Vol. 45, No. 4
Printed in U.S.A.
T H E AMERICAN JOURNAL OP CLINICAL PATHOLOGY
Copyright © 1906 by The Williams & Wilkins Co.
ERYTHROPOIESIS IN THE HUMAN THYMUS
S. ALBERT, M.D., PAUL L. WOLF, M.D., I. PRYJMA, M.S., AND J. VAZQUEZ, M.T. (ASCP)
Department of Pathology, Wayne State University School of Medicine, and the
Detroit Institute of Cancer Research, Detroit, Michigan
I t is generally believed that the thymus is
a lymphopoietic organ necessary for proper
development in many species.3 Recently, it
was found that erythropoiesis is frequently
observed in the thymus in mice.1' 2 The
present investigation was made to determine
whether erythropoiesis also occurs in the
human thymus.
MATERIALS AND
METHODS
The thymuses used in this study were
obtained postmortem from 4 Caucasian
pediatric patients between 45 days and 53^
years of age. Smears were made of thymus
cell suspensions and stained with either
Leishman's or Wright's stain, or specifically
for hemoglobin with Ralph's stain, according to procedures previously described. 1 ' 2
Portions of each thymus were fixed in
Bouin's solution, sectioned at 6 ^, and
stained with hematoxylin and eosin (conventional sections).
Received, August 16, 1965.
This investigation was supported in part by
Public Health Service Research Grants CA-02151,
CA-02903, and CA-02624 from the National
Cancer Institute, and in part by an institutional
grant to the Detroit Institute of Cancer Research
from the United Foundation of Greater Detroit,
allocated through the Michigan Cancer Foundation.
RESULTS
Microscopically, in the conventional sections, normal thymus architecture was seen
(Fig. 1), with the cortex consisting of cells
resembling small lymphocytes (Fig. 2). On
the other hand, smears indicated the
presence of many erythroid cells in various
stages of maturation. Pronormoblasts (Fig.
3), basophilic (Fig. 4), polychromatophilic
(Figs. 5 and 6), and orthochromic (Figs. 5
and 7) normoblasts were readily identified.
Occasionally, erythropoietic cells with
asynchronous nuclei were seen (Figs. 6 and
7). In some smears, erythroid cells with
light blue nuclei and cytoplasm in various
stages of hemoglobinization were observed
(Figs. 8 and 9). Frequently, dark and light
staining "naked" nuclei were found scattered
among the erythroid cells (Figs. 4, 7 to 9).
These structures, which resembled small
lymphocytes, are believed to be the extruded
nuclei of erythroid cells (Fig. 9). The reasons
for this interpretation have been discussed
fully in a previous report.2 Occasionally,
erythropoietic cells whose nuclei seemed to
be undergoing hemoglobinization (Fig. 10)
and erythroblastic islands (Fig. 11) were
observed.
Further evidence for the erythropoietic
nature of many of the thymus cells was
obtained by staining specifically for hemo-
Fio. 1 (upper left). Conventional section from the thymus of a 5]^-year-old girl, showing relatively
normal architecture of a thymic lobule. Hematoxylin and eosin. X 60.
FIG. 2 (upper right). High power view of the thymic cortex shown in Figure 1, demonstrating many
cells that resemble small lymphocytes and an occasional reticular cell. Hematoxylin and eosin. X 800.
FIG. 3 (second row, left). Cells from the thymus of a 5J-<j-year-old girl, to illustrate a pronormoblast.
Leishman. X 1200.
FIG. 4 (second row, right). Cells from the thymus of a 45-day-old boy, showing a basophilic normoblast and a dark "naked" nucleus. Leishman. X 1200.
FIG. 5 (third row, left). Cells from the thymus of a 45-day-old boy, demonstrating an orthochromic
normoblast, and adjacent to it a polychromatophilic form. Wright. X 1200.
FIG. 6 (third row, right). Cells from the thymus of a45-daj'-old boy, illustrating a polychromatophilic
form in transition to the orthochromic stage, with an asynchronous nucleus. Wright. X 1200.
FIG. 7 (lower left). Cells from the thymus of a 45-day-old boy demonstrating 2 orthochromic normoblasts; the nucleus of 1 is asynchronous and there are several dark "naked" nuclei. Wright. X 1200.
FIG. 8 (lower right). Thymus cells from a 5j^-year-old girl. In the center of the field there is a polychromatophilic erythroid cell with a light blue staining nucleus (arroio). Many light "naked" nuclei
may be seen in the field. Wright. X 1200.
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ALBERT ET AL.
globin. In these preparations, many cells
whose cytoplasm was strongly positive for
hemoglobin were observed (Figs. 12 and 13).
The nuclei of a large proportion of these
erythroid cells resembled many of the
"naked" nuclei that were seen nearby,
further supporting the interpretation that
they were extruded from these cells. The
cytoplasm of many cells stained yellow-brown
(Fig. 13), indicating the presence of hemoglobin, and that these cells were polychromatophilic forms.
