and from the intact remnants of epithelia
of the utricular glands and surface epithelia
the new epithelia is formed by the mitotic
process, as noted by Amann. In the endo-
metrium new formed glands by invagina-
tion of the surface epithelia either in regen-
eration or hyperplasia is not probable.
This assertion should not be confounded
with erosion of the portio vaginalis uteri as
that has relation with the fiat epithelia of
the vagina.
W&m
Fig. 6 (J. A. Amann) represents typi-
cally the glands of the cervical endometrium.
Cdr, acinous cervical glands. Note how
irregular the gland wall and how small the
mouth. The secretion of large amounts of
mucus which may dry, become inspissated
toward the mouth explains why obstruction
so frequently occurs at the mouth, producing
dilitation of the glands — follicles of Naboth.
The stroma cells of the endometrium are
regenerated from existing remnants by mi-
tosis. The) present a rich mitosis scattered
here and there among the cells. In some
cases the mitosis cells are forced partially
from the adjacent cells by collections of
fluid. The endometrial stroma cells re-
quire regeneration slightly after menstrua-
tion, but especially after parturition and
curettage.
The endothelia of the blood and lymph
vessels in the endometrium regenerate by
mitosis. The mitotic cells project toward
the lumen of vessel. It appears that the
endothelia mitosis progresses independent
of the stroma or epithelial cells of the endo-
metrium. Endothelial mitosis is required
in curettage, but especially subsequent to
menstruation and parturition. Histogeni-
tically no differentiation can be made be-
tween the regeneration of the elements of
the endometrium and hyperplasia of the
THECHARLOTTE MEDICAL JOURNAL.
441
same. Hyperplasia of endometrial elements
's perhaps excessive regeneration only.
Hyperplasia of the endometrium refers
to a proliferation or the excessive forma-
tion of nevsr elements. It affects (a) the
Fig. 7 (J. A. Amann). Erosion during
healing, a, flat epithelia which has grown
over the glands and depressions, b, cylin-
drical epithelia, c, c, proliferated glands
and cylindrical epithelial gland like cavities,
d, infiltration of leucocytes, e, utricular
glands, o, glandular cystic dilitation (Ovu-
lum Nabothi).
glandular epithelia ; (b) the surface epithe-
lia ; (c) the stroma cells; (d) the endothe-
lial cells ; (e) lymph cells. Doubtless the
hyperplasia may affect part or all of the
elements. The hyperplasia may not be in-
duced by mitosis, but by chemical products,
bacterial products, malassimilation due to
circulation disturbance, dislocations and
disturbed pelvic mechanism, distant re-
flexes, etc. No mucosa possesses such a
wide range of physiology (function) or
anatomy (structure) as the endometrium.
Extensive regeneration is required for the
profound passive changes at each menstrua-
tion and parturition. Besides at each of
these frequent occurring processes of men-
struation and parturition the endometrium
is subject to inflammatory invasions. Also,
however, it may be noted that it is just in
the endometrium where hyperplasia is fre-
quent.
(a) The hyperplasia of the epithelia of
the utricular glands is peculiar in that it
produces a variety of strange forms as
Fig. 8 (J. A. Amann). Erosion during
healing. Observe the advancing of the flat
epithelia through mitosis, and the forcing
upward of the cervical cylindrical epithelia.
PI, flat epithelia advancing through a rich
mitosis and undermining and pushing aside
the cervical cylindrical epithelia. The flat
epithelia in its native ground (the portio
vaginalis uteri) is making a fight for exist-
ence by attempting to recover the field now
occupied by displaced cylindrical epithelia,
with flat native epithelia.
spiral, saw-shaped, invaginations and other
irregular forms. This is due to the fact
that the proliferating glandular epithelia
always produces an increase in flat surfaces.
In mitosis of the epithelia the division axis
of the cell stands parallel to the base of the
cell, so that two daughter epithelial cells
exist side by side, each possessing a basic
or fixed end. and a free or secreting end*
In the mitotic epithelia cell the nucleus is
large, requiring more space than the resist-
ing cell, hence it projects above the level of
the secondary epithelial cells or into the
gland lumen. If the mitosis or epithelial
cell proliferation be active the nuclei of the
epithelial cells may not stand in a level
plain because the nuclei of the proliferating
or mitotic cell being large force themselves
out of the regular even plain. Yet the epi-
thelial cell always possesses a fixed, basal
end, and a free secreting end.
