Download THE CELLULAR STRUCTURE OF CARCINOMA OF THE LUNG

T H E CELLULAR STRUCTURE O F CARCINOMA O F T H E LUNG
BELA HALPERT, M.D., AND BJARNE PEARSON, M.D.
(From the Departments of Pathology and Bacteriology of the Charity Hospital of Louisiana at
New Orleans and the Louisiana State University School of Medicine)
This study of the microscopic structure of carcinoma of the lung was undertaken in order to assemble data concerning the cellular origin of these growths.
The material was derived from 92 cases of carcinoma of the lung observed
in a series of 7433 necropsies performed at the Charity Hospital of Louisiana
at New Orleans on persons over one year old. I t includes 74 cases previously
analyzed (1) and 18 additional cases which were encountered between July
1, 1938, and June 30, 1939. Routine microscopic preparations from each
primary growth and, when possible, from sites of metastases, were used in
the analysis.
On the basis of the' individual and group characteristics of the neoplastic
cells the 92 growths were classified, as previously suggested (2, 3), as squamous-cell, columnar-cell, and reserve-cell carcinomas. Forty-nine tumors, or
53.26 per cent, were classified as squamous-cell, 17, or 18.47 per cent, as
columnar-cell, and 26, or 28.25 per cent, as reserve-cell carcinomas. The
distribution among white and colored males and females is given in Table I.
TABLEI : Race and Sex Incidence of Pulmonary Carcinomas
Number of necropsies on persons over
oneyearold.Jan.1.1931-June30.1939
Squamous-cell carcinoma
Columnar-cell carcinoma
Reserve-cell carcinoma
Total
White male
2183
23
10
15
I
White female
987
1
-48
I
Colored male
2618
I
Colored female
I645
1
Total
1433
2
3
0
24
4
10
0
0
1
49
17
26
5
38
1
92
The growth was classified as squamous-cell carcinoma when the tumor
cells were arranged more or less concentrically to form epithelial pearls, and
the cells toward the center of the cell nests disclosed varying degrees of
keratinization or were transformed into keratinized scales or dCbris. The
grouping was not altered by the coincident presence of columnar cells forming
acinar or tubular structures and of undifferentiated or reserve cells, either alone
or in combination.
The cellular and structural variations in this group of carcinomas were
marked. All grades of transition were observed, from slight central keratinization to pearl formation. In one instance broad zones of reserve cells con213
tained minute keratinized centers (Fig. 1). In several predominantly squamous-cell growths, low cuboidal or columnar cells forming acinar or tubular
structures appeared here and there (Fig. 2 ) . In some fields of such growths
cells of all three types were present in almost equal proportions. The number
of nuclei in mitosis, the amount and character of the stroma, and the amount
of inflammatory reaction, varied in the individual tumors.
In the metastases of some of the growths occasional areas were observed
composed entirely of reserve cells without keratinization; the peripheral cells
in these areas exhibited a palisade arrangement.
The growths were classified as columnar-cell carcinomas when the tumor
cells were columnar or cuboidal and were arranged in acinar, tubular, or
papillary structures. The grouping was not altered by the presence of additional masses of undifferentiated or reserve cells.
There was considerable variation. in the individual tumors of this group
as regards the height of the cells forming the acini, the number of acinar and
tubular structures present, and the number of cells aggregated into solid
masses. Among the cells forming these solid masses, reserve cells were occasionally seen. In some growths the acinar and tubular structures simulated
in a haphazard way the normal epithelial structures of the air passages in that
the columnar cells resembled goblet cells or were ciliated. The lumina of
these structures contained pink or lavender-staining secretion in the form of a
network. In some growths the papillary arrangement was more marked than
the acinar and tubular formations, and there was little variation in the height
of the cells (Fig. 3 ) . In the growths in which well formed acinar, tubular, or
papillary structures were observed, the stroma was usually scanty. I t was
more abundant in the growths composed 'of low cuboidal cells. There was
considerable variation in the individual growths as to the number of nuclei in
mitosis, the amount of necrosis and hemorrhage, and the inflammatory reaction
in the stroma.
The growth was classified as reserve-cell carcinoma when the tumor cells
were of the same size, the nuclei were round, oval or elongated, and stained
deeply, the cytoplasm was scanty, and the cell borders were hardly discernible.
The cellular arrangement formed no particular pattern; in some growths the
cells were arranged in whorls, in others there was a palisade arrangement of
the peripheral cells.
The cellular and structural variations were slight in this group. More or
less extensive areas of necrosis were present in the centers of some cell sheets.
The connective-tissue stroma was usually scanty and delicate, and at times
presented little inflammatory reaction about the advancing margins of the
growth. The cellular pattern of the primary tumor was perfectly reproduced
in the metastases to regional lymph nodes and to distant organs such as the
Iiver (Fig. 4) and the kidneys.
