HAS THE CANCEIl CELL ANY DIFFERENTIAL
CHARACTERISTICS?
WILLIAM CABPENTER MAcCARTY, M.D.
~ i ~ U i U i f of
J ~ l8 u r g k d
P d k U k J g y , The Mayo ClilLic
AND
EVA HAUMEDEB, M.D.
Graduate Btuiient in Pathology, The Mayo Fouwlatioii, Rocheuter, Mintiesotu
In 1925 the following statement was made ( 8 ) : “Both reparative
regenerative and maligiiant regenerative cells possess one o r more
nucleoli but as a rule those of the malignant cell are much larger in
proportion to the nucleus tliaii those of the reparative cells.” This and
a
b
IN REPARATIVE
REUENERMI’IVE
CELLS (a)
FIQ.1. COMPARATIVE SIZE OF NUCLEOLI
M.4LlQNANT CELLS ( h )
AND
CELLS
FIQ. 2. FRESH,UNFIXEDMALIOXAST
the following statement were made after years of study with measurements of cells and thcir parts in perfectly fresh unfixed and unembedded tissues removed a t surgical explorations and operations. I n
the same year (1925) it was also said ( 7 ) : “The cancer cell may not
always be distinguished from a normal regenerating cell, but this can be
done frequently because there is a difference in the volume-relationship
1Read before the Americnn Association for Cancer Resoarch, Washington, D. C., May 8,
1933.
20
403
404
WILLIAM CARPENTER MACCARTY AND E V A HAUMEDER
between nucleolus, nucleus and the whole cell in reparative regenerative
cells and malignant regenerative cells” (Figs. 1,2 and 3).
In January 1933, a preliminary report on a new series of observations was made (9) in which it was stated: “The mean areas of the
nucleoli OF malignant cells are greater than those of corresponding nonmalignant cells, . . The difference between the nucleolar areas in malignant and non-malignant cells is greater than that between the nuclear
areas. . . In the individual cell the range of the ratio of nucleolar
.
.
. ..
FIG.
3.
SKETCHER, TO SCALE, OF
.
MAIJQNANTCELLS
, ,
FROM
MANY 8OUECEB
They represent those for rnrcinoma, sarcoma, lymphosarcoma, lymphatic leukemia, and
nialignnnt endothelioma. It is inipossible t o distinguish one from the other, but each hue
niorpl~ologiccharacterietics unlike any nornial regenerativo or adult cell in the human body.
area to nuclear area varied from 1:5 to 1:17 for malignant cells and
1: 13 to 1: 45 for non-malignant cells.”
The malignant material of the present report includes 65 cases, and
was taken from the breast, stomach, large intestine (cecum, ascending
colon, transverse colon, descending colon, sigmoid, and rectum), small
intestine, uterus, skin, vulva, ovary, omentum, ureter, kidney, and
lymph nodes. Both primary and secondary or metastatic growths were
dudiecl. Tlie diagnoses were adenocarcinoma, colloid carcinoma, epithelioma, and lyrnphosarcoma.
The non-malignant material was derived from 22 patients with
$1
.h
F
12
11
10
9
FIa. 4.
CO3lPARISON OF SIZES OF NV(’Ll?OI,I OF M.4LIONANT AND
Area
FIG. 8.
NON-MALIQNANT
CELLS
in square micra
COMPARISON OF MEAN AVERAQE SIZE€? OF THE AREAS OF NUCLEI
AND OF NUCLEOLI
OF
MALIONANT
AND NON-MALIGNANT
CELLS IN FORTY-TWO CASES OF VARIOUS
1)IREASES OF THE BREAST
405
406
WILLIAM CAllPENTEIl MACCAl1'L'Y A N D EVA HAUMlWEIl
dironic inflammation, who were definitely known to possess no form of
malignant or benign neoplasms.
