infrequently seen in the tissue outside a lobule in rows three
or four deep ; again, they are found in the interfascicular spaces
among thelymphoid-cells," that have been already mentioned.
These large, granular, and nucleated corpuscles are said to be
filled with a bright yellow or golden pigment. Now, Creighton
has pointed out that the periodical subsidence of the mammary
function is accompanied by the formation of much corpuscular
waste material. And the production of these remarkable yel-
low cells, which finally leave the gland by way of the lymph-
vessels, is, according to him, but a final phase of this process.
The mammary epithelium which paves the acini has been
variously described as consisting of flat polyhedral (Reinhard) ;
FIG. 190. Transverse section
through the terminal vesicles of the
gland in a nursing woman, showing
mteralveolar capillaries. Langer.
THE MAMMARY GLAND.
cubical, cylindrical (Kolessnikow) ; small polyhedral (Langer) ;
and prismatic (Kehrer) cells. This discrepancy of opinion re-
ceives its explanation from the fact that the epithelial cells
FIG. 191. Lobule of a mamma near the resting state. Numerous large pigmented cells within the
acini and in the interlobular flbrillar tissue. Creighton.
have a different appearance in the various conditions interven-
ing between full activity and complete rest of the gland.
Creighton has given a very satisfactory description of mam-
mary epithelium. He states that in the fully expanded gland
" the floor of an acinus in section is covered by a mosaic of
polyhedric epithelial cells, usually to the number of fifteen
or twenty, while in the larger elongated
acini as many as thirty may be counted.
The cells are usually pentagonal or hex-
agonal, and the corners are sometimes
rounded. In each cell there is a central
round nucleus, which colors brightly
with the staining fluid, and abroad fringe
of protoplasm, which stains less deeply."
The nucleus varies in its relative size,
generally having a diameter equal to
about one-third that of the entire cell.
" In a profile view of an acinus, the epithelium appears as a
circlet of oblong cells, in which the nucleus at the centre occu-
pies almost the entire thickness of the cell. The mammary
epithelial cell may therefore be described as a flattened poly-
hedric body, with a thickness about one-half of its breadth.
The substance of the nucleus is apparently homogeneous, with
FIG. 192. Fully expanded aci-
nus, showing mosaic of polyhedral
MANUAL OF HISTOLOGY.
a deeper line of staining round the margin ; a nucleolus is not
always prominently seen."
Structure of involuted mamma. Having thus briefly indi-
cated the main histological features of a fully evolved gland,
we are now prepared to examine the mamma in a condition of
advanced involution. By involution, in this sense, is meant
the periodical return to inactivity, and not to final retrograde
metamorphosis, which culminates in complete senile atrophy.
The glandular lobules, then, in the involuted organ are again
found to be composed of closely crowded alveoli. But all the
lobules appear to have become smaller, and
their acinous components are likewise shrunk-
en. The basement-membrane of the latter
does not appear to be materially altered, but
its cellular contents are considerably changed.
In place of the beautiful mosaic characteristic
of the active gland, there now appears only
an aggregation of nucleated corpuscles to the
number of five or ten. Creighton describes
them as " nothing else than a somewhat ir-
regular heap of naked nuclei, with no fringe
of protoplasm round them, and in size little,
if at all, larger than the nucleus alone of the
P^fect epithelium." ' This description, how-
ever > applies only to hardened specimens, for
in fresh preparations the nuclei, as a rule,
show a broader or narrower surrounding zone of protoplasm.
As regards the diameter of the involuted acini, it is about one-
fourth that of the actively secreting alveoli.
Owing to the shrinkage in the glandular parenchyma, the
blood-vessels and excretory ducts, as already stated, are more
prominent in an involuted than in an active gland.
