Embryologic and histologic studies of the human thymus

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Content EMBRYOLOGIC AND HISTOLOGIC STUDIES
OF
THE HUMN THYMUS
A Thesis
Presented to
the Department of Zoology
University of Southern California
In Partial Fulfillment
of the Requirements for the Degree
Master of Arts
by
Cornelius Oliver Bailey, M.D.
May 1937
UMI Number: EP67097
All rights reserved
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a note will indicate the deletion.
UMI
DissiMation PublisNng
UMI EP67097
Published by ProQuest LLC (2014). Copyright in the Dissertation held by the Author.
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This thesis, w ritten by
.......CQKTELIUS.OLI^ .......
under the direction of hLB Faculty Committee,
and approved by a ll its members, has been
presented to and accepted by the C ouncil on
Graduate Study and Research in p a rtial fu lfill
ment of the requirements fo r the degree of
...............
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Dean
Secretary
Date l i ^ . , 1 2 5 7 ...........................
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Chairman
CONTENTS
PAGE
INTRODUCTION.................................................. 1
REVIEW OF LITERATURE............... 2
MATERIALS AND METHODS........... 7
DISCUSSION OF MATERIALS
Ten Millimeter Specimen..................................... 10
Twenty Five Millimeter Specimen............................. 14-
Thirty Millimeter Specimen ................................. 21
Forty Millimeter Specimen................. 23
Seventy Millimeter Specimen................................. 30
Eighty Five Millimeter Specimen • • « ..................... 34
One Hundred Millimeter Specimen............................. 36
One Hundred Thirty Five Millimeter Specimen................. 38
Term Still Birth Specimen ................................... 40
Six Hour Viable Specimen................................... 41
DISCUSSION............. 42
GENERAL SUMMARY................................................ 50
BIBLIOGRAPHY.................................................. 51
- 1-
INTRODUCTION
There is much confusion in the medical profession regarding the
thymus; and it is believed that, owing to conflicting opinions as to
its embryology, histology, and physiology, many sudden deaths in in
fants occur that could be avoided if a more stable foundation could
be established upon which to build a clinical structure. It is the
hope that this investigation will aid in building such a foundation
to the end, that the infant mortality rate will be further reduced.
It is the purpose in this study to collate the literature on
the embryology of the thymus; and to determine by the study of a
series of stages which has the more secure basis in fact. It is
hoped that further studies planned will link the embryology and the
normal histology of the gland with the clinical problem of saving
and preserving human life.
ACKNOWLEDGMENTS
The writer wishes to express his thanks to the members of his com
mittee, particularly Bruce M. Harrison, Ph.D., for his untiring efforts
in the supervision of this work; also to Roland H. Osborne, M.D.,
Pathologist, for his counsel in the microscopic study of the sections.
- 2-
BEVIEW OF LITERATURE
The word, thymus, is taken from the Latin term, thymus, which is
a name applied to a genus of plants with a two-lobed calyx, and serves
to emphasize its bi-lobed shape. The thymus is still the "enigmatic
organ" of the ancients. Little was vnritten about the organ until recent
years, except in 1700;
Tauvry had drawn attention ... to the diminution of the thymus
after birth. - Needham.
and in 1717:
Bellinger believed that the maternal blood was transformed by
the embryonic thymus gland into proper nourishment for itself, after
which it was secreted into the mouth by the salivary ducts and so
went to form meconium without the necessity for deglutition. -
Needham.
In 1879 modern histologic methods made possible a careful study,
and KoeHiker published his view that all of the cells of the thymus
were epithelial in origin. His (l88l) opposed this view with a theory
that the small round cells which engorged the cortex of the gland were
lymphocytes and hence mesenchymal in origin. For forty years an argu
ment has been waged over the matter of the origin of these cells. The
disputants divided into two groups. On Koelliker*s side we find Bell
(1906), Stoehr (1906), and Dustin (1920). It was Dustin who wrote an
able conclusion follovfing his review of the literature and his work on
_ 3—
anurans:
vath regard to histogenesis of the thymus that the small cells are
derived from the epithelial cells of the anlage. They are trans
formed by a series of "diminishing" divisions from the large epithe
lial cells to the small cells which resemble lymphocytes, a process
which can be traced through its successive stages. At no period can
an invasion of the anlage by lymphocytes be demonstrated.
Also Gottesman joined Koelliker*s group in 1926.
The other group, headed by His, joined by Stieda (1881), Maximow
(1912), Hammar (l92l), and Popoff (1926) contends that the reticulum and
thymic corpuscles are the only elements developed from the original epi
thelial anlage while the small thymic cells, i.e., the lymphocytes, also
the eosinophils, arise from the mesenchyme. It is believed that these
cells migrate into the epithelial structure from the surrounding tissues
and that the further development of the thymus is of a true lymphoid
organ.
The author thinks it appropriate at this juncture to quote from
Hammar*s able article (1921) as he has formulated the summary of the
literature up to that date.
The proof of the immigration of the lymphocytes into the thymus
anlage during development and, in connection with this, the trans
formation of the latter into an epithelial reticulum, the far-reaching
morphological resemblance between the small thymus cells and typical
lymphocytes (Laurel, Pappenheimer, 1913, Pinner, 1920, etc), the great
resemblance between the two kinds of cells from a biological point of
view, amoeboid movement (Hammar, 1905, Jolly 1914)> great sensibility
to Roentgen rays Heineke, 1905, Rudberg, 1907, 1909, Regaud and
Gremieu, 1911, 1912, etc) the identity of the two kinds of cells from
a serological point of view (Ritchie, 1908, FeHander, 1912, etc) and,
finally, the analogous conditions of the lymphocytes in the thymus
on the one hand, in the real lymphoid tissue and the blood on the
other, during involution and other conditions - about which more will
be found below - all these factors form so strong a chain of evidence
in favor of the "small thymus cells" having the very much discussed
- 4-
nature of real lymphocytes that even in the latest post-humous
editions of Stoehr*s own text book his view of them as epithelial
cells has now been abandoned.
Popoff joined the His group in 1926 with an excellent report of
his work on thymus tissue cultures, transplantation, and regeneration.
His findings are worthy of quoting:
The regenerative processes in the transplants of the thymus
duplicate the histogenetic processes of this organ in the embryo.
The essential feature in both cases is the infiltration of epithe
lium with true lymphocytes. The epithelium gradually becomes trans
formed into a reticulum. At the same time the vessels continue to
branch between the epithelial masses and form a network of embryonic
connective tissue, penetrating the epithelial network, and serving
as a source of lymphocytes and histiocytes.
The regeneration of the stump of the remaining part of the thymus
duplicates in all essential features the regenerative process in the
transplants.
The lympho-epithelial nature of the thymus and the presence of a
perivascular mesenchymal reticulum in this organ are decisively
shown by these experiments with tissue cultures, autotransplanta
tions and regeneration. No evidence of the development of the small
thymus cells from the epithelium was found.