Fresh tissue sections, 6 to 12 microns thick, stained with Terry's
modification of Unna 's polychrome methylene blue, were studied under
an oil immersion lens (Spencer obj. 1.8 mm.; N.A. 1.25; tube length
150 mm.; ocular 6x). No description of a method of taking area measurements of cells could be found in the literature; consequently the following method was adopted. The shadows of a number of nuclei aiid
nucleoli, approximately twenty of each specimen, from different parts
of the section, were projected through a constant distance, onto paper,
by means of a camera lucida, and traced. Nearly 4,000 cells and sections of fresh and fixed tissue were studied. The previously traced
nuclei and nucleoli then had to be enlarged in order to obtain measurable
arcas of the latter (Spencer obi. 48 mm.; N.A. 0.08; ocular 1 x ; tube
FICI.
6.
RATIO OF
NWLEUSTO NUCLIWLIIS
OF MALIGNANT
AND
NON-MALIQNANT
CELL6
length 250 mm.). A planimeter was used to determine the projected
areas of nuclei and nucleoli. F r o m these measured areas of the enlargements, the actual areas were obtained by dividing by the appropriate constant of magnification; the final areas were expressed in
square microns (Figs. 4,5,and 6 ) .
If these observations are correct, there is certainly a great diffcrence between malignant (cancerous) cells and those which might be confused with them; that is,. such regenerative forms as fibroblasts, endothelioblasts, and other immature cells. If this difference exists, it
points to the absolute necessity for histopathologists to become fresh
tissue cytologists, if cancer is to be recognized in its early stages,
It seems fair to conclude that the cancer cell has at least one differential characteristic, and that this must be used by those who expect
to reduce the tremendous mortality from cancer.
A search of the literature reveals no comparative studies of the
HAS THE CANCEW CELL ANY I)IFFERENTIAL CHAHAOTEHISTICS?
407
nucleolus and nucleus, although the size of the nucleus has been studied
by Hartmann (a), Oertel (lo), Boveri ( 2 ) , Epantschin (3), Heiberg
(5,6), and Borst and Nomicos (1).
BIBLIOGRAPHY
1. BORSTAND NOMICOR
:Quoted by Heiberg.
2. BOVERI, THEODOR:
The origin of malignant tumors, Baltimore, Williams and Wilkins,
1929. 119 pp.
3. EPANTSCHIN,
WLADIMIR
: Kernmessungen beim Teerkrebs der weissen Maus, Ztschr.
f. Krebsforsch 26 : 439449, 1927.
4. HARTMANN,
OTTO: Ueber das Verhalten der Zell-, Kern- und Nucleolengrosse und
ihrer gegenseitigen Beziehungen bei Cladoceren wiihrend des Wachstums, des
Generationscyclus und unter Clem Einfluss ausserer Faktoren, Arch. f . Zellforsch.
15: 1-94, 1921.
5. HEIBERQ,
K. A.: Uber die Erkliirung einer Verschiedenheit der Krebszellen von
anderen Zellen, Nord. med. Ark. 3 f., viii, afd. ii, No. 4, 1-20, 1908.
6. HEIBERG,
K. A. : Studien iiher Haut-Epithel-Atypie bei Krebs- und Granulationsgewebe und die diagnostisrhe Verwendung rler Kerngrosse, Virchows Arch. f. path.
Anat. 234: 46-80,
1921.
7. MACCARTY,
W. C. : The cancer cell and nature's defensive mechanism. Surg., Gynec.
L Obst. 41 : 783-793,1925.
8. MACCARTY,W. C.: The early diagnosis of ranerr, Arch. Clin. Cancer Research 1:
11-20,1925.
g. MACCARTY,
W. C., HAUYEDER,
EVA,AND BERKSON,
JOSEPH
: A differential characteristic of malignant cells, Proc. Staff Meet. Mayo Clinic 8: 38-45, 1933.
10. OERTEL,HORST:
On the histogenesis of tumors, particularly cancer, New York M. J.
86: 14-21, 1907.