STUDIES ON LUNG TUMOR 1
A STATISTICAL STUDY OF AUTOPSY CASES OF TUMORSAND THEIR LUNG METASTASIS
Kotoko NAGANO
The 2nd Division of The Tuberculosis Research Institute, Kyoto University(Received for publication August 4, 1960)

As proof of the rapid increase of tumor cases in recent years, the Ministryof Welfare reported last year that death rate from tumors had taken the first rankwith that of cerebral hemorrhage and thrombosis in death rate in Japan. It might
possibly be inferred the reason for the increase of tumor cases is relative, depending on the decrease of death rate due to serious bacterial infections, especiallytuberculosis, and the prolongation of human life.
However, the remarkable increase of lung cancers is of special significancein clinic of chest disease. Many such tumor cases have also been examined at
the clinic of Tuberculosis Research Institute of Kyoto University. However, it
is also necessary for investigation of lung tumors to deal not only with patients
suffering from primary lesions but with metastatic lung tumors from resectedmaterials. From this point of view, pathologic specimens in the depertment ofPathology of Kyoto University were reexamined to statistically clarify the incidence of tumors in various organs and the metastases from those to the lung.
MATERIALS AND METHODS;

The records of 8915 autopsy cases that those which had been examined at theDepartment of Pathology of Kyoto University since April 1901, were reviewed.
Thirty additional cases were omitted from the total death rate because of inadequate records.
The rate of incidence of tumors in various organs and the rate of metastasis
to the lung from those tumors were determined by checking the cases recorded
from 1946 until the present time. At the same time microscopic examinations of all
specimens on file were performed in addition to the checking of the records.
RESULTS;a)Statistics of diseases by cause of death.

As to the cause of death, almost all of tuberculosis cases were pulmonary andmiliary. Extrapulmonary tuberculosis was seen in a few cases. The total of tumor
cases includes some deaths from post-operative complications.

40

Kotoko NAGANO

The vast majority of pulmonary cancers were primary lung cancers including a
few primary cases of sarcoma and fibroma. Among mediastinal and pleural tumors,those thought to be of primary lung origin were added to the pulmonary tumors.
The results, divided into 5 year groups, are shown in Table 1 and Fig. 1.
%_40Tumor cases
Tuberculosis cases

o30201001901-5 6-10 11-1516-2021-2526 -3031-3536-4041-4546-5051 ;"'5556-59
Fig. 1.

Percentages of tuberculosis and tumor cases in the all autopsy cases atthe Department of Pathology of Kyoto Univ.

Table 1.

Statistics of autopsy cases at the Department of Pathology of Kyoto Univ.

~119011190611911 1191611921 1192611931 193611941 1194611951 11956~5 ~10 ~15 -20 -25 -30 -35 1-40 -45 -50 -55 -60
IIAutopsy cases I 796
on fileTuberculosis
271
Percentage of34
all cases

ITumor
Percentage of
all cases

143

1045

906

624

759

681

428

468

426

573

894

312

322

162

128

245

187

101

95

90

50

61

32

31 I

1720

33

28

25

23

21

97248

185

108

123 I 160

121

82 I 106

222

390

20

20

18

16

23

28

20

24

38

43

I

18

I

III!

Lung tumor
Percentage of
all tumor cases

3
2__945

177

18I_I

21 I

732120143 I

1741211 I

20153811The death rate of tuberculosis was the highest from 1901 to 1905 (34%), and thendecreased progressively. The rapid increase found in the period from 1920 to 1930
was caused by the incaease of autopsy cases from a newly established Utano
National Sanatorium. Apparent decrease of death from tuberculosis since 1951 wasthought to be the result of chemotherapy. In contrast with tuberculosis, the death
rate due to neoplasm increased year after year. But the rapid increase from 1951

Lung tumors. 1. Statistical study of autopsy cases of tumors and lung metastasis

41

was rather suprising, and in the last five years since 1955 alone the number of deaths
from neoplasms reached to 40 --50% of the total death rate. It may be worth
mentioning of the increase of pulmonary cancer. During the period from 1901
to 1940, primary pulmonary cancers were 1--2% of all tumors, and after that
increased rapidly to 11% in the last five years. In 1959, the number of pulmonary
tumor cases surpassed those due to tuberculosis. Table 2 and Fig. 2 compare thedeath of tuberculosis with that of neoplasm since 1945.
%

60_Tumor cases

oTuberculosis cases

50403020
100

1946Fig. 2.