Recall that the endometrial glands consist
442
THE CHARLOTTE MEDICAL JOURNAL.
of two distinct zones or layers, viz. : a su-
perficial zone of straight and parallel glands
in which mitosis is abundant and active,
also a sinuous zone or fundal layer of glands
in which mitosis is passive or very slight.
Fig. 9 (J. A. Amann). The corporeal
endometrium showing the zone of straight
glands za, and the zone of sinuous glands
zb. The zone of regular straight parallel
tubular glands (za) is the locality of active
mitosis, it is the location where the regen-
erating proliferating glandular epithelia in-
vaginates toward the myometrial or sinuous
gland zone, it is the locality which becomes
the compact cellular layer during gestation,
and it is the zone which is expelled at par-
turition.
The zone of irregular, sinuous glands (zb)
is the locality of inactive mitosis, it is the
region of dilated and branched glands, it is
the territory where epithelia folding occurs
on account of space, it is the cellular layer
of gestation, it is not expelled at parturi-
tion, but remains to regenerate new utricu-
lar glands and the zone of cystic dilitation.
In other words, the surface zone of straight
glands is the region of active mitosis, pro-
liferation, while the fundal zone of sinuous
glands are the territory of non-proliferation,
passive mitosis. In glandular hyperplasia
the utricular glands are elongated, and when
considerably elongated the glands shifts
always toward the large and fundal lumen,
i. e., in the direction of the least resistance
and when in its course the gland meets with
no regular resistance it assumes various
forms.
Fig. lO (J. A. Amann). Hyperplasis
glandularis. The glands are elongated sin-
uous and spiral, and on section appear ser-
rated or saw-toothed. The glands are, per-
haps, not increased in number, i. e., they
are not new glands, but the gland epithelia
is proliferated, multiplied and hence occurs
the epithelial folding, the invaginations and
corkscrew spiral form. The spiral form is
assumed when the epithelia of the gland is
generally proliferated, multiplied and the
adjacent stroma offers uniform resistance.
The utricular glands penetrates the myo-
metrium.
Glandular invagination is of special inter-
est, since in microscopical sections strange
forms appear. For example, in certain
cross sections several consecutive glandular
lumina may be observed, or one large gland
lumen with several irregular shaped lumina
near each other.
Glandular invaginations arise by the fol-
lowing methods : (a) In the great elonga-
tion of the growing gland where it meets
with an obstruction along the wall the epi-
thelia begins to fold, to invaginate toward
the glandular lumen, and like an intestinal
invagination, the smaller lumen projects or
invagmates into the larger. A section of
such an invagination gland shows three
concentric rings, or three gland lumina.
Of the concentric circular glandular lu-
mina the inner is usually intact, the middle
may be intact, but is frequently ruptured,
when one sees only two concentric circular
layers It is the outer or external layer
THE CHARLOTTE MEDICAL JOURNAL.
443
which presents distension and consequently
flattened epithelia which may be flattened
to such a degree as to be mistaken for endo-
thelia. Whether the section of the inva-
internal layers lie in contact applied to each
other. Hence, the location of the nucleus
diagnosis the layers in glandular invagina-
tions. The subject of glandular invagina-
w
CV«
''^
/r
Fig. II (J. A. Amann). Glandular hyperplasia. Londitudinal- section of a utri-
cular gland in active epithelia regeneration or mitosis. The mitotic cells move toward
the gland lumen, the locality of the least resistance, Diaster on the right. On the
left two skeins from mitotic cell. Two dotted lines point to two leucocytes which
wandered through the epithelial layer. Four leucocytes lie in the gland lumen.
The nuclei lie so close to the epithelial base that it appears 'ike a cervical gland. Ob-
serve the large oval and round nuclei of the stroma cells of the endometrium which sur-
round the utricular gland.
ginated gland be made transverse, oblique,
or longitudinal, it will present its individ-
ual peculiarities. The microscopist must
orientate himself by the location of the nu-
cleus of the utricular gland epithelia. Re-
member the nucleus of the epithelial cell in
the cervix is at the base, while the nucleus
of the corporeal epithelial cell is in the mid-
dle. In cross sections of a single invagin-
ated gland the nucleus will be located basal-
ward in the external layer. In the middle
layer it will also be basalward, but exactly
in the opposite location to the external gland
layer as the secreting surface of the external
and middle layer will be in contact, applied
to each other. The nucleus of the internal
layer will be basalward but opposite to that
of the middle layer.
