thyroid glands obtained both from
the post-mortem room and from the operation theatre has made very
evident to me the frequency with which these organs become the seat
of heemorrhage. In case after case received from Dr. Shepherd and
from Dr. Bell there have been indications not merely of recent haem-
orrhages, which might have been accounted for by operative inter-
ference, but also of old extravasations of blood with the presence of

On Hemorrhagic Cysts of the Thyroid Gland

deposits of modified blood pigment, or again of large cells containing
the characteristic modified haemoglobin.

In Plate XV, Fig. 2, is shown one of these hsemorrhages.
The section was obtained from the upper part of the left lobe of
the thyroid of a patient who died in the Royal Victoria Hos-
pital some weeks after drinking a large dose of potash lye,
taken apparently with suicidal intent. In the region indicated
was a roughly spherical tumour, a little over two centimetres in
diameter, of comparatively firm consistence and of a rich red colour.
Sections through the tiimour showed that the hsemorrhage, which
must have been comparatively recent, inasmuch as the red corpus-
cles were in general well preserved, was limited in extent to one lobule
of the organ. Around it was a well-defined margin, formed of the
connective tissue separating the lobule containing it from the sur-
rounding lobules. In the affected lobule not all the tissue was the
seat of haemorrhage, sundry follicles and the surrounding interstitial
tissue being entirely free from extravasated blood (Plate XV, Fig. 2,d).
But, in general, there was clearly marked evidence of haemorrhage.
The blood had passed into the vesicles, and also into the interstitial sub-
stance. Many of the vesicles were very greatly distended with blood,
and presented a thin, flattened epithelium; in one place 'an area was
clearly distinguishable where there had been rupture of a small ves-
sel, with a pouring out of blood both into the follicle and into the
interstitial tissue. It was interesting to notice that in many places
follicles distended with blood could be recognised, around which there
was not the slightest sign of interstitial haemorrhage. The appearance
suggested strongly that the follicles communicate with each other,
and that haemorrhage had taken place into the follicles of one or more
communicating systems, while other systems had remained free.
Whether such communication is normal or acquired I will not ven-
ture to state. In several of the sections the conununications between
the injected follicles could be recognised; they were undistinguish-
able from what might have been produced by pressure atrophy,
though, at the same time, natural and not acquired communications
might present a similar appearance.

W. I. Bradley

In this case, then, we have an example of a heemorrhage limited
to and distending one lobule of the thyroid and of rupture of the
vessels resulting in distention of the follicles with interstitial disturb-
ance. Of actual cyst formation the specimen showed no sign.

Plate XV, Fig. 3, represents a much further advanced condition.
The case from which this was taken was one of parenchymatous goitre
in a woman of twenty years, with diffuse hypertrophy of the organ
most marked upon the right side. For four or five years the growth
had been slow ; during the last twelve months it had been more rapid.

Examined microscopically, the vesicles were found to vary greatly
in size (from 15 /ti to 300 fi in diameter, the average appearing to
be from 25 /i* to 30 /t). The larger vesicles were relatively rare,
and occurred mainly in the deeper, more central portion of the gland.
The contents of the vesicles had a shrunken appearance, and their
epithelium was of well-formed columnar type. There was a certain
amount of hyaline change in the interstitial tissue.

The enlarged gland presented several haemorrhages, and upon a
closer study of these under the microscope some vesicles were seen
filled with blood, as in the previous case. There had, however, been
more abundant extravasation into the interstitial substance, and, fol-
lowing upon this, a rupture of numerous follicles. In this way spaces
had been produced filled with blood, and showing here and there along
their edges layers of columnar epithelial cells, the remains of the
burst follicles. Small collections of cells and masses of dislocated
tissue could be recognised here and there in the blood-stained fluid,
filling these rents in the thyroid. The haemorrhages were not en-
tirely recent, for in the interstitial substance and in some of the vesi-
cles large pigment-containing cells could be seen.

Two series of changes might reasonably be expected to occur in
connection with a lesion such as has been described. Either the epi-
thelium of the ruptured follicles might undergo atrophy, the effused
blood might become absorbed, and, through simple inflammatory and
reparative processes, the lesion be eventually represented by a small
mass of fibroid cicatricial tissue containing more or less blood pig-
ment. In other regions of the specimen last described patches of

On Ilcemorrhagic Cyds of the Thyroid Gland

fibroid tissue of this nature were observed, and their presence would
seem to indicate that small htemorrhages had been frequent in this
^ case. Or, on the other hand, where the hsemorrhage has been very
extensive, there might be developed in the thyroid, as in the brain,
a hsemorrhagic cyst, the contents of which, according to the age of
the cyst, might, as in other heemorrhagic cysts, vary from almost pure
blood, with some admixture of the destroyed tissue of the part, to a
straw-coloured fltiid.

Such would seem to be the nature of the cysts here described.
The two would possess features in all respects similar. Hsemorrhagic
cysts of the nature I have indicated would tend to be limited by the
interlobular connective tissue; within the boundary wall there would
be not only fluid contents, but a lining of glandular tissue represent-
ing those portions of the lobule not destroyed at the time of the orig-
inal haemorrhage, and gaining a collateral circulation from the vessels
of surrounding lobules.