The concepts of older writers concerning the cellular origin of carcinomas
of the lung were lucidly presented by Moi'se (4) in 1921. In 1929 Weller
(5) contributed another review in which was assembled most of the information then available on this subject. . I n 1932 Fried (6) ably supported the
idea that all carcinomas of the lung are derived from a common ancestor cell,
and this view is accepted by a number of recent observers, including Sweany
( 7), JaffC (8),Lindberg (9), Samson ( l o ) , Rosedale and McKay ( 11) , Fabris
( 12), Brines and Kenning ( 13), Stein and Joslin ( 14), Tod ( IS), and Ochsner
and DeBakey (16).
A consideration of the normal epithelial structures of the air passages and
their embryonic derivation suggests a logical explanation for the variety in the
cellular structure of carcinoma of the lung. The epithelial cells lining the
mucous membrane of the bronchial tree from the stem to the minute branches
are entodermal cells which exhibit varying degrees of differentiation and
specialization. The entodermal ancestor cell is capable of developing into a
variety of cells which include columnar cells with cilia; goblet cells; cuboidal
cells, which form acinar or tubular structures and which produce a mucous or
serous secretion; indifferent cells lining the ducts of these glands; and cuboidal
or low cuboidal cells, without cilia, which line parts of the terminal bronchioles.
In addition to these cells, varying numbers of other epithelial cells lie
beneath the ciliated columnar and goblet cells, filling the gap between them
and the basement membrane. Some of these epithelial cells, like the basal
cells in the epidermis, are lined up along the tunica propria, and their oval
nuclei form one or several rows. Their cytoplasm is scanty and the cell borders
are scarcely discernible. They appear to be the only epithelial cells in the
mucous membrane of the bronchial tree which are concerned with cell division
and cell differentiation: I t seems reasonable, therefore, to look upon them
as the reserve cells from which the ciliated columnar cells and goblet cells are
replenished. These reserve cells naturally also possess the qualities of their
ancestor cells in that they may differentiate into any kind of epithelium which
an entodermal cell is capable of producing. If we assume with Whitmore
(17) that the epithelial cells which replace other epithelial cells in a given area
retain their embryonic potentialities, it is easy to see how in the course of
forced and frequent cell division dominant characteristics may be supplanted
by recessive ones and how stratified squamous epithelium may be produced by
the reserve cells.
The assimption that the reserve cells are the parent cells of all three types
of carcinoma'of the lung is substantiated by. the following facts: ( I ) the occurrence of carcinomas of the lung composed entirely of reserve cells; (2) the
demonstrable transformation of reserve cells into either squamous cells or
columnar cells; (3) the occurrence of carcinomas composed of all three types
of cells.
SUMMARY
AND CONCLUSIONS
The 92 carcinomas of the lung upon which this study is based were encountered in 7433 necropsies on persons over one year of age. According to
their microscopic structure, 49 were squamous-cell, 17 columnar-cell, and 2 6
The cellular pattern of the primary growth is perfectly reproduced in metastasis in the liver
('36204).
reserve-cell carcinomas, a distribution of approximately 50 per cent, 20 per
cent, and 30 per cent respectively.
The occurrence of growths composed entirely of reserve cells, the demonstrable transformation of reserve cells into. either squamous cells or columnar
cells, and the occurrence of carcinomas composed of all three types of cells
seem to support the concept that the reserve cell is the parent cell of all
carcinomas of the lung.
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B., AND HALPERT,
B.: Am. J. Path. 15: 567, 1939.
2. HALPERT,
B.: New Orleans M. & S. J. 91: 439, 1939.
3. HALPERT,B.: Surgery 8: 903, 1940.
4. MOISE,T . S.: Arch. Int. Med. 28: 733, 1921.
5. WELLER,C. V.: Arch. Path. 7: 478, 1929.
6. FRIED,B. M.: Primary Carcinoma of the Lung, Williams & Wilkins Co., Baltimore, 1032.
7. SWEANY,
H. C.: Am. J. Clin. Path. 5: 1, 1935.
8. JAFFE,R. H.: J. Lab. & Clin. Med. 20: 1227, 1935.
9. LINDBERG,
K.: Arb. a. d. path. Inst. d. Univ. Helsingfors 8: 225, 1935.
10. SAMSON,
P. C.: Am. J. Cancer 23: 741, 1935.
11. ROSEDALE,
R. S., AND MCKAY,D. R.: Am. J. Cancer 26: 493, 1936.
12. FABRIS,A,: Tumori 23: 19, 1937.
13. BRINES,0 . A., AND KENNINC,J. C.: Am. J. Clin. Path. 7: 120, 1937.
14. STEIN,J. J., AND JOSLIN,H.L.:Surg., Gynec. & Obst. 66: 902, 1938.
15. Ton, M. C.: Edinburgh M. J. 46: 95, 1939.
16. OCHSNER,
A., AND DEBAKEY,
M.: Surg., Gynec. & Obst. 68: 435, 1939.
17. WHITMORE,E. R.: Bol. Liga contra el ciincer 13: 263, 1938.