(d) The free or secreting surface of the
internal layer projects toward the glandular
lumen, while the free or secreting surface
of the middle layer projects toward the wall
of the gland — external layer. The basal or
fixed ends of the epithelia of the middle and
Fig. 12 (J. A. Amann). Glandular hy-
perplasia. Mitosis or regeneration of the
glandular epithelia, D, diaster, K, skein
for mitotic cell, S, nuclei of interglandular
444
THE CHARLOTTE MEDICAL JOURNAL.
cells, M, spindle shaped connective tissue
cell forming basement membrane of utricu-
lar gland. Observe that the nuclei of the
epithelial cells are not all on the same level.
Fig. 13 (J. A. Amann). The cut to the
left represents a diaster in the proliferating
glandular epithelia. I, perhaps, is a vacu-
ole, D, diaster. Observe that the diaster
assumes, v^^ith its nuclei, a position above
the level of the nuclei of the epithelia; 5,
an epithelial cell and its nucleus shows that
pressure forces the cell body to assume an
oval shape and the nucleus to present a
round shape. Adjacent forces shape the
soft epithelial cell body and its nucleus as
the adjacent abdominal organs mould the
liver. The glandular hyperplasis is also
observed.
The cut»to the right, which represents an
oligocene mitosis, (i. e., a few homogeneous
threads or intermediate stages) in the glan-
dular epithelia ; 3, points to the mitotic cell
which is so large that it is forced to the
softer and more yielding portions of the
epithelia ; 6 and 8 note the different levels
which are assumed by the nuclei of the epi-
thelial cells. At 6 it appears that the nu-
clei are poled one on the other.
tions is beautifully and typically illustrated
in sections of proliferating glandular endo-
metritis, or glandular hyperplasia, during
the pre-menstrual or intra-menstrual phases.
With structures intact an invaginated gland
represents three concentric circular glandu-
lar lumina, but not infrequently the middle
layer becomes ruptured during invagination
whence one glandular layer glides into the
other like a stove pipe. The nuclei are
basalward and the basal ends of the nuclei
layer of the epithelia rest on the secreting
surface of the external layer. With rup-
tured middle epithelia layer the section ap-
pears as only two circular concentric epi-
thelia layers.
(b) In the fundal or basal end of a gland
which rests on or in the myometrium there
Fig. 14 (J. A. Amann). Glandular hyperplasia, especially representing glandu-
lar invaginations, a, 4, and other points where two concentric circular gland lumina
are noted, observe that in several places where one gland lumen lies inside of the
other, that the epithelia composing the external gland lumen are short cylinders, pres-
sure and stretching has flattened tiiem out. At b, the left hand edge 3 glandular epithe-
lial layers may be observed. C and 2 shows a large circumscribed area with irregular
THE CHARLOTTE MEDICAL JOURNAL.
445
glandular epithelial invaginations and foldings. Numerous round or oval clear open-
ings may be observed which represents vessels. This cut represents glandular hy-
perplasia, i. e., the utricular glands are not increased in number, but they are increased
in size (hypertrophy). Note that the glands are not uniformly distributed. The reason
of the non-uniform distribution of utricular glands is the inter-glandular stroma is also
hypertrophic; the stroma cells are increased in number, proliferated to such a degree
that the glands are forced out irregularly acconling to the adjacent stroma resistance
which account for the glandular invagination. If the stroma was uniformly resistent
these glands would assume a spiral arrangement. Hence, this cut represents hyper-
plasia diffusa. The gland adjacent to 3. is ruptured.
I"ig. 15 (J. A. Amann). Multipolar mitosis in surface epithelia. Also multipolar
mitosis in the inter-glandular stroma cells. It is benign hyperplasia diffusa, i, 2 and
5, multipolar mitosis in the endothelial stroma cells; 6, body of stroma cells; 4,
vacuole. Observe that the nuclei of endometrial stroma cells are forced wide asunder
on account of inter cellular lymph fluid. It is perhaps edematous, as shown by the ac-
tive mitosis and the distance between the nuclei. Note the definite outline of the
surface epithelia and the fairly definite position of the nuclei in the epithelia. No
cilia are represented, as it is generally desquamated in hardened specimens.