Authorities generally agree that the anlage of the human thymus
originates bilaterally from the entodermal epithelium of the third pair
of branchial clefts. Jordan (1930) goes a step further and states:
The thymus gland begins its development during the sixth week,
when it becomes discernible as a pair of solid sprouts from the
ventrolateral walls of the third pharyngeal pouches.
Ewing (1928) thinks the thymic cells come from entodermal epi
thelium.
In later studies Kingsbury (1936) indicates that the thymus is
one of a system of endocrine organs possessing doubtless a distinct
though obscure internally secreting function by virtue of the pro
- 5-
duction of a specific hormone or hormones. It seems that the develop
mental origin of this organ is from the pharyngeal epithelium along with
certain other glands of internal secretion - thyroid and para-thyroid.
Its anlage is a portion of the entoderm which morphologically constitutes
the third pharyngeal outpocketing or branchial pouch. From its place of
origin the thymus migrates caudally into the thorax reaching the peri
cardium upon which it is moulded.
Thvmir corpuscles are important structures of the thymus. It is
generally held.that they first appear at about two and one half months
of foetal life; there seems to be a general agreement that these cor
puscles appearing as laminated rests of flattened epithelial cells are
of entoderm origin. Hammar (l92l) says:
The analysis that was carried out shows how the number of
Hassall's corpuscles quickly increases. They are started as small
formations of 10-25 microns in diameter, often in the neighborhood
of some small vessel. One or two adjacent reticulum cells increase
in size and assume a spherical shape. When on this enlargement they
reach neighboring cells in the medullary reticulum, the latter cells
are thrust to the siâf» owing to the pressure of growth and take up a
position close to the central cell or cells, which they concentrical
ly enclose like the scales of an onion. Even the peripheral cells
often fairly soon become hypertrophied, so that the formation grows
farther and fresh cells are joined to its periphery. When the growth
proceeds in this manner two or more corpuscles may reach each other,
join together, and continue to grow as a unit. In this way there
arise the so-called compound Hassallian corpuscles, which are formed,
however, mostly in the later embryonal or postembryonal stages. The
lymphocytic and leucocytic forms found in a great number of the
Hassall*s corpuscles do not take part in the formation, but are as a
rule in a more or less advanced state of disintegration. Their
number is sometimes so great in a Hassallian corpuscle that it is
expanded by them like a little cyst.
The majority of Hassall's corpuscles do not normally attain, even
in postnatal life, a greater diameter than 25-50 microns. With in
— 6-
creasing diameter the larger forms are as a rule more and more rare.
It is very rare for any Hassallian corpuscles to attain a greater
diameter than 200 microns during embryonal life. Postfoetally, on
the other hand, the maximum limit is, as a rule, about 500 microns,
i.e., 0.5 mm., only in some exceptional cases have I found still
larger forms postfoetally, up to a diameter of 1 mm. and more.
Kingsbury thinks thymic corpuscles may be understood best as
structural expressions of a growth in confined space of the original
epithelial constituent from which it is generally agreed they arise.
- 7-
MATERIALS AND METHODS
In this study human embryos were obtained from the pathology
departments of two class A, Los Angeles hospitals upon the author*s
personal pledge that all specimen obtained would be used only for
scientific and professional investigation.
The following specimen were used:
LENGTH CR SECTION
APPROXIMATE
GESTATION PERIOD
1 0 mm. Gross section serial 6 weeks
2 5 "
» 1 1 1 1
8
w
30 " Sagittal
It 1 1
8&
n
40 " Gross
1 1 1 1
9 &
n
70 «
1 1 n It
1 2
n
8 5 "
ft II 1 1
1 3 *
II
1 0 0 "
n 1 1 II
1 5 *
1 1
1 3 5 ”
u 11 n
1 7 #
II
Term (Still birth) 3 6
1 1
Term (Six hour life) 40
«
Tissues were prepared by fixing in Bouin^s solution, dehydrated
in alcohols, cleared in xylene, infiltrated by the usual method, ten
per cent bayberry and paraffin wax, and sectioned at eight to twelve
microns•
Staining methods as follows:
1. Weigert's Iron Hematoxylin
2. DelafieId * s Hematoxylin
3. Jensen’s Differential Technic
- 8-
Slides are stained in Delafield’s Hematoxylin base and counter
stained in Jensen’s stain as follows:
(a) Formula:
1. Orange G (lOOcc.) 700mg.
2. Picric Acid Sat, Solution, Aq.
3* Acid Fuchs in (500cc.) 540mg.
(B) Solution:
1. Picric Acid Sat, Aq. Solution 80cc.
2. Acid Fuchsin Solution 30cc.
3* Absolute Ethyl Alcohol 30cc.
(0) Dispensing:
To 200cc. of (B) add lOOcc. of Orange G.
All solutions but (A-2), 30^ Alcohol.
(D) For use:
Dilute (C) by adding one third volume 30^ Alcohol.
Note: The forty millimeter embryo is stained with hematoxylin
and eosin.
According to Arey’s charts, we should find in a forty three milli
meter embryo the thymic epithelium tranforming to reticulum and the early
beginnings of thymic corpuscles, and in the sixty eight millimeter embryo
the organ begins to form into medulla and cortex and resembles more near
ly the structure of the palatine tonsil, i.e., it is becoming distinctly
a lobulated lymphoid organ. In the succeeding embryos the cortex, medul
la, and thymic corpuscles are more differentiated and normal in appear
ance. The reticulum is definitely fibrous tissue while the thymocytes
have the distinct characteristics of lymphocytes.
Figure 1
A portion of a serial cross section of a ten
millimeter human embryo showing the oval-shaped right
thymic column in the cervical region»
0 Esophagus
N Nerve
Tr Trachea
Th Thymus
(I90x)
- 9'
m m
A
m m k
Figure 1
•10-
THE TEN MILLIMETER EMBRYO
The ten millime^ter human embryo, Fig. 1, was cut in serial cross
sections, twelve microns thick, and stained with hematoxylin. At a
point low in the pharynx apparently next to the last pouched irregulari
ty of the lateral pharyngeal wall, two small groups of cells are noted
which seem to be connected with the pharynx by a rather indefinite
channel. Immediately caudad this channel becomes slightly more distinct
and seems to represent the earliest trace in the development of the
thymus. The point of union is about the junction of the ventral and
middle thirds of the lateral pharyngeal wall. Just cephalad to this
point two small groups of cells appear suddenly in a round space some
distance lateral to the tracheal bud. Laterally and dorsally are seen
a large blood sinus, a band of nerve tissue, the vagus, and two large
groups of epithelioid cells, probably the sympathetic ganglia.
Further caudad this canal persists on the left side, while on the
right are signs of a similar channel passing just ventral to a blood
vessel. The difference on the two sides is probably due to sections
having been cut slightly obliquely. Still further caudad a similar
canal is identified, which apparently extends to a group of cells
medial to the vagus trunlc. This canal is more definite than that on
the left side and in some places seems to form a poorly defined tube.