Frequently, large cells which contained
ingested "naked" nuclei and erythrocytes
were seen (Fig. 14). Often, these phagocytic
cells seemed to be associated with other
morphologically similar cells that seemed to
be undergoing degeneration by hyalinization
of the cytoplasm (Fig. 15). These aggregations of degenerating macrophages resembled
the Hassall's corpuscles found in conventional sections (Fig. 16). The possibility that
these phagocytic cells may in some manner
be associated with the formation of these
structures is currently under investigation.
possible to demonstrate that a large proportion of thymus cells were erythi-opoietic.
Many of the erythroid cells found in the
human thymus bear a strong resemblance to
those foimd in mice. Erythroid cells with
light blue nuclei and cells whose nuclei
seemed to be undergoing hemoglobinization
were observed in both species;4 however,
certain differences were noted. Occasional
megaloblastoid cells were found in the thymus of normal mice, but thus far such
cells have not been observed in human
thymuses, and the nuclei of cells of the
normoblast line in mice tend to be more open
and less condensed at later stages of maturation than in human beings.
Inasmuch as the thymuses used in the
present study were obtained at autopsy, the
possibility that red blood cell formation is a
pathologic function must be considered.
Whether or not erythropoiesis also occurs
normally, as it does in the thymus of the
mouse,1 • 2 remains to be determined, and is
currently under investigation.
SUMMARY
DISCUSSION
The postnatal human thymus is not
regai'ded as an erythropoietic organ,
although a nucleated erythroid cell may
occasionally be observed under extremely
adverse conditions.5 By means of smear
preparations of cell suspensions and standard
hematologic staining procedures, it has been
Smears were made of cell suspensions of
human thymuses obtained at autopsy from
pediatric patients. They were stained with
either Leishman's or Wright's stain, or
specifically for hemoglobin with Ralph's
stain. A large proportion of the cells was
found to be erythropoietic. All stages of
maturation were observed. In addition to
FIG. 9 (upper left). Cells from the thymus of a 5.H>-year-old girl, demonstrating in the center of the
field an orthochromic erythroid cell extruding its light blue nucleus. Many light "naked" nuclei are
also present. Wright. X 1200.
FIG. 10 (upper right). Thymus cells from a 5K-year-old girl, illustrating many cells {arrows) whose
nuclei are hemoglobinized. Wright. X 1200.
FIG. 11 (second row, left). Cells from the thymus of a 45-day-old boy, illustrating 3 erythroblastic
islands, composed of normoblasts in various stages of maturation surrounding reticular cells. Leishman.
X 800.
FIG. 12 (second row, right). Cells from the thymus of a 45-day-old boy stained specifically for hemoglobin and showing an orthochromic normoblast whose nucleus resembles the "naked" nuclei scattered
throughout the field. Ralph's stain counterstained with Harris' hematoxylin. X 1200.
FIG. 13 (third row, left). Thymus cells from a 5J£-year-old girl stained specifically for hemoglobin.
In the field are forms (thin arrows) with hemoglobinized nuclei and negative cytoplasm, and cells (wide
arrows) whose cytoplasm stains yellow-brown, which indicate the presence of hemoglobin, and are polychromatophilic normoblasts. Ralph's stain counterstained with Harris' hematoxylin. X 1200.
FIG. 14 (third row, right). Thymus cells from a 53^-year-old girl, showing a large phagocytic cell with
ingested dark and light "naked" nuclei and some erythrocytic remnants. Leishman. X 1200.
FIG. 15 (lower left). Thymus cells from a 45-day-old boy, illustrating a group of epithelioid cells whose
nuclei resemble those of the phagocytic cell in Figure 14, and which are surrounded by a thin rim of cytoplasm which seems to be undergoing or to have undergone hyalinization. This structure is believed
to be a Hassall's corpuscle. Leishman. X 1200.
FIG. 16 (lower right). Conventional section from the thymus of a 45-day-old boy, demonstrating a
typical Hassall's corpuscle. Hematoxylin and eosin. X 800.
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ERYTHROPOIESIS IN HUMAN THYMUS
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ALBERT ET AL.
cells of the normoblast type, erythroid cells
with light blue nuclei and with nuclei
undergoing hemoglobinization were also
observed.
Acknowledgments. Dr. A. Joseph Brough,
Associate Pathologist, Children's Hospital of
Michigan, supplied the pediatric thymus tissue,
and Mrs. Katherine Marselis gave stenographic
assistance.
REFERENCES
1. Albert, S., Wolf, P., and Pryjma, I.: Evidence
of erythropoiesis in the thymus of mice. J.
Reticuloendoth. Soc, 8: 30-39, 1965.
Vol. 45
2. Albert, S., Wolf, P., Pryjma, I., and Vazquez,
J.: Variations in morphology of crythroblasts of normal mouse thymus. J. Reticuloendoth. Soc, 2: 158-171, 1965.
3. Good, R. A., and Gabrielsen, A. E. (Editors):
The Thymus in Immunobiology. Structure,
Function, and Role in Disease. New York:
Hoeber Medical Division, Harper & Row,
1964.
4. Gross, S., and Keefer, V.: The identification of
intranuclear hemoglobin. Am. J. Clin.
Path., Jfi: 559-560, 1964.
5. Potter, E. L.: Pathology of the Fetus and the
Infant, Ed. 2. Chicago: Year Book Medical
Publishers, Inc., 1962.