Whether or not the remaining epithelium of the burst follicles

continue to be well nourished and to pour out its excretion is a matter

of possible doubt. For myself, I have never in a well-developed cyst

seen the slightest indication of even a localized presence of an internal

layer of thyroid epithelium; on the other hand, it must be acknowl-

I edged that the contents are at times very glairy, and strongly suggest

1 some admixture of dilute colloid material. I regret to say that I did

I not at the time test the contents of any of the cysts for the presence

' of colloidal bodies.

On the theory of rupture and destruction of thyroid tissue, there
is an anatomical basis for the frequent presence of large masses of
thyroid tissue projecting into the cyst from its medial aspect. To
this must be added the fact that the macroscopical and microscopical
appearances of these ingrowths are wholly against the supposition that
they are neoplastic; their surface is covered with a fairly dense layer
of fibrous tissue, continuous with the internal layers of the cyst wall;
their peduncles are, in general, broad, and pass imperceptibly into a
layer of tissue containing thyroid vesicles, which, on the one hand,
merges into the layer of glandular tissue lining the inner surface of

W. I. Bradley

the cyst wall, and, on the other hand, did not in any specimen ex-
amined by me appear to be sharply differentiated from the surround-
ing and deeper thyroid tissue; in short, the vesicles in these papillae
resemble the vesicles of the tissue surrounding the cyst. I have
already pointed out the many ways in which the contents of these
cysts differ from ordinary thyroid secretion, and approach in char-
acter to hsemorrhagic products.

I. am led, therefore, to regard these large solitary or rare cysts
of the thyroid gland as being hsemorrhagic in origin, and I would
speak of them as hsemorrhagic or post-hsemorrhagic cysts of the
organ.

Many circumstances combined would seem to render the thyroid
gland an organ peculiarly liable to be the seat of haemorrhages. There
is, in the first place, the peculiarly vascular character of the organ;
in the second, its relatively exposed situation; and, in the third, there
may be mentioned, as tending to explain the greater frequency of
haemorrhages, both small and large, in this organ in the female, the
changes, apparently to a large extent vascular, which occur in con-
nection with sexual disturbances. It is, however, clear, from the de-
scription given to me by Dr. Shepherd and recorded by him in his
article in the Annals of Surgery, that in most, if not all, of the cases
these gross cysts do not develop in healthy thyroids, but that there
would seem to have been already some pre-existing morbid condition
of the gland predisposing to their production. Judging from the por-
tions of tissue surrounding the cysts that were sent to me, the condi-
tion most frequently associated with their development is that of a
more or less advanced parenchymatous goitre.

As I have pointed out, in the parenchymatous goitre, even if there
be no definite cyst production of a gross type, there may be numerous
haemorrhages; and when it is remembered how delicate are the walls
of the distended cysts in this condition, and how abundant at the same
time is the vascular supply of the organ and the network of capillaries
immediately surrounding the distended vesicles, it is not difficult to
realize why it is that such haemorrhages occur, more especially when
the relatively exposed situation of the enlarged gland is taken into

On lIcBmorrhagio Cysts of the Thyroid Gland

account. Here, in short, exists the most favourable combination of
circumstances for the production of extensive haemorrhages and of
heemorrhagic cysts of the thyroid.

There is one feature of these large cysts which is certainly difficult
to explain. I refer to the frequent history given of progressive en-
largement, more especially in the early stages. Unfortunately, the
clinical histories of my cases are not of a detailed nature. In only
one case is it definitely stated that the tumour appeared with compara-
tive suddenness — after violent seasickness — and, when once devel-
oped, the patients have yielded no definite information as to whether
the earlier growth was gradual, periodic, or irregular. In the later
stages, in five out of the seven histories, it is noted that there was sud-
den or rapid increase. The grumous and blood-stained contents would
seem clearly to indicate that this later and sudden increase in size is
due to repeated hsemorrhages. In Cases II and VII the thyroid en-
largement had been noticed for ten and six years respectively; never-
theless, the contents gave evidence of relatively recent effusion of
blood. It is remarkable how frequent were the evidences of hcemor-
rhage in the projecting masses and surrounding tissue. Possibly the
earlier growth is due to a like cause, but, as I have said, the clinical
histories do not throw light upon this point.

The progressive enlargement can not be due to secretion from the
epithelium lining ruptured vesicles, for in none of the cases of well-
developed cysts have I encountered any sign of even localized epi-
thelial lining.

It is possible that the cysts occur in and replace nodular parenchy-
matous hypertrophies or adenomata of the gland tissue, and that in
some of the cases the progressive enlargement noticed in the earlier
stages was due to the gradual growth of such nodules, which later
became the seat of haemorrhage and cyst formation. The material
at my disposal, which consisted of the enucleated cysts and their con-
tents, is incapable of deciding this question one way or the other.