Table 2.

47

49

48

5051

52.

53

54

55

56

58

59

Percentages of tuberculosis and tumor cases in autopsy cases at theDepartment of Pathology of Kyoto Univ. at the latest fourteen years
Tuberculosis and tumor cases observed in autopsy cases at the Departmentof Pathology of Kyoto Univ. at the latest fourteen years

II~~~~I1946 47

,

48

49

50

I,

I

51

53

52

54

IiI

55

57

58

144 187

252

228

227

1893

1324

14

10200710641088

102 I 109

718

49

35

46[483891559

914885

92

7390

86

79

1001132

Tuberculosis

1824161220

710 I 12129

Percentage of
all cases

2126

221

13

23

9101

910632

43

118

III

I

22

I

17

23

27 i

22

Total

II

22

I I I 1591
56

Autopsy caseon file

Tumor

57

58

6291

I

1

Percentage of
all cases

2426

23

26

24

33

32

33

48

42--1I

Lung tumor
Percentage oftumor cases

001b)

0000I

21

75

12

53

81671

3481

757918I

Investigations with reference to the primary organs of neoplasms.

Tumors were classified into two large categories, that is, benign and malignant. Leukemia and sarcoma were separated from other malignant neoplasms

42

Kataka NAGANO

into special classes. Tumors originating in the brain or nervous system wereomitted from the present study because of their special nature and difficulty inclassification. In addition, all tumors listed in the tables as neoplasms from thesensory organs were almost entire from the skin. Classification is shown inTable 3.
Table 3.

Classification of tumor cases according to the organs fromwhich the tumor originatedI

1946 47 [ 48 I 49 50 51 52 53 54 55 56 57 58 59[ Total:r~a:~~-~-Y:I
OrganII

Sensory organs
Internal secretionorgansDigetative organs
Liver and pancreas
Respiratory organs
Urinar organs (~)
Genital organs (9)""OthersTotal of Cancers

II

I

I

1

152
17Brain
Sarcoma
Leukemia
Benign tumor

122Total

I 22\292
11315
1
151

1043531124112120

141
17

132

11
11I221I

171 2312334182819101129
18
929
16
151989467

4
114669

4424

26778

3
711105416541554

121314
24

7128

13235

2
162
1533
91~18691321

43 1 5862\

3
32~I221

27\

3

192
62~1I

112322I

11254I

338~II118[836267

482

66
42523

311943759
82
1688 \ 101 \ 1091

717

71
8,:1 :1

8110291:1

As a characteristic of neoplasms in Japan, it is shown also in this study thatcancer from gastrointestinal organs is the most frequent of all cancers. Liver,pancreas and genital organs followed in descending order. Cancer of respiratoryorgans is the fifth, but has increased since 1949 and it is of interest that thisincrease shows a sharp rise since 1956. Genitourinary cancer also has increasedrecently.
As for cancers in the other organs, neither apparent increase nor decreaseis noted as in the case with sarcoma and leukemia.
c)Investigation with reference to the metastasis of neoplasm to the lung.

It has been shown in Table 4 that in a total of 504 cancer cases, metastasis
to lung occurred in 194 cases. This is 38% of all cancer cases. Besides, it isfound that the metastasis of sarcoma to the lung is 48% of all sarcoma cases
and is likely a little more frequent than that of carcinoma. When all cancers
are divided according to anatomical systems, it is shown that the rate of metastasis is the highest in the genitourinary system and the lowest in the digestive

Lung tumors.

431. Statistical study of autopsy cases of tumors and lung metastasis

Table 4.