However, the epithelium of the pharynx and trachea are desquamated so
-li
the appearance here cannot be relied on too greatly. There seems to
be a more definite pouch formation in the right pharyngeal wall, from
which this channel arises. Meanwhile the cell group on the right side
is lost to sight temporarily, however two symmetrically located small
groups of cells are seen medial to the vagus nerves, about opposite the
ventral margins of the jugular sinuses, and the trachea is represented
by a tube shaped structure as it is cut in longitudinal section. The
left group of epithelial cells is located at a level somewhat dorsal
to the right. The groups are of equal size and are located medial and
ventral to the vagus trunks.
Gradually moving caudad the thymic columns retain their relations
with the vagus nerves and are closely related to somewhat smaller blood
vessels, probably the carotid arteries. The right lies ventral to the
nerve and ventrolateral to the vessel. The left lies at first between
the nerve and artery which is medial and ventral to t he thymic group,
but it gradually passes forward to lie laterally to the artery and
finally a little ventral to it. Further caudally the left column seems
to break into two or three groups of cells. The cells present round or
oval deeper stained nuclei with varying amounts of cytoplasm. The
columns seem to be fairly well encapsulated, the one on the right being
more distinct.
Passing posteriorly three fairly definite groups of thymic cells
are seen on the right side. On the left, however, the thymic group
disappears rather suddenly, being clearly seen here for the last time.
- 12-
A little more caudad the division of a rather large vessel occurs in
the midline some distance ventral to the trachea. The right thymus
again appears as a single oval group which is apparently elongated by
a lateral pressure. This group continues to move ventrally and slightly
medially and becomes smaller and is last seen as a wedge-shaped mass.
It lies a short distance medial and just ventral to the ventral border
of the right jugular vein. At a similar distance dorsally is a fairly
large blood vessel which passes laterally to the right and is the right
subclavian artery. Dorsal to its lateral extremity the vagus nerve
appears•
SUMMARY
From this study indistinct canals have been identified which
apparently arise from the third or fourth ventral pharyngeal pouches.
Groups of cells form more or less definite columns which remain in
fairly constant relationship with the vagus nerves and carotid arteries.
The cells are definitely epithelial in type. The right thymus has been
traced through a thickness of material which represents a distance of
four tenths of a millimeter.
•13-
Figure 2
A serial cross section of a tv/enty five millimeter
human embryo showing both columns of the thymus at the
level of the manubrium sterni.
0 Esophagus
Tr Trachea
Th Thymic lobes
M Itflanubrium
(95x)
- 13 - ^
■’ \ V A ' , % %
T h
M
**ter
h ,
y. _
•:4.„
^ ' C'-t ' . --M.
> , . ■ /
;
-
Figure 2
— 14“
THE TWENTY FIVE MILLIMETER EMBRYO.
The twenty five millimeter human embryo. Fig, 2, is cut in serial
cross sections, ten microns thick, and stained with hematoxylin. The
most anterior appearance of the thymic body in cross section is seen on
the left side as a group of some fifteen grayish cells, with which are
mingled a number of hyper-chromatic irregular small bodies. These are
probably pyknotic nuclei and nuclear remains. At this level this group
of distinctive cells lies in contact with the ventral surface of the
vagus nerve. It extends caudally, ventrally, and slightly laterally,
through one hundred and sixty one sections of ten microns each or a
distance of one and sixty one hundredths millimeters. Laterally at the
cephalic end of the thymus the jugular vein forms a large blood filled
sinus. On the ventral and medial sides of this embryonic muscle fibers
are noted, and medial to these the thyroid is in evidence, showing some
formation of imperfect follicles. A mass of calcifying mesenchymous
cells is seen some distance ventrolaterally, which is the left clavicle.
At this level no thymic precursor is seen on the right side.
Located just medial to the ventral portion of the vagus is a small group
of connective tissue cells. There can also be seen a few small dark
nuclear fragments, mingled with a number of the fibroblastic cells and
surrounded by a light capsule. As you pass posteriorwards this group
increases in size remaining well encapsulated. The trachea lies on the
- 15-
media 1 aspect and thyroid tissues on the ventral, and a short distance
dorsally is the right carotid artery.
Caudally one hundred and fifty microns the left thymic cells
grow more distinct and assume more definitely the appearance of other
epithelial structures. They are larger, more deeply stained and the
whole group presents a rather clearly defined capsule. At this level
the trachea appears as an irregular six-sided figure having the outline
of an inverted "Ü" in the ventral portion combined with a "W" in the
dorsal portion. Symmetrically located on the right side is a round mass
of cells which is the right thymic body. It lies, however, a short
distance medial to the ventral surface of the right vagus. This group
decreases in size as we pass caudally, and nearly disappears, but does
not resemble that of the left thymus. It is definitely of a fibroblastic
nature and represents an obliterative fibrosis of the thymic cord with
atrophy of the epithelium. However thirty microns further caudad the
first appearance of cells identical with those in the left thymus is
noted. They are in a small poorly encapsulated group about half the size
of the left thymus. The only change in relations worthy of note from
the former stage is the decreased amount of thyroid tissue, which is
replaced ventrally and slightly lateially by connective tissue stroma
supporting several small venous channels.
Still further caudad the left thymus appears a short distance
ventral to the vagus. It presents a round, somewhat shrunken group of
cells separated from the surrounding ring of connective tissue by a
-16-
narrow clear space. It makes little change throughout, many sections
being about one-third larger than the cell mass on the right side.
Further on, a number of distinct changes in the right thymus are
noted. It shows definite encapsulation but decreases considerably in
size with fibrous obliterative changes, and nearly disappears shortly
thereafter. It then splits into two groups of cells. The lateral of
the two increases in size and soon gives rise to three groups. Here a
group lying somewhat dorsally disappears. The medial group increases
in size and the lateral decreases. These changes become more marked,
the latter soon fusing with the medial group. At this point six hundred
and thirty microns from the cephalic end of the thymus the bodies are
practically equal in size, however the right soon increases to about
twice the size of the left thymus.
Advancing caudally the left thymic body lies just ventral and
medial to the ventral surface of the jugular vein. The left carotid
artery is directly lateral to the trachea while the right carotid is
opposite to the ventral border of the trachea. On the left side a
curving rib is present while on the right a calcifying cartilage con
stitutes the early clavicle, and the articulation with the manubrium
is marked by a thin layer of mesodermal tissue. The thymic bodies
appear oval from pressure on the lateral sides. Four thin walled
vessels lie between the thymic bodies and the right carotid. Here
the left subclavian vein empties into the jugular. Little change is
seen in the blood vessels. The right carotid presents a horizontal
-17-
curvature extending laterally which probably represents the subclavian
artery.
At two hundred microns further on the left thymus, now a circular
group of cells has become considerably smaller and the right in a flat
tened oval form has increased slightly in size. The left jugular vein
lies dorsal to both thymic bodies. The right carotid is just ventral
to the trachea, and the left jugular vein has received another small
vein^described above^at a point dorsal to the right thymus.