That the growth, if gradual and cystic from the onset, is due to
effusion or imbibitions of serous and colloid fluid from the surrounding
vessels and lymphatics is but a remote possibility. •

W. I. Bradley

The most I can venture to state with any degree of certainty is
that the more rapid and sudden enlargements of the cysts in the later
stages can be ascribed to repeated haemorrhages. I must leave to
others possessing fuller opportunities the explanation of the nature
of the gradual growth which, from the patients' reports, would seem
to be the rule at the onset.

The view here enunciated may involve, it is true, only a slight
modification of Wolfler's theory; nevertheless, it seems to me im-
portant to recognise the distinction between such spontaneous rupture
of distended thyroid vesicles, as is urged by him, and the more in-
herently probable traumatic rupture with htemorrhage, as here sug-
gested.

Conclusions,

1. All the features peculiar to the gross cysts of the thyroid
gland which possess fluid contents appear to indicate that they are
essentially of hsemorrhagic origin.

2. While these gross cysts would seem more especially to occur
in glands which already present the features of parenchymatous
goitre, the theory of Wolfler that they originate as a consequence of
spontaneous rupture of the vesicles is unsatisfactory.

3. It would seem more probable that these large cysts are due
to rupture, traumatic or otherwise, of some of the vessels of the organ.
The frequent signs of small hsemorrhages in cases of parenchymatous
goitre without evidence of associated gross change in the surround-
ing vesicles, the structure of the organ and its exposed position, all
appear to favour this view.

Finally, I beg to express my indebtedness to Dr. Shepherd for his
kindness in affording me, while working mainly in the pathological
department of the Koyal Victoria Hospital, the material from the
Montreal General Hospital, which has formed the groundwork of this
paper. I beg to thank also Dr. James Bell for the rest of my material,
and Prof. Adami, at Avhose suggestion I undertook this research, and
to whom I am indebted for advice throughout its course.

On IIiemorrha</lc CysU of the Thyroid Gland

Description of Plate XV.

Fig. 1. — From a hteinurrhugic area in one of the masses projecting into
the cysts in Case I. Magnified 250 diameters.

The hieniorrhages in the projecting masses in this case were extensive
but entirely interstitial, but the colloid contents, a a, of the vesicles had im-
bibed the blood-colouring matter and possessed a deep-brown colour, while in
addition (in these hffimorrhugic areas only) there were to be seen the large in-
travesicular crystals, b b. The vesicular epithelium presented numerous fine
vacuoles and other indications of degeneration, c c, blood effused between
the vesicles.

Fig. 2. — From the interlobular hipmorrhage in the thyroid of Mrs. C. to
show interstitial and intravesiculur effusion of blood. Magnitied 2U0 diame-
ters.

a. Interstitial hoemorrhage. b. Vesicles filled with blood; disappearance
of colloid material and very great distention, with flattening of epithelium,
c. Region of rupture, d. Intact vesicles with colloid contents, f. Large pig-
mented wandering cells.

Fig. 3. — From an extensive hseniorrhage, very recent, in a case of paren-
chymatous goitre, Mrs. F., aged twenty years. Magnified 200 diameters. The
figure shows rupture of the thyroid tissue. The effused blood is bordered
in part by the epithelium of large ruptured vesicles, in part by interstitial
tissue. (The former condition was only exceptionally observed in the sec-
tions.)

a. Intact vesicles of medium size. b. " Embryonal " masses of glandular
tissue, c. Epithelium of large ruptured vesicles bordering upon the haemor-
rhage, d. Broken-down thyroid tissue, f. Eft'used blood.

Fig. 4, — Section through the wall of one of the cysts, from Case IV. Mag-
nified 250 diameters.

The section has been taken through a region where there was a low pro-
jection of thyroid tissue into the cyst, and the figure only includes the ex-
ternal portion of this and is not continued to the outermost portion of the
cyst wall, where it passed into the surrounding thyroid tissue (beyond li) .

a. Healthy vesicles lying along the inner wall of the cyst. b. Terminal
portion of a long vesicle lying along the main fibrous tissue of the cyst wall.
This contained blood, and, as shown in the figure here and there, along its
outer aspect there was an absence of epithelium, this being replaced by a
layer of flattened cells, c. Undeveloped gland tissue, d. Lymph space (?).
f. Simple connective tissue forming the cyst wall. g. Undevelopec" and com-
pressed gland tissue in the thickness of the cyst wall. h. Lymph spaces, or
vesicles that are atrophied and devoid of epithelium, filled with honiogpneous
colloid material, m. Corpuscles containing blood pigment, n. Epithelium of
a vesicle tinged with blood* pigment.

[All the figures have been drawn by means of a Zeiss'a camera lucida.
Fig. 3, taken from a somewhat thick section rich in deeply stained nuclei,
while correct in its outlines, has its details rendered purposely in a slightly
conventional manner.]

THK JOURNAL OF EXPERIMENTAL MEDIOrNE. VOL

PLATE XV.

*'----_.^^K'^'

•)• O- A. DEL,

A^ HMN ft OO.