Lung metastasis of tumors

Number oftumor cases

OrganSensory organs

Cases of lungmetastasis

3218
192
9264247(1946-1959)
Percentage%

Number ofhilar
lymph nodemetastasis

Percentage

%

1442
1835
41(33)

119125182323Total

6139504529
14194(67)
39
33
41
39
46
45
48
3638

Sarcoma

50

2448

1122554

218

39

136

25

Internal secretory organs
Digestive organs
Liver and pancreas
Respiratory organs
Urinar organs( C3 )

Geni tal organs(Others

Total<;:> )

I1163
38
25
1122222055
179system. The difference between the rate of metastasis from these two system is
not so great, but marked differences were found when the tumors were classified
by organ or tissue in which the tumor originated.
Table 5 shows the rate of metastasis to the lung from each organ. It seems
that metastasis of cancer from the maxilla, breast, kidney and ovary are ofrelatively high frequency and those from rectum, urinary bladder, pancreas andstomach occur less frequently. The rate of metastasis of hepatic cancer is about
50576, and this value is almost the same as the rate of metastasis of hepatoma.
It is of interest that the rate of metastasis of chorioepithelioma is very high, 12
out of 13 cases, showing almost 100%, whereas the rate of metastatic cancer ofthe uterus is rather low, showing 25%. Metastases from the brain is very rare,
and its rate is only 5 %.
Table 5 also shows the classification according to Welther's type!). Thisshows the type of hematogeneous spread of tumor metastases; type II being
called the hepatic type, type III, the large circulatory type, and type IV, theportal type. The rate of both type II and III is 50% and that of type IV is only
329'0. This seems to indicclte that the cancer cells are filtered and removed fromthe blood stream in the liver and thus metastase to the lung is prevented.
Metastasis to the hilar lymph nodes of the lung is shown in Table 4. Metastasis
to the hilar lymph nodes from each organ is only 9 --23%, except for the respiratory organ. It is clear that metastasis to the hilar nodes is less than that to thelung tissue. As for the lung tumor metastasis to the hilar lymph nodes is veryfrequent, showing a rate of 5%, and this rate is two times as high as the rateof metastasis to the other lung. The rate of metastasis of sarcomas to the hilar
lymph nodes is 2296 and is almost equal to the rate of cancer metastasis.

44

Kotoko NAGANO
Table 5.

Lung metastasis of tumors according to Welther's classification----

Welther'stype------------------

Organ.

I

Liver
Liver (Hepatoma)

II

Cases
examined---

I

53

Total

Case ofmetastasis
II131026207

Gall-duct (Intrahepatic)

I pe~::age~-_.--[326I----------------

MaxillaParotisTongueThyroid

11ThymusPharynx
Larynx252381920(100)080

4523326067916767837879264258644

Bladder
Uterus1535492625

Uterus (Chorioepithel)
Ovary
Prostata

13981263Penis
Skin

130116480

237533Colon
Peritoneal

163
1578

Gallbladder
Total

3219

070

Brain
Hypophysis

38
320

50

Total

41

27I

BreastOesophagus

IIII5050
4350

I Rectum
KidneySuprarenal

ITotal

I10067137033503-----~~

Pancreas

I StomachGall-duct (Extrahepatic)

IVI

30
3320343I

3I

5738032IDISCUSSION AND SUMMARY;

Although the number of autopsies performed at the Department of Pathology,
Kyoto University, are rather small in comparison with the number done inEuropean and American labolatories, it seems that the number of 8915 is not

Lung tumors.