As we pass a little further back, the thymic bodies are about
equal in size, the left jugular vein is well over to the right of the
midline and is separated from its fellow by a thin band of connective
tissue. Closely following this the complete union of the jugulars
occurs, also a beginning of the separation of the carotids at a point
ventral to the left of the trachea. The left thymus is increasing in
size. The fusion of the bilateral complements of the manubrium is
evident at a point one and five hundredths millimeters from the cephalad
beginning of the thymus which is fifty six hundredths of a millimeter
from the caudal end. The right vagus lies against the trachea at which
point both thymic bodies are increasing in size and present an oval form.
An arterial trunk, probably the aortic arch, lies to the left of the
middle.
Further caudally, one hundred and twenty microns, an increase in
the size of the left thymus is seen, and mother large blood sinus, pro
bably the left auricle, lies lateral to it. The pericardial sac is
- 18 -
definitely formed, and the left thymus is still slightly larger, lying
a little ventral to the right.
At a point one and thirty three hundredths of a millimeter from
the beginning a blood vessel is found ventral to the thymic bodies, and
a rather prominent blood channel passes between the two lobes, communi
cating with the sinus situated dorsally. Later the two thymic bodies
are closely approximated in the dorsal portions. They are separated by a
thin strand of connective tissue for about one-third their anterior
posterior extent. In the ventral two-thirds they are separated from
one another by much more connective tissue. At this level this stroma
contains several very small blood vessels.
The greatest development of the thymic bodies is seen one hundred
microns cephalad to their caudal end where the epithelium has assumed a
reticular type. The lobes do not fuse but are separated by a thin
strand of connective tissue, and capsulation seems to be quite definite.
In relation to them dorsally and to the right is a large blood filled
sinus, while on the left they are separated from another sinus by the
pericardial cavity. Ventrally a bridge of connective tissue of varying
width connects with the mesenchymal tissue behind the manubrium. The
clavicle extends laterally from the ventral portion of the manubrium.
In the angle thus formed are the internal mammary vessels. A small blood
vessel curves around the ventral portion of the left thymic body, and
dorsal to the thymic bodies in order, are the large blood sinus, men
tioned above which is probably the right auricle, the ascending aorta.
-19-
trachea, esophagus, vertebral body, and the spinal cord. The left lung
presents several cavities while on the right side the lung is not yet
seen. The caudal extremity of the thymus disappears rather abruptly,
the right cell group extending slightly lower than the left.
SUMMARY
In a twenty five millimeter embryo the thymus has been traced
from a point just slightly above the lower border of the thyroid in two
solid cords of cells which extend caudally to rest upon the pericardium.
The thymic cords vary considerably in size and small buds have been
noted which may represent early lobular formations. The cephalic ends
lie ventral to the vagus nerves and medial to the jugular veins. They
gradually approach each other as they grow caudally and eventually lie
in close contact separated from each other by a very thin fibrous stroma.
The epithelial cells show a definite reticular appearance throughout the
course of the thymic cords. An obliterative fibrosis of the right thymic
cord has been seen cephalad to the true body of thymic epithelium.
-20 .
Figure 3
A portion of a thirty millimeter human embryo cut
in sagittal section near the mid-line of the body, showing
a part of the thymus gland lying dorsal to the manubrium
sterni*
To Tongue
V Vertebra
Tr Trachea
M Manubrium sterni
Th Thymus
(25x)
— 20 —
i
Figure 3
- 21 -
THE THIRTY MILLIMETER EMBRYO
The thirty millimeter human embryo, Fig. 3, was cut in sagittal
section, ten microns thick, and stained with hematoxylin. Here the
sections are taken near the midline for the notochord is visible at least
once in each section and varying lengths of the esophagus and the trachea
are seen. The manubrium sterni appears throughout the area and below it
are several costal cartilages showing varying degrees of fusion with each
other. No pronounced change is observed in the general position and re
lationships of the thymus.
In the beginning are found two groups of thymus tissue dorsal to
the cephalic portion of the manubrium. The internal mammary vessels pass
between the upper thymic body and the manubrium. This body consists of
three, almost fused, groups of cells. The central mass is about three
times the size of the other groups. The cephalic group lies a short
distance caudal to the thyroid gland and is separated from the large
group by some cellular fibrous stroma. Projecting slightly ventrally
and caudally is a small nodule of thymic tissue. The large mass lies a
short distance ventral to a large blood sinus. Almost directly caudal
to this sinus is another small round group of thymic cells, A thin
layer of connective tissue separates this group from the pericardial
cavity. Soon the large cephalic group disappears, while the caudal mass
increases in size. The cephalic mass reappears opposite the cephalic
- 22 -
margin of the large blood vessel and increases rapidly until it is
about fifty per cent larger than the caudal mass.
The thymic epithelium consists of rather deeply stained cells
which vary considerably in size and shape. Many of the nuclei contain
nucleoli while others show a peripheral distribution of the chromatin
material. There seems to be an occasional mitotic figure and a few
small lymphocytes. These, however, may be in some of the capillary
channels. Between the two islands of tissue are several small blood
vessels. The surrounding stroma is of a loose fibroblastic nature.
The thymus in this embryo shows a more cellular tissue, and the
reticular structure is less evident here than in the twenty five milli
meter embryo.
- 23 -
THE FORTY MILLIMETER EMBRYO
The forty millimeter human embryo is cut in serial section,
twelve microns thick, and stained with hematoxylin and eosin. Almost
immediately posterior of the thyroid, two delicate cords of epithelial
cells extend toward the thorax. They consist of delicately encapsu
lated groups containing a few deeply stained nuclei. They represent the
cephalic extremity of the thymic bodies. The right is located ventral
to the medial margin of the carotid artery and not quite level with the
ventral border of the trachea. The left is apparently near the mid
line, ventral to the lateral margin of the trachea and situated some
what dorsally as compared with its fellow. On the right the vagus
trunk lies almost lateral but very slightly ventral to the carotid
artery, while on the left the carotid is just dorsal to the nerve.
Further caudad the left thymic cord soon enlarges slightly while
the right remains indistinct for a short distance and appears to be
undergoing some fibrous obliteration. These cords are widely separated
almost at opposite sides of the trachea, but very gradually converge.
Still further the left thymus is about three times as large as the right,
but the latter soon attains an equal size. Here the structure of the
clavicles, tracheal rings, and vertebral body are readily recognized.
The esophagus and trachea contain double rows of lining epithelium.
The muscular wall and nerve supply of the esophagus are well developed.
—2^ —
The thymic bodies continue to grow very slowly and continue to approach
each other. The left is now slightly larger, and the cephalic end of
the manubrium becomes visable. The thymic cords have changed a little
in size and are still converging.
Caudad from the cephalic extremity of the manubrium sterni there
is a temporary decrease in the size of the left thymic cord, and this
is followed by a temporary decrease in the size of the right thymus.
However here the first slight tendency to a lobular formation is noted.