It is not our purpose here to trace, step by step, the various
processes by which a gland passes from the resting state to
that condition of complete evolution which is alone compatible
with active secretion. For the details of this interesting subject,
the reader is referred to the work of Creighton. We may, how-
ever, very briefly summarize this author's account of the trans-
formations in question. The one essential circumstance char-
acterizing the whole change is a process of vacuolation, which
Creighton assumes to take place in the secreting cells. "The
THE MAMMARY GLAND. 447
most definite and unmistakable form of vacuolation is the sig-
net-ring type." This process is, according to him, a true one
of endogenous cell formation, resulting in this instance in the
formation of milk. Moreover, large, granular, nucleated cells,
filled with a bright yellow or golden pigment, "found both
within the alveoli and in the interfibrillar spaces without them"
FIG. 194. Vacnolation of alveolar epithelium. From the udder of a ewe shortly after the end of lac-
tation. The cells in situ are vacuolated cells, with the usual thin and, for the most part, uncolored hoop
or ring of the vacuole, and the deeply stained peripheral mass. Creighton.
characterize the last stage of involution, "and the pigment
that belongs to them is to be found strewn over the lobules
that have reached the resting state." Finally, Creighton as-
serts that " the various forms of cells that characterize the
various stages of involution must have resulted from a trans-
formation de novo of the renewed epithelium, and not from
successive changes upon the same cell." Each epithelial cell,
therefore, that is used up in the formation of milk, has been at
one time a perfect polyhedral corpuscle or fully equipped cell,
and "has rapidly undergone the cycle of changes whereby
its whole substance has been converted into milk."
A distinguishing feature of one stage of evolution which
MANUAL OF HISTOLOGY.
deserves to be mentioned, is " the presence in the cavities of
the acini of a peculiar granular material, the coagulated con-
dition of a fluid." Partsch has also described the occurrence
of this granular mass within the alveoli, and he states that the
secreting epithelia, though of normal size, were furnished with
shrunken nuclei, and showed numerous light spots, as if the
cells were perforated and sieve-like. It
would appear that this writer has ob-
served the stage of vacuolation with-
out, however, interpreting the same in
Creighton also describes in certain
glands the connective-tissue stroma as
crowded with cellular elements, which
he considers equally with the pigmented
corpuscles as waste-cells of the secre-
tion. Others (Winkler, Brunn, and par-
ticularly Rauber) have assigned a far
different significance to these bodies, as
will appear farther on. Finally, Creigh-
ton explains that the secretion of the
mammary gland " may be said to be pro-
duced by a transformation of the sub-
stance of successive generations of
epithelial cells, and in the state of full activity that transfor-
mation of the substance is so complete, that it may be called a
Although Creighton's investigations did not extend to the
human mammary gland, there is ample ground for the belief
that changes of evolution and involution similar to those which
he has described in animals, constantly take place in the hu-
man female as well. And even if we accept only some of his
views on the inter-relations of physiological action and histo-
logical appearance, the discrepancy still existing in the de-
scriptions given by different authors will receive a more rational
explanation than has hitherto been offered by writers on this
subject. Certainly some of his assertions appear rather fanci-
ful in their far-reaching novelty, nevertheless they deserve the
attentive consideration which we have, at least, in part bestowed
From the results of our own examinations, we are unable
FIG. 195. Acini from a partly
expanded gland, some of them
filled with a granular material.
From the mamma of a pregnant
THE MAMMARY GLAND. 449
to concede in all respects the correctness of Creighton's inter-
pretations. The evidences of epithelial destruction for purposes
of milk secretion, are not positive and convincing. In the Har-
derian gland, as well as in the mamma, we have observed the
extrusion of fat-droplets from cells replete with them without
destruction of the cell itself. Partsch agrees with us in assum-
ing that the cells may burst or otherwise discharge their con-
tents, and yet retain enough protoplasm to maintain their vital-
ity ; and also that the vital contractions of the protoplasm
may force out the oil-globules without destruction of the epi-
thelium. What Creighton has called vacuolation does not mean
death to the cells concerned in this action, for they retain their
nuclei and sufficient protoplasm to become re-established as
perfect epithelia. That this reformation of old epithelium
takes place, is proven by the fact that a new formation by
proliferation has never been observed, and by the additional
circumstance that the mammary acini never show more than
a single layer of lining-corpuscles, and, moreover, always show
this layer complete.
In this, as in many other respects, the mamma closely re-
sembles the Harderian gland, more particularly of the roden-
tia, as described by one of the writers in a monograph. The
basement-membrane of the acini in every particular also corre-
sponds in the two kinds of glands, being in both a homoge-
neous, apparently structureless membrane, with superimposed
branched adventitial cells, the so-called Stutzzellen of German
writers. A basket-shaped reticulum, such as has been described
by Boll, Langer, Kolessnikow, Moullin, and others, is never
found to constitute this membrana propria, although artifi-
cially, appearances simulating a structure of this kind are
readily obtained, and have been interpreted by several histolo-
gists as natural occurrences.