1. Statistical study of autopsy cases of tumors and lun6 metastasis

45

too small to show the variation of important diseases in Japan throughout these
60 years as revealed by autopsy findings.
The present investigations dealing with tuberculosis and neoplasm show
marked changes in occurrence and death rates. In the past 10 years, death fromtuberculosis rapidly decreased on account for the chemotherapy. Contrarily deathfrom neoplasm increased year after year, and rapidly increased in the past tenyears. Especially the recent increase of the pulmonary cancer was remarkable,
and the death of cancer became more frequent than that of tuberculosis in autopsy
cases.
Among deaths from neoplasm during the past ten years, death of sarcoma
and leukemia totaled 512 cases. The death rate of cancer is about 3 ---4 times asmuch as that of sarcoma.
No remarkable difference is seen when the rates of metastasis to the lungare classified according to organ systems. When classified, however, according tochanges of spesific organs or tissues, the rate of metastasis is quite different.
When organs are classified according to Welther into the hepatic type, the large
circulatory type and the portal type, the metastasis to the lung from the former
two types are certainly less than the third one.
In the data of Maehara (1959)2) which was obtained by histological investigation of 134 tumor cases classified according to the Welther's type, the frequencyof lung metastasis of these tumors is the highest in the large circulatory type(62.29~), the second in the portal type (52.896), and the lowest in the hepatictype (47.096). It must be considered that the disagreement of this data withpresent writer's data shows the deficiency of importance of the transport wayof tumor cells. The principle of WeIther's metastatic type was excluded fromthe data in which the tumor types were listed separately from types of tumors
originating in the same organ.
Lung metastasis of tumors results from direct extension and hematogeneousand lymphogeneous spread. Metastasis by the bronchogeneous route is mostfrequently observed in the extension of lung cancer to another part of the samelung and is not important in the lung metastasis from extrapulmonary tumors.
Direct extension need not be included in this statistics of lung metastasis becauseof the rare occurrence of mediastinal and pleural tumors. Lymphogeneous(especially retrogressive) metastasis have been considered the main route of implantation of tumor cells because of the high percentage of metastasis to hilar
lymph nodes. The presence of cancerous lymphangitis was again shown in theKuwahara's data (1952)3) as in the old report of Recklinghausen (1885)4). But
as shown in the Table 4, the rates of metastasis of cancer and sarcoma to hilar
lymph nodes are almost the same (22 and 23%) and these are far less than thepercentage of lung metastasis. This may refute the hypothesis that metastasis
to the lung mainly occurs through the lymph pathway instead of the blood canal.

46

Kotoko NAGANO

There are quite a few reports concerning the rate of metastasis to the lung.
Schmidt (1904) 5) stated that the occurrence of lung metastasis was 68.3% of all
autopsy cases on patients who died of neoplasms. Later the rate of lung metastasis was reported to be 28.6% by the research of Katain (1922)6\ 57.3% byDeelman (934)7), 58.3% by Kost (926)'n, 82.4% by Kawachino (936)9\ 30.3%
by Turner (1940)10), 28.7% by Hubeny (1940)11\ 27.7% by Welther (1948)1), 46.4%
by Abrams (1950)12\ 47.5% by Kuwahara (1952)3), 29% by Willis (952)13\ 22% by
Lee (1955)14\ and 64.2% by Maehara (1959)2\ In the present writer's research,
it is clear that 38% of all cancer cases exclusive of primary pulmonary tumors
have some macroscopic or microscopic evidence of lung metastasis. These datareported by many authors are not unit ;--fm according to the materials and methods
used. So it is difficult to attempt to show any correlation in common among
these different data.
Additionally, as the percentages of lung metastc_sis of tumors vary as towhether primary foci are classified according to organ systems, organs, or typesof neoplasms, it may not be significant to discuss universal rates of metastasisof neoplasms to the lung.
In conclusion, we believe that (1) the lung metastasis of cancer is only alittle less than that of sarcoma, and (2) the fact that metastasis to the lungoccurs much more frequently than those to the pulmonary hilar lymph nodes,
may suggest that the majority of metastasis of cancer to the lung pass throughthe blood canal of the greater circuratory system. Histological findings supporting this hypothesis will be reported in detail in the subsequent papers.
This auther greatly indebted to Prof. Suzue and Prof. Okamoto (Departmentof Pathology, Kyoto University) for records of autopsy cases and requisite materials.
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Deelman, H. T.: Ztschr. Krebsf. 40; 271, 1934.
Kost, G. F. W.: Ztschr. Krebsf. 43; 291, 1936.
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