Further three true lobules appear suddenly ventral to the right thymus;
develop rapidly; and fuse with the main mass, making the right somewhat
larger than the left.
The greatest portion of the thymus appears one and eighty four
hundredths millimeters from the cephalic end. Here the cells exhibit
very little cytoplasm generally and are closely packed. The nuclei are
deeply stained, and the presence of small round cells are noted. These
resemble the lymphocytes of the blood stream. Mitoses are quite numer
ous. Some areas show a slight reticular arrangement, and an occasional
group of lightly stained cells is noted. These resemble endothelial
cells of mature type and probably represent a development of blood
vessels within the thymic substance. At this level the pericardial
cavity is revealed just lateral, the right side ©f the aorta as an
irregular triangular space marking its location. Just ventral to the
pericardial cavity and extending laterally is the right thymus. Between
these structures is a rather delicate layer of fibrous stroma.
-25-
Lung tissue appears as we move caudad showing five gland-like
structures in a loose mésothélial stroma. The left thymus shows little
change in size but the right gradually decreases. The pericardial
cavity now extends entirely across the ventral surface of the aorta and
dorsal to the left thymus. For a time the right thymus decreases more
rapidly in size than the left. Then the latter loses much of its
substance, and they are practically equal in size. They seem to become
separated by a fold of the pericardial cavity and their caudal extremi
ties tend to separate quite widely. They decrease in size, and the
separation continues until the left thymus is last seen as two small
groups of cells in a loose vascular network of fibroblastic tissue, and
the right thymus soon disappears in a similar manner.
SUMPMRY
In the forty millimeter embryo the thymus appears as two delicate
cords immediately below the lower margin of the thyroid. They are widely
separated but gradually increase and converge until they lie in close
relationship to each other in front of the aorta and upper margin of the
pericardium. They remain separated by a thin band of connective tissue.
The appearance of lymphocytes is noted and there is definite evidence of
lobule formation with occasional tendency to a reticular structure in
the thymic cells. The thymus extends well down on the pericardial
tissue. It has been traced through approximately one hundred and eighty
seven sections of twelve microns which would indicate a total extent of
two and twenty five hundredths millimeters.
- 26 -
Figure 4
A longitudinal section of a lobe of the thymus
gland of a seventy millimeter human embryo which shows an
early differentiation of the cortex and medulla and the
topography of the lobe, revealing deep fissures in the
surface, forming lobules; and also showing the connective
tissue capsule.
L Lobe
C Cortex
Me Medulla
Lu Lobule
S Capsule
(95x)
- 26 -
<;¥
Figure A-
-27-
Figure 5
A high power photograph of a portion of the
section in the previous figure which brings out -details
of the reticular stroma of the medulla, the engorgement
of the cortex with small round thymic cells, and the
detailed structure of the interlobar capsule.
M Medulla
C Cortex
S Capsule
(190x)
-27-
Figure 5
-28-
Figure 6
A high pov/er magnification of a thymic
corpuscle revealing details of its structure.
N Cell nucleus
C Center of undifferentiated material
L Laminated cell with degenerating nuclei
(2000%)
- 28 - .
a
■ L
>
r
m
Figure 6
-29 -
Figure 7
A section of the human thymus showing a highly
differentiated medulla and cortex, and also a thymic
corpuscle.
C Cortex
M Medulla
T Thymic corpuscle
(190x)
-29-
e\.
M
Figure 7
-30-
THE THYMUS OF TÎŒ SEVENTY MILLIMETER EMBRYO
The heart and thymus of the seventy millimeter human embryo.
Figs. A9 5, 6, and 7, are cut in longitudinal sections, twelve microns
thick, and stained with hematoxylin. Here we find the trachea prior to
its bifurcation, and Just ventral to it lies the thymus which has now
taken on the multilobular appearance of the term organ. The cortex and
medulla are readily differentiated, and the thymocytes are numerous.
The anterior end of the thymus is an irregular group of epithe
lial cells. The group lies dorsal and slightly medial to a small vein,
at some distance from the right ventral aspect of the trachea. On the
left side of the trachea, lying between it and an artery, is a larger
irregular group of cells which is believed to be thymic cells. This
disappears posteriorly; but the group on the right becomes larger and
more clearly defined, lying medial to the adjacent vein. There appears
also a definite group of thymic cells in a rather fibrous island of
tissues lying centrally between the left jugular vein, left carotid
artery, and a ventrally placed large nerve trunk, the vagus. The left
group persists in a mass of varying size and lobulated appearance. Small
deeply stained cells are closely packed in the peripheral portions. At
the same time the right group moves ventrally and disappears in the
ragged edge of the tissue.
Another group of cells appearing as a round mass of vascular
~ 31“
tissue near the trachea grows steadily larger, and soon two others
appear a short distance dorsally and laterally. The peripheral crowding
of the cells continues in these groups. At this point a small group
of cells appears in a similar central location on the left side, between
the nerve, artery, and vein. It increases in size for a time; then
recedes and disappears. A group suddenly appears on the right side
opposite the ventral border of the trachea. It increases and meanwhile
the dorsal group disappears, to be replaced by several small lobules
which are given off laterally in a fibrous stroma. The left thymic
body and a new group on the right, ventral to the larger posterior
group of lobules, reappears and grows rather rapidly, resembling the
groups previously described. On the left, however, the now large
group is rather dispersed with grayish fascicular nuclei and a few
infiltrating lymphocytes and plasmic cells. Three groups of similar
cells appear ventral to the jugular vein, one on each side of a small
blood vessel and another ventral to the vagus. The right posterior
group is only an irregular fibrous island, except for the brief appear
ance of a small dot of epithelial cells.
Later we find one large island on the right some distance later
al to the trachea, with part of a smaller island ventral to a portion
of the vagus, which soon disappears. The left side shows two groups,
a small one dorsal to the vagus and a larger one ventral to it. They
all exhibit more of a reticular structure except the large group on the
right, which shows numerous deeply stained and closely packed cells.
—32-
Dorsal to it three other groups soon appear and fuse together and a new
nodule is seen on the left ventrally. This grows rapidly with several
lobules. Another group appears at the medial end and ventral to the
jugular vein, which also develops posteriorly into a lobulated structure.
A group also appears dorsal to the large island on the right side. All
develop rapidly into multilobed structures containing many small blood
vessels. The surrounding tissues also contain many vessels. On the
right side, however, no new thymic tissue appears.
A small group of epithelioid cells which appears to be an early
thymic corpuscle occurs in a lobule projecting medially from the large
ventrally placed thymic lobe. Another area which is more definite is
seen in the center of the large ventral lobe. The bifurcation of the
trachea is noted to be complete a few microns above this area.