projects a tit-like process and it gives the
myometrial end of the gland a branched ap-
pearance when the gland becomes hyper-
plastic or proliferates it meets the local
points of opposition and folds its epithelial
wall here and there, the tit-like projection
in the fundus becomes a point for increased
folding toward the lumen. On sections
near the base of such a gland it will present
two consecutive circular epithelial layers,
however, with the secreting surfaces ap-
plied to each other and the nuclei in oppo-
site directions. In this form of basal glan-
dular invagination the gland may become
dilated like the ampulla of the oviduct and
the continued pressure of secreting contents
produce additional invagination or foldings
of the epithelial layer presenting more and
more glandular epithelia lumina on section,
(c) The lateral walls of the epithelia
layers of the gland may present papillog like
projections toward the gland lumen. The
regular papillary formed projections of the
epithelial layer in the lumen of the gland
are liable to be formed at local points of
dilatation of the whole gland lumen. The
irregular resistance offered by the stromal
wall accounts for the papillary invagina-
Fig. 16 (J. A. Amann. Disaster in sur-
face epithefia. It is parallel to the base of
the epithelia. i, Disaster, 2, nucleus of
interglandular stroma, cell, 3, the proto-
446
THE CHARLOTTE MEDICAL JOURNAL.
plasmic body of stroma cell. Observe that
the nuclei of the surface epithelia and those
of the interglandular stroma cell resemble
each other in size, shape, and relative po-
sition.
tions of the epithelial layer of the gland
depends whether the invaginations begin :
(a) in the zone of the straight glands and
proceed to the myometrial end; (b) or be-
gin in the myometrial end, the zone of sin-
uous glands and proceed toward the free
surface of the endometrium, or (c) whether
the glands be invaginated from the lateral
wall by inter-glandular papillae. In other
Fig. 17 (J. A. Amann). Irregular change in the surface epithelia (DE) Pre-metaplas-
tic stage; e, skein in a cross section of a vessel; L, lymphocele (disaster) in mitosis,
dividing in the inter-glandular endothelial cells; i, giant skein from cell proliferation
perhaps in a pre-carcinomatous stage. The mitosis of the surface epithelia is suspicious.
3, points to three nuclei of the endometrial stroma cells; 2, the proto-plasmic body of
the stroma cell. The nuclei of the surface epithelia are not only irregular in size, shape
and distribution, but those of the stroma cells are still more similarly atypical. The
stroma cells are not only forced asunder by the ordinary fluids in the lymph channels,
but the lymph fluids have become so abundant that oedema and transuded serum exists.
^^ ^-0 1 ^W„
F'g- iS (J. A. Amann) is a cut to show the surface epithelia (in places sectioned
obliquely) and endometrial stroma cells. The stroma cells are irregularly forced asun-
der by accumulations of blood (tissue haematoma). In the hagmatoma is a leucocyte,
L, of the disaster form; M, mitosis in the endometrial or interglandular struma cells.
Note the accumulation of fluid on one side of the mitotic cell (m), separating it from
THE CHARLOTTE MEDICAL JOURNAL.
447
the adjacent stroma cells. 5, points to two
to the position of the surface epithelial cells
words the invagination of the ^utricular
glands begins at the free end, myometrial
end, or form at the lateral wall. The in-
vagination is due to the increase of surface
epithelia through excessive mitosis or pro-
liferation of epithelia.
The form assumed by the utricular glands
in the glandular hyperplasia, due to exces-
sive mitosis, is of considerable interest clin-
ically and microscopically. In the first
place benign mitosis or epithelial prolifera-
tion consists in increase of surface area,
and not increase of the super-unformed epi-
thelial layers. Benign hyperplasia of glan-
dular epithelia always consists in the in-
creased area of a single epithelia layer sev-
eral glandular epithelia layers placed over
each other, super-unformed, are suspicious
of malignancy.
The form of the hyperplastic gland will
depend on the location of the proliferation.
If vigorous epithelial proliferation arises in
the territory of the zone of straight, narrow,
glands, either the lumen of the gland must
dilate or the proliferating epithelial layer
enlarged surface area must fold toward the
gland lumen. Also, the form of the pro-
liferating gland depends on the resistance
of the adjacent inter-glandular stroma. Be-
sides the subsequent secretions alters the
form of the gl.md by pressure as its mouth
may be partialK or wholh closed forcing
its e\ aginations of epithehal into the sur-
rounding stroma.
nuclei of the surface epithelia. 4, points
above or distal to the nuclei.
or stroma cells, are regular in size, distribu-
tion and shape. M, stroma proprium mu-
cosae cell, or stroma cell in mitosis division.
It is on equatorial plate. L, lymphocyte,
two daughter cells already divided lying in
a fluid medium (lymph) which is forcing
asunder the stroma cells, i, points to three
stroma cell nuclei, and 3 lies on the stroma
cell bodies. The lymphocyte cells may be
mitotic at any point intra-stromal or intra-
epithelial.
Some authors describe the evaginations of
the epithelial layer into the adjacent stroma
as divisions or branches of glands, but as
remarked by Amann the examination of
abundant material does not support the
view.