In the cutaneous sebaceous glands the secreting vesicles are
filled with several superimposed layers of epithelia, and it is
this circumstance which leads to an entirely different mode
of secretion. For there it would indeed appear that the cells
undergoing fatty degeneration become detached from their
bases and find their way into the narrow lumen of the acinus.
The older or inner generation of cells thus vanishing is replaced
by new corpuscles formed by gradual proliferation from the
450 MANUAL OF HISTOLOGY.
RaiCber* s mews on the mamma and the lacteal secretion are
somewhat startling, but must occupy our attention here. From
a series of very carefully conducted examinations, principally
on the glands of guinea-pigs during and after pregnancy, he
feels justified in concluding that milk owes its orgin to the
entrance of countless leucocytes into the lumen of the gland-
vesicles. The emigrated lymphoid elements, he believes, pene-
trate the alveolar walls, passing through the single layer of
epithelial cells which line them. Arrived in the interior of an
ultimate acinus, the leucocytes undergo fatty metamorphosis,
and thus at length furnish the most essential and characteristic
ingredient of milk, viz., the milk-globules. Rauber, therefore,
discards the notion that the formed particles of the lacteal
secretion originate in the glandular epithelium, and represent
the elaborated products of its functional activity. He also
denies that previously formed milk globules, or colostrum cor-
puscles, ever pass through the alveolar walls. Thus the prim-
itive opinion advanced by Empedocles, describing milk as white
pus, is in a measure revived, and milk is held to be directly
-derived from the white corpuscles of the blood.
Preparations of mammary glands taken from animals still
suckling their young, according to him, invariably show the
intraglandular lymph-vessels replete with leucocytes, the stro-
ma similarly infiltrated, identical corpuscles in greater or less
abundance within the vesicles, and transitional forms between
lymphoid-corpuscles and milk-globules. These claims, granted
to be facts, and considered in conjunction with the circum-
. stance that epithelial proliferation is not seen, would certainly
.go far to make Rauber's theory seem a somewhat plausible
one. Nevertheless, we require corroborative evidence from
Bothers, before his views can be accepted as anything more than
an ingenious hypothesis.
Rauber has also described the occurrence of a delicate stri-
.ation within the epithelial cells of the alveoli. These striae are
said to be in all respects similar to those found in the secreting
elements of certain portions of the salivary glands and the
iubules of the kidneys.
As regards the corpuscles of Donne, or colostrum bodies,
most authors regard them as the products of desquamation of
the alveolar epithelium, the latter being in a condition of fatty
degeneration (Winkler, De Sinety, Buchholtz, and others).
THE MAMMARY GLAND. 451
Some histologists, like Strieker, hold that oil-globules may be
expelled from the interior of fat-filled cells without disintegra-
tion of their protoplasmic bodies. It is an undoubtable fact
that colostrum corpuscles, when managed with proper precau-
tions, may be seen to yield droplets of fat under the micro-
scope, just as amoebae reject similar contained particles. Rau-
ber, however, maintains that these bodies represent leucocytes
in various stages of fatty metamorphosis, and he calls such
corpuscles, when found in the gland vesicles, galactoblasts.
In the gland of Harder, one of the writers has found the
spacious gland vesicles lined with very large epithelia ; and
these cells were in many animals entirely fat-filled. They se-
creted a greasy substance not unlike thick milk. Yet destruc-
tion of the cell-body did not occur, at least evidences of such
a process could not be obtained. Partsch has therefore antici-
pated the authors in their conclusion that the secretion of milk
is accomplished in much the same way in which the creamy pro-
ducts of the Harderian gland are formed, i.e., without total
destruction of epithelial cells. According to our view, then,
and it nearly coincides with the opinion of Strieker, Winkler,
and especially Partsch, the cells containing the fat-globules
may, indeed, burst and discharge their contents, but the nu-
cleus and sufficient protoplasm are retained to enable the epi-
thelium to recuperate, and in the course of time again and
again discharge its contents. Along with this mode of milk
secretion, a second process occurs. This consists of the gradual
extrusion of oil-droplets, the cell body remaining entirely in-
tact, since the mere vital contractions of the protoplasm suf-
fice to drive out one milk-globule after another.