SUMMARY
In the seventy millimeter embryo the heart and thymus have been
serially sectioned and examined. The obliteration, fibrosis, and atro
phy of thymic cells is marked in the cephalic portion, with nodes of
cells appearing and receding for some distance. The greatest develop
ment of the thymic bodies is seen where the separation of cortical and
medullary portions are distinct. The cortex is closely packed with
deeply stained cells of lymphocytic and plasmic appearance. Mitoses
appear rather frequently. The medullary portion presents a loosely
arranged network of epithelioid or endothelioid cells. There are
- 33-
numeroüs blood vessels in the cephalic and central portions of the
thymus, indicating a vascular active organ whose functions are still
quite uncertain.
The first thymic corpuscles are also seen at this stage, and
vary considerably in density and size, with not much of the typical
concentric arrangement. In the caudal portion the thymus again becomes
very cellular as the cortex is seen in section. The left thymic lobe
extends somewhat lower than the right lobe.
~~3A~
THE EIGHTY FIVE MILLIMETER EMBRYO-THYMUS
The eighty five millimeter human embryo-thymus is cut in serial
sections, ten microns thick, and stained with hematoxylin. The right
and left lobes of the thymus are each seen in groups of cells which
differ greatly in arrangement. The right seems to be a spindle shaped
group, lying transversely and made up of a network with a closely
packed cortex. This soon obliterates and an irregularly lobed round
group appears ventrally. The first thymic corpuscle is found in this
lobe. The left thymus appears as a round gland-like group of cells
which appears almost cystic in nature. Later two other groups appear
and fuse into one. These contain a thin colloid material. The right
lobe is now larger than the left; and a large well developed thymic
corpuscle is seen as well as a new island of thymus ventral to the
left lobe.
The thymic tissue increases gradually in amount as we pass
caudally, with a new nodule appearing between the two lateral groups.
All have a multilobed arrangement on the periphery with the central
portion loose and reticular in nature, supporting a few small round
cells, as compared to the lobules which are of closely packed cells
making the typical cortical structure. The vascularity of the thymic
tissue throughout is striking. Each large lobe contains a blood vessel
passing almost vertically through it and numerous blood channels enter
-35-
or leave In the sulci between the lobules. Thymic corpuscles are
occasionally seen throughout the medulla.
The ventral group of thymic cells fuses with that on the right,
which grows laterally to a considerable degree. New islands appear
ventrally and laterally to the main portion of the left thymus, and
increase rapidly in size to fuse with it into a large mass. More new
groups appear near the mid-line and dorsal to the right lobe. A group
arises in similar relations with the left lobe which later unites with
it. These areas represent the greatest extent of the thymic tissue.
The beginning of regressive changes, especially in the size of the left
thymus, appears here; and progresses gradually until all trace of thymus
is lost, the left lobe disappearing last.
SUMMARY
In the thymus of an eighty five millimeter embryo thymic cor
puscles of the mature type are seen in numerous instances. The separa
tion into cortical and medullary portions is distinct. The numerous blood
vessels entering or leaving the thymus are striking.
- 36-
THE ONE HUNDRED MILLIMETER EMBRYO-THYMUS
The one hundred millimeter human emhryo-thymus is cut in serial
sections, ten microns thick, and stained with hematoxylin. The earliest
thymic corpuscle in this thymus occurs where the tissue is rather poorly
differentiated into cortex and medulla. There are numerous small blood
vessels in and around the thymic tissue, and the whole is surrounded by
a delicate stroma of fibroblastic type. This dips deeply between the
various peripheral lobules, which are for the most part quite cellular.
The medullary portion occupies nearly all the tissue which does not
enter into the form of lobules, and though it contains many small
round cells in its stroma, it appears very light and loose in contrast
to the cortical portion. Thymic corpuscles have become more numerous
and distinct than in the previous stage. Some present large grayish
vesicular nuclei with surrounding layers of concentric cells. Others
contain a yellowish brown or nearly black rounded mass which resembles
keratinized epithelial cells of squamous origin, while still others
contain a few pylmotic, deeply stained nuclei in cells with shrunken
cytoplasm. The cytoplasm of the first layer of concentric cells fre
quently contains granules of black pigment generally arranged at the
periphery of the cell.
In this stage considerable regression is seen, the decrease
being due to breaking up of the large lobes into several small islands
-37-
of cells, which are separated by light fibrous stroma, ard which do not
reunite again. The medullary tissue grows less with these changes, with
relative increase in the cortical portion.
The thymus grows progressively smaller and less complicated until
the rather simple lobes of equal size with well differentiated cortex
and medulla remain. The vascular nature remains prominent throughout,
and it has been impossible to show any particular relation between thymic
corpuscles and the obliterating blood vessels, as some authors suggest.
SUMMARY
Numerous thymic corpuscles are seen in the thymus of the one
hundred millimeter embryo. They present varying central structures. No
relation is discovered between their formation and obliteratlve changes,
said to occur in the blood vessels. It appears, if this is true, that
some relation should be demonstrable, in view of the fact that at this
age the corpuscles are rapidly increasing in number. Since this cannot
be done, we conclude for the present, that this theory does not explain
their frequent occurrence in a satisfactory manner.
-38-
THE ONE HUNDRED THIRTY FIVE MILLIMETER EMBRYO-THYMUS
The one hundred thirty five millimeter human embryo-thymus was
cut in serial sections, eight microns thick, and stained with hematoxy
lin. The cortex and medulla are not well differentiated and the thymus
appears as four lobes separated by fibrous strands in which prominent
blood vessels are seen. No marked change occurs here except the size
of the thymus is slightly larger. However, the cortex and medulla
become much more distinct, and the thymic corpuscles appear rather
frequently. The tissue consists of many more lobules penetrated by
bands of connective tissue which usually contains a congested blood
vessel. The thymus grows progressively larger, however, the thymic
corpuscles are considerably fewer in these slides. The two lobes are
not distinct in this case, neither do they shoT at any point the com
plete fusion which was apparent in the one hundred millimeter embryo.
The organ shows a continuous decrease in size with the medullary tissue
being replaced by the cortical type of structure. The occurrence of
two separate lobes is seen, one on each side, one being several times
larger and much more vascular than the other.
SUMMARY
In this embryo a large number of congested vessels appear in the
fibrous capsule and its penetrating trabeculae. The thymic cells give
-39-
the appearance of being slightly shrunken in a rather edematous tissue.
The cells tend to be separated by wider clear spaces than is ordinari
ly expected. The thymic corpuscles appear frequently but present no
additional indication regarding their origin.
THE HUMAN THYMUS ^ TERM. STILL BIRTH
The human thymus at term, still birth, is cut in serial cross
section, thirteen microns thick, and stained with hematoxylin. In this
specimen the thymus consists of lobules of varying size and shape. The
cortex and medulla are distinct, even though the medullary portion
contains many small round cells, The thymic corpuscles are numerous
and present varying appearances as previously described. The whole
tissue is quite vascular, and a few instances are noted in which blood
vessels are lined by two or three layers of concentrically arranged
cells with elongated nuclei. Around the group of cells is a layer of
rather dense fibrous stroma. Structures of this type do perhaps give
some weight to the theory of oblitérâtive vascular changes as the source
of the thymic corpuscles.