If the whole gland epithelia vigorously
proliferates and the adjacent stroma wall
presents uniform resistance the elongated
utricular gland assumes a spiral or cork
screw form.
On section a spiral shaped utricular gland
presents a serrated or saw-tooth form. It
is doubtful whether surface epithelia of the
endometrium is invaginated to form new
utricular glands. But it is sufficiently pro-
bable that utricular glands proliferate from
other utricular glands only.
Fig. 19 (J. A. Amann) represents the
surface epithelia and the stroma cells (stra-
tum proprium cells). The surface epi-
thelia (D) as well as the nuclei of same
(2) are quite rogular in size, shape and po-
sition. The stratum proprium mucosae cells,
Fig. 20 (J. A. Amann) represents the
surface epithelia resting on three stroma
ceils. It shows a lymphocyte (L) which
has wandered through the surface epithelia
as the monaster form, i, is the nuclei of the
surface epithelia ; 3, the nuclei of the stroma
cells. The shape, size and distribution of
the nuclei of the epithelia are quite uniform.
From the various forms of excessive pro
liferation of utricular glands invaginated,
spiral, serrated, cystic, folded, evaginated,
in short, the increase of surface area in a
single glandular epithelial layer has received
various names, as endometritis glandularis,
hyperplesia glandularis, glandularis hyper-
THE CHARLOTTE MEDICAL JOURNAL.
trophia, glandularis
ectatica.
cystica, glandularis
The two characteristics of glandular hy-
perplasia in the endometrium are : (a) sur-
face area increase of a single epithelia layer,
limited to transitional stages of epithelia
located adjacent to the os uteri externum.
Hyperplasia of the surface epithelia of
the corporeal endometrium is much less
known than that of the cervical. Amann
â– ^'g- 21 (J. A. Aman). Interglandular hyperplasia and mitosis (M) with rich but
irregular forms. L, two lymphocyte disasters. The glandular epithelia is partially des-
troyed, coalesced, from a previous inflammatory invasion. Observe that a large lateral
segment of two glands are destroyed.
(b) definite limitations of the proliferating
epithelia to the utricular gland.
Hyperplasia of the surface epithelia of
the endometrium is especially manifest in
' congenital or acquired erosions of the portio
vaginalis. The cervical cylindrical epithelia
may be displaced found among the flat epi-
thelia of the vaginal portion or vice versa.
The process may consist in excessive pro-
liferation, hyperplasia of the serface epithe-
lia of the cervical endometrium invading
the territory of the flat vaginal epithelia.
The metaplasia consisting in the presence
of flat epithelia in the cervical endometrium
I have never observed, however, some au-
thors mention it, as Amann, Abel, Gebhart,
Schroeder, Veit, Ruge, Winter, etc. It is
especially noticeable in the new-born. The
dislocation metaplasia of the flat epithelia
to the cervical epithelia was due to narrow-
ing and obstruction of the cervical glands
ending in cystic dilatation. It may be pru-
dent to observe that many such cases are
with his much microscopical experience
says it is rare to note flat epithelia on the
corporeal surface endothelia. (Fig. 15, 16
and 17.)
In rare instances of active regeneration
irregular circumscribed swellings are found
covered with flat epithelia which, as noted
by Prof. Rosthorn, may be now and then
quite typical.
Hyperplasia of the embryonal or inter-
glandular stroma cells of the endometrium
is a common gynecological manifestation.
In this hyperplasia the stroma cell pro-
liferates excessively, preponderating over
the epithelial cell to such a degree that the
name endometritis interglandularis or hy-
perplasia interglandularis is applied. The
endometrial stroma cells multiply and in-
crease in size. The protoplasm of the body
may become so large as to be mistaken for
a decidual cell. The differential diagnosis
is difficult between the enlarged endometrial
stroma cell and the cells found in dysmen-
THE CHARLOTTE MEDICAL JOURNAL.
orrhoea exfoliative (decidua menstrualis).
According to the intensity of the prolifer-
ating process one finds the mitotic process
in similar grade the kind of mitosis is gen-
erally formed, but it may by hypochromatic,
The anatomic findings of endometritis are
according to the three principal symptoms,
viz. : (a) In vigorous mucus secretions
(cervical endometrium) there exists glandu-
lar hyperplasia with migration of leucocytes
Fig. 22 (J. A. Amann) represents inter glandular hyperplasia. M, mitosis; L,
lymphocytes numerously distributed among the nuclei of the stroma cells. L, to the left
points to a lymphocyte in disaster form; 2, points to the nuclei of the stroma cells of