When the activity of the gland is suddenly heightened in
the period immediately before childbirth, some few epithelial
cells are desquamated. These, appearing in the milk of most
women, are identical with the bodies known and described as
Of other anatomical constituents of normal milk, we only
find the milk- or oil-globules. They are suspended in the fluid
emulsion which milk truly represents, in countless numbers.
They vary in size from 0.002 to 0.009 mm. A very delicate
fringe of protoplasm adheres to their periphery, and it is for
this reason that they may appear to become stained when sub-
mitted to the action of proper dyes.
MANUAL OF HISTOLOGY.
DEVELOPMENT OF THE GLAND.
Like the other cutaneous glands of the body, the mamma
is first formed by a proliferation inward of certain epidermal
cells. In other words, the breast results from a downward
extension of epiblastic corpuscles. The first unmistakable indi-
cation of the future gland is seen about the third or fourth month
of pregnancy. At that time it consists of a solid plug, or pro-
Fio. 196. 1. Rudimentary form of gland
in human fcetus: a, 6, epidermis : c, aggrega-
tion of cells ; d, connective tissue layer. 2. From
a seven-months' foetus : a, central substance ;
&, larger, and c, smaller outgrowths. Frey.
FIG. 197. Embryonal mamma : a, cen-
tral mass, with 6, and c, variously shaped
cess, extending downward from the rete-mucosum of the skin.
This has been called Drusenfeld, by Huss. From the internal
end of this solid process, sprouts, or offshoots, are developed,
and they represent the future separate glands constituting the
mature organ. These buds have a pyrif orm, or club-like shape,
and are surrounded by ordinary embryonal connective tissue.
The further growth of the gland takes place by a process of
continuous extension and subdivision, but indications of the
latter are not always found at birth. Ducts are already visible
in the new-born infant, but the aggregations of cells represent-
ing the future acini, remain without lumina for a much longer
Th. Kolliker describes as a constant occurrence, especially
marked in the breasts of female infants, the dilatation of a
greater or smaller number of milk-ducts. Such ectatic-canals
DEVELOPMENT OF THE GLAND. 453
liave their lumina filled with desquamated epithelial cells, and
a whitish, granular material. Formerly, these occurrences were
considered to be exceptional, and were regarded as having a
pathological significance. During the first year of extra-uterine
life, this characteristic process of progressive dilatation may
assume such large dimensions, that the mamma may come to
resemble cavernous tissue, the ectatic spaces of which are
paved with flattened epithelium. Within certain limits, Kolli-
ker regards this as a perfectly normal physiological event. But
he adds that an exaggerated process of this kind may result in
early mastitis. Such an occurrence, he thinks, may explain
the rudimentary development of the breasts observed in some
women of otherwise normal growth.
The post-embryonal growth of the mamma has been care-
fully studied by Langer, and his results and conclusions having
been confirmed by the investiga-
tions of Kolliker, Huss, and others,
must still be received as represent-
ing the true condition of things, in
spite of the novel and heterodox
views advanced by Creighton.
Up to the time of puberty, the
growth of the breast is very grad-
ual and quite insignificant, even in
females. Then, however, the ducts
begin to rapidly ramify in all di-
rections, and, by offshoots from va-
rious points, true acini are at length
developed. But they remain of
small size until the stimulus of
pregnancy causes a further evolution. In the male, the exist-
ing ducts, as a rule, atrophy with advancing age. The evolu-
tion changes which the mamma undergoes during pregnancy,
have already been set forth, and there remain to be considered
only those final phases of metamorphosis which take place in
the climacteric period of life.
These are readily understood, consisting essentially of a
complete atrophy of all the secreting acini. Simultaneously
with these atrophic changes the epithelia of the galactophorous
ducts become flattened, and finally shrink, so as to form only
squamous plates, which line the ramifying processes of connec-
454 MANUAL OF HISTOLOGY.
tive tissue representing the former lactiferous canals. The
terminal portions of these larger duct-remnants are sometimes
connected with minute channels, the latter being the remnants
of collapsed smaller ducts. In some measure we find a com-
pensatory production of fat, which partly replaces the faded
acini. The breasts of old women, therefore, consist of fibrous
tissue, with a large proportion of elastic elements, fat-cells, and
the remnants of the ducts. It may be remarked that the latter
frequently show cystic dilatations, the cavities being filled with
a dirty, slimy fluid. The blood and lymph-vessels, but especi-
ally the latter, participate in the general atrophy of the tissues.
This succinct account concerning the histogenesis of the
mammary gland, does not, as already intimated, represent the
unchallenged opinion on its first development. For Creighton,
in the remarkable work already cited, radically opposes the
view that the mamma takes its origin from the epiblast. He
believes, on the contrary, that it starts from the mesoblast, or
connective-tissue layer of the embryo, and not the upper epi-
thelial layer or epiblast. According to him, moreover, and his
conclusions are based on developmental studies, chiefly of the
guinea-pig's gland, the process may be justly described as a
centripetal one, whereas the current view represents this gland-
develpoment as essentially centrifugal. We have already ex-
pressed our adherence to the current view, attributing this
growth to extension from a central point. Nevertheless, it
seems proper to briefly give the conclusions of Creighton, es-
pecially since they appear to be singularly corroborative of the
account given by Goodsir of this process, as early as 1842, an
account which has apparently remained almost unnoticed by
workers in this branch of scientific medicine.
, Creighton then concludes his inquiry as follows :
" 1. The mammary acini of the guinea-pig develop at many
separate points in a matrix -tissue. The embryo cells from
which they develop are of the same kind that give origin to
the surrounding fat-tissue. The process of development of the
mammary acini is, step-for-step, the same as that of the fat-
" 2. The ducts of the mamma develop from the same matrix-
tissue, by direct aggregation of the embryonic-cells, along
predetermined lines. The ducts develop, in the individual
guinea-pig, before the acini, whereas, in the phylogenetic sue-
DEVELOPMENT OF THE GLAND. 455
cession, the ducts are a later acquisition. This reversal of the
order of acquisition of parts is in accordance with the prin-
ciple stated by Herbert Spencer, that 'under certain circum-
stances the direct mode of development tends to be substituted
for the indirect.' '
Hints regarding the histological study of the mamma.
The evolution of the mammary structure progresses paripassu
with the development of its functional activity. It is the stim-
ulus of pregnancy which determines both. Nevertheless,
even during the period of its fullest physiological bloom, i.e.,
during lactation, variations in the degree of functional activity
normally take place. Moreover, the same gland may contain
lobules which are comparatively at rest, and others which are
at the full height of activity. This should always be borne in
mind in interpreting the results of histological inspection of
this organ, lest erroneous impressions be conveyed.
The alveolar epithelial cells will, therefore, not be found
alike in the different acini, nor yet even in the same vesicle.
We may find cuboidal cells, and cylindrical ones, and flattened
corpuscles, and in addition, various transitional forms between
The nucleus will appear round, or oval, and about 6-7 j* in
diameter. Sometimes two nuclei may be found in one cell.
The radiating striation observed by Rauber in many cells, has
already received mention. It is a noteworthy fact that the
cells themselves contain only a very small proportion of fatty
granules, whereas the intra-alveolar lumen is often replete
with the same.
In order, then, to study the histology of the gland at the
high- water-mark of its functional activity, animals should be
chosen which have either just given birth to their young,
or are about to do so. For the normal conditions of the
human mamma are rapidly transformed by post-mortem change,
if not previously altered in consequence of the disease which
caused the death of the individual. The organ may be exam-
ined fresh, or else hardened and then cut in sections to be
stained and mounted in the ordinary manner.
456 MANUAL OF HISTOLOGY.
RUDOLFI. Bemerkungen ueber den Bau der Briiste. Abhandl. der Berliner Akad.
DONNE, AL. Du lait, etc., en particulier de celui des nourrices. Paris, 1837.
COOPER. Anatomy of the Breast. 1839.
GUTERBOCK. Ueber die Donneschen Corps granuleux. Miiller's Archiv. 1839.
HENLE. Ueber die mikroskop. Bestandth. d. Milch. Froriep's Notizen. 1839.