The main body of the gland shows much more cortical tissue than
the medullary portion. The entire tissue is congested and contains
numerous areas of hemorrhagic extravasation. The thymic corpuscles
are one and one half times as numerous. Their central structures show
considerable variation in content and staining reaction. Some contain
basophilic granules in the central cells, others show an acidophilic
reaction in the granular material which resembles necrotic cells.
Others resemble keratinized cells as previously described, A few seem
to show infiltration by polymorphonuclears though some of this appear
ance may be due to pyknosis and nuclear fragmentation.
— 4 -1 *"
THE THYMUS OF TERM CHILD, VIABLE SIX HOURS
A term child thymus, viable six hours, is cut in serial cross
sections, ten microns thick, and stained with hematoxylin. The findings
in regard to the term child are very much like those of the previous
term embryo, no differences in normal structures being noted.
We have a multilobular organ with each lobe having almost entire
ly a cortex appearance, i.e., the reticulum is heavily infiltrated with
small, round cells. The medulla is largely composed of reticular cells
and many thymic corpuscles.are seen. These structures incidentally
have increased almost double in size to those in the eighty five milli
meter specimen, and they lie exclusively in the medulla. Also, thymic
corpuscles are seen in the caudal tip of the organ. They seem entirely
confined to the deeper reticular structures.
-42.
DISCUSSION
No discussion of the origin of the thymus gland would be complete
without notice being taken of the opinions of early authors, and due
credit given. But since these are dajs of rapid progress, and since
many outstanding professional articles written twenty years ago are
now more or less valueless, too much space will not be given here to
them.
Practically all authors agree that the anlage of the thymus
originates from the epithelium of each of the third pharyngeal pouches;
that later it becomes epithelioid in structure as it extends as paired
strands caudally, and slightly ventrally into the thorax; and nothing
in the author’s findings is in conflict with the foregoing.
Grossly the thymus at birth is described as a bilobed organ, and
the two lobes are fastened together by a fascial tissue which gives it
a bilobed appearance; but there is no isthmus of thymic tissue between
the lobes such as we see in the thyroid, hence the organ is actually
made up of two thymic lobes. Each lobe is divided into lobules by the
connective tissue capsule which sends its numerous trabeculae into the
lobe. Each lobule consists of a medulla, and a cortex which entirely
surrounds it. The medulla is made up of loosely arranged reticular
cells and extends into each lobule. The cortex consists of the same
cell structure and is engorged with cells having the appearance of small
—43—
lymphocytes.
In the author’s microscopic studies of the ten millimeter human
embryo the thymus was found to consist of two strands of distinctly
epithelial tissue about four tenths of a millimeter in length which
appear to come from the level of the third pharyngeal pouch and extend
caudad to the level of the right subclavian artery. The epithelial
character of the organ is evident throughout its course.
In the twenty five millimeter embryo the cells become more and
more loosely arranged and the organ takes on an epithelioid appearance,
the cells giving off processes which anastomose to form a reticulum.
The cephalic ends of the thymic cords lie ventral to the vagus
nerves and medial to the jugular veins. They gradually approach each
other as they grow caudally and ventrally lie in close contact, sepa
rated only by a thin fibrous stroma. These findings agree with Hammar
(1921) when he states:
With regard to the details of the histogenesis in men it may be
mentioned that the infiltration of the epithelial anlage by lympho
cytes begins as early as towards the end of the second month of
prenatal life, at an embryonal length of about 30 mm...............
At the end of the second month the organ already consists of two
conical lobes, situated close together in the anterior mediastinum,
each with a longer or shorter pointed upper end, the thymus horn,
and a basal end usually bent round backwards in the shape of a hodq
the cardiac bends. Towards the middle of each lobe septa of connect
ive tissue penetrate, especially its thickest parts from all sides,
dividing the cortex into so-called cortical follicles. The medulla
remains undivided. At the same time as the organ continues to in
crease rapidly in size, mitotic division both of the lymphocytes
and the reticulum cells, the formation of medulla - the result of
the enlargement of the reticulum cells - encroaches upon the inner
parts of the cortical follicles, which consequently assume the
character of lobuli, consisting of both medulla and cortex.
— 44 —
With regard to the reticulum the general feeling is that it is
of entodermal origin* Pappenheimer (1910) says, "The cell outlines
are indefinite, the cell protoplasm being drawn out into irregular
prolongations which form extensive protoplasmic intercellular connec
tions." Certainly these cells form the stroma of the gland and hold
the small thymic cells in its cortex.
The thirty millimeter embryo, having been cut in sagittal section,
is chiefly of value in studying the thymus in relation to other struct
ures. We find the organ located dorsal to the cephalic portion of the
manubrium sterni. It is well caudal to the thyroid gland and none of
the organ is seen in this section remaining in the cervical region.
The author was informed by the Los Angeles County autopsy surgeon that
he has never encountered thymus tissue remaining cephalad to the manu
brium sterni in any autopsies done on simple hypertrophy of the thymus
or on cases of status-thymico-lymphaticus.
It is about this stage of development of the embryo that the
small thymus cells first come up for consideration. And as previously
mentioned the origin of these cells is debatable. This subject was
considered under a previous heading, but the conclusions of Popoff (1926)
following transplantation of the gland are quoted here because they
appear to have an excellent biological basis. He says :
After seven days regeneration becomes very distinct. The epithe
lium presents itself in the form of thick growing lobated buds con
taining many mitoses. The vessels accompanied by embryonic connective
tissue penetrate deep into the folds between the epithelial buds.
Whenever the connective tissue comes in contact with the epithelium
- 45-
the cells of the former become mobilized as large, medium sized and
small lymphocytes. The latter penetrate by means of ameboid move
ments between the epithelial cells and show many mitoses as do also
the epithelial cells. In many places the lymphocytes give rise to
special myelocytes; these are mostly of the darkly nucleated, micro-
myelocytic variety. After eight days the lymphocytes outnumber the
epithelial elements.
The regenerative processes in the transplants of the thymus dupli
cate the histogenetic processes of this organ in the embryo. The
essential feature in both cases is the infiltration of epithelium
with true lymphocytes. The epithelium gradually becomes transformed
into a reticulum. At the same time the vessels continue to branch
between the epithelial masses and form a network of embryonic connect
ive tissue, penetrating the epithelial network, and serving as a
source of lymphocytes and histiocytes.
The regeneration of the stump of the remaining part of the thymus
duplicates in all essential features the regenerative process in the
transplants.
The lympho-epithe liai nature of the thymus and the presence of a
perivascular mesenchymal reticulum in this organ are decisively
shown by these experiments with tissue cultures, autotransplantations,
and regeneration. No evidence of the development of the small thymus
cells from the epithelium was found.
Briefly, in support of the view that the small thymic cells are
true lymphocytes, are the facts that these two types of cells resemble
each other in their morphological characteristics, in their susceptibility
to roentgen ray injury, in their serologic reactions, and in having ame
boid movement. And since the more recent authors have generally adopted
the theory which classes the small thymus cells as inwandering lymphocytes
and hence of mesenchymal origin, this author believes that this theory is
the most acceptable.
The forty millimeter human embryo presents what might be termed
the picture of a transition. One visualizes the gland as being two
- 46—
strands of thymic tissue extending from the cervical region to the
pericardium as in previous embryos, but one finds that the gland has
completely changed from the epithelial structure of the ten millimeter
embryo to the reticular appearance which began in the twenty five milli
meter specimen and which has become thoroughly infiltrated with inwander
ing lymphocytes to present a picture lacking only two important details
of that of the term thymus. The two details lacking are: differentiation
of cortex and medulla, and the appearance of thymic corpuscles. Its re
lations in regard to other sturctures remain much the same as in the
thirty millimeter specimen, particularly that its largest portion lies
immediately behind the manubrium sterni and ventrocephalic to the peri
cardium. It is directly ventral to the trachea. It is of interest to
note that the ratio of the length of the thymus in three measured speci
men is: ten millimeters — one to forty, the twenty five millimeter
and the forty millimeter — one to fifteen, revealing the growth as being
more rapid about this period.
In passing to the thymus of the seventy millimeter embryo the
time factor is about eighteen days. During this time marked changes
have taken place in the thymus. The organ presents the gross appearance,
except for size, of the term thymus. Each lobe is divided into lobules
by connective tissue strands from the capsule. The cortex and medulla
are markedly differentiated, and the cortex is engorged with small lympho
cytes. The first thymic corpuscle is seen in the medulla, and it is small
and relatively immature. The thymic corpuscles are a distinguishing
-47-
feature of thymic tissue, and first appear in the seventy millimeter
embryo which corresponds to findings of Cowdry (1934) and F. B. Bailey
(1936).
There are several theories as to their origin. Cave11 (1932)
summarized the four views of the origin of thymic corpuscles:
(1) Modified epithelial cells
KoeHiker 1979, His 1280
(2) Epithelial rest of the original anlage
Stied 1891, Mauer 1899, Ver Ecke 1899, Badertscher 1915
(3) From proliferating wall of blood vessels
Nussbaum and Machowski 1902
(4) From reticulum of medulla
This is described by Hammar 1921 as follows:
They are started as small formations of 10-25 microns diameter,
often in the neighborhood of some small blood vessel. One or two
adjacent reticulum cells increase in size and assume a spherical
shape. When on this enlargement they reach neighboring cells in the
medullary reticulum, the latter cells are thrust to the side owing
to the pressure of growth and take up a position close to the central
cell or cells, which they concentrically enclose like the scales of
an onion. Even the peripheral cells often fairly soon become hyper
trophied, so that the formation grows farther and fresh cells are
joined to its periphery. When the growth proceeds in this manner two
or more corpuscles may reach each, join together, and continue to
grow as a unit.
Bell 1906 characterizes the corpuscles as a modified area of the
epithelial syncytium of the medulla containing one or more nuclei
and whose cytoplasm has been in part or wholly changed into colloid.
He uses the term colloid as meaning "hyaline substances of epithelial
origin that do not give the reaction of mucin." He classifies the
corpuscles according to their mode of development as follows;
—4 -8—
A, Concentric Corpuscles
a. Simple
1. Ordinary type
2. Epithelioid type
3. Cystic type
b. Compound
B, Irregular Corpuscles
a. Compact type
b. Reticular type
As to the function of the Hassall’s corpuscles, Jordan and
Kindred 1930 express the opinion in their textbook of embryology,
that there is no evidence of a hormone activity to the Hassall’s
corpuscles. Bell 1906 writes:
Since the lymphocyte-forming function of the thymus is probably
secondary, it is not unreasonable to suppose that its primitive
function was the formation of a colloid secretion, such as occurs in
the thyroid, and that the corpuscles are abortive expression of this
primitive function.
The author’s findings agree with Cowdry (1934) that the thymic
corpuscle is an area of focal degeneration, as high powered microscopic
examination reveals an undifferentiated mass in the center of each cor
puscle.
In the eighty five millimeter embryo thymus a slightly more mature
organ is seen. There is a markedly increased vascularity noted, also a
sharply differentiated cortex and medulla, and more mature thymic cor
puscles are presented.
In the one hundred millimeter embryo thymus we find the medulla
and cortex less clearly marked, but it is believed that this is tempo
rary and of no importance. There is a marked increase in the number of
thymic corpuscles.
In the one hundred thirty five millimeter embryo thymus there is
—49—
a noticeable increase in the cortical portion of the gland apparently
at the expense of the medulla, A number of congested vessels appear in
the corpuscle which may explain the engorgement of the cortex. Thymic
corpuscles are numerous.
The human thymus at term still birth presents a slightly differ
ent picture from the foregoing specimen. Cortex and medulla are distinct,
thymic corpuscles are numerous, cortex is engorged, and the entire
tissue is congested with numerous hemorrhagic extravasation. The terra
viable six hours specimen is almost identical with the above description.
The history of these cases indicate thymic hyperplasia and probable
thymus death in both.
•50-
GENERAL SUMMARY
1. The human thymus begins as a thickening of the entoderm of
the third pharyngeal pouch in close proximity to the origin
of the thyroid and parathyroid,
2. In early embryos the gland appears as two narrow strands of
thymic tissue extending caudally and ventrally until in the
thirty millimeter embryo we find the greater portion lying
just dorsally to the manubrium sterni.
3. The reticulum of the thymus appears to be endodermal in
origin.
4. It is believed that the small round cells which are s o
noticeable in the cortex are lymphocytes.
5. It is believed that the thymic corpuscles are formed from
the reticulum of the medulla.
6. Of particular inportance for therapeutic measures is the
position of the body of the thymus dorsal to the manubrium
sterni, ventrolateral to the trachea, and ventrocephalad to
the pericardium.
-51-
BIBLIOGRAPHY
Arey, L. B.
Badertscher, J. A,
Bailey, F. B.
Beard, J.
Bell, E. T.
Bellinger, F.
Cave 11, K, H.
Cowdry, E. V.
Danchakoff, Vera
Decker, H. R,
1930 Developmental Anatomy," Saunders Co.,
Philadelphia, 2nd Ed.
1915 Development of thymus in the pig,
I. Morphogenesis. Am, J. Anat.
17:317, 1914.
1936 Textbook of Histology (Elwyn & Strong)
9th Ed., pp. 328, Wm. Wood & Co.,
Baltimore.
1903 Zool. Jahrb. 17:403.
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Asset Metadata

Creator Bailey, C. O. (author)

Core Title Embryologic and histologic studies of the human thymus

Contributor Digitized by ProQuest (provenance)

Degree Master of Arts

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag Biological Sciences,health and environmental sciences,OAI-PMH Harvest

Format application/pdf (imt)

Language English

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c39-253965

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Dmrecord 253965

Document Type